@article {pmid42135779, year = {2026}, author = {Abu Elnga, NE and Safina, MK and Shehata, MR and Ayoub, MT and Soliman, A}, title = {Reliability and oncological safety of pedicled skin island therapeutic mammoplasty as an alternative to Grisotti mastopexy for centrally located breast cancer patients.}, journal = {World journal of surgical oncology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12957-026-04399-z}, pmid = {42135779}, issn = {1477-7819}, abstract = {BACKGROUND: Centrally located breast cancers (CLBC) involving the nipple-areolar complex (NAC) pose a significant challenge for breast-conserving surgery, often necessitating mastectomy. The Grisotti flap, while a valuable oncoplastic technique, has limitations in vascular reliability and applicability, especially post-neoadjuvant chemotherapy. We introduce a novel "Pedicled Skin Island Therapeutic Mammoplasty" (PSI-TM) as an alternative.

METHODS: This single-center retrospective study analyzed 23 consecutive patients with CLBC infiltrating or fixed to the NAC who underwent PSI-TM between April 2018 and June 2023. All patients had medium-to-large breast volumes (Cup C/D). Data on demographics, tumor characteristics, surgical outcomes, complications, aesthetic results, and oncological safety were collected and analyzed.

RESULTS: The cohort was predominantly premenopausal (82.6%) with invasive ductal carcinoma (87.0%). Most patients (73.9%) were treated post-neoadjuvant chemotherapy. The overall complication rate was 21.7% (5/23), all Clavien-Dindo Grade I-II, with no returns to the operating room. The combined ratings from the surgeon and independent observer were 'Good' or 'Very Good' in 73.9% of cases (17/23). Over a median follow-up of 50 months, there were no instances of positive margins, local recurrence, or distant metastasis.

CONCLUSION: PSI-TM is a feasible and safe oncoplastic technique for CLBC with NAC involvement. It may offer improved vascular security compared to the traditional Grisotti flap based on theoretical anatomical advantages, leading to low complication rates, excellent aesthetic results, and encouraging early oncological outcomes, even in a post-neoadjuvant setting.}, } @article {pmid42138073, year = {2026}, author = {Morigny, P and Ji, H and Cussonneau, L and Zorzato, S and Kwon, Y and Riols, F and Kaltenecker, D and Maier, A and Karthikaisamy, V and Corrà, S and Krauss, T and Seeliger, C and Gillani, SQ and Tissink, JJ and Lacas-Gervais, S and Samanci, TF and Maida, A and Terron-Exposito, R and Trinca, A and von Toerne, C and Nogara, L and Claussnitzer, M and Prokopchuk, O and Bachmann, J and Berriel Diaz, M and Bindels, LB and Kuda, O and Hauner, H and Haid, M and Herzig, S and Viscomi, CF and Gilleron, J and Zeigerer, A and Blaauw, B and Rohm, M}, title = {Inhibition of ceramide synthesis ameliorates body wasting in a cancer cachexia model.}, journal = {The Journal of clinical investigation}, volume = {136}, number = {10}, pages = {}, doi = {10.1172/JCI194687}, pmid = {42138073}, issn = {1558-8238}, mesh = {Animals ; *Ceramides/biosynthesis/antagonists & inhibitors/genetics ; *Cachexia/metabolism/pathology/etiology/drug therapy/genetics ; Mice ; Male ; Humans ; Liver/metabolism/pathology ; Disease Models, Animal ; Fatty Acids, Monounsaturated/pharmacology ; Serine C-Palmitoyltransferase/metabolism/antagonists & inhibitors/genetics ; Cell Line, Tumor ; *Colonic Neoplasms/metabolism/pathology/complications ; Mice, Inbred C57BL ; }, abstract = {Cachexia is a metabolic wasting syndrome affecting many patients with cancer, with poor survival outcomes. Disturbed lipid metabolism is a hallmark of cachexia, and our previous work has identified increased levels of circulating ceramides, which are bioactive lipids with adverse effects in metabolic diseases, as biomarkers for cachexia in mouse models and patients. Here, we investigated the role of ceramides on cachexia development using the well-established C26 colon carcinoma model. We demonstrated that elevated ceramides in cachexia arose from increased liver synthesis. We showed that ceramides directly contributed to impaired mitochondrial function and energy homeostasis in cachexia target tissues. Targeting ceramide synthesis using miRNA interference, or myriocin, an approved compound targeting the key synthesis enzyme serine palmitoyltransferase (SPT), improved markers of muscle atrophy in cachectic male mice. Importantly, we demonstrated that key enzymes involved in ceramide production were also elevated in livers, but not in other organs, of patients with cancer cachexia, correlating with disease severity. Our data place ceramides as contributors to metabolic dysfunction in cachexia and highlight the suitability of the ceramide synthesis pathway for therapeutic targeting.}, } @article {pmid42121358, year = {2026}, author = {Qu, L and Li, J and Ding, S and Long, Q and Yi, W}, title = {Exploring key biomarkers associated with axillary lymph node metastasis in breast cancer using single-cell RNA sequencing and Mendelian randomization.}, journal = {The International journal of biological markers}, volume = {}, number = {}, pages = {3936155261443650}, doi = {10.1177/03936155261443650}, pmid = {42121358}, issn = {1724-6008}, abstract = {BackgroundAxillary lymph node metastasis (ALNM) serves as a critical prognostic determinant in breast cancer, yet the molecular drivers governing lymphatic dissemination remain poorly characterized. Integrating single-cell transcriptomic profiling with Mendelian-randomization (MR)-based genetic prioritization may help reveal cell type-specific mechanisms underlying metastatic progression.MethodsWe analyzed the GSE195861 single-cell RNA sequencing dataset encompassing six invasive ductal carcinoma (IDC) samples and paired ALNM specimens. t-distributed Stochastic Neighbor Embedding-based clustering and SingleR annotation delineated cellular heterogeneity, while differential expression analysis identified metastasis-associated genes in epithelial compartments. MR analysis employing five robust methods (inverse variance-weighted, weighted median, MR-Egger, simple/weighted mode) integrated genome-wide association study data (GCST90018799) to establish causal gene-breast cancer associations. CellChat reconstructed ligand-receptor networks across nine annotated cell types.ResultsUnsupervised clustering resolved 27 cell clusters into nine lineages, revealing ALNM-specific expansion of monocytes, pre-B cells, and CD34+ hematopoietic stem cells (HSCs). Epithelial cells exhibited 2421 differentially expressed genes (DEGs) between IDC and ALNM, including 12 genes whose genetically predicted expression showed significant associations with breast cancer risk in MR analysis (P < 0.05). CD53 (odds ratio (OR) = 1.110, 95% confidence interval (CI) = 1.019-1.209, P = 0.017) and TCDD-inducible poly-ADP-ribose polymerase (TIPARP) (OR = 1.153, 95% CI = 1.032-1.288, P = 0.012) were prioritized as candidate genes, as their genetically predicted expression was associated with increased breast cancer risk in weighted median MR. Cell-cell communication analysis implicated macrophage-derived midkine-nucleolin signaling and B-cell-orchestrated macrophage migration inhibitory factor-(CD74 + CXCR4) axis in metastatic crosstalk. Functional enrichment linked DEGs to extracellular matrix remodeling and MAPK/PI3K-Akt activation.ConclusionThis multi-omics integration prioritizes CD53 and TIPARP as ALNM-associated candidate genes with genetically supported associations with breast cancer risk, with macrophage-epithelial and B-cell-HSC interactions serving as potential therapeutic targets. Our findings provide a roadmap for developing metastasis-interceptive strategies through precision targeting of the ALNM-associated tumor microenvironment.}, } @article {pmid42131880, year = {2026}, author = {Mapoko, BSE and Atenguena, E and Moun, ANN and Bell, ED and Tabola, L and Anaba, D and Sango, A and Tayou, R}, title = {Clinical, therapeutic and prognostic characteristics of de novo metastatic breast cancer in Cameroon.}, journal = {Ecancermedicalscience}, volume = {20}, number = {}, pages = {2092}, pmid = {42131880}, issn = {1754-6605}, abstract = {INTRODUCTION: The dilemma of the incurability of metastatic breast cancer has driven therapeutic advances aimed at prolonging survival. However, access to these innovative treatments remains a significant challenge in low-income countries. Consequently, a diagnosis of de novo metastatic breast cancer (dnMBC) may be perceived as a diagnosis of imminent death. We aimed to analyse the clinical, therapeutic and prognostic characteristics of dnMBC in a Cameroonian context.

METHODOLOGY: We conducted a cross-sectional, descriptive study with retrospective data collection from 116 patients with dnMBC followed in two cancer reference hospitals in Yaoundé, Cameroon, between 2020 and 2022. Data were analysed using SPSS version 25 and Excel 2019.

RESULTS: Of 1,006 confirmed breast cancer cases, 116 were dnMBC (prevalence: 11.53%). The mean age was 47.4 ± 12.1 years, and males accounted for 1.72% of the sample. Pathologically, the predominant subtype was invasive ductal carcinoma (92.2%; n = 83), with hormone-sensitive hormone receptor+/HER2 human epidermal growth factor receptor 2 - tumours being the most frequent among those with available immunohistochemistry (IHC) (58%; n = 18). The disease was often polymetastatic (69.8%), with the most common sites being the lungs (72.4%) and liver (40.5%). Treatments were mainly systemic (53.2%), sometimes combined with surgery (43%). The median overall survival was estimated at 24 months (95% CI = 14.21-33.78).

CONCLUSION: Survival outcomes for dnMBC remain poor, limited by the lack of full access to optimal care, including systematic IHC testing. A more effective multidisciplinary approach to the disease and the factors affecting survival is needed for optimal utilisation of available therapeutic regimens.}, } @article {pmid42135205, year = {2026}, author = {Schiebl, M and Trnková, P and Heilemann, G and Jindráková, M and Tögl, S and Georg, D and Lechner, W}, title = {A probabilistic framework for risk-bounded patient-specific quality assurance in volumetric modulated arc therapy based on measured and calculated gamma pass rates.}, journal = {Zeitschrift fur medizinische Physik}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.zemedi.2026.04.003}, pmid = {42135205}, issn = {1876-4436}, abstract = {This study introduces a probabilistic framework for patient-specific quality assurance (PSQA) in volumetric modulated arc therapy (VMAT), using gamma pass rates obtained from both measurement-based and independent calculation-based PSQA. The model quantifies the probability that treatment plans classified as acceptable by an independent dose calculation (IDC) algorithm would nevertheless fail measurement-based verification. This probability, referred to as the false omission rate, represents the residual risk of skipping measurements for plans classified as unproblematic by the calculation. Receiver operating characteristic (ROC) analysis demonstrated limited discriminative performance of the IDC, underscoring that reliance on calculation alone entails non-negligible miss probabilities. In a retrospective cohort of 1346 clinical VMAT plans across multiple anatomical sites, false omission rates ranged from below 1% in well-represented groups such as prostate to above 20% for sparsely represented treatment regions. Based on these empirically derived miss probabilities, the framework allows the definition of measurement intervals that constrain the cumulative probability of undetected plan failure below a predefined institutional threshold. In this way, PSQA strategies involving reduced measurement schedules for selected plans can be quantitatively assessed and constrained within explicit probabilistic safety limits. The proposed method is transparent, independent of complex machine learning models, and directly applicable to empirical QA datasets. By making the risk of undetected failure explicit and quantifiable, it enables structured, risk-informed PSQA policies grounded in defined safety constraints.}, } @article {pmid42135608, year = {2026}, author = {Dy, A and Lennerz, JK}, title = {Ki-67 as a Treatment Decision Modifier in Breast Cancer.}, journal = {The oncologist}, volume = {}, number = {}, pages = {}, doi = {10.1093/oncolo/oyag183}, pmid = {42135608}, issn = {1549-490X}, abstract = {Ki-67 is widely used in breast cancer; however, the fraction of patients in whom it meaningfully alters treatment decisions is not well established. Using a guideline-based approach anchored in National Comprehensive Cancer Network (NCCN) recommendations (v2.2026), we identified clinical scenarios in which Ki-67 directly modifies adjuvant therapy decisions and estimated their prevalence using population-level data and complementary datasets, recognizing that fully annotated datasets capturing all relevant clinicopathological variables remain limited. A back-of-the-envelope model suggests that only a small fraction of patients meet the combined criteria of HR+/HER2- subtype, T2 stage, grade 2 histology, and Ki-67 ≥ 20%. This estimate, compared to population-scale (n = 117,990 patients) and curated datasets (n = 1,356 patients), indicates that the clinically relevant subset remains in the low single digits (3-5%). Ki-67 meaningfully impacts care only in specific decision settings, particularly near clinically relevant thresholds where small analytic variation may translate into treatment changes; outside these contexts, its routine use has limited evidence for clinical utility. Its application should therefore be selective, context-dependent, and focused on scenarios in which threshold-adjacent precision is clinically consequential.}, } @article {pmid42120740, year = {2026}, author = {Chen, C and Liu, X and Wu, S and Lin, SX and Feldman, AS and Wu, CL and Dahl, DM}, title = {Cribriform/Intraductal carcinoma exhibits superior prognostic value over Gleason pattern 4 percentage and tertiary pattern 5 in Gleason pattern 4 prostate cancer.}, journal = {World journal of urology}, volume = {44}, number = {1}, pages = {}, pmid = {42120740}, issn = {1433-8726}, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/surgery ; Neoplasm Grading ; Retrospective Studies ; Prognosis ; Middle Aged ; Aged ; Prostatectomy ; Neoplasm Recurrence, Local/epidemiology ; }, abstract = {BACKGROUND: In the absence of primary or secondary pattern 5, Gleason pattern 4 encompasses Gleason scores 3 + 4, 4 + 3, and 4 + 4 at radical prostatectomy (RP). The associated adverse pathological features, including Gleason pattern 4% (%GP4), cribriform/intraductal carcinoma (Crib/IDC), and tertiary pattern 5 (TP5), have become particularly important factors for improving postoperative risk stratification. However, few studies have simultaneously evaluated the prognostic significance of %GP4, Crib/IDC, and TP5 specifically within Gleason pattern 4 disease.

OBJECTIVE: To investigate the prognostic significance of %GP4, Crib/IDC and TP5 for biochemical recurrence (BCR) and metastasis in RP patients with Gleason pattern 4 disease.

METHODS: A retrospective cohort of RP patients with Gleason pattern 4 disease was identified from 2008 to 2014 at Massachusetts General Hospital. Pathological variables included %GP4, Crib/IDC, and TP5. Patients were stratified by these features to assess their prognostic impact. Cox proportional hazards models were applied to evaluate their prognostic associations with BCR and metastasis.

RESULTS: Among 559 RP patients with Gleason pattern 4 disease, 55.1% had %GP4 ≥ 50%, 49.0% were Crib/IDC-positive, and 12.3% exhibited TP5, with these three variables exhibiting clear interrelationships. All three adverse morphological features were associated with significantly worse BCR-free survival and metastasis-free survival (log-rank P < 0.001). In multivariable Cox regression, Crib/IDC demonstrated the strongest prognostic association, independently predicting an 80% increased risk of BCR (HR 1.80, 95% CI 1.35-2.40) and 90% increased risk of metastasis (HR 1.90, 95% CI 1.19-3.03). %GP4 remained a significant continuous predictor of both endpoints (HR 1.009 per 1% increase for BCR; HR 1.016 for metastasis), whereas TP5 retained significance as a predictor only for BCR (HR 1.47, 95% CI 1.04-2.06) but not for metastasis (HR 1.31, P = 0.298).

CONCLUSION: %GP4, Crib/IDC, and TP5 were correlated and adverse features in RP patients with Gleason pattern 4 disease and were associated with worse oncologic outcomes. Crib/IDC demonstrated the strongest prognostic relevance, supporting consideration of standardized reporting beyond Gleason score alone.}, } @article {pmid42115324, year = {2026}, author = {Munari, E and Antonini, P and Cima, L and Polati, R and Caliò, A and Gobbo, STM and Colecchia, M and Netto, GJ and Antonelli, A and Bertolo, RG and Grisi, C and Litjens, G and Brunelli, M}, title = {The evolution of prostate cancer grading: from Gleason score to risk taxonomy and the artificial intelligence revolution.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {}, number = {}, pages = {}, pmid = {42115324}, issn = {1432-2307}, abstract = {Histopathological grading remains the cornerstone of risk stratification in prostate cancer, yet conventional Gleason-based assessment is limited by interobserver variability and by the biological heterogeneity concealed within Gleason pattern 4. This review examines the evolution of prostate cancer grading from the original Gleason system to contemporary Grade Groups and to newer morphology-based frameworks that seek to refine prognostic stratification. Particular attention is given to the distinction between patterns 3 and 4, which remains clinically pivotal but diagnostically challenging, especially in the setting of poorly formed glands. By contrast, cribriform architecture has emerged as one of the most reproducible and prognostically adverse components of pattern 4. Intraductal carcinoma of the prostate (IDC-P), which often overlaps morphologically and biologically with cribriform carcinoma, is similarly associated with aggressive disease and is now addressed within a more unified diagnostic and grading framework following the recent joint GUPS/ISUP recommendations. Outcome-based morphometric studies further suggest that a diameter threshold of approximately 0.25 mm can identify large cribriform glands with particularly adverse behavior, although standardization remains incomplete. These observations have contributed to the development of a risk-oriented taxonomy in which adverse architectural features may carry greater prognostic weight than numerical grade alone. Finally, we discuss how digital pathology and artificial intelligence are extending this conceptual shift by improving diagnostic reproducibility, enabling quantitative detection of cribriform morphology and supporting outcome-oriented histology-based risk prediction. Together, these developments suggest that prostate cancer grading is moving from a purely descriptive system toward a more integrated and biologically informed model of risk assessment.}, } @article {pmid42117483, year = {2026}, author = {Haq, MM and Benson, C and Kunz, M and Cheung, EYL}, title = {Unraveling myoepithelial cell plasticity in breast cancer: a transcriptomic approach.}, journal = {Journal of histotechnology}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/01478885.2026.2655881}, pmid = {42117483}, issn = {2046-0236}, abstract = {Myoepithelial cells (MECs) are integral to mammary gland physiology, classically serving a structural and tumor-suppressive role. While their function in normal breast tissue and ductal carcinoma in situ is well characterized, their behavior in human invasive breast cancer has not been previously examined. In this study, we performed a comprehensive transcriptomic analysis of MECs isolated from seven archived human breast cancer specimens, directly comparing them with MECs from adjacent normal tissue to define gene expression changes associated with invasive progression. The analysis revealed marked transcriptomic reprogramming across three key domains: extracellular matrix (ECM) interactions, epithelial-mesenchymal transition (EMT), and cellular signaling. Notable findings include stromal remodeling characterized by overexpression of 17 distinct collagen genes; compromise of the basement membrane through upregulation of matrix metalloproteinases (MMPs 2, 9, 11, and 14); and dysregulation of epithelial markers (KRT5, KRT7, KRT14), consistent with a phenotypic shift toward a cancer-associated fibroblast (CAF)-like state. In addition, increased expression of pro-tumorigenic mediators such as SPARC, POSTN, and integrin subunits was observed. Despite the limited sample size, these results indicate substantial molecular plasticity in MECs, suggesting a transition from a tumor-suppressive to a tumor-promoting phenotype during invasive disease. Overall, this study identifies a fundamental shift in myoepithelial identity and provides a critical framework for future investigations into the role of MEC plasticity in driving breast cancer progression.}, } @article {pmid42107952, year = {2026}, author = {Hassan, M and Al-Askeri, M}, title = {INTEGRATED ANALYSIS OF ERΑ, TP53, AND PGR PROTEINS WITH MIR-372, MIR-373, AND MIR-519D DYSREGULATION IN FEMALE BREAST CANCER.}, journal = {Georgian medical news}, volume = {}, number = {372}, pages = {171-179}, pmid = {42107952}, issn = {1512-0112}, mesh = {Humans ; Female ; *MicroRNAs/genetics/blood ; *Breast Neoplasms/genetics/blood/pathology/diagnosis ; *Estrogen Receptor alpha/genetics/blood ; *Tumor Suppressor Protein p53/genetics/blood ; Middle Aged ; Case-Control Studies ; Gene Expression Regulation, Neoplastic ; *Receptors, Progesterone/genetics/blood ; Biomarkers, Tumor/genetics/blood ; Adult ; ROC Curve ; Aged ; }, abstract = {BACKGROUND: Breast cancer is the most prevalent cancer among women in the world and is one of the causes of mortality due to cancer. Estrogen receptor alpha (ERα) and progesterone receptor (PGR), as well as tumor suppressor protein TP53, are the hormone receptors that are of critical importance in tumor progression and response to treatment. There is emerging evidence that miRNAs (miR-372, miR-373 and miR-519d) have a role to play in breast cancer pathogenesis by post-transcriptionally regulating genes. Nevertheless, the joint analysis of these protein markers and miRNAs is not studied thoroughly.

OBJECTIVE: To evaluate serum levels of ERα, TP53, and PGR proteins and assess the expression of miR-372, miR-373, and miR-519d in breast cancer patients compared with healthy controls, and to determine their diagnostic and clinicopathological significance.

METHODS: This case-control study included 53 female breast cancer patients and 25 healthy controls. Serum protein concentrations of ERα, TP53, and PGR were measured using sandwich ELISA. Total RNA was extracted from peripheral blood leukocytes, and miRNA expression was quantified using RT-qPCR with the 2^-ΔΔCT method. Statistical analyses were performed using SPSS, including independent t-tests, ANOVA, Pearson correlation, and ROC curve analysis. Statistical significance was set at p≤0.05.

RESULTS: ERα and TP53 levels in serum were extremely high in patients with breast cancer as compared to controls (p<0.001). There was a significant difference in PGR levels between the stage III and IV disease (p=0.01). Invasion ductal carcinoma (IDC) had significantly higher ERα levels than lobular carcinoma (p=0.03), whereas lobular carcinoma had significantly higher TP53 levels (p=0.05). The miR-372, miR-373 and miR-519d levels of expression were found significantly lower in the patients than in the controls (p<0.001). ROC curve analysis indicated that ERα (AUC=0.99), TP53 (AUC=1.0) and PGR (AUC=0.98) had excellent diagnostic results, whereas miRNAs under study had inverse discriminatory performance. There was strong positive association between ERα, TP53 and PGR (p=0.001) as well as there was strong positive association between the miRNAs being studied (p=0.001). Interestingly, there were significant negative relationships between the level of proteins and the level of miRNA (p=0.001).

CONCLUSION: High levels of serum ERα, TP53 and PGR have a close correlation with the presence of breast cancer and its subtype variation and have high diagnostic specificity. The down regulation of miR-372, miR-373 and miR-519d may indicate a possible tumor-suppressive effect and regulatory interplay with hormone and tumor suppressor pathways. These results show that protein and miRNA biomarkers are both useful in relation to breast cancer diagnosis, and possibly in determining individual therapeutic approaches.}, } @article {pmid42108880, year = {2026}, author = {Okonogi, N and Karasawa, K and Murata, K and Omatsu, T and Murata, H and Wakatsuki, M and Ishikawa, H}, title = {Carbon-Ion Radiation Therapy as Nonsurgical Treatment for Early-Stage Breast Cancer: 5-Year Results From the Phase 2 Part of the First Prospective Clinical Trial.}, journal = {International journal of radiation oncology, biology, physics}, volume = {124}, number = {4}, pages = {971-976}, doi = {10.1016/j.ijrobp.2025.10.020}, pmid = {42108880}, issn = {1879-355X}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/radiotherapy/mortality/drug therapy/chemistry ; Middle Aged ; Aged ; Prospective Studies ; *Carcinoma, Ductal, Breast/pathology/radiotherapy/mortality/drug therapy/chemistry ; *Heavy Ion Radiotherapy/adverse effects/methods ; Aromatase Inhibitors/therapeutic use ; Disease-Free Survival ; Neoplasm Staging ; Aged, 80 and over ; }, abstract = {PURPOSE: To evaluate the long-term efficacy, safety, and cosmetic outcomes of carbon-ion radiation therapy (C-ion RT) as a nonsurgical treatment option for patients with early-stage breast cancer.

METHODS AND MATERIALS: This single-center, prospective phase 1/2 trial enrolled women aged ≥60 years with stage I (cT1N0M0), estrogen receptor-positive, human epidermal growth factor receptor type 2-negative invasive ductal carcinoma, ≤2 cm in diameter. Patients received C-ion RT at a total dose of 60 Gy (relative biological effectiveness) in 4 fractions, followed by adjuvant aromatase inhibitors. The primary endpoint was 5-year local control. Secondary endpoints included complete response (CR) rate, adverse events (AEs), cosmetic outcomes, disease-free survival, and overall survival. Imaging was used for evaluating tumor response, and follow-up was conducted for a median of 73 months.

RESULTS: Twelve patients were treated in the phase 2 component of the trial. The CR rate was 100%, with a median time to CR of 12 months (range, 4-36 months). The 5-year local control and disease-free survival rates were both 92%, and the overall survival rate was 100%. One case of in-field recurrence occurred in a patient with a high Ki-67 index. Acute grade 1 dermatitis was observed in 6 patients. No grade ≥2 acute AEs were reported. Regarding late AEs, grade 1 rib fractures (n = 2) and grade 1 mastitis-related pain (n = 3) were managed conservatively. Magnetic resonance imaging revealed subclinical pectoral muscle inflammation in 7 cases. All patients except one (who underwent mastectomy due to recurrence) maintained excellent cosmetic outcomes.

CONCLUSIONS: C-ion RT demonstrated excellent long-term tumor control with minimal toxicity and favorable cosmetic outcomes in selected patients with early-stage breast cancer. These findings support its potential as a nonsurgical alternative for patients who are medically inoperable or decline surgery, warranting further investigation in larger, controlled trials.}, } @article {pmid42110080, year = {2026}, author = {Gumbs, S and Kwentoh, I and Atiku, ES and Donaldson, B}, title = {A Race Against Time: Endovascular Removal of an Intracardiac Foreign Body.}, journal = {Cureus}, volume = {18}, number = {4}, pages = {e106718}, pmid = {42110080}, issn = {2168-8184}, abstract = {Endovascular foreign body fragmentation, migration, and embolization to the right heart is a rare and late complication of the central venous port systems. The MediPort (Bard Medsystems, Reading, Massachusetts, USA) device consists of a port chamber attached to a central catheter implanted into the central venous system and used in patients with cancer for the administration of chemotherapy, parenteral nutrition, or blood transfusions. Interval radiologic survey, both intraoperatively and post-procedure, is crucial for investigating the possibility of both early and late complications, such as fracture and migration of the catheter, and for planning intervention. We detail a case of a 51-year-old woman with a background of estrogen receptor-positive invasive ductal carcinoma of the left breast, status post lumpectomy, neoadjuvant chemotherapy via right subclavian vein MediPort, and beam radiation. She presented for the removal of the MediPort device following completion of chemotherapy. However, intraoperatively, the catheter was noted to be 9 cm shorter in length, with an irregular tip, appearing incomplete from the original length, indicating fragmentation. Chest X-ray demonstrated a fractured catheter approximately 9 cm in length coursing from the right atrium to the right ventricle from its original tip at the distal superior vena cava. Vascular surgery emergently completed intracardiac foreign body retrieval from the right heart using the Bard 30 mm loop snare catheter system successfully.}, } @article {pmid42111276, year = {2026}, author = {Jadhav, AR and Fong, BL and Schwartz, MR and Deavers, MT and Pandya, D and Kamat, AA}, title = {Rare extra-gastrointestinal stromal tumor of the vulva: a case report.}, journal = {Gynecologic oncology reports}, volume = {65}, number = {}, pages = {102096}, pmid = {42111276}, issn = {2352-5789}, abstract = {INTRODUCTION: Extragastrointestinal stromal tumors (EGISTs) are rare mesenchymal neoplasms that originate outside the gastrointestinal (GI) tract and share histologic and immunohistochemical features with gastrointestinal stromal tumors (GISTs). Occurrence in the vulva is exceptionally uncommon, with limited reports describing their clinical course and management. Recognition is critical due to potential for local recurrence and malignant behavior.

METHODS: We present the case of a 53-year-old woman with a history of invasive ductal carcinoma of the breast who developed a recurrent vulvar mass. Clinical evaluation, imaging, surgical excision, and pathologic evaluation with immunohistochemistry were performed. Molecular testing guided clinical management.

RESULTS: Initial excision of a 4 cm left labial mass demonstrated a spindle cell neoplasm with strong immunoreactivity for c-KIT, DOG-1, and CD34; and negative immunostaining for other markers. Next-generation sequencing showed a KIT exon 11 mutation. Surgical margins were positive, and MRI revealed a recurrent perineal lesion without metastasis. GI workup including endoscopy and colonoscopy was negative. The patient subsequently underwent radical vulvar excision with partial anal sphincter excision, followed by sphincter repair with colorectal surgery and labial flap reconstruction with plastic surgery. Pathology confirmed vulvar EGIST with spindle cell morphology and diffuse c-KIT/DOG-1 positivity. Postoperatively, the patient recovered well and was treated with adjuvant imatinib.

CONCLUSION/IMPLICATIONS: This case highlights the diagnostic and therapeutic challenges of vulvar EGISTs, an exceedingly rare entity that can mimic more common vulvar lesions. Comprehensive workup, wide excision with negative margins, and targeted therapy are essential. Increased awareness and reporting are needed to guide management.}, } @article {pmid42100430, year = {2026}, author = {Slocum, AK and Tastekin, D and Duraj, T and Seyfried, TN}, title = {Management of advanced HR-positive breast cancer using metabolically supported chemotherapy and repurposed drugs: a case report.}, journal = {Frontiers in oncology}, volume = {16}, number = {}, pages = {1795402}, pmid = {42100430}, issn = {2234-943X}, abstract = {INTRODUCTION: Metastatic hormone receptor-positive (HR+) breast cancer is largely incurable once resistance to conventional treatments occurs. Emerging evidence suggests that progression free and overall survival can improve by targeting the distinct metabolic phenotype of cancer cells (Warburg effect). We report a durable response in a patient with advanced metastatic breast cancer treated with a multimodal "press-pulse" metabolic strategy.

CASE PRESENTATION: A 49-year-old female from Torino, Italy presented with Stage IV (cT4N1M1) invasive ductal carcinoma (HR+/HER2-, grade 3) with extensive osseous and lymph node metastases, poor performance status (ECOG 3) and severe, debilitating pain. She underwent a combinatorial protocol at ChemoThermia Oncology Center (Istanbul, Turkey) comprising of Metabolically Supported Chemotherapy (MSCT) consisting of docetaxel, doxorubicin, and cyclophosphamide administered following a 14-hour fast and low dose insulin-induced mild hypoglycemia, alongside a strict ketogenic diet (GKI < 2.0). Adjunctive therapies included local and whole-body hyperthermia, hyperbaric oxygen therapy (HBOT), and a combination of repurposed drugs (metformin, aspirin, doxycycline, mebendazole, ivermectin, and famotidine) designed to target metabolic, inflammatory, and survival pathways.

RESULTS: This multimodal treatment protocol was well tolerated, and grade 3/4 adverse events were not observed. The patient noticed symptomatic improvement and functional recovery shortly following the onset of therapy. Follow-up PET-CT scan conducted at 3 months revealed reduced tumor burden. At 6 months, the patient was reported to have a near complete response with the resolution of active bone metastases. On a maintenance schedule, the patient remains in sustained remission as of January 2026, over three years following diagnosis, with a full return to normal daily activities (ECOG 0).

CONCLUSION: This case highlights the potential of a comprehensive metabolic approach to cancer treatment that combines therapeutic ketosis, metabolically supported chemotherapy, physical modalities (hyperthermia/HBOT), and repurposed drugs. A durable response in a patient with otherwise poor prognosis was achieved after systematically targeting cancer cell bioenergetics and the tumor microenvironment. These findings support further clinical investigation into multimodal metabolic therapies for advanced HR+ breast cancer.}, } @article {pmid42107075, year = {2026}, author = {Das, J and Bhui, U and Chakraborty, GS and Mazumder, D and Shil, S and Sah, AK and Akter, B and Hossain, J and Nayak, S and Basak, S and Debnath, B and Nath, R and Belagodu Sridhar, S and Panigrahy, UP}, title = {Comparative oncology of male and female breast cancer: diagnostic paradigms and machine learning approaches in treatment.}, journal = {Journal of basic and clinical physiology and pharmacology}, volume = {}, number = {}, pages = {}, pmid = {42107075}, issn = {2191-0286}, abstract = {Breast cancer is associated mostly with women; however, breast cancer also appears in men, which dictates the need to know about gender-specific differences in the pathology and treatment. Male breast cancer constitutes less than 1 % of all cases and is usually diagnosed when the patient is older, with bigger tumors and at later stages than breast cancer in women. The most widespread subtype in both genders is invasive ductal carcinoma. The effect of hormone receptor positivity is very prominent in the treatment of men, and the risk factors include the BRCA2 mutations and the hormonal imbalance. The management approach, such as surgery, chemotherapy, radiotherapy, and hormonal therapy, is like that of women, and it may vary in treatment effectiveness because of hormonal and biological differences. The prognostic data in males are scarce, with generally worse outcomes, most likely because of delayed diagnosis and low rates of clinical trial representation. Men with breast cancer also face special psychosocial obstacles with regard to stigma and support. The use of artificial intelligence (AI) and machine learning are emerging options that have the potential to improve detectability and personalized treatment in both genders. The current review draws similarities between breast cancer in males and females to promote gender-specific interventions and better outcomes.}, } @article {pmid42096037, year = {2026}, author = {Okawa, S and Ogiyama, H and Amano, T and Saiki, H and Yamaguchi, Y and Fukutake, N and Furuta, K and Ishida, H and Azama, T and Oshita, M}, title = {Simultaneous gastric and colonic metastasis of invasive lobular carcinoma of the breast.}, journal = {Clinical journal of gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {42096037}, issn = {1865-7265}, abstract = {Breast cancer commonly metastasizes to the lungs, bones, liver, and brain; however, gastrointestinal involvement is uncommon. Simultaneous metastases to both the stomach and colon are extremely rare. We report the case of a 53-year-old woman with bilateral breast cancer (right invasive ductal carcinoma and left invasive lobular carcinoma [ILC]) who developed gastric and colonic metastases, presenting with rare endoscopic findings characterized by multiple polypoid lesions, along with disseminated carcinomatosis of the bone marrow. Biopsies from the stomach and colon revealed poorly differentiated adenocarcinomas that were estrogen receptor-positive and negative for E-cadherin in the colon, consistent with ILC metastases. Endocrine therapy with letrozole led to systemic improvement. However, diarrhea and abdominal pain persisted until palbociclib was initiated, after which both symptoms markedly improved. Follow-up endoscopy demonstrated regression of the gastric and colonic lesions. This case is of educational value because it demonstrates, with high-quality images, subtle mucosal changes with a polypoid appearance that are not widely recognized as typical findings of colonic metastasis from ILC, and includes a review of previously reported cases. In patients with breast cancer, particularly ILC, persistent gastrointestinal symptoms may suggest metastasis. Careful endoscopic evaluation with biopsy is essential for diagnosis and monitoring the treatment response.}, } @article {pmid42090880, year = {2026}, author = {Sharma, S and Tamang, J and Nepal, B and Gupta, S}, title = {Diagnostic accuracy of sonomammography in the evaluation of palpable breast masses: Correlation with histopathology.}, journal = {Radiography (London, England : 1995)}, volume = {32}, number = {4}, pages = {103426}, doi = {10.1016/j.radi.2026.103426}, pmid = {42090880}, issn = {1532-2831}, abstract = {INTRODUCTION: Ultrasonography plays an important role in evaluating palpable breast masses, particularly in women with dense breast tissue. Although the Breast Imaging Reporting and Data System has standardized ultrasound reporting. This study aimed to evaluate the diagnostic accuracy of sonomammography in differentiating benign and malignant breast masses and to correlate specific ultrasound features with histopathological findings, including differentiation between invasive ductal carcinoma and ductal carcinoma in situ (DCIS).

METHODS: This prospective observational study included patients presenting with palpable breast masses who underwent sonomammographic evaluation between January 2019 and December 2022. A total of 98 patients with lesions categorized as BI-RADS 4 or 5 on ultrasonography were included. High-resolution ultrasound examinations were performed using a 3-12 MHz linear transducer, and lesions were characterized according to the BI-RADS lexicon. Histopathological examination served as the reference standard. Statistical analysis included the Chi-square test, univariate, and multivariate analyses.

RESULTS: A total of 98 lesions, including 57 malignant and 41 benign lesions. Sonomammography demonstrated a diagnostic accuracy of 84.69%, with a sensitivity of 92.98% and a specificity of 73.17%. Significant sonographic predictors of malignancy (p<0.05) included irregular shape, non-circumscribed margins, non-parallel orientation, and hypoechoic or complex echotexture. Irregular lesion shape and non-circumscribed margins showed a significant association with invasive ductal carcinoma compared with DCIS (p<0.05).

CONCLUSION: BI-RADS-based sonomammographic evaluation provides valuable diagnostic information in the assessment of palpable breast masses. Specific ultrasound features demonstrate significant correlation with histopathological outcomes and may assist in differentiating benign from malignant lesions.

IMPLICATION OF PRACTICE: The findings highlight the clinical value of BI-RADS-guided breast ultrasound in improving lesion characterization and supporting appropriate biopsy decisions in patients presenting with palpable breast masses.}, } @article {pmid42095654, year = {2026}, author = {Birnbaum, GE and Zholtack, K}, title = {They Are Just Not That Into You: Does Sexual Arousal Impair Perception of Rejection Cues?.}, journal = {Personality & social psychology bulletin}, volume = {}, number = {}, pages = {1461672261439417}, doi = {10.1177/01461672261439417}, pmid = {42095654}, issn = {1552-7433}, abstract = {Sexual arousal elicits approach-oriented motivation. In early romantic encounters, however, this desire to pursue a connection must be balanced against the risk of rejection. Across four studies, we investigated whether sexual priming affects risk regulation, causing people to perceive potential partners as romantically interested despite ambiguous cues. Unpartnered participants watched either sexual or nonsexual videos before engaging in an online chat with a confederate who conveyed mixed signals across different interaction phases. Participants rated the confederate's desirability as a partner and perceived interest. Independent raters also coded participants' written impressions for perceived romantic interest. Results showed that sexual priming increased participants' perceptions of the confederate's desirability, which, in turn, predicted both self-reported and coded perceptions of the confederate's interest. These findings suggest that sexual arousal creates "tunnel vision," leading people to interpret ambiguity in ways that prioritize approach goals over self-protective concerns, with implications for misunderstandings in early romantic encounters.}, } @article {pmid42086345, year = {2026}, author = {Tammaro, S and Di Fiore, F and Crocetto, F and Manfredi, C and Ruvolo, CC and Califano, G and Barone, B and Arcaniolo, D and Spirito, L and Calace, FP and Reccia, P and Fusco, F and De Sio, M and Balsamo, R}, title = {Urodynamic de-obstruction and symptom improvement after thulium laser vaporization (ThuVAP): evidence from a prospective paired study.}, journal = {The Canadian journal of urology}, volume = {33}, number = {2}, pages = {249-259}, pmid = {42086345}, issn = {1488-5581}, mesh = {Humans ; Male ; Prospective Studies ; *Urodynamics ; Aged ; *Urinary Bladder Neck Obstruction/surgery/etiology/physiopathology ; *Thulium/therapeutic use ; *Prostatic Hyperplasia/surgery/complications ; Middle Aged ; *Lasers, Solid-State/therapeutic use ; *Laser Therapy/methods ; Treatment Outcome ; }, abstract = {BACKGROUND: Thulium laser vaporization of the prostate (ThuVAP) is an established treatment for benign prostatic obstruction, but its impact on urodynamic parameters remains poorly defined. This study aimed to quantify the de-obstructive efficacy of ThuVAP through pre- and postoperative urodynamic comparisons and to assess the relationship between urodynamic improvement and symptom relief.

METHODS: In a prospective single-center cohort (June 2022-June 2024), men with urodynamically confirmed obstruction underwent standardized ThuVAP with a 200-W thulium:YAG system. Baseline and 6-month invasive urodynamics and 12-month clinical follow-up were performed. The primary endpoint was the change in the bladder outlet obstruction index (BOOI); secondary endpoints included Qmax, postvoid residual volume (PVR), bladder voiding efficiency (BVE), detrusor pressures, and International Prostate Symptom Score (IPSS).

RESULTS: Sixty-four patients (mean age 67 years; prostate volume 52 mL) were analyzed. BOOI decreased from 55.9 ± 17.2 to 21.3 ± 11.2 (p < 0.001), with obstructed cases dropping from 79.7% to 7.8%. Schäfer grade fell from 3.6 to 0.3 (p < 0.001). Detrusor pressure halved, Qmax rose from 7.9 to 20.8 mL/s, PVR declined from 121 to 22 mL, and BVE improved from 64% to 94% (all p < 0.001). Low compliance and involuntary detrusor contractions (IDC) decreased notably. IPSS improved from 26.2 to 3.4 (p < 0.001) and correlated with the magnitude of urodynamic de-obstruction.

CONCLUSIONS: ThuVAP provides substantial, objectively verified relief of bladder outlet obstruction with consistent improvements in voiding efficiency and symptoms. The correlation between urodynamic and clinical outcomes underscores the procedure's efficacy and the utility of urodynamics in documenting therapeutic benefit.}, } @article {pmid42089011, year = {2026}, author = {Ojo, T and Cablay, K and Emara, N and Meyer, A}, title = {Pulmonary Hypertension Following the Use of Trastuzumab Biosimilars.}, journal = {Case reports in pulmonology}, volume = {2026}, number = {}, pages = {1076907}, pmid = {42089011}, issn = {2090-6846}, abstract = {BACKGROUND: HER2-positive breast cancer comprises 14%-20% of breast cancer cases and was previously linked with aggressive progression. Trastuzumab and its biosimilars have improved survival significantly, but their pulmonary toxicities remain underrecognized. While left ventricular dysfunction is a well-documented adverse effect, pulmonary hypertension, pulmonary arterial hypertension (PAH), and right heart failure are rarely reported.

CASE PRESENTATION: We report the case of a 53-year-old woman with Stage IV HER2-positive invasive ductal carcinoma and well-controlled HIV who presented with shortness of breath, edema, and weakness. She previously completed five cycles of trastuzumab biosimilars (trastuzumab-anns or trastuzumab-dttb), Perjeta (pertuzumab), and Taxotere (docetaxel) and then transitioned to maintenance therapy with just trastuzumab-anns and pertuzumab for one cycle due to neuropathy. Pretreatment and interim echocardiograms showed preserved left ventricular and right ventricular function. Shortly after her last trastuzumab dose, she was hospitalized with severe anasarca, bilateral pleural effusions, and respiratory failure. Right heart catheterization revealed severe precapillary pulmonary hypertension (mPAP 40 mmHg [normal < 20 mmHg], PAWP 8 mmHg [normal ≤ 15 mmHg]), consistent with WHO Group I PAH. Despite aggressive diuresis and respiratory support, her condition deteriorated, and she elected for comfort-focused care.

DISCUSSION: Although rare, pulmonary vascular complications such as PAH have been linked to HER2-targeted therapies. Reports from clinical trials, FAERS data, and national registries have documented cases of trastuzumab-associated PAH, suggesting a possible vascular mechanism, potentially through ACVRL1 pathway involvement. This case highlights the importance of considering pulmonary hypertension as a potential adverse event in patients on trastuzumab, particularly those with pulmonary metastases.

CONCLUSION: Clinicians should be aware of pulmonary complications in patients receiving HER2-targeted therapies, even when left ventricular function is preserved. Early recognition and monitoring of right-sided pressures in high-risk patients may improve outcomes. This case adds to emerging evidence on trastuzumab's pulmonary risks.}, } @article {pmid42090312, year = {2026}, author = {Lippy, RD and Bayer, MJ}, title = {Mental health support for Naval Surface Forces in LSCO.}, journal = {Military psychology : the official journal of the Division of Military Psychology, American Psychological Association}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/08995605.2026.2664981}, pmid = {42090312}, issn = {1532-7876}, abstract = {U.S. Navy ships have not engaged in heavy combat operations since World War II. Although naval warfare and navy ships have advanced technologically since that time, the fundamental violence of combat and resultant human factors of war have not. This article discusses how the Navy is not fully prepared for the expected large number of combat stress casualties likely to occur in any maritime large-scale combat operations (LSCO) such as the threat by China to invade Taiwan by 2027. U.S. Naval Surface Forces began assigning mental health providers to support Navy surface combatant ships in 2019. These mental health professionals provide psychological support to shipboard Sailors but do not deploy with these ships. Rather, Navy surface combatant ships are supported by a single Independent Duty Corpsman (IDC) paraprofessional with limited training in mental health. Therefore, in any LSCO scenario, the acute psychological needs of these shipboard Sailors will be provided by these medical assets. The article discusses how U.S. Naval Surface Forces is preparing shipboard Sailors for combat stress reactions as well as training organic shipboard resources (i.e. IDCs, chaplains) in applying psychological first aid and legacy combat psychiatry principles (i.e. PIES - Proximity to the frontline, Immediacy of treatment, Expectancy of recovery, Simple interventions). The article concludes with a discussion of future directions for closing the current gaps in training needed to enhance psychological support to Naval Surface Forces ships/Sailors in preparation for future LSCO scenarios.}, } @article {pmid42082151, year = {2026}, author = {Sachdev, V and van Loon, NM and Kingma, J and Ottenhoff, R and Tan, JME and van den Berg, M and Duijst, S and Jongejan, A and Levels, JHM and Rensen, PCN and Kooijman, S and de Boer, JF and Kuipers, F and Kuentzel, KB and Kratky, D and Kwon, Y and Zeigerer, A and Hendrix, S and Zelcer, N}, title = {Loss of the E3 ubiquitin ligase MARCHF6 alters hepatic lipid metabolism and drives spontaneous hepatosteatosis.}, journal = {Molecular metabolism}, volume = {}, number = {}, pages = {102379}, doi = {10.1016/j.molmet.2026.102379}, pmid = {42082151}, issn = {2212-8778}, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, steatohepatitis (MASH), feature excessive hepatic fat accumulation, yet the relative contributions of dietary vs. endogenous fats and their interactions has remained enigmatic. Here, we identify the endoplasmic reticulum-associated E3 ubiquitin ligase MARCHF6 as a pivotal regulator of hepatic lipid metabolism. Global or hepatocyte-specific deletion of Marchf6 induced spontaneous accumulation of triglycerides and cholesteryl esters under chow-fed conditions, revealing a cell-autonomous hepatic defect independent of caloric excess. Loss of MARCHF6 stabilized its substrate squalene epoxidase (SQLE), enhancing sterol pathway flux while concomitantly activating the SREBP1-associated lipogenic transcriptional program and increasing lipoprotein clearance. Accordingly, lipidomic analyses demonstrated remodeling of the hepatic lipidome towards polyunsaturated, long-chain neutral lipids, consistent with increased lipogenesis-driven NADPH consumption. In line with this, pharmacological inhibition of the oxidative pentose phosphate pathway reduced lipid accumulation in MARCHF6-deficient human hepatocytes. Congruently, transcriptomic data from human MASLD/MASH patients revealed reduced hepatic MARCHF6 expression alongside an increase in that of the lipogenic genes SREBF1, FASN, and SCD1. Overall, these data establish MARCHF6 as a multifaceted gatekeeper that integrates sterol turnover, NADPH usage, and lipogenesis to maintain hepatic lipid homeostasis.}, } @article {pmid42069142, year = {2026}, author = {Hladik, C and Sekhri, M and Cen, HH and Elayapillai, SP and Lee, S and Gao, B and Dooley, W and Milligan, T and Hill, H and Filatenkov, A and Wellberg, EA and Hannafon, BN}, title = {Spatially Resolved Obesity-Driven Molecular Changes in Early Breast Cancer.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2026.03.016}, pmid = {42069142}, issn = {1525-2191}, abstract = {Obesity is an established risk factor for invasive breast cancer; however, the specific molecular heterogeneity distinguishing invasive ductal carcinoma (IDC) from ductal carcinoma in situ (DCIS) within the obese tumor microenvironment is not well defined. In the current study, spatially resolved transcriptomics was utilized to profile the epithelial, stromal, and immune compartments of DCIS and IDC lesions stratified by host body mass index, categorized as non-obese (≤29.9 kg/m[2]) or obese (≥30 kg/m[2]). These analyses reveal that the transcriptional signatures defining the invasive state differ significantly across BMI categories. In non-obese patients, IDC lesions exhibited canonical profiles driven by proliferation and epithelial-to-mesenchymal transition, compared with DCIS. Conversely, the obese setting was characterized by a distinct "stress-adaptive" phenotype, enriched for metabolic adjustment, oxidative stress response, and inflammatory signaling. The epithelial component was accompanied by a fibro-inflammatory stromal signature and an immunosuppressive niche characterized by B cell depletion and M2 macrophage enrichment. Furthermore, SULF2, an extracellular endosulfatase involved in extracellular matrix organization and signaling, was consistently upregulated within the obese epithelium, providing a plausible link between metabolic stress and structural remodeling. Collectively, these data indicate obesity-associated differences consistent with an alternative invasive transcriptional program that is less dominated by classical proliferative drivers in this cohort. Consequently, standard prognostic markers may be context-dependent, highlighting the need to integrate metabolic health into precision risk stratification.}, } @article {pmid42072229, year = {2026}, author = {Neri, I and Gallivanone, F and Venturini, E and Canevari, C and Caleri, C and Rotmensz, N and Ghezzo, S and Bezzi, C and Mapelli, P and Panizza, P and Picchio, M and Di Micco, R and Chiti, A and Gentilini, OD and Scifo, P}, title = {Hybrid [[18]F]FDG PET/MR Imaging Parameters for the Prediction of Tissue Biomarkers in Invasive Ductal Breast Cancer.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {13}, number = {4}, pages = {}, doi = {10.3390/bioengineering13040435}, pmid = {42072229}, issn = {2306-5354}, support = {RF-2018-12368096//Ministero della Salute/ ; }, abstract = {Breast cancer (BC) requires the evaluation of tumor aggressiveness features to guide treatment decisions. Biopsy-derived prognostic information may differ from surgical histopathology due to tumor heterogeneity. Hybrid PET/MRI can provide additional information for tumor characterization, supporting initial therapy planning and prognosis. In this work, we acquired 157 BC patients using a hybrid PET/MRI scanner. The PET data were combined with ADC and semi-quantitative DCE-MRI metrics to derive "hybrid PET/MRI parameters." Pathological data such as tumor grade, hormone receptors, proliferation index (Ki67), and surrogate molecular subtype were collected, and we evaluated their associations with hybrid imaging, also comparing with the PET and MRI data analyzed separately. Ki67 showed moderate correlations with PET, ADCmin, and most hybrid parameters. The PET and hybrid data differentiate histopathological factors, while ADCmin differentiates G1 vs. G2 and luminal A vs. luminal B. In the ROC analysis, hybrid SUVmax/ADCmin shows better performance to predict luminal B from luminal A (AUC 0.720, sensitivity 73.1%, specificity 63.2%, PPV 54.3%, NPV 79.7%) than SUVmean alone. Our findings suggest that these novel hybrid PET/MRI parameters may help the characterization of tumor tissue in IDC. However, a multivariate analysis is needed to confirm our preliminary results.}, } @article {pmid42072243, year = {2026}, author = {Comert, RG and Yilmaz, R and Cingoz, E and Bayramoglu, Z and Bayram, A and Mollavelioglu, B and Muslumanoglu, M and Bagci, U}, title = {Evaluating the Predictive Value of Post-Treatment Superb Microvascular Imaging for Complete Response to Neoadjuvant Chemotherapy in Invasive Breast Cancer.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {13}, number = {4}, pages = {}, doi = {10.3390/bioengineering13040449}, pmid = {42072243}, issn = {2306-5354}, abstract = {Purpose: To compare the efficacy of Superb Microvascular Imaging (SMI) with grayscale ultrasound (US) and dynamic contrast-enhanced MRI in predicting pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in invasive breast cancer. Methods: A total of 115 patients included in the study were evaluated based on their pre-treatment imaging findings (US, mammography, and MRI). Following completion of NAC, all patients underwent grayscale US and SMI examinations. In patients with available post-NAC MRI, treatment response was additionally assessed by comparing MRI findings. Imaging results were correlated with postoperative pathological outcomes, which served as the reference standard. pCR was defined as the absence of residual invasive carcinoma, regardless of ductal carcinoma in situ. Molecular subtype, Ki-67, and axillary status were recorded. Statistical analyses included chi-square tests and stepwise multiple logistic regression. Significance was set at p < 0.05 (95% CI). Results: The median age was 51 years (range: 30-75). Most tumors were high-grade (55%) and invasive ductal carcinoma (95%). Breast-pCR was achieved in 43% of patients. Significant predictors of pCR included hormone receptor negativity, HER-2 positivity, high Ki-67 expression (≥40%), non-luminal subtype, and complete radiologic response on US and MRI (p < 0.05). Lower SMI index values were strongly associated with pCR (p < 0.001), with an optimal cut-off of 1.8 demonstrating good diagnostic performance (AUC = 0.804, 95% CI: 0.721-0.887). In multivariate analysis, the combined model including US, SMI, HER-2 status, and MRI showed the highest predictive performance (AUC = 0.890, 95% CI: 0.829-0.950), explaining 55.1% of the variance in pCR. Conclusions: An SMI index < 1.8, HER-2 positivity, and complete response on US and MRI are independent predictors of pCR after NAC. Combining SMI with multimodal imaging significantly improves predictive accuracy.}, } @article {pmid42073582, year = {2026}, author = {Akkoc Mustafayev, FN and Fountzilas, E and Munsell, MF and Layman, RM and Yam, C and Gutierrez, AM and Albarracin, CT and Ahmed, Z and Schlacher, K and Tainer, JA and Arun, BK}, title = {Characteristics and Clinical Outcomes of BRCA Germline Mutation Carriers with Advanced Breast Cancer Treated with PARP (Poly ADP-Ribose Polymerase) Inhibitors: A Single-Institution Experience.}, journal = {Cancers}, volume = {18}, number = {8}, pages = {}, doi = {10.3390/cancers18081258}, pmid = {42073582}, issn = {2072-6694}, support = {RP180813//Cancer Prevention and Research Institute of Texas/ ; NCI Grant P30CA016672//Cancer Center Support Grant/ ; }, abstract = {Background/Objectives: Several trials have highlighted the importance of PARP inhibitors (PARPi) in the treatment of BRCA-associated breast cancers (BC), initiating changes in practice. However, data on the real-life outcomes of PARPi therapy is limited. In this study, we characterized the clinical characteristics and outcomes of patients with advanced BC and germline BRCA pathogenic variants (PVs) who received PARPi therapy. Methods: We conducted a retrospective single-institution cohort study of patients with advanced BC and germline BRCA1/2 PVs treated with PARPi. Outcomes included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Survival was estimated using Kaplan-Meier methods, and prognostic factors were evaluated using Cox regression analysis. Results: Of the 107 patients treated with PARPi, 48 (44.9%) and 59 (55.1%) had BRCA1 and BRCA2 PVs, respectively. Ninety-seven patients (90.7%) had invasive ductal carcinoma and 42 (39.3%) had triple-negative BC. Nineteen (17.8%) patients had de novo metastatic BC. Sixty-two (57.9%) patients received at least one line of systemic therapy before PARPi; 24 (22.4%) patients received prior platinum. ORR was 62.6%, and the median duration of response (DoR) was 7 months (range, 2.1-96.2). The median PFS was 9 months (95% CI, 6.9-10.5) and median OS was 25.8 months (95% CI, 18.7-31.5). In multivariable models for PFS, bone metastases (HR = 2.25; 95% CI, 1.40-3.61; p = 0.0008) and lung metastases (HR = 2.40; 95% CI, 1.45-3.98; p = 0.0007) were independently associated with increased risk of progression or death. In multivariable models for OS, brain metastases (HR = 3.54; 95% CI, 1.59-7.90; p = 0.0020), bone metastases (HR = 2.22; 95% CI, 1.27-3.88; p = 0.0050), and lung metastases (HR = 2.38; 95% CI, 1.38-4.11; p = 0.0018), were independently associated with increased risk of death. Conclusions: The clinical outcomes of our real-world patients are similar to those reported in previous clinical trials. In addition, metastatic site distribution was independently prognostic for survival outcomes and may support baseline risk stratification at the time of PARPi initiation. Further studies of predictive markers of response and resistance, as well as sequencing with platinums and combinations with other targeted agents, are needed to optimize the benefits of PARPi in this patient population.}, } @article {pmid42074728, year = {2026}, author = {Kaviani, A and Bruyninx, G and Patocskai, E}, title = {Posterior Approach Partial Mastectomy (MAPP): Early Clinical Experience with a Novel Oncoplastic Technique.}, journal = {Journal of clinical medicine}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/jcm15082925}, pmid = {42074728}, issn = {2077-0383}, abstract = {Background: Oncoplastic breast surgery aims to combine oncologic safety with optimal cosmetic outcomes. However, many established techniques require visible anterior breast incisions or substantial tissue rearrangement, which may compromise cosmetic results in selected patients. Posterior access to the breast through the retromammary space may allow tumor excision while preserving the anterior breast envelope. Methods: We report an early clinical experience with Posterior Approach Partial Mastectomy (MAPP), a breast-conserving technique that accesses the lesion through a concealed inframammary or lateral breast crease incision. This single-center retrospective case series included consecutive patients undergoing excision using this approach. Patient selection, surgical technique, and early outcomes-including margin status, complications, and need for re-excision-were evaluated. Results: Eight patients underwent breast-conserving excision using the MAPP technique. Six patients had malignant lesions (invasive ductal carcinoma with or without ductal carcinoma in situ or pure DCIS), while two benign lesions were included for technical completeness. Tumor size ranged from 9 to 78 mm. All malignant cases achieved negative surgical margins (R0), and no patient required re-excision. Posterior access was successfully achieved in all cases using concealed inframammary or lateral crease incisions. One patient experienced minor wound discharge that resolved with conservative management, and no major postoperative complications were observed. Follow-up ranged from 2 to 12 months. Conclusions: Posterior Approach Partial Mastectomy appears to be a feasible oncoplastic approach with encouraging early oncologic outcomes in carefully selected patients undergoing breast-conserving surgery. By preserving the anterior skin envelope and concealing the surgical incision, this technique may offer cosmetic advantages while maintaining oncologic adequacy. Larger studies with longer follow-up are needed to further define its role in oncoplastic breast surgery.}, } @article {pmid42076415, year = {2026}, author = {Hassain, ZAA and Farhan, MJ and Elwi, TA}, title = {Design of an Ultra-Sensitive Multi-Resonant Moore Fractal SRR Microwave Sensor for Non-Invasive Blood Glucose Monitoring.}, journal = {Sensors (Basel, Switzerland)}, volume = {26}, number = {8}, pages = {}, doi = {10.3390/s26082306}, pmid = {42076415}, issn = {1424-8220}, mesh = {*Microwaves ; *Blood Glucose/analysis ; Humans ; Fractals ; *Blood Glucose Self-Monitoring/instrumentation/methods ; *Biosensing Techniques/methods/instrumentation ; Equipment Design ; }, abstract = {This study details the design and development of an ultra-sensitive microwave sensor for non-invasive blood glucose monitoring, achieved by analyzing variations in the response of a split-ring resonator (SRR) through advanced engineering methodologies. There were three design phases in the development process. In the first phase, a standard SRR design was used. It had a resonant frequency of 2.975 GHz in S21 and a sensitivity of only 0.0032 dB/(mg/dL). In the second phase, an interdigital capacitor (IDC) was added to the SRR structure. This made it work better and made it more sensitive, with a sensitivity of 0.015 dB/(mg/dL) at 4.1 GHz. The third phase was to use a fourth-order Moore fractal geometry to improve the resonance properties of the design a lot. From the obtained S11, the maximum sensitivity was 0.042 dB/(mg/dL), which was a huge improvement in sensing efficiency compared to earlier designs. Several resonant frequencies were recorded between 4.84 and 7.56 GHz. The addition of the fractal structure made the electromagnetic field stronger in the resonant space and made the waves interact more with small changes in the biological medium, all without changing the sensor's size (80 mm × 40 mm). These results show that fractal architecture is a promising way to create non-invasive, accurate, and easily integrated sensors in biological systems that can continuously measure blood glucose levels.}, } @article {pmid42068564, year = {2026}, author = {Yi, L and Chen, K and Wang, D and Wang, R and Zhu, X and Chai, J and Jia, X and Xu, F and Gu, M and Cui, C and Zhang, W}, title = {Co-Pathogenic Role of BRCA1 and OBSCN Deletions in Chinese Familial Breast Cancer: A Case Report.}, journal = {The American journal of case reports}, volume = {27}, number = {}, pages = {e951196}, doi = {10.12659/AJCR.951196}, pmid = {42068564}, issn = {1941-5923}, mesh = {Humans ; Female ; Adult ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/genetics/pathology ; *BRCA1 Protein/genetics ; Pedigree ; Gene Deletion ; *Triple Negative Breast Neoplasms/genetics ; East Asian People ; }, abstract = {BACKGROUND The incidence of breast cancer is high among women, with a significant proportion of cases being familial. However, the driver genes for breast cancer can differ across families. CASE REPORT Our patient was a 37-year-old woman diagnosed with triple-negative breast cancer (TNBC) by pathology, revealing invasive ductal carcinoma of the outer upper quadrant of the breast, WHO grade 3. The maximum diameter of the microscopic invasive cancer was approximately 0.5 cm. No definite vascular tumor thrombus or nerve invasion was observed. Some (30-90%) of the tumor cells disappeared, and the remaining tumor cells showed degeneration, interstitial sclerosis, scattered lymphocyte infiltration, and hemosiderin deposition. No cancer was found in the nipple and base resection margins, or in the other quadrants. The chemotherapy response was classified as grade III according to the MP (Miller and Payen classification) scoring system. Blood samples were collected from affected family members. Whole-exome sequencing (WES) and bioinformatics analyses were used to identify potential driver genes, followed by Sanger sequencing for validation, which ultimately confirmed the pathogenic gene and the underlying mechanism in this family. CONCLUSIONS A series of analyses suggested that the co-occurrence of heterozygous deletions in BRCA1 and OBSCN was the main cause of breast cancer in this family. The simultaneous association of 2 genes with the occurrence of breast cancer was discovered for the first time in this family, which could help guide disease prevention for family.}, } @article {pmid42068677, year = {2026}, author = {Kumar, H and Hu, Y and Tahir, M and Tozbikian, G and Parwani, AV and Li, Z}, title = {Incidence, Clinicopathologic Features, and Follow-up Results of Invasive Ductal Carcinoma With Lobular-Like Growth Pattern.}, journal = {Clinical breast cancer}, volume = {26}, number = {6}, pages = {25-31}, doi = {10.1016/j.clbc.2026.04.003}, pmid = {42068677}, issn = {1938-0666}, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two most common breast cancers. A subset of tumors with discohesive, lobular-like growth but retained membranous E-cadherin expression-termed invasive ductal carcinoma with lobular-like growth pattern (IDC-LL)-is increasingly recognized, yet its clinicopathologic and prognostic significance remain unclear.

MATERIALS AND METHODS: We retrospectively reviewed 2,413 invasive breast carcinomas (1,872 IDC, 230 IDC-LL, 311 ILC) diagnosed between 2016 and 2022. Clinicopathologic features, biomarker expression, margin status, nodal involvement, and survival outcomes were compared. A second cohort of 441 ER-positive/HER2-negative early-stage carcinomas with available Oncotype DX results (335 IDC, 38 IDC-LL, 68 ILC) was also analyzed.

RESULTS: IDC-LL accounted for 9.5% of all invasive carcinomas. Patients with IDC-LL (mean age 62) were older than IDC but younger than ILC. Grade 3 tumors were more frequent in IDC-LL than ILC (13.5% vs. 4.8%, p = 0.001) but less than IDC (30.5%, p = 0.0001). Hormone receptor positivity in IDC-LL (ER 89.1%, PR 79.6%) was intermediate between IDC and ILC, while HER2 positivity was lower than IDC and similar to ILC. IDC-LL also showed intermediate Oncotype DX and Magee scores. Overall survival was worse in IDC than in IDC-LL or ILC (p = 0.0006), while disease-free survival did not differ among groups.

CONCLUSION: IDC-LL demonstrates clinicopathologic and molecular features intermediate between IDC and ILC. Recognition of IDC-LL as a distinct morphologic category is warranted to optimize diagnosis and surgical management.}, } @article {pmid42063482, year = {2026}, author = {Sacks, S and Mo, B}, title = {Pancreatitis, panniculitis, polyarthritis syndrome as an initial manifestation of metastatic pancreatic cancer in a breast cancer patient: Importance of early recognition and multidisciplinary management: A case report.}, journal = {SAGE open medical case reports}, volume = {14}, number = {}, pages = {2050313X261438390}, pmid = {42063482}, issn = {2050-313X}, abstract = {Pancreatitis, panniculitis, and polyarthritis syndrome is a rare extrapancreatic triad associated with pancreatic disease and occasionally malignancy. We report a 51-year-old woman with prior hormone receptor-negative, human epidermal growth factor receptor 2-positive breast invasive ductal carcinoma (bilateral mastectomy, adjuvant trastuzumab/pertuzumab, radiation) who developed abrupt painful erythematous nodules of both legs and progressive polyarthralgia of the hands, knees, and ankles. Symptoms were initially treated as inflammatory rheumatic disease with systemic corticosteroids and disease-modifying therapy without benefit, leading to severe functional decline. Imaging later revealed a large hepatic mass; biopsy confirmed metastatic pancreatic acinar cell carcinoma, unifying the presentation as pancreatitis, panniculitis, and polyarthritis syndrome. Coordinated multidisciplinary care, oncology-directed chemotherapy, interventional pain management, and psychological support, improved pain control and mobility. This case adds to the limited pancreatitis, panniculitis, and polyarthritis literature and highlights that absent gastrointestinal symptoms can delay diagnosis; early recognition and collaborative management are essential in malignant pancreatitis, panniculitis, and polyarthritis presentations.}, } @article {pmid42056522, year = {2026}, author = {Liskiewicz, D and Novikoff, A and Khalil, A and Akindehin, S and Campbell, JE and Candela, P and Castelino, RL and Coupland, C and Culot, M and Dodson, WS and Douros, JD and Embring, H and Feuchtinger, A and Finan, B and Garcia-Caceres, C and Gao, XB and Gosselet, F and Grandl, G and Gutgesell, RM and Haas, DT and Jastroch, M and Karaoglu, E and Kakimoto, P and Kaltenbach, AC and Keuper, M and Kusminski, CM and Leander, DC and Liskiewicz, A and Liu, X and Maity-Kumar, G and Martinez, SM and Mowery, SA and Nogueiras, R and Paisley, M and Perez-Tilve, D and Petersen, PSS and Pfluger, PT and Prakash, S and Steffens, S and Cebrian-Serrano, A and Tost, M and Wean, J and Weber, C and Yoshida, J and Gerhart-Hines, Z and Horvath, TL and Scherer, PE and Seeley, RJ and DiMarchi, RD and Tschöp, MH and Krahmer, N and Knerr, PJ and Müller, TD}, title = {GLP-1R-GIPR-PPARα/γ/δ quintuple agonism corrects obesity and diabetes in mice.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {42056522}, issn = {1476-4687}, abstract = {There are increasing numbers of effective drugs to improve obesity-linked metabolic dysfunction; GLP-1R-GIPR co-agonism is effective in the management of obesity and type 2 diabetes[1,2], and lanifibranor-a nuclear-acting small-molecule triple agonist of PPARα, PPARγ and PPARδ-is in clinical phase 3 trials for the treatment of metabolic dysfunction-associated steatohepatitis[3]. Here, seeking to further improve the metabolic efficacy of GLP-1R-GIPR co-agonism, we report the development of a unimolecular quintuple agonist that combines the body weight-reducing and blood glucose-lowering effects of GLP-1R-GIPR co-agonism with the insulin-sensitizing and anti-inflammatory effects of lanifibranor via its targeted delivery into GLP-1R- and GIPR-expressing cells. In vitro, GLP-1-GIP-lanifibranor is indistinguishable from GLP-1-GIP in relation to incretin receptor signalling and shows equal stimulation of insulin secretion in isolated mouse islets. In vivo, however, GLP-1-GIP-lanifibranor outperforms GLP-1R-GIPR co-agonism and semaglutide, further decreasing body weight, food intake and hyperglycaemia in obese and insulin-resistant mice through synergistic incretin and PPAR action. The metabolic action of GLP-1-GIP-lanifibranor is blunted in mice with genetic or pharmacological inhibition of GLP-1R, GIPR or PPARδ and is absent in DIO double incretin receptor-knockout mice, collectively suggesting that GLP-1-GIP-lanifibranor has substantial therapeutic value in the treatment of obesity and diabetes.}, } @article {pmid41857548, year = {2026}, author = {Gupta, R and Gopalsamy, IK and Nadukkandy, AS and Singh, A and Tangella, CR and Alexander, LE and Nair, RA and Cordani, M and Kumar, LD}, title = {GCNT3 and ST3GAL1 expression correlates with HER2 status and MUC1/β-catenin/Cyclin D1 axis in breast cancer.}, journal = {BMC cancer}, volume = {26}, number = {1}, pages = {}, pmid = {41857548}, issn = {1471-2407}, support = {13(9130)-2020-Pool//CSIR Scientist's Pool Scheme fellowship/ ; RYC2021-031003I//Agencia Estatal de Investigación/ ; MLP 0037//CSIR-CCMB/ ; }, abstract = {UNLABELLED: The status of human epidermal growth factor receptor 2 (HER2) is a critical determinant of breast cancer progression and outcome, but the role of glycosylation in modulating HER2-related pathways remains poorly understood. Here, we examined the relationship between HER2 and the glycosyltransferases ST3GAL1 and GCNT3, combining data mining with experimental and clinicopathological validation. In silico analyses across public BC cohorts showed that higher expression of ST3GAL1, GCNT3, and HER2 was associated with reduced survival. Immunohistochemistry on invasive ductal carcinoma specimens (n = 25) demonstrated increased ST3GAL1 and GCNT3 in advanced stages/grades. Cross-platform correlation analyses revealed a positive association between ST3GAL1 and HER2, whereas GCNT3 showed an inverse association with HER2. Functional assays in HER2-negative cell lines (MCF7, MDA-MB-231, MDA-MB-435) and the HER2-positive line SKBR3 indicated that GCNT3 supports migratory capacity and clonogenicity, consistent with an oncogenic role independent of HER2 status. Gene set enrichment pointed to upregulation of MUC1 and β-catenin; tissue validation of MUC1, β-catenin, and Cyclin D1 confirmed their clinicopathological relevance, with HER2 expression inversely correlated with β-catenin and Cyclin D1. Collectively, these findings suggested a model in which GCNT3-driven O-glycosylation might remodel the MUC1/β-catenin/Cyclin D1 axis in BC, adding a glyco-regulatory layer to HER2-linked pathobiology. From a diagnostic perspective, ST3GAL1 (positive with HER2) and GCNT3 (inverse with HER2) could be considered as candidate biomarkers that might complement HER2 assessment for risk stratification. This work suggests a plausible mechanistic and clinicopathologic foundation for incorporating glycosylation markers into precision pathology workflows in breast cancer.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-026-15821-w.}, } @article {pmid41851799, year = {2026}, author = {Guo, Q and Chang, Y and Cai, Y and Yang, S and Liang, J and Zhou, Z}, title = {Clinicopathological and prognostic significance of stromal maturity, tumour-infiltrating lymphocytes, and systemic environment in breast cancer.}, journal = {Diagnostic pathology}, volume = {21}, number = {1}, pages = {}, pmid = {41851799}, issn = {1746-1596}, abstract = {BACKGROUND: The tumour microenvironment and systemic inflammatory environment are related to the diagnosis, treatment and prognosis of various tumours. This study aimed to evaluate the clinicopathological significance and prognostic value of the tumour microenvironment and systemic environment in patients with breast invasive ductal carcinoma (IDC).

METHODS: A total of 222 patients with breast IDC who underwent radical mastectomy were included. Stromal maturity and tumour-infiltrating lymphocytes (TILs), along with a series of systemic inflammatory cell indicators from venous blood, were evaluated. Chi-square tests were performed to explore the relationships between the parameters. Kaplan‒Meier analysis and Cox proportional hazards regression models were used for survival analysis.

RESULTS: Stromal maturity was significantly correlated with tumour necrosis, lymphovascular invasion, axillary lymph node metastasis, and clinical stage (all P < 0.001). TILs were significantly associated with nuclear grade, histopathological grade, tumour necrosis, lymphovascular invasion, and clinical stage (all P < 0.001). High TIL numbers were often accompanied by more mature stroma. No significant correlations were detected between stromal maturity/TILs and systemic inflammatory markers. Multivariate Cox proportional hazards model analysis revealed that TILs, pathological grade, clinical stage, and molecular subtype were independent prognostic factors for patients with IDC. ROC curve analysis revealed that the accuracy of stromal maturity detection was greater than that of TILs alone, and the combined assessment of both parameters achieved the best predictive performance.

CONCLUSIONS: Stromal maturity and TILs in patients with breast IDC have important clinicopathological and prognostic significance, providing clinical guidance and a theoretical basis for the precise diagnosis and prognostic evaluation of this disease.}, } @article {pmid42046781, year = {2026}, author = {Hashemi, H and Olfatbakhsh, A and Moghadam, S and Aghanajafi, A and Heydari, L and Rostami, M and Haghighat, S}, title = {Vacuum-Assisted Excision and Assessing Residual Tumor Burden in Patients With Breast Cancer Following Neoadjuvant Chemotherapy (A Pilot Study).}, journal = {International journal of breast cancer}, volume = {2026}, number = {}, pages = {9951029}, pmid = {42046781}, issn = {2090-3170}, abstract = {AIM: The objective of this study is to evaluate the accuracy of vacuum-assisted excision as a minimally invasive method for assessing residual tumor burden in distinct breast cancer subtypes following neoadjuvant chemotherapy.

MATERIALS AND METHODS: In this pilot clinical trial, 20 patients with breast cancer scheduled for neoadjuvant chemotherapy were assessed. Upon completion of chemotherapy, patients underwent ultrasound-guided vacuum-assisted excision of the tumor site, performed by a radiologist. Subsequently, surgical excision of the tumor was carried out. The pathology reports from the vacuum excision were compared with the surgical specimens to determine the concordance in detecting residual tumor tissue.

RESULTS: Among the 20 patients who underwent vacuum-assisted excision, 13 patients demonstrated no residual tumor in both vacuum pathology and surgical pathology. However, in four patients, including three cases of Ductal Carcinoma In Situ (DCIS) and one case of Invasive Ductal Carcinoma (IDC), a false negative vacuum excision was reported. In three patients, residual tumor was reported both in surgical and vacuum pathology. The positive predictive value, negative predictive value, and accuracy of vacuum excision for detecting residual tumor were 100%, 76.5%, and 80%, respectively. The sensitivity and specificity of vacuum excision were 42.9% and 100%, respectively.

CONCLUSION: Based on the findings of this study and considering the accuracy of vacuum excision in identifying residual tumors (80%), it is evident that vacuum excision cannot currently serve as a substitute modality for surgery in the management of patients with post-neoadjuvant breast cancer. Further research with a larger sample size is warranted to enhance our understanding in this area.

TRIAL REGISTRATION: IRCT20241204063942N1.}, } @article {pmid42051841, year = {2026}, author = {Pereira, W and Krishnappa, R and Deep, S and Puri, A}, title = {Male Breast Carcinoma in an Elderly Patient: A Rare Presentation and the Importance of Individualized Management.}, journal = {Cureus}, volume = {18}, number = {3}, pages = {e106033}, pmid = {42051841}, issn = {2168-8184}, abstract = {Male breast carcinoma (MBC) is a rare malignancy and often presents at an advanced stage due to low awareness and social stigma. Management is largely extrapolated from female breast cancer and must be individualized, particularly in elderly patients. An 87-year-old male patient presented with a painless left breast lump since three months and an ulcer over the nipple for since one month. Examination revealed a firm retroareolar mass with a healed ulcer over the lower aspect of the nipple and no palpable axillary lymphadenopathy. Imaging suggested a suspicious lesion, and core needle biopsy confirmed invasive ductal carcinoma. Staging workup with fludeoxyglucose-18 (FDG) positron emission tomography-computed tomography (PET-CT) showed no distant metastasis. The patient underwent a modified radical mastectomy with axillary lymph node dissection. Histopathology revealed Grade II invasive ductal carcinoma with nodal involvement (pT4bN1a, Stage IIIB). Immunohistochemistry demonstrated estrogen and progesterone receptor positivity, human epidermal growth factor receptor 2 (HER2) negativity, and a low proliferative index, consistent with a luminal A subtype. Following multidisciplinary tumour board discussion, adjuvant chemotherapy was omitted, considering advanced age and performance status. The patient was treated with tamoxifen and adjuvant chest wall + axillary radiotherapy. At follow-up, he remains disease-free with a good quality of life. This case highlights the importance of early suspicion in male breast lesions and emphasizes individualized management integrating tumor biology, stage, and patient factors.}, } @article {pmid42044933, year = {2026}, author = {Barber, MRW and St Pierre, Y and Peschken, CA and Legge, A and Hanly, JG and Vinet, E and Pineau, CA and Bernatsky, S and Touma, Z and Urowitz, MB and Gladman, DD and Fortin, PR and Clarke, AE}, title = {Forgotten costs of systemic lupus erythematosus: estimating indirect healthcare costs in a national prospective observational Canadian lupus cohort.}, journal = {Lupus science & medicine}, volume = {13}, number = {1}, pages = {}, doi = {10.1136/lupus-2025-001851}, pmid = {42044933}, issn = {2053-8790}, mesh = {Humans ; *Lupus Erythematosus, Systemic/economics ; Female ; Male ; Adult ; Canada ; Prospective Studies ; Absenteeism ; Middle Aged ; *Health Care Costs/statistics & numerical data ; *Cost of Illness ; Presenteeism/economics ; Efficiency ; Sex Factors ; Young Adult ; Sick Leave/economics ; }, abstract = {OBJECTIVES: To assess indirect costs (IDC) due to lost productivity in paid/unpaid labour, stratified by sex, in a national prospective observational multicentre Canadian SLE cohort.

METHODS: Patients from six centres reported on lost productivity in paid/unpaid labour. IDC included: absenteeism (time lost from paid labour because of illness), presenteeism (degree of productivity impairment in paid/unpaid labour) and opportunity costs (additional time patients would be working in paid/unpaid labour if not ill). Opportunity costs were the difference between the time patients reported working and the time worked by an age, sex and geography-matched general population. IDC were valued using Statistics Canada wages (2024 Canadian dollars) with unpaid labour calculated using the opportunity cost method (OCM) and replacement cost method (RCM). The association of sex with IDC components was assessed (adjusted for race/ethnicity, age, disease duration, education and the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index) using regression modelling.

RESULTS: Of the 2180 patients who participated, 90.5% were female and 67.1% were white; the mean age at diagnosis was 33.2 years and mean SLE duration was 14.7 years. Patients completed an average of 3.4 questionnaires with 51.2% of women and 47.1% of men employed at baseline. Total annual IDC were significantly higher among women using the OCM (women $35 330; men $32 016) and did not differ using the RCM (women $26 114; men $26 136). Regressions showed total IDC did not differ using either method. Unpaid labour costs were significantly higher among women (OCM: women $22 680; men $11 591 and RCM: women $13 465; men $5711) and paid labour costs were significantly higher among men (women $12 651; men $20 425). Regressions showed similar results.

CONCLUSION: IDC in SLE, particularly resulting from unpaid labour, are substantial, especially in women, where they represent up to 64.2% of total IDC versus 36.2% in men. Hence, economic analyses of novel/emerging therapies should incorporate lost productivity, including unpaid labour costs, which are of particular importance in diseases disproportionately affecting women.}, } @article {pmid42033778, year = {2026}, author = {Takahashi, N and Funasaka, C and Shimura, M and Hirota, A and Uematsu, M and Fukuda, M and Baba, K and Mamishin, K and Nakajima, H and Kondoh, C and Harano, K and Matsubara, N and Hosono, A and Kawasaki, T and Onishi, T and Naito, Y and Mukohara, T}, title = {Efficacy of perioperative pembrolizumab for triple-negative breast cancer with apocrine feature or metaplastic carcinoma.}, journal = {The oncologist}, volume = {}, number = {}, pages = {}, doi = {10.1093/oncolo/oyag159}, pmid = {42033778}, issn = {1549-490X}, abstract = {BACKGROUND: The KEYNOTE-522 (KN522) trial demonstrated significantly improved outcomes with neoadjuvant chemotherapy (NAC) combined with pembrolizumab in high-risk triple-negative breast cancer (TNBC). However, the efficacy of this chemoimmunotherapy for histologically uncommon TNBC subtypes, such as invasive ductal carcinoma (IDC) with apocrine feature (IDCapo) or metaplastic carcinoma, remains unclear.

PATIENTS AND METHODS: This retrospective study examined clinicopathological characteristics and outcomes of patients with clinical stage II or III TNBC treated with either the KN522 regimen or conventional NAC without immunotherapy at the National Cancer Center Hospital East between August 2014 and December 2024. Patients pathologically diagnosed with IDC, IDCapo, or metaplastic carcinoma were included. We compared outcomes of the KN522 regimen among histologic subtypes and evaluated its efficacy versus conventional NAC in patients with IDCapo or metaplastic carcinoma.

RESULTS: Seventy-two patients with TNBC received the KN522 regimen: 58 IDC, 10 IDCapo, and 4 metaplastic carcinoma. The pathological complete response (pCR) rate was significantly lower in IDCapo than in IDC (3/10 [30.0%] vs. 41/58 [70.7%], P = 0.027), and this difference remained after adjustment for clinical factors. There were no metaplastic carcinoma patients with pCR (0/4, 0%). Compared with conventional NAC, the KN522 regimen yielded a higher pCR rate in IDCapo (3/10 [30.0%] vs. 0/19 [0%], P = 0.033), but not in metaplastic carcinoma (0/4 [0%] vs. 1/10 [10.0%], P = 1.00).

CONCLUSION: The pCR rate of NAC with pembrolizumab was significantly lower in IDCapo than in IDC but was improved compared with conventional NAC. No meaningful benefit was observed in metaplastic carcinoma.

IMPLICATIONS FOR PRACTICE: This study suggests that neoadjuvant chemoimmunotherapy can improve pathological complete response rate in invasive ductal carcinoma with apocrine feature, known as therapeutically resistant uncommon histology of the breast cancer. Pathological complete response rates of the neoadjuvant chemoimmunotherapy is dismal in metaplastic breast carcinoma, which sheds light to highly unmet need of novel therapeutic strategies for such aggressive breast cancer.}, } @article {pmid42038143, year = {2024}, author = {Sadeghi Moghimi, E and Ghanbari, Z and Mirmalek, SA and Aeinfar, K and Salimi Tabatabaee, SA and Zaferani Arani, H and Ghasemi, A and Jangholi, E and Abbasy, Z and Rahimi, M and Derayati, F}, title = {Frequency Survey of Brain Metastases and Its Associated Factors Among Iranian Women with Breast Cancer: A Cross-sectional Study in Tehran City.}, journal = {Galen medical journal}, volume = {13}, number = {}, pages = {e3238}, pmid = {42038143}, issn = {2322-2379}, abstract = {BACKGROUND: Brain metastases are serious complication of breast cancer (BC) that poses a critical management challenge. Hence, this study aimed to evaluate clinical findings, the status of hormonal receptors, and their correlation with brain metastasis among patients with BC.

MATERIALS AND METHODS: This cross-sectional study was performed on women with BC that was newly diagnosed with brain metastasis from 2020 to 2023. Also, hormonal receptor status (such as p53, estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor2 [HER2]), histopathological type of BC, duration of disease, type of treatment, local cerebral invasions, and initial presentations were recorded. A P-value less than 0.05 was considered as statistical significance.

RESULTS: Of a total of 302 patients, 49 (16.2%) patients had brain metastasis. The mean age of patients was 45.21±8.3 years, which was significantly lower in patients with metastasis (45.96±11.31 vs. 51.13±12.61 years, P=0.008). There was a significant association between the duration of disease in patients with and without brain metastasis (2.76±1.03 vs. 5.55±3.32 years, P=0.002). Also, the most prevalent histopathological type of BC was invasive ductal carcinoma (IDC). Headache was the most common clinical presentation among patients with brain metastasis. In addition, the most and the least common positive receptors among patients with metastasis were Ki-67 (93.87%) and PR (55.1%), respectively. Compared to patients without metastasis, HER2-positive and P53-positive receptors were markedly associated with brain metastasis (P=0.03 and P=0.021, respectively). However, there was no significant association between treatment methods and metastasis status.

CONCLUSION: Patients with younger age, IDC, and positivity of HER2 and P53 receptors were at an increased risk of developing brain metastases.}, } @article {pmid42031398, year = {2026}, author = {Gonzalez, J and Singh, V and Burgers, J}, title = {Diagnostic challenges and management of primary accessory axillary breast cancer.}, journal = {BMJ case reports}, volume = {19}, number = {4}, pages = {}, doi = {10.1136/bcr-2025-268191}, pmid = {42031398}, issn = {1757-790X}, mesh = {Humans ; Female ; *Breast Neoplasms/therapy/pathology/diagnosis ; Axilla/pathology ; *Carcinoma, Ductal, Breast/therapy/pathology/diagnosis ; Middle Aged ; *Breast ; Sentinel Lymph Node Biopsy ; Mastectomy, Segmental ; }, abstract = {A perimenopausal woman presented with a slowly enlarging right axillary mass initially suspected to be a sebaceous cyst. An incisional biopsy revealed high-grade invasive ductal carcinoma arising from accessory axillary breast tissue. Imaging showed no orthotopic breast lesion and staging was cT1N0M0. She underwent axillary lumpectomy and sentinel lymph node biopsy, confirming pT1bN0M0 invasive carcinoma. Adjuvant therapy included whole breast radiation, hormonal therapy with anastrozole and goserelin. At 2 years, she remains disease-free. This case highlights the diagnostic challenge of accessory axillary breast cancer (AABC), a rare entity often missed on routine imaging. Early recognition and application of standard breast cancer treatment protocols can result in excellent outcomes. Clinicians should maintain a high index of suspicion for AABC in axillary masses, especially in patients with no primary breast findings on imaging to ensure timely diagnosis and appropriate management.}, } @article {pmid42027077, year = {2026}, author = {Blaas, L and Bartelt, A}, title = {Fast & fuelious: the malate-aspartate shuttle in brown adipocyte lipid metabolism.}, journal = {The FEBS journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/febs.70557}, pmid = {42027077}, issn = {1742-4658}, support = {TRR333//Deutsche Forschungsgemeinschaft/ ; N/A//Else Kröner-Fresenius-Stiftung/ ; }, abstract = {Brown adipose tissue (BAT) produces heat in response to cold exposure, for which it relies on the coordination of aerobic and anaerobic metabolism. However, how reaction intermediates connect these two essential pathways is unclear. In this issue of The FEBS Journal, Veliova et al., report that the malate-aspartate shuttle (MAS) supports norepinephrine-induced lipolysis in brown adipocytes. Disruption of MAS during adrenergic activation impairs lipolysis without reducing respiration. These findings indicate that cytosolic redox balance influences thermogenic metabolism. By linking NAD+ regeneration to lipid metabolism, the study highlights the MAS as an important node coordinating metabolism, redox balance, and thermogenesis.}, } @article {pmid42028343, year = {2026}, author = {Haas, L and Gal, J and Gauthier, M and Schiappa, R and Hannoun-Levi, JM}, title = {Single fraction based-partial breast irradiation: 10-year results of the SiFEBI phase 2 prospective trial.}, journal = {Clinical and translational radiation oncology}, volume = {59}, number = {}, pages = {101173}, pmid = {42028343}, issn = {2405-6308}, abstract = {PURPOSE: This analysis updates the SiFEBI phase 2 trial (NCT01727011) evaluating accelerated partial breast irradiation (APBI) delivered as a single fraction (sfPBI) of postoperative multicatheter interstitial HDR brachytherapy (MIB) in elderly patients with low-risk breast cancer.

MATERIALS AND METHODS: Patients aged ≥ 70 years (Balducci I-II) with low-risk breast cancer were enrolled. After lumpectomy, intraoperative catheter implantation was performed and postoperative sfPBI (16 Gy) was delivered. The primary endpoint was cumulative incidence of local recurrence (ciLR). Secondary endpoints included cumulative incidence of distant metastasis (ciDM), cancer-specific survival (CSS), overall survival (OS), late toxicity, cosmetic outcome, and endocrine-therapy (ET) adherence.

RESULTS: From 11/12 to 09/14, 26 patients were enrolled. Median age was 76.6 years; median tumour size was 10.4 mm. Most tumours were invasive ductal carcinoma (76.5%), all of luminal subtype. After a median follow-up of 137 months, 10-year ciLR was 5%. Ten-year ciDM, CSS, and OS were 0%, 100%, and 81%, respectively. Late toxicity was observed in 9 patients (34.6%) with a total of 12 events (G1: 83.3%, G2: 16.6%). Reported late effects included breast pain, hypopigmentation, telangiectasia and breast fibrosis. Ten-year cosmetic outcomes were reported in 18 pts as excellent in 14 patients (77.8%) and good in 4 patients (22.2%). Median ET duration was 59 months; 14 pts (53.8%) were non-adherent.

CONCLUSION: In this elderly, low-risk cohort, single fraction postoperative MIB sfPBI provided excellent long-term oncological outcomes with acceptable toxicity and cosmesis. Larger studies with extended follow-up are warranted.}, } @article {pmid42028513, year = {2026}, author = {Ahmad, CM and Tadakamalla, R and Kastle, RA and Weitoschova, A and Abboud, A}, title = {Early Nodal Metastasis in an 81-Year-Old Woman With Subcentimeter Retroareolar Invasive Ductal Carcinoma: A Case That Defies Indolence Expectations.}, journal = {Cureus}, volume = {18}, number = {3}, pages = {e105719}, pmid = {42028513}, issn = {2168-8184}, abstract = {Retroareolar invasive ductal carcinoma (IDC) represents an anatomically distinct subset of breast cancers that may evade early clinical detection. In elderly patients, small, estrogen receptor (ER)-positive tumors with low proliferative indices are often presumed to follow an indolent course. We report the case of an 81-year-old woman diagnosed with a 0.6-cm Grade II/III retroareolar IDC exhibiting strong ER expression, low Ki-67 (~6%), and human epidermal growth factor receptor 2 (HER2) negativity, yet with synchronous axillary lymph node metastasis confirmed at initial biopsy. This case underscores the limitations of relying on tumor size, age, and proliferation markers alone to estimate metastatic risk and highlights the importance of comprehensive axillary evaluation, even in clinically and biologically favorable presentations.}, } @article {pmid42031136, year = {2026}, author = {Walsh, AR and Dove-Medows, E and Loder, CM and Kalpakjian, C and Moore, C and Ernst, S and Munro-Kramer, ML}, title = {A Cross-Sectional Survey of University Students' Lifetime Experiences of Inappropriate, Disrespectful, and Coercive Behavior During Sensitive Exams.}, journal = {Journal of pediatric and adolescent gynecology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jpag.2026.04.008}, pmid = {42031136}, issn = {1873-4332}, abstract = {STUDY OBJECTIVE: To describe university students' lifetime prevalence of inappropriate, disrespectful, and coercive (IDC) experiences during sensitive physical exams and explore differences across sexual orientation and gender identities (SOGI).

METHODS: This cross-sectional study analyzed survey data from a representative sample of students at a large public university (US, 2021, N=2779). Lifetime prevalence of 13 IDC experiences (e.g., painful exams, ungloved exams, attempts to sexually arouse patient) and trust in sensitive exam providers was estimated for the sample and within SOGI groups (gender minority (GM), sexual minority (SM) cisgender female/male, heterosexual cisgender female/male). Item prevalence and SOGI associations were assessed with 2-sided t-tests and X[2] tests.

RESULTS: Lifetime prevalence of sensitive exam IDC experiences ranged from 0.6% (took pictures of patient's body without permission) and 2.5% (genital, pelvic, or rectal exam without gloves) to 19.9% (excessive wait while undressed). Significant associations (P<0.05) between SOGI and negative experience prevalence estimates were identified; GM students reported the highest prevalence, and cisgender heterosexual male students the lowest, for all but 1 IDC item. 7.9% of students reported not trusting any healthcare providers during sensitive exams with 30.9% of GM students compared to 3.1% of heterosexual cisgender men reporting no trust (P<0.001).

CONCLUSION: GM university students experienced more IDC experiences during sensitive exams and have lower trust in sensitive exam providers than cisgender students, particularly cisgender heterosexual males. Ensuring informed consent, offering chaperones, and clear communication are critical to build trust and ensure continued healthcare engagement and positive long-term health outcomes, particularly for SOGI patients.}, } @article {pmid35344029, year = {2022}, author = {Lassman, AB and Sepúlveda-Sánchez, JM and Cloughesy, TF and Gil-Gil, MJ and Puduvalli, VK and Raizer, JJ and De Vos, FYF and Wen, PY and Butowski, NA and Clement, PMJ and Groves, MD and Belda-Iniesta, C and Giglio, P and Soifer, HS and Rowsey, S and Xu, C and Avogadri, F and Wei, G and Moran, S and Roth, P}, title = {Infigratinib in Patients with Recurrent Gliomas and FGFR Alterations: A Multicenter Phase II Study.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {28}, number = {11}, pages = {2270-2277}, pmid = {35344029}, issn = {1557-3265}, support = {P30 CA013696/CA/NCI NIH HHS/United States ; P50 CA211015/CA/NCI NIH HHS/United States ; UG1 CA189960/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Follow-Up Studies ; *Glioma/drug therapy/genetics ; Humans ; Microtubule-Associated Proteins ; *Neoplasm Recurrence, Local/drug therapy/genetics ; Phenylurea Compounds ; Protein Kinase Inhibitors/adverse effects ; Pyrimidines ; Receptor, Fibroblast Growth Factor, Type 3/genetics ; }, abstract = {PURPOSE: FGFR genomic alterations (amplification, mutations, and/or fusions) occur in ∼8% of gliomas, particularly FGFR1 and FGFR3. We conducted a multicenter open-label, single-arm, phase II study of a selective FGFR1-3 inhibitor, infigratinib (BGJ398), in patients with FGFR-altered recurrent gliomas.

PATIENTS AND METHODS: Adults with recurrent/progressive gliomas harboring FGFR alterations received oral infigratinib 125 mg on days 1 to 21 of 28-day cycles. The primary endpoint was investigator-assessed 6-month progression-free survival (PFS) rate by Response Assessment in Neuro-Oncology criteria. Comprehensive genomic profiling was performed on available pretreatment archival tissue to explore additional molecular correlations with efficacy.

RESULTS: Among 26 patients, the 6-month PFS rate was 16.0% [95% confidence interval (CI), 5.0-32.5], median PFS was 1.7 months (95% CI, 1.1-2.8), and objective response rate was 3.8%. However, 4 patients had durable disease control lasting longer than 1 year. Among these, 3 had tumors harboring activating point mutations at analogous positions of FGFR1 (K656E; n = 2) or FGFR3 (K650E; n = 1) in pretreatment tissue; an FGFR3-TACC3 fusion was detected in the other. Hyperphosphatemia was the most frequently reported treatment-related adverse event (all-grade, 76.9%; grade 3, 3.8%) and is a known on-target toxicity of FGFR inhibitors.

CONCLUSIONS: FGFR inhibitor monotherapy with infigratinib had limited efficacy in a population of patients with recurrent gliomas and different FGFR genetic alterations, but durable disease control lasting more than 1 year was observed in patients with tumors harboring FGFR1 or FGFR3 point mutations or FGFR3-TACC3 fusions. A follow-up study with refined biomarker inclusion criteria and centralized FGFR testing is warranted.}, } @article {pmid42017194, year = {2025}, author = {Haberl, H and Baumgart, A and Zeidler, J and Schug, F and Frantz, D and Palacios-Lopez, D and Fishman, T and Peled, Y and Cai, B and Virág, D and Hostert, P and Wiedenhofer, D and Esch, T}, title = {Weighing the global built environment: High-resolution mapping and quantification of material stocks in buildings.}, journal = {Journal of industrial ecology}, volume = {29}, number = {1}, pages = {159-172}, pmid = {42017194}, issn = {1088-1980}, abstract = {UNLABELLED: Buildings provide indispensable services for human well-being, but their construction and use are responsible for a substantial fraction of societies' resource requirements and greenhouse gas emissions. Mapping and quantifying the material stocks in buildings is a key research frontier in industrial ecology. Reliable and spatially highly resolved maps of material stocks in buildings worldwide are so far not available. Existing approaches based on nighttime light data allow large-scale coverage, but their spatial resolution is usually ∼0.5-1 km. Other methods using light detection and ranging (LiDAR) and cadaster data achieve higher resolution and accuracy, but do not allow wall-to-wall mapping of large regions. Based on high-resolution Earth Observation data combined with material intensity factors (kg per m[3] of building volume), we quantify and map material stocks in buildings at the unprecedented resolution of 90 m globally. We distinguish 18 types of materials in five types of buildings. We find that global material stocks in buildings amount to 547 (391-672) Gt, approximately half of total global societal material stocks. We find highly unequal distributions of material stocks in buildings per capita and per unit area of each country. Our results agree well with previous detailed estimates of material stocks in buildings in dedicated regions or individual cities. Improved and harmonized material intensity factors emerge as a key research area for improving the accuracy of material stock maps. Our results are available as data products with high spatial and thematic resolution to facilitate future studies; for example, of secondary resource potentials. This article met the requirements for a gold-gold JIE data openness badge described at http://jie.click/badges. http://jie.click/badges.

SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1111/jiec.13585) contains supplementary material, which is available to authorized users.}, } @article {pmid42018242, year = {2026}, author = {Schuster, CR and Aslami, ZV and Taccheri, C and Azizi, A and Saab, D and Coon, D and Camp, MS and Liang, F}, title = {Preoperative breast cancer screening before chest masculinization surgery.}, journal = {Breast cancer research and treatment}, volume = {217}, number = {2}, pages = {}, pmid = {42018242}, issn = {1573-7217}, mesh = {Humans ; Female ; Middle Aged ; Adult ; Retrospective Studies ; *Breast Neoplasms/diagnosis/surgery/diagnostic imaging ; Male ; *Early Detection of Cancer/methods ; Young Adult ; *Preoperative Care/methods ; Mammography ; Adolescent ; Magnetic Resonance Imaging ; }, abstract = {PURPOSE: Detecting malignancy before gender-affirming chest masculinization surgery (GACMS) can alter surgical planning and prevent reoperation, yet a lack of standardized preoperative breast imaging guidelines has resulted in inconsistent, surgeon-dependent practices and potential missed diagnoses. Limited data evaluating the efficacy of pre-GACMS imaging further contributes to this gap. This study aimed to characterize patterns, indications, and outcomes of preoperative breast imaging before GACMS, and to assess the impact of preoperative imaging on cancer detection, surgical decision-making, and timing to surgery.

METHODS: A single-institution, retrospective review of adults who underwent GACMS between January 2017-September 2024 was conducted. Descriptive statistics summarize preoperative imaging frequency, indications, modalities, outcomes, and postoperative pathology. Alterations in surgical management based on preoperative versus postoperative cancer detection, as well as an institution-wide screening algorithm, are described.

RESULTS: Of 368 patients, 91.8% (n = 338) were under 40 (mean 27.2, range 18-63). Preoperative breast imaging was recommended in 11.7% (n = 43) and performed in 11.1% (n = 41). Modalities included screening mammography (70.7%, n = 29), diagnostic mammography (29.3%, n = 12), MRI (9.8%, n = 4), and ultrasound (7.3%, n = 3). Indications included age (41.9%, n = 18), family history (30.2%, n = 13), physical exam finding (23.3%, n = 10), and BRCA2 mutation (2.3%, n = 1). Imaging revealed irregular findings in 17.1% (n = 7), with malignancy confirmed in 2 patients (4.9% of imaged; 0.5% overall). One patient who did not receive preoperative imaging was found to have invasive ductal carcinoma on postoperative pathology, resulting in 0.8% (n = 3) overall breast cancer diagnoses perioperatively. Preoperative detection altered surgical planning. Median time to surgery did not significantly differ between imaged and non-imaged patients (3.1 vs. 3.7 months, p = 0.2).

CONCLUSION: Preoperative breast cancer imaging before GACMS identified malignancies that significantly influenced surgical planning, preventing additional procedures postoperatively. Implementing a decision-making algorithm could guide and standardize breast imaging before GACMS.}, } @article {pmid42020373, year = {2026}, author = {Walth-Hummel, AA and Jouffe, C and Weber, P and Motzler, K and Geppert, J and Sterr, M and Gan, W and Szczerbinska, I and König, AC and Hauck, SM and Terron-Exposito, R and Hass, D and Wang, C and Dyar, KA and Lyon, JG and Lickert, H and Ämmälä, C and Herzig, S and Ashcroft, FM and Bakhti, M and MacDonald, PE and Rohm, M}, title = {TBL1X/TBL1XR1 govern β-cell identity through a PAX6-containing gene regulatory network.}, journal = {Nature communications}, volume = {17}, number = {1}, pages = {}, pmid = {42020373}, issn = {2041-1723}, support = {DFG FOR5795-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, mesh = {*Insulin-Secreting Cells/metabolism ; Animals ; Mice ; Mice, Knockout ; *PAX6 Transcription Factor/metabolism/genetics ; *Gene Regulatory Networks ; Humans ; Histone Deacetylases/metabolism/genetics ; Insulin/metabolism/genetics ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; *Repressor Proteins/metabolism/genetics ; Promoter Regions, Genetic ; Male ; *Nuclear Proteins/metabolism/genetics ; Gene Expression Regulation ; Transducin/metabolism/genetics ; }, abstract = {A main mechanism of β-cell dysfunction in diabetes is loss of identity, controlled by transcription factors that induce identity gene expression and disallowed gene repression. How transcription factors facilitate simultaneous expression and repression is not fully understood, representing a knowledge gap in diabetes research. We identify the transcriptional co-factors transducin β-like 1 x-linked (TBL1X) and its homolog TBL1X-related (TBL1XR1, together TBL/R1) as crucial regulators of β-cell identity and determinants of diabetes development and progression. β-cell specific TBL/R1 knockout in mice leads to progressive hypoinsulinemia and hyperglycemia. scRNA-sequencing reveals loss of β-cells, emergence of polyhormonal cells, and reduced β-cell maturity upon TBL/R1 knockout. Interactome screens and chromatin immunoprecipitation show TBL/R1 directly regulate insulin promoter activity through a PAX6-HDAC3 gene regulatory network, evident also in human models. TBL/R1 associates with diabetes in humans, thus our study uncovers an additional regulatory layer maintaining β-cell identity crucial for diabetes development and progression.}, } @article {pmid41814374, year = {2026}, author = {Zhu, C and Huang, L}, title = {Synchronous breast carcinoma and diffuse large B-cell lymphoma: a case report and literature review on diagnostic challenges and management implications.}, journal = {World journal of surgical oncology}, volume = {24}, number = {1}, pages = {}, pmid = {41814374}, issn = {1477-7819}, abstract = {BACKGROUND: Synchronous breast carcinoma and diffuse large B-cell lymphoma occurring as independent primary malignancies is exceptionally rare. Because these tumors differ markedly in histological origin, biological behavior, and treatment strategies, their coexistence can easily lead to diagnostic pitfalls and therapeutic dilemmas. Reporting such a case provides new insights into the clinical recognition and management of rare dual primaries.

CASE PRESENTATION: A 54-year-old woman presented with a painless left cervical (neck) mass. Imaging revealed a left breast lesion with multi-station lymphadenopathy (including cervical nodes), initially interpreted as metastatic breast carcinoma. Breast core biopsy confirmed HER2-overexpressing invasive ductal carcinoma with strong ER/PR positivity. Cervical (neck) lymph-node biopsy established diffuse large B-cell lymphoma (non-GCB/MCD) with TP53, MYD88, and CD79B mutations. The patient received rituximab-based therapy plus a Bruton tyrosine kinase inhibitor and underwent simple mastectomy. The breast carcinoma has remained controlled without evidence of recurrence, whereas the relapsing lymphoma ultimately determined the disease course.

CONCLUSIONS: This case emphasizes the need for independent biopsies of suspicious lesions to avoid misclassification as metastatic disease. Management should follow a “lymphoma-first” approach with careful sequencing to balance treatments for both malignancies and to minimize overlapping toxicities. Prognosis is largely driven by the biological features of the lymphoma, particularly in high-risk molecular subtypes. A dual-track follow-up strategy, recording outcomes for each tumor separately, may improve clarity in assessing prognosis and guiding individualized care. This report underscores the importance of multidisciplinary collaboration and highlights potential directions for future research on the mechanisms and management of synchronous dual primaries.}, } @article {pmid42009450, year = {2026}, author = {Fatima, I and Jaffarsadiq, A and Faquih, AE and Hlavacek, C and Sehbai, A}, title = {Triple-negative breast cancer with neurofibromatosis type 1: management challenges.}, journal = {BMJ case reports}, volume = {19}, number = {4}, pages = {}, doi = {10.1136/bcr-2025-270134}, pmid = {42009450}, issn = {1757-790X}, mesh = {Humans ; Female ; *Neurofibromatosis 1/complications ; *Triple Negative Breast Neoplasms/pathology/therapy/complications/surgery/diagnosis ; Adult ; Mastectomy/methods ; Sentinel Lymph Node Biopsy ; *Carcinoma, Intraductal, Noninfiltrating/pathology/therapy ; }, abstract = {Neurofibromatosis type 1 (NF1) is an autosomal dominant RASopathy associated with increased risk of early-onset breast cancer, particularly triple-negative breast cancer (TNBC). We report a woman in her early 40s with NF1 who presented for elective cosmetic breast surgery and was incidentally found to have a suspicious right breast lesion on screening mammogram. Biopsy confirmed high-grade ductal carcinoma in situ (DCIS) with invasive ductal carcinoma, immunohistochemically triple-negative. Staging investigations revealed no nodal or distant disease. She underwent bilateral mastectomy with right sentinel lymph node biopsy (SLNB), followed by adjuvant docetaxel-cyclophosphamide chemotherapy. Radiotherapy was avoided given the elevated risk of radiation-induced sarcoma (RIS) in NF1. Postoperative reconstruction was staged and ultimately successful. At more than 3 years of follow-up, she remains disease-free with satisfactory cosmetic outcomes. This case highlights the importance of vigilant breast surveillance in NF1, challenges in balancing oncologic control with treatment-related risks, and the need for individualised multidisciplinary care.}, } @article {pmid42011409, year = {2026}, author = {Ruicci, KM and Helou, J and Barry, A and Ye, XY and Koch, CA and Croke, J and Han, K and Rodin, D and Hahn, E and Kwan, JYY and Yan, M and Liu, FF and Lindsay, P and Javor, J and Bedard, P and Cescon, D and Kumar, V and Amir, E and Nadler, MB and Lee, R and Glicksman, RM}, title = {The role of stereotactic body radiotherapy in oligoprogressive breast cancer: A site-specific analysis of the prospective, phase-II RADIANT trial.}, journal = {Clinical and translational radiation oncology}, volume = {59}, number = {}, pages = {101164}, pmid = {42011409}, issn = {2405-6308}, abstract = {BACKGROUND: Standard-of-care management for patients with progressive metastatic breast cancer is changing systemic therapy lines. For patients with limited disease progression ('oligoprogression'), there is interest in treating progressive sites with stereotactic body radiation therapy (SBRT) whilst maintaining the current systemic therapy. Here we report on the clinical, quality of life (QOL) and adverse event findings for a cohort of patients with oligoprogressive breast cancer enrolled on the prospective, phase-II RADIANT clinical trial.

METHODS: RADIANT (NCT04122469) was a single-arm, phase-II basket trial which included patients with oligoprogressive metastatic breast cancer. Patients on systemic therapy for ≥ 3 months received SBRT over 1-5 fractions, targeting up to 5 metastases with radiographic progression. The primary endpoint was cumulative incidence of change in systemic therapy. Secondary endpoints included local control, progression-free survival, overall survival, adverse events and health-related (HR) QOL. Analysis by disease histology was planned a priori.

RESULTS: Thirty patients were enrolled and analyzed; the median age was 60.0 years, 80% had invasive ductal carcinoma and 90% were estrogen-receptor (ER)-positive. Most patients had recurrent metastatic disease (63.3%), while 36.7% had de novo metastatic disease. Most patients were on first-line (66.7%) systemic therapy. Median follow-up time was 33.7 months (range 2.5-57.2 months). The cumulative incidence of change in systemic therapy at 1-year was 30.0% (95% CI, 17.2-52.4%) and at 2-years was 50.4% (95% CI, 34.9-72.8%). At 1-year, local control rate was 90.0% and distant control rate was 56.7%. There were no grade ≥ 3 adverse events attributable to SBRT. HRQOL was maintained throughout the follow-up period.

CONCLUSION: Among this cohort of patients with oligoprogressive breast cancer, SBRT is a safe and promising intervention, with potential to delay next-line systemic therapy. However, as a significant cohort of patients do require a change in systemic therapy within 1-2 years of SBRT, biomarkers are needed to best select patients who would benefit clearly from this approach.}, } @article {pmid42014352, year = {2026}, author = {Sato, S and Urabe, F and Imai, Y and Iwamoto, Y and Iwatani, K and Tashiro, K and Tsuzuki, S and Umemori, M and Miki, J and Kimura, T and Shimoda, M and Takahashi, H}, title = {Prognostic impact of large cribriform architecture and intraductal carcinoma of the prostate in diagnostic biopsies of mCSPC receiving ARPI-based therapy.}, journal = {Japanese journal of clinical oncology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jjco/hyag067}, pmid = {42014352}, issn = {1465-3621}, abstract = {BACKGROUND: A cribriform architecture and intraductal carcinoma of the prostate (IDC-P) are recognized as aggressive histopathological features in prostate cancer. However, their prognostic significance in metastatic castration-sensitive prostate cancer (mCSPC), when assessed from diagnostic biopsy specimens, remains uncertain.

METHODS: This retrospective multicenter cohort study included 131 patients with mCSPC who received doublet or triplet therapy incorporating an androgen receptor pathway inhibitor. Diagnostic prostate biopsy specimens were examined for cribriform structures and IDC-P. When the former were present, they were subclassified as small or large types. The primary endpoint was castration-resistant prostate cancer-free survival (CRPC-FS).

RESULTS: Large cribriform structures were identified in 54.2% of patients, while small ones were observed in 19.8%. IDC-P was present in 67.2% of cases and was strongly associated with the large-type cribriform architecture (P < .001). Patients with that pattern experienced significantly shorter CRPC-FS compared to those without cribriform structures (P = .013), whereas the small-type architecture was not associated with disease progression. In multivariable analysis, IDC-P and an extent of disease score ≥ 3 were independently associated with shorter CRPC-FS, whereas large cribriform architecture did not retain independent significance. However, incorporation of large cribriform architecture improved model discrimination for predicting castration-resistant prostate cancer progression.

CONCLUSIONS: In diagnostic biopsy specimens, the large-type cribriform architecture is associated with adverse outcomes in mCSPC patients receiving androgen receptor pathway inhibitor-based therapy. Although its prognostic impact overlaps with that of IDC-P, its identification at diagnosis may provide clinically relevant information for contemporary mCSPC management.}, } @article {pmid42003471, year = {2026}, author = {Zhu, R and Li, Y and Zhang, J and Yang, X and Guo, H and He, Z and Cui, X and Liang, T and Guo, L}, title = {Multi-Machine Learning Elucidates Clinical Potential of Epithelial-Mesenchymal Transition-Associated Long Non-Coding RNAs in Breast Cancer Progression.}, journal = {Biotechnology journal}, volume = {21}, number = {4}, pages = {e70229}, doi = {10.1002/biot.70229}, pmid = {42003471}, issn = {1860-7314}, support = {62571264//National Natural Science Foundation of China/ ; 62171236//National Natural Science Foundation of China/ ; BE2022799//the Key Project of Social Development in Jiangsu Province/ ; 22KJA180006//Key Projects of Natural Science Research in Universities of Jiangsu Province/ ; //Qinglan Project of Jiangsu Universities in Jiangsu Province/ ; }, mesh = {Humans ; *RNA, Long Noncoding/genetics/metabolism ; *Epithelial-Mesenchymal Transition/genetics ; *Breast Neoplasms/genetics/pathology ; *Machine Learning ; Female ; Biomarkers, Tumor/genetics ; Gene Expression Regulation, Neoplastic ; Disease Progression ; Prognosis ; }, abstract = {Breast carcinoma (BRCA) involves multiple molecular markers, including epithelial-mesenchymal transition (EMT), which induce cell migration. However, the specific impact of long non-coding RNAs (lncRNAs) on EMT in BRCA remains uncertain. In this study, a prognostic model was constructed using EMT-associated lncRNAs (EALs), with utilization of integrative machine learning algorithms. The optimal model consisted of 15 EALs, with an AUC of 0.89 at 5 years, showing its potential as a plausible biomarker for BRCA. Among high-risk individuals, a significant increase in pathways linked to the preservation of equilibrium and immune defense was observed. Moreover, it was indicated that immunotherapy elicited negative responses in this group. Somatic mutations displayed higher TP53 rates in high-risk patients and increased CDH1/PIK3CA in low-risk ones. Notably, AC055854.1 and MIR205HG, important EALs in the model, probably regulate BRCA development through the lncRNA-microRNA-mRNA axis. Spatial transcriptome analysis revealed higher expression levels of EALs and high-risk related genes in ductal carcinoma in situ (DCIS), invasive mixed ductal/lobular carcinoma (IDC), and triple-negative BRCA (TNBC) than in breast metastasis (BMS) samples. And neutrophils were exclusively observed within the tumor microenvironment (TME) of BMS. All these findings emphasized EALs' value in revolutionizing clinical decision-making for personalized treatment strategies in BRCA cases.}, } @article {pmid42003938, year = {2026}, author = {Kareem, TF and Kamal, AM and Nakash, MA}, title = {Dynamic curve type serves as an effective tool for the diagnosis of benign or malignant non-mass enhancements on breast MRI.}, journal = {Oncology letters}, volume = {31}, number = {6}, pages = {212}, pmid = {42003938}, issn = {1792-1082}, abstract = {Identifying malignant non-mass enhancement (NME) in contrast-enhanced breast magnetic resonance imaging (MRI) remains a notable diagnostic challenge due to overlapping imaging features between benign and malignant lesions. Although the delayed-phase kinetic patterns are well-established, the diagnostic value of the initial-phase kinetics has not been fully elucidated. The present study aimed to evaluate the dynamic and morphological characteristics of NME lesions, to determine whether incorporating initial-phase kinetics with delayed-phase analysis improves the discrimination between benign and malignant cases. A prospective study was conducted at the Oncology Teaching Hospital (Baghdad, Iraq) from April to December 2022, including patients referred for breast MRI. Only cases with pure NME (without associated mass lesions) were included. A core biopsy was performed for all cases, with excisional biopsy when indicated. Data collection followed the Breast Imaging Reporting and Data System 5th edition criteria. Among 38 enrolled patients (mean age, 45±11.45 years; range, 26-75 years; median, 44 years), 63.2% presented with a breast lump and 26.3% underwent screening. Histopathology confirmed malignancy in 26 cases (68.4%), comprising 12 cases of ductal carcinoma in situ and 14 of invasive ductal carcinoma. Segmental enhancement was the most common malignant pattern [positive predictive value (PPV), 83.3%], followed by regional enhancement (PPV, 64.3%). Benign lesions had slow (58.3%) or medium (41.7%) initial upslopes, whereas 50% of malignant tumors exhibited a rapid initial slope (P=0.001). Persistent delay was observed in 75% of benign cases but in only 26.9% of malignant cases (P=0.005). Integrating the initial upslope with the plateau-phase kinetics increased the PPV for malignancy from 75 to 81.8%. In conclusion, the integration of initial-phase kinetics with traditional delayed-phase and morphological assessment improves the diagnostic accuracy for malignant NME lesions. This multi-parametric approach could potentially serve as a valuable tool to reduce the rate of unnecessary biopsies in the future.}, } @article {pmid42005625, year = {2026}, author = {Shamim, AM and Hossan, A and Hossen, MS and Barek, MA and Rashid, MA and Islam, MS}, title = {Linkage Between miR-218-2 (rs11134527) Genetic Polymorphism and Breast Cancer Risk: A Case-Control Study in the Bangladeshi Women.}, journal = {Health science reports}, volume = {9}, number = {4}, pages = {e72092}, pmid = {42005625}, issn = {2398-8835}, abstract = {BACKGROUND AND AIMS: The growth and spread of breast carcinoma are influenced by genetic factors. Diverse forms of cancer have been reported to display multiple subtypes of the microRNA gene. Therefore, the current study aimed to explore the connection between the miR-218-2 (rs11134527) and breast cancer risk.

METHODS: A total of 303 participants (158 breast cancer patients and 145 healthy controls) were enrolled. Clinical and demographic data were collected through structured questionnaires and hospital records. Genotyping of miR-218-2 rs11134527 was performed using the T-ARMS-PCR technique. Statistical analyses were conducted with SPSS v25.0 and MedCalc v19.0.7. The adjusted odds ratio (aOR) using binary logistic regression that controls for age and BMI was employed to investigate the relationship between the targeted SNPs and the risk of breast cancer.

RESULTS: Among the patients, invasive ductal carcinoma was the most frequent histological type (49.61%), followed by lobular carcinoma (17.22%). Grade II tumors (63.75%) were predominant. Ultrasound (64.18%) and biopsy (68.66%) were the most common diagnostic tools. Chemotherapy was the principal treatment (62.12%), with cyclophosphamide (69.62%), doxorubicin (53.80%), and paclitaxel (56.33%) as the most prescribed agents. Genotype analysis revealed that individuals carrying the AA genotype had a significantly higher risk of breast cancer than those with GG (additive model 2: OR = 2.48, 95% CI = 1.12-5.48, p = 0.025). Significant associations were also observed under the recessive model (AA vs. GG + AG: OR = 1.96, 95% CI = 1.0-3.86, p = 0.051) and the allelic model (A vs G: OR = 1.59, 95% CI = 1.06-2.39, p = 0.026).

CONCLUSION: The miR-218-2 rs11134527 A allele confers an increased risk of breast cancer in Bangladeshi women, supporting its potential role as a population-specific genetic biomarker for susceptibility assessment.}, } @article {pmid42005806, year = {2026}, author = {Waugh, SB and Maku, HO and Antosh, DD and Rozycki, SK and Kamat, AA and Okoye, EI and Coffey, DM and Deavers, MT and Schwartz, MR and Ge, Y}, title = {A rare case of multifocal vulvar carcinoma of mammary gland type (AMGT) with mucinous features: Differential diagnosis and literature review.}, journal = {Gynecologic oncology reports}, volume = {64}, number = {}, pages = {102068}, pmid = {42005806}, issn = {2352-5789}, abstract = {BACKGROUND: Primary vulvar adenocarcinoma of mammary gland type (AMGT) is a rare gynecologic cancer with only 54 reported cases to date. The tumor may have variety of histologic patterns and can be confused with other more common entities of vulvar tumors. Here, we report a rare mucinous variant of AMGT coexisting with ductal carcinoma in situ (DCIS) and benign mammary-like glands in the vulva. We further review the clinicopathological features of previously reported cases in the literature and discuss the differential diagnosis and treatment updates of this rare entity.

CASE PRESENTATION: A 78-year-old woman with a complex gynecological history who presented with gradually enlarging vulvar nodules and underwent wide local resection. Histological examination revealed mucinous adenocarcinoma and DCIS arising from benign mammary-like glands. The tumor shared histological and immunohistochemical features with invasive ductal carcinoma of the breast, including immunoreactivity to GATA binding protein 3 (GATA3), estrogen receptor (ER), progesterone receptor (PR), and gross cystic disease fluid protein 15 (GCDFP-15). Additional imaging did not reveal primary tumor in the breast, gastrointestinal tract, or other organs.

CONCLUSION: Accurate diagnosis of AMGT relies on awareness of this rare entity, recognition of its typical "milk line" location, and familiarity with its morphological and immunohistochemical similarities to breast carcinoma. The diagnostic importance of identifying tumor-associated benign mammary-like glands or DCIS cannot be overemphasized. Immunohistochemistry is critical in identifying the "mammary-like" phenotype of AMGT and excluding other primary and metastatic tumors of vulva. The unique biologic profile of AMGT dictates a treatment strategy distinct from other primary vulvar tumors.}, } @article {pmid42000472, year = {2026}, author = {Pessoa, EC and Couto, HL and Kamyia Carvalho Pessoa, CP and da Silva Pina, AB and de Luca Vespolli, HM and de Souza Almeida Filho, B and de Paula, DR and Petri Nahas, EA}, title = {Breast MRI biomarkers of tumor biology: integrating imaging with pathology to guide clinical care.}, journal = {European journal of radiology}, volume = {200}, number = {}, pages = {112863}, doi = {10.1016/j.ejrad.2026.112863}, pmid = {42000472}, issn = {1872-7727}, abstract = {BACKGROUND: Breast cancer is biologically heterogeneous, and tissue biomarkers derived from core biopsy may be limited by sampling and spatial heterogeneity. Breast MRI provides multiparametric information on tumor morphology, enhancement behavior, and peritumoral tissue characteristics. We evaluated whether standardized BI-RADS MRI descriptors are independently associated with histopathological features, immunohistochemical markers, and molecular subtypes in invasive breast cancer.

METHODS: This retrospective, single-center study included 340 consecutive women with invasive ductal carcinoma of no special type or invasive lobular carcinoma who underwent pretreatment 3T breast MRI between 2014 and 2019. MRI features were assessed using the BI-RADS MRI lexicon by a single experienced breast radiologist (>20 years), blinded to pathological data. Imaging descriptors were correlated with histological grade, lymphovascular invasion (LVI), ER, PR, HER2, Ki-67, and immunohistochemistry-defined molecular subtypes. Multivariable logistic regression was used to identify independent imaging predictors.

RESULTS: In multivariable models, peritumoral edema independently predicted LVI (OR 2.12, 95% CI 1.18-3.81) and high proliferative activity (Ki-67 ≥ 20%; OR 3.02, 95% CI 1.89-4.83). T2 mixed/hyperintense signal independently predicted high Ki-67 (OR 2.67, 95% CI 1.47-4.85) and HER2 positivity (OR 3.12, 95% CI 1.72-5.66). Rim enhancement was independently associated with the triple-negative subtype (OR 3.83, 95% CI 1.48-9.94) and high Ki-67 (OR 4.12, 95% CI 2.03-8.36). Washout kinetics independently predicted high Ki-67 (OR 3.18, 95% CI 1.82-5.56) and were inversely associated with Luminal A tumors (OR 0.15, 95% CI 0.06-0.37). HER2 positivity was independently associated with peritumoral edema, T2 hyperintensity, plateau kinetics, non-mass enhancement (OR 2.05, 95% CI 1.18-3.56), and segmental non-mass distribution (OR 3.28, 95% CI 1.12-9.61). Across analyses, a consistent imaging pattern combining edema, T2 hyperintensity, rim enhancement, and washout kinetics clustered in biologically aggressive tumors.

CONCLUSIONS: Standardized BI-RADS breast MRI descriptors demonstrate consistent and independent associations with established pathological biomarkers and molecular subtypes. Although MRI does not replace tissue-based assessment, these imaging phenotypes may provide complementary biological context and support radiopathological correlation in multidisciplinary care. Given the retrospective, single-center design with single-reader assessment and absence of external validation, these findings should be interpreted with appropriate caution and require prospective multicenter confirmation before clinical implementation.}, } @article {pmid41994693, year = {2026}, author = {Tezuka, H and Matsui, A and Murata, Y and Odani, E and Tsukiyama, E and Sato, M and Sasahara, M and Seki, H and Kinoshita, T}, title = {Synchronous Bilateral Breast Invasive Ductal Carcinoma With Osteoclast-Like Stromal Giant Cells in a 44-Year-Old Woman: A Case Report.}, journal = {Cureus}, volume = {18}, number = {3}, pages = {e105310}, pmid = {41994693}, issn = {2168-8184}, abstract = {Breast carcinoma with osteoclast-like stromal giant cells (OCGC) is a rare histological variant of invasive breast carcinoma. While it typically presents as a unilateral disease, its clinicopathological significance and the mechanisms underlying its formation remain incompletely understood. To our knowledge, a case of synchronous bilateral primary invasive ductal carcinoma with OCGCs has not been previously reported. A 44-year-old premenopausal woman was diagnosed with synchronous bilateral invasive ductal carcinoma with OCGCs. Imaging revealed small masses in both breasts, and core needle biopsies demonstrated invasive carcinoma with associated non-invasive components and numerous OCGCs in the tumor stroma. Both tumors were hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative (luminal A-like). The patient underwent bilateral mastectomy and sentinel lymph node biopsy, which showed no lymph node metastasis. The postoperative course was uneventful, and the patient has remained recurrence-free for six months after surgery. Notably, final pathological examination confirmed independent ductal carcinoma in situ (DCIS) components with OCGCs in both breasts, supporting the diagnosis of bilateral primary tumors rather than metastatic disease. Immunohistochemically, the OCGCs were CD68-positive, confirming their macrophage lineage. Genetic testing showed no pathogenic BRCA1/2 variants. This report highlights an extremely rare, pathologically confirmed case of synchronous bilateral primary breast carcinoma with OCGCs. The presence of OCGCs in both invasive and in situ components suggests that their formation can be induced at early stages of tumor development, likely reflecting a distinct immune-reactive tumor microenvironment driven by host-related factors.}, } @article {pmid41997937, year = {2026}, author = {Lundgren, JG and Flynn, MG and Winkler, AR and Rivera, BN and Tanabe, LM and Stemmer, PM and Chen, LM and Chai, KX and List, K}, title = {Metastasis suppressing properties of the cell-surface anchored serine protease prostasin: new functional and mechanistic insights from breast cancer.}, journal = {Oncogenesis}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41389-026-00615-3}, pmid = {41997937}, issn = {2157-9024}, support = {R01CA160565//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R01CA222359//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; T32-CA009531//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; 5T32-GM142519-04//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P30ES036084//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P30CA022453//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; S10OD030484//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; }, abstract = {Serine proteases play multifaceted roles in cancer, affecting tumor formation, progression, and metastasis. While most serine proteases studied act as tumor promoters by remodeling the extracellular matrix and activating signaling pathways, others can function as tumor suppressors. Prostasin is a glycosylphosphatidylinositol-anchored serine protease that is expressed in epithelial tissues, including the ductal epithelium of the breast. We found that prostasin protein expression is lost in high-grade, poorly differentiated, invasive ductal carcinoma in both mice and humans. To test whether prostasin impacts tumor progression and metastasis, prostasin-deficient mice were crossed into the oncogene-induced transgenic MMTV-PymT mammary tumor model. While prostasin deficiency did not affect primary tumor growth, it resulted in a significantly increased spontaneous dissemination of cancer cells to the lungs, suggesting a causal relationship between the loss of prostasin expression and progression to distant metastasis of breast cancer. At the cellular level, re-expression of prostasin in human breast cancer cells that have lost endogenous prostasin attenuated their invasive properties. Importantly, silencing prostasin expression in non-transformed human mammary epithelial cells (HMECs) resulted in the disruption of epithelial integrity and the loss of tight junctions (TJs), an early hallmark of cells acquiring an invasive phenotype. Discovery proteomics identified HMEC-expressed fibronectin (FN) as a regulatory target of prostasin and revealed increased levels of FN upon prostasin silencing. Mechanistically, cellular FN plays a causal role in TJ integrity in HMECs, and concomitant silencing of FN and prostasin rescues the defects caused by prostasin loss. Prostasin-mediated FN regulation represents a novel mechanism for regulating mammary epithelial cell TJ integrity and a potential candidate pathway for targeted therapy in breast cancer patients.}, } @article {pmid41988437, year = {2026}, author = {Behzad, S and Shahsavani Asl, A and Rouientan, H and Akhlaghpoor, S}, title = {Feasibility of delayed post-radiofrequency ablation biopsy in a pulmonary nodule metastatic from breast carcinoma: a case report.}, journal = {Oxford medical case reports}, volume = {2026}, number = {4}, pages = {omag036}, pmid = {41988437}, issn = {2053-8855}, abstract = {Thermal ablation is an established treatment for pulmonary nodules, conventionally performed after histopathologic confirmation of malignancy. We report the case of a 66-year-old woman with a history of left breast invasive ductal carcinoma (Bloom-Richardson grade II, score 7) with a 3-cm primary tumor and 3/19 axillary lymph nodes involved (pT2N1), and HER2 amplification detected by fluorescence in situ hybridization, who presented with a right lower lobe pulmonary nodule suspicious for metastasis. In contrast to standard practice, the lesion was first ablated under CT guidance, after which a coaxial core biopsy was obtained from the ablation zone. Histopathological analysis confirmed metastatic breast carcinoma, with preserved tissue architecture and immunohistochemical integrity (HER2 immunohistochemistry was 2+, and CISH confirmed HER2 amplification), despite a 4-hour interval between ablation and biopsy. No immediate procedural complications were observed. This case underscores the feasibility and diagnostic adequacy of delayed post-ablation biopsy and suggests that diagnostic integrity can be maintained even several hours after ablation.}, } @article {pmid41985721, year = {2026}, author = {Jordan, T and Chan, NNN and Rimm, DL and Zhan, H}, title = {Pathological Response to Herceptin-containing Neoadjuvant Therapy in HER2 IHC2+/ISH+ and IHC3+ Early-Stage Invasive Ductal Carcinoma.}, journal = {Human pathology}, volume = {}, number = {}, pages = {106121}, doi = {10.1016/j.humpath.2026.106121}, pmid = {41985721}, issn = {1532-8392}, abstract = {BACKGROUND: HER2-positive breast cancers exhibit heterogeneous responses to neoadjuvant therapy. This study compared pathologic response between IHC 3+ and IHC 2+/FISH+ invasive ductal carcinomas (IDCs) treated with trastuzumab/pertuzumab-containing chemotherapy.

METHODS: We identified 202 patients with HER2-positive early-stage IDC who received neoadjuvant T/P-containing chemotherapy followed by surgery between 2017 and 2024. Patients were categorized as IHC 3+ (n = 165) or IHC 2+/FISH+ (n = 37). Clinicopathologic parameters from pretreatment biopsies and post-treatment excisions were reviewed. Residual cancer burden (RCB) score and recurrence-free survival (RFS) at 36 months were analyzed.

RESULTS: The complete pathologic response (pCR) rate was significantly higher in IHC 3+ compared with IHC 2+/FISH+ tumors (67% vs. 27%, p < 0.001). IHC 3+ tumors were more frequently ER-/PR- than IHC 2+/FISH+ tumors (56% vs. 16%, p < 0.001). In the subset with complete FISH data (n = 49), increasing RCB class was inversely associated with both HER2/CEP17 ratio and HER2 copy number. At 36 months, recurrence rates were numerically lower in IHC 3+ compared with IHC 2+/FISH+ tumors (1.7% vs. 9.4%, p = 0.07). Kaplan-Meier analysis demonstrated a non-significant trend toward improved RFS in IHC 3+ tumors among hormone receptor-positive cases (p = 0.14).

CONCLUSIONS: Compared with IHC 3+ IDC, IHC 2+/FISH+ IDC demonstrated lower pCR rates and inferior RFS in hormone receptor-negative subset following neoadjuvant trastuzumab/ pertuzumab-containing therapy. Pathologic response correlated inversely with HER2/CEP17 ratio and HER2 copy number. Reassessment of HER2 expression with more sensitive quantitative methods, particularly in IHC 2+/FISH+ tumors, may improve therapeutic stratification.}, } @article {pmid41986415, year = {2026}, author = {Al-Masri, M and Alayyan, O and Safi, Y}, title = {Invasive ductal and lobular carcinoma and receptor status in the genetic context of breast cancer.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-44029-y}, pmid = {41986415}, issn = {2045-2322}, abstract = {Invasive lobular carcinoma (ILC) represents about 10% of invasive breast cancers and is increasingly considered a unique disease entity. Certain genetic mutations predispose patients to ILC, as such this study aims to explore the ILC and IDC (invasive ductal carcinoma) in a genetic context. This is a retrospective chart review study. Any patient diagnosed with either ILC or IDC and a germline mutation with a predisposition for breast cancer is included in the study. Data was analyzed by patient's demographics, group stage, family history, and genetic mutation. Additionally, each tumor was analyzed for grade and receptor status. This study reviewed 372 patients of which 88.4% had IDC and 11.6% had ILC. Our results indicate that several variants in ATM, BRCA2, CDH1, CHEK2, EPCAM, PALB2, and PMS2 are more strongly associated with ILC - to varying degrees. [p < 0.001]. Additionally, ILC tumors kept several characteristics, even in the genetic context. ILC patients had a higher median age at presentation [p = 0.043], were more likely to have a lower grade compared to ductal tumors [p < 0.001]. and be estrogen receptor positive [p < 0.001] progesterone status positive [p < 0.001] and HER2 negative [p = 0.043]. ILC patients are more likely to have certain genetic mutations over others. This can help clinicians adapt when counseling these patients. Furthermore, ILC keeps its distinctive characteristics independent of the genetic backdrop.}, } @article {pmid41976402, year = {2026}, author = {Syrigos, N and Mougiakos, A and Konstantinidou, A and Panagiotou, E and Karachaliou, A and Fyta, E and Vamvakaris, I and Karagianni, E and Kotteas, E and Lanitis, S and Markopoulos, C and Troupis, T and Grapsa, D}, title = {Immunohistochemical Expression of IDO and PD-L1 in Distinct Compartments of Breast Cancer Tissue: Correlation with Clinicopathological Features and Outcomes.}, journal = {Cancers}, volume = {18}, number = {7}, pages = {}, doi = {10.3390/cancers18071180}, pmid = {41976402}, issn = {2072-6694}, abstract = {Background: Indoleamine 2,3-dioxygenase (IDO) is an immune checkpoint that has been shown to play a key immunomodulatory role in various solid tumors, including breast cancer (BC). Although increased IDO expression has been previously observed in some BC subtypes, mainly triple-negative BC (TNBC), the clinical relevance of this protein across the entire range of BC and its exact correlations with other immune checkpoints remain to be elucidated. We herein aimed to further investigate the differential expression patterns of IDO and programmed death-ligand 1 (PD-L1) in variable BC subtypes and in distinct compartments of breast cancer tissue, and to explore their potential associations with standard patient- and tumor-related clinicopathological parameters as well as prognosis. Methods: This was a retrospective multi-center cohort study of 150 female patients with BC. The clinicopathological parameters analyzed were retrieved from the medical records of patients while sections from archival formalin-fixed, paraffin-embedded (FFPE) tissue blocks were also obtained for the performance of immunohistochemistry. The expression of IDO and PD-L1 was evaluated separately on tumor cells (IDO/CA, PD-L1/CA), lymphocytes (IDO/L, PD-L1/L) and stromal cells (IDO/S, PD-L1/S) and the results were correlated with the remaining clinical and pathological features of patients, as well as with local recurrence, metastasis and survival. Results: The mean age of patients was 59.5 years (SD = 13.4 years). Positive expression of IDO/CA, IDO/L and IDO/S was found in 6%, 93.3% and 90.7% of tissue samples, respectively, while 4%, 11.2% and 6.7% of tumors were positive for PD-L1/CA, PD-L1/L and PD-L1/S, respectively. A significantly higher rate of positive IDO/CA expression was observed in triple-negative BC (TNBC) patients (p = 0.037). Positive expression of IDO-CA was also significantly associated with positivity for PD-L1/L and PD-L1/S (p = 0.001 and p = 0.015, respectively). Multivariable logistic regression analysis showed independent correlations between IDO/CA and IDO/L and the presence of invasive ductal carcinoma (IDC) (OR = 1.10; p = 0.026) and N1 status (OR = 10.93; p = 0.039), respectively, IDO/S and both N1 (OR = 14.64; p = 0.018) and positive HER2 status (OR = 6.11; p = 0.019), PD-L1/L and high Ki67 (OR = 7.96; p = 0.001) as well as negative ER (OR = 0.08; 0.003) and PR status (OR = 0.09; p = 0.002), PD-L1/S and both NST (no special type) histology (OR = 4.68; p = 0.032) and negative ER status (OR = 0.21; p = 0.044). No statistically significant associations were observed between the expression patterns of the examined biomarkers and recurrence, metastasis or survival. Conclusions: In our study, IDO expression on tumor cells was predominantly observed in TNBC and was found to correlate with PD-L1 expression in the lymphocytic and stromal compartments. Furthermore, expression of PD-L1 among lymphocytes was found to independently correlate with unfavorable clinicopathological parameters, including high proliferation rate and negative hormone receptor status.}, } @article {pmid41978785, year = {2026}, author = {Ida, E and Ohashi, M and Kanehisa, F and Komai, M and Itoi, N and Urata, Y and Nagata, M and Lee, T}, title = {Radiation-Associated Angiosarcoma of the Breast: A Case Report with Review of Reported Cases in Japan.}, journal = {Surgical case reports}, volume = {12}, number = {1}, pages = {}, pmid = {41978785}, issn = {2198-7793}, abstract = {INTRODUCTION: Radiation-associated angiosarcoma of the breast (RAASB) is an extremely rare but serious complication that can occur several years after breast-conserving surgery and adjuvant radiotherapy. Owing to its rarity and nonspecific cutaneous manifestations, the diagnosis of RAASB is often delayed. There is no established treatment for RAASB, and its prognosis remains poor.

CASE PRESENTATION: A 63-year-old woman developed progressive breast edema 14 years after breast-conserving surgery with axillary lymph node dissection and adjuvant radiotherapy for invasive ductal carcinoma. Two years later, she presented with breast masses with purpura and biopsy-confirmed angiosarcoma. Wide mastectomy with skin grafting was performed, followed by weekly administration of adjuvant paclitaxel. The patient remained recurrence-free for 12 months postoperatively.

CONCLUSIONS: RAASB can develop long after breast-conserving therapy and may be preceded by subtle skin changes or persistent breast edema. Long-term follow-up and patient education are essential for patients who have undergone breast irradiation. Early imaging or biopsy should be considered when breast lymphedema is observed.}, } @article {pmid41979822, year = {2026}, author = {Kanasaki, R and Suzuki, K and Ota, T and Akashi-Tanaka, S and Nagashima, Y and Sakai, S}, title = {Estimation of histopathological types from breast MRI findings using a large language model.}, journal = {International journal of computer assisted radiology and surgery}, volume = {}, number = {}, pages = {}, pmid = {41979822}, issn = {1861-6429}, abstract = {PURPOSE: Large language models (LLMs) may hold the potential to infer pathological diagnoses from imaging findings such as computed tomography or magnetic resonance imaging (MRI). This retrospective study investigates whether an LLM can accurately predict histopathological types of breast lesions based on descriptive findings in contrast-enhanced breast MRI reports written in natural language.

METHODS: We retrospectively analyzed findings from diagnostic imaging reports of consecutive cases of contrast-enhanced breast MRI performed between January and December 2024. Textual descriptions of imaging findings were entered into an LLM (OpenAI o3), and its predictions of histopathological types were compared with the actual pathological diagnoses.

RESULTS: A total of 186 lesions from 180 patients were classified into 10 histopathological types, including lesions with combinations of these types. The LLM o3 generated predictions for eight of these types. For the most prevalent type, invasive ductal carcinoma (123 lesions), the model achieved 83.7% sensitivity, 60.8% specificity, a positive predictive value (PPV) of 76.9%, and a negative predictive value (NPV) of 70.6%. For the second-most frequent type, ductal carcinoma in situ (38 lesions), the model achieved 57.9% sensitivity, 89.6% specificity, PPV of 56.4%, and NPV of 90.2%.

CONCLUSION: The latest LLM accurately inferred invasive ductal carcinoma with typical breast MRI findings, supporting the hypothesis that LLMs can predict histopathological types based on imaging descriptions.}, } @article {pmid41969031, year = {2026}, author = {Thabit, DM}, title = {Immunohistochemical expression of POC1A, NUF2, and Ki-67 in invasive ductal carcinoma of the breast: prognostic significance with insights into triple-negative breast cancer.}, journal = {American journal of clinical pathology}, volume = {165}, number = {4}, pages = {}, doi = {10.1093/ajcp/aqag011}, pmid = {41969031}, issn = {1943-7722}, } @article {pmid41969442, year = {2026}, author = {Hua, W and Gu, Y and Yuan, Y and Zhu, J and Wu, H}, title = {RNAscope-based HER2 mRNA detection shows high concordance with fluorescence in situ hybridization in invasive breast carcinoma: a retrospective study.}, journal = {Translational cancer research}, volume = {15}, number = {3}, pages = {174}, pmid = {41969442}, issn = {2219-6803}, abstract = {BACKGROUND: Human epidermal growth factor receptor 2 (HER2) status is critical for guiding targeted therapy in invasive breast cancer (BC). Immunohistochemistry (IHC) is routinely used for HER2 screening, but equivocal (IHC 2+) cases require confirmatory testing. RNAscope is an emerging RNA in situ hybridization technique with proven consistency and sensitivity. We investigated whether RNAscope can reliably determine HER2 status and enhance diagnostic concordance with FISH in IHC 2+ invasive ductal carcinoma (IDC).

METHODS: In this retrospective study, 104 IDC cases from January 2020 to January 2024 were reviewed. Thirty-five cases with IHC 2+ scores were randomly selected. Each case underwent RNAscope and fluorescence in situ hybridization (FISH) for HER2. Concordance between RNAscope and FISH results was evaluated using Cohen's kappa statistic. Next-generation sequencing (NGS) was performed on discordant cases to confirm HER2 gene status.

RESULTS: RNAscope and FISH results were concordant in 85.7% (30/35) of IHC 2+ cases [κ=0.678, 95% confidence interval (CI): 0.425-0.872], indicating substantial agreement. RNAscope detected HER2 positivity in all 12 FISH-positive cases (100% agreement) and in 5 of 23 FISH-negative cases, identifying additional positive cases. Among the 5 discordant cases, NGS confirmed HER2 amplification or overexpression in 4 (80%) of the RNAscope-positive/FISH-negative cases. These findings suggest that RNAscope may detect HER2-positive cases missed by FISH.

CONCLUSIONS: RNAscope shows high agreement with FISH in determining HER2 status in IHC 2+ IDC. RNAscope may serve as an effective adjunct to current HER2 testing, offering a sensitive alternative for ambiguous cases.}, } @article {pmid41969954, year = {2026}, author = {Zhang, X and Lin, Y and Lin, Y and Yang, Q}, title = {Survival outcomes of invasive micropapillary carcinoma of the breast: a SEER population-based study.}, journal = {Gland surgery}, volume = {15}, number = {3}, pages = {66}, pmid = {41969954}, issn = {2227-684X}, abstract = {BACKGROUND: The prognostic significance of invasive micropapillary carcinoma (IMPC) histology in breast cancer is still debated. Additionally, the relationship between different molecular subtypes and survival outcomes in patients with IMPC and invasive ductal carcinoma (IDC) remains unknown. The objective of this study was to investigate whether breast cancer-specific survival (BCSS) and overall survival (OS) differ between IMPC and IDC across molecular subtypes, to better inform subtype-aware risk stratification and personalized management.

METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database to identify breast cancer patients, we retrospectively analyzed 959 IMPC and 174,591 IDC cases diagnosed between 2010 and 2016 with non-metastatic diseases that underwent surgery. We compared long-term outcomes of BCSS and OS.

RESULTS: IMPC had a better BCSS (P=0.04) but showed no significant difference in OS (P=0.09) compared with IDC. In multivariate Cox analysis, IMPC histologic type was an independent favorable prognostic factor for both BCSS [hazard ratio (HR) =0.509, P=0.002] and OS (HR =0.637, P=0.003). After propensity score matching (PSM), IMPC still had a better BCSS (P=0.001); we observed no significant difference in OS (P=0.38). While different molecular subtypes have different impacts on survival outcomes, no significant differences were observed in BCSS and OS between IMPC and IDC in relation to Luminal B, human epidermal growth receptor 2 (HER2)-enriched, and triple-negative subtype. In relation to the Luminal A subtype, IMPC had better BCSS (HR =0.399, P=0.001) and OS (HR =0.508, P=0.001). In the case-control cohort, IMPC had a better BCSS (HR =0.423, P=0.005), while no significant difference was observed in OS (HR =0.767, P=0.22) in Luminal A subtype.

CONCLUSIONS: Relative to IDC, IMPC presents better long-term survival outcomes, and the survival benefits are confined to the Luminal A subtype.}, } @article {pmid41970174, year = {2026}, author = {El Houbri, FE and Idrissi, N and Roche, M and Valentin, S}, title = {PADI-Location-AR-EN: A normalized Arabic-English spatial entity dataset for epidemiological surveillance.}, journal = {Data in brief}, volume = {66}, number = {}, pages = {112698}, pmid = {41970174}, issn = {2352-3409}, abstract = {The location of events in multilingual texts, particularly in Arabic, represents a challenge for epidemiological monitoring. Systems such as PADI-web rely on English translation to extract spatial entities, but the scarcity of annotated spatial entities in Arabic can hamper the reliability of translations and extraction. In this context, PADI-Location-AR-EN, which is a dataset of 328 spatial entities that were manually extracted from 96 Arabic-language news articles collected by the PADI-web epidemiological monitoring system, is presented in this paper. Each entity was manually translated into English, normalized using the GeoNames database, and then classified according to its type and spatial category. The dataset can be used to evaluate the translation quality of three machine translation systems (DeepL, Microsoft Azure and Reverso) as well as the performance of named entity recognition models on the translated texts.}, } @article {pmid41972059, year = {2026}, author = {Wang, Y and Li, Q and Zhao, L}, title = {An interpretable weighted ensemble based on routinely collected clinical data for the accurate prediction of axillary lymph node metastasis.}, journal = {Quantitative imaging in medicine and surgery}, volume = {16}, number = {4}, pages = {318}, pmid = {41972059}, issn = {2223-4292}, abstract = {BACKGROUND: Axillary lymph node (ALN) status is a primary prognostic indicator in breast cancer, yet conventional surgical staging for determining ALN status is invasive. We aimed to develop an interpretable, noninvasive weighted ensemble model for ALN metastasis prediction using only routine, universally accessible clinicopathological data.

METHODS: We analyzed a retrospective cohort of 915 patients (training set: n=732; test set: n=183). Twelve routine clinicopathological variables, including age, tumor diameter, histological grade, and biomarkers [estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67], served as predictors. A two-stage weighted ensemble was developed through the integration of logistic regression (LR) and extreme gradient boosting (XGBoost) via Python version 3.9. Model performance was evaluated with the held-out test set according to the area under the receiver operating characteristic curve (AUC), area under the precision-recall curve (AUPRC), and sensitivity. Model interpretability was achieved through Shapley additive explanations (SHAP).

RESULTS: The weighted ensemble model achieved a superior AUC of 0.762 on the test set, outperforming optimized XGBoost (AUC =0.752) and tuned LR (AUC =0.741). The model demonstrated a robust AUPRC of 0.575 and achieved a high sensitivity of 0.800. SHAP analysis revealed that model predictions were primarily driven by tumor diameter, invasive ductal carcinoma pathology type, and plateau time-intensity curve patterns.

CONCLUSIONS: The interpretable weighted ensemble model, based only on standard tabular clinicopathological data, provides accurate and transparent ALN risk stratification. Its high sensitivity supports its use as a valuable triage tool for identifying low-risk patients who may safely forego invasive axillary surgery.}, } @article {pmid41958339, year = {2026}, author = {Sutanto, H and Savitri, M and Hendarsih, E and Ashariati, A}, title = {Early hematologic dynamics and their association with patient-reported symptom burden in breast cancer pharmacotherapy: a prospective cohort study.}, journal = {Future oncology (London, England)}, volume = {}, number = {}, pages = {1-16}, doi = {10.1080/14796694.2026.2656388}, pmid = {41958339}, issn = {1744-8301}, abstract = {BACKGROUND: Systemic pharmacotherapy for breast cancer frequently induces hematologic toxicity and inflammatory changes that may affect symptom burden and treatment tolerance. This study evaluated baseline hematologic profiles, early treatment-related changes, and their association with patient-reported outcomes during the first cycle of therapy.

METHODS: In this prospective cohort study, 106 women receiving systemic pharmacotherapy at two secondary referral centers in Indonesia were enrolled. Hematologic parameters and inflammatory indices-including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV)-were measured. Patient-reported outcomes were assessed using the EORTC QLQ-C30.

RESULTS: The mean age was 51.9 ± 9.7 years, with most patients presenting with locally advanced disease and invasive ductal carcinoma. Early pharmacotherapy caused marked hematologic suppression, with leukocyte and neutrophil nadirs at week 1 and partial recovery by week 3 (p < 0.001). PLR, MLR, and PIV changed significantly over time (p < 0.001). Anemia increased from 51.9% to 74.0%, while neutropenia rose to 41.7% at week 1 before declining to 1.1% by week 3. Selected hematologic biomarkers correlated with patient-reported symptom burden, and only baseline MLR differed between survival subgroups (p = 0.043).

CONCLUSION: Early breast cancer pharmacotherapy induces dynamic hematologic and inflammatory changes associated with patient-reported symptoms, supporting integrated monitoring to improve toxicity management.}, } @article {pmid41959893, year = {2026}, author = {Addasi, R and AbuMahfouz, B and Subuh, A and Obeidat, M and Zenah, A and Haddar, R and Hamdan, S}, title = {Racial disparities in breast cancer subtypes, recurrence, and survival: a longitudinal cohort analysis.}, journal = {Frontiers in oncology}, volume = {16}, number = {}, pages = {1732495}, pmid = {41959893}, issn = {2234-943X}, abstract = {INTRODUCTION: Racial disparities in breast cancer subtype distribution and clinical outcomes are well documented, yet integrated longitudinal analyses examining subtype, recurrence, and survival within standardized cohorts remain limited. This study examines race-associated differences in breast cancer subtypes, recurrence patterns, and survival outcomes using a retrospective longitudinal cohort.

METHODS: A total of 922 women from the Duke Breast Cancer MRI dataset were analyzed. Race was categorized a priori into three groups (White, Black, and Other) for primary comparative analyses.

RESULTS: The median age at diagnosis (in years) was 52.2 (IQR 45.4-60.8), with Black patients presenting at younger median ages compared with White patients (p< 0.001). Black women had the highest prevalence of triple-negative breast cancer (29.6%). Sixty-five (47.1%) of black patients presented with stage III Nottingham grade at presentation (P< 0.001). The overall recurrence rate was 9.4%, and mortality rate was 6.7%, with no statistically significant difference between groups.

DISCUSSION: Black patients demonstrated a higher prevalence of aggressive tumor biology at presentation; however, survival differences were attenuated after multivariable adjustment. Given the limited number of mortality events, adjusted survival estimates should be interpreted cautiously, as these findings underscore the need for larger, prospective studies integrating genomic, imaging, and socioeconomic data to better define drivers of outcome disparities in breast cancer.}, } @article {pmid41959899, year = {2026}, author = {Alsharif, H and Wesolowski, R and Cebulla, CM and Davenport, AP and Gatti-Mays, ME and Johnson, KCC and Lopetegui-Lia, N and Quiroga, D and Roy, AM and Shujaat, M and Stover, DG and Bader, G}, title = {Case Report: Late choroidal metastasis from hormone receptor-positive, HER2-negative breast cancer responsive to first-line endocrine therapy.}, journal = {Frontiers in oncology}, volume = {16}, number = {}, pages = {1719671}, pmid = {41959899}, issn = {2234-943X}, abstract = {Distant metastatic breast cancer can occur years after initial diagnosis, with choroidal metastasis being a rare but significant manifestation. This case report presents a patient with a history of estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) invasive ductal carcinoma (IDC) of the left breast, who developed late choroidal metastasis. The patient underwent systemic therapy with an aromatase inhibitor and cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor leading to regression of choroidal metastases. We also conducted a literature review of similar cases. External beam radiotherapy is the gold standard for management of choroidal metastases. However, it appears that first-line treatment with endocrine therapy and CDK4/6 inhibitors in patients with ER+ and HER2- breast cancer is likely effective for the treatment of choroidal metastases secondary to ER+/HER2- breast cancer and may allow a delay in the use of local invasive interventions.}, } @article {pmid41961346, year = {2026}, author = {Aziz, S and Rasheed, F and Bibi, S and Shahzad, A and Riaz, S and Noor, H and Ijaz, UZ and König, S}, title = {Case report of invasive ductal carcinoma of the breast in a Pakistani male aged 55.}, journal = {Discover oncology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12672-026-04996-0}, pmid = {41961346}, issn = {2730-6011}, support = {MR/Z50628X/1/MRC_/Medical Research Council/United Kingdom ; }, } @article {pmid41963283, year = {2026}, author = {Gong, N and Gouda, M and Balaz, AM and Song, J and Kranz, G and Hess, J and Baumeister, P and Unger, K and Katalina, V and Canis, M and Gires, O}, title = {EpCAM supports exit from pluripotency of embryonic stem cells via Eomes.}, journal = {Cell death & disease}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41419-026-08734-w}, pmid = {41963283}, issn = {2041-4889}, support = {Gi 540/3-4//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; INST 409/223-1 FUGG//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, abstract = {Epithelial cell adhesion molecule (EpCAM) is a tumor-associated antigen that marks pluripotent embryonic stem cells (ESCs). Regulation of Epcam expression yields a spatiotemporal patterning during embryogenesis that is thoroughly mimicked in a 3D model of spontaneous differentiation of embryoid bodies (EBs). Here, we present a role of EpCAM in exit from pluripotency of murine ESCs (mESCs) to establish cardiomyocytes in EBs. Comparative transcriptomic analysis of wildtype and Epcam-knockout mESCs at strategic time points of spontaneous differentiation uncovered molecular deficiencies of Epcam-knockout ESCs in "Wnt signaling" and "Heart development". Multi-level bioinformatic analyses revealed central lineage-defining transcription factors Eomes, Foxa2, and Gata6 as differentially expressed genes (DEGs) that are misregulated in Epcam-knockout mESCs. Gene expression association of Epcam with Eomes, Foxa2, and Gata6 was prominent at day three of spontaneous differentiation, representing primitive streak formation in EBs. Interrogation of public single-cell RNA sequencing (scRNAseq) datasets supported a co-expression of Epcam and Eomes at early stages of murine embryogenesis in epiblast, primitive streak, nascent mesoderm, extraembryonic ectoderm and endoderm. Newly generated scRNAseq of wildtype mESCs in spontaneous differentiation delineated the formation of epiblast, primitive streak, endo- and mesoderm cells, and cardiomyocytes. Expression and pseudotime analysis positioned Epcam expression slightly ahead of Eomes at the transition of early to late primitive streak, along with rising Wnt signaling. Accordingly, conditional re-expression of Epcam or Eomes but not of Foxa2 or Gata6 complemented differentiation defects of Epcam-knockouts and confirmed an involvement of Wnt signaling in the EpCAM-dependent activation of Eomes. Hence, defective exit of pluripotency in Epcam-deficient ESCs is linked to Eomes regulation via Wnt signaling.}, } @article {pmid41963621, year = {2026}, author = {Leshem, Y and Golomb, I and Zubkov, A and Bar, Y and Strulov Shachar, S and Lerner, S and Keren-Khadmy, N and Sonnenblick, A}, title = {Neoadjuvant twelve weekly paclitaxel-carboplatin with trastuzumab and pertuzumab in HER2-positive breast cancer.}, journal = {Breast cancer research and treatment}, volume = {217}, number = {1}, pages = {}, pmid = {41963621}, issn = {1573-7217}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/pathology/genetics/mortality/metabolism ; Middle Aged ; Paclitaxel/administration & dosage/adverse effects ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects/administration & dosage ; Aged ; Neoadjuvant Therapy ; *Erb-b2 Receptor Tyrosine Kinases/metabolism/genetics ; Trastuzumab/administration & dosage ; Carboplatin/administration & dosage/adverse effects ; Antibodies, Monoclonal, Humanized/administration & dosage ; Retrospective Studies ; Adult ; Treatment Outcome ; Neoplasm Staging ; Aged, 80 and over ; }, abstract = {PURPOSE: Standard neoadjuvant therapy for early HER2-positive breast cancer consists of 18 weeks of carboplatin, docetaxel, trastuzumab, and pertuzumab. However, treatment intensity may limit feasibility in frail patients and exceed therapeutic needs in selected early-stage disease. We report here real-world clinical outcomes of patients receiving a shortened 12-week neoadjuvant regimen of weekly paclitaxel and carboplatin administered with trastuzumab and pertuzumab (12wTCHP).

METHODS: We conducted a retrospective analysis of patients with HER2-positive breast cancer treated with neoadjuvant 12wTCHP in a single tertiary medical center.

RESULTS: Of forty-four eligible patients receiving 12wTCHP, 41 had invasive ductal carcinoma (IDC, 93%), and 64% were ER-positive. The majority of the cohort had stage IIA (73%, median age 59 years), while the remainder had stage IIB or stage III disease and were significantly older (median age 64 and 76 years, respectively; p = 0.007). Grade 3-4 neutropenia (20%) and diarrhea (19%) were the most frequent toxicities. No treatment-related deaths occurred. Pathological complete response (pCR) rate was 61%: 54% in ER-positive tumors and 75% in ER-negative tumors (p = 0.208). After a median follow-up of 30 months, only two recurrences (5%) were observed. None of the 30 patients with stage IIA IDC had disease recurrence.

CONCLUSIONS: In this retrospective cohort study, neoadjuvant 12wTCHP was well tolerated and associated with high pCR and low early recurrence rates. These findings are hypothesis-generating and support further evaluation of de-escalated 12wTCHP regimen in selected patients.}, } @article {pmid41952463, year = {2025}, author = {Harshe, AI and Cruz, HS and Desai, A and Mangal, R and Avisar, E}, title = {Patient Reported Satisfaction Outcomes After Breast Radiation Using Intraoperative Radiation Therapy vs. External Beam Radiation Therapy.}, journal = {European journal of breast health}, volume = {21}, number = {3}, pages = {11}, pmid = {41952463}, issn = {2587-0831}, abstract = {OBJECTIVE: Intraoperative radiation therapy (IORT), is an alternative to postoperative whole breast irradiation for early-stage breast cancer. The aim of this study was to assess patient reported outcomes (PRO) on cosmetic results and radiation related adverse effects after IORT vs. external beam radiation therapy (EBRT).

MATERIALS AND METHODS: Patients treated with IORT for ductal carcinoma in situ (DCIS) or early-stage breast cancer between 2017-2023 were asked to submit the pre-validated BREAST-Q survey tool for objective aesthetic evaluation. A matching cohort of patients treated with EBRT during the same time interval was also asked to submit the same survey.

RESULTS: Eighty-eight patients were included, 56 (63.0%) with invasive ductal carcinoma (IDC) and 32 (36%) with DCIS. Thirty (68%) patients with IDC and 14 (31%) patients with DCIS had IORT. Patient satisfaction scores with breast cosmesis was higher in IORT group compared to EBRT (mean, 83.7 vs. 74.2; p = 0.05). Less radiation related adverse effects were reported after IORT (mean, 7.7) as compared with EBRT (mean, 10.6) (p<0.05).

CONCLUSION: This study suggests that in comparison to EBRT, patients treated with IORT have higher satisfaction scores related to breast cosmesis and less radiation related adverse effects.}, } @article {pmid41955584, year = {2026}, author = {Chelpanova, IV and Volos, LI and Dudash, AP and Paltov, YV and Poliiants, AV and Dudok, OV and Hnidyk, YV}, title = {Evaluation of Е-cadherin expression in invasive ductal breast cancer.}, journal = {Wiadomosci lekarskie (Warsaw, Poland : 1960)}, volume = {79}, number = {2}, pages = {255-264}, doi = {10.36740/WLek/218713}, pmid = {41955584}, issn = {0043-5147}, mesh = {Humans ; *Cadherins/metabolism ; Female ; *Breast Neoplasms/metabolism/pathology ; *Carcinoma, Ductal, Breast/metabolism/pathology ; Middle Aged ; Prognosis ; Adult ; Biomarkers, Tumor/metabolism ; Receptors, Estrogen/metabolism ; Aged ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Antigens, CD ; }, abstract = {OBJECTIVE: Aim: To evaluate E-cadherin expression in various clinical and pathological prognostic scenarios to determine its significance in the development of molecular subtypes of invasive ductal breast cancer.

PATIENTS AND METHODS: Materials and Methods: A comprehensive morphological and immunohistochemical study of 80 cases of invasive ductal carcinoma (IDC) was conducted to determine the molecular phenotype. The expression of E-cadherin, ER, PR receptors, c-erbB2, and Ki-67 was evaluated according to the manufacturer's standardized protocols using appropriate positive and negative controls. The degree of tumor malignancy was determined using the modified Scarff-Bloom-Richardson system. Semi-quantitative assessment of E-cadherin expression was performed using the Qureshi scale. Pearson's criterion was used for statistical analysis. Differences were considered statistically significant at p < 0.05.

RESULTS: Results: Low E-cadherin expression was associated with stage 3, pT3, and G2/G3 grades of IDBC malignancy, confirming its unfavorable prognostic significance and correlation with the molecular profile. High E-cadherin expression was characteristic of ER-positive luminal A tumors, regardless of menopause, indicating a regulatory role for ER expression. The low proliferative activity of luminal IDBC cells was explained by high E-cadherin expression, which increased adhesive properties. Low E-cadherin expression is also a prognostic marker for TNBC.

CONCLUSION: Conclusions: E-cadherin is a potent tumor suppressor in breast cancer. Its role in disease progression is confirmed by the correlation between partial or complete loss of E-cadherin expression and poor prognosis for patients.}, } @article {pmid41955993, year = {2026}, author = {Zhang, J and Wang, L and He, Y and Sun, H and Niu, J and Duan, M and Miao, C and Li, J and Cao, W and Wang, X and Wang, X and Yang, Y and Fan, Z and Yu, X}, title = {Efficacy of scalp cooling system versus chemical cooling cap in preventing chemotherapy-induced alopecia in breast cancer (COHAIR Study): a prospective randomized trial.}, journal = {Breast (Edinburgh, Scotland)}, volume = {87}, number = {}, pages = {104784}, doi = {10.1016/j.breast.2026.104784}, pmid = {41955993}, issn = {1532-3080}, abstract = {INTRODUCTION: A prospective, randomized trial was conducted at a tertiary cancer hospital, to investigate the efficacy of scalp cooling system and chemical cooling cap in preventing chemotherapy-induced alopecia (CIA) in early breast cancer.

METHODS: Patients were randomly assigned to scalp cooling system group or chemical cooling cap group. Alopecia was assessed using the World Health Organization toxicity grading scale for anticancer drug and Quality of life and psychological status were evaluated using the European Organization for Research and Treatment of Cancer Quality of life Questionnaire Core 30 and the Hospital Anxiety and Depression Scale.

RESULTS: A total of 152 patients were included in the random grouping process. The mean age of the participants was 44.6 ± 9.0 years (range 27-65 years), and 97.4% patients were diagnosed invasive ductal carcinoma. Among 117 patients completed the observation period with four cycles of anthracycline followed by four cycles of taxane regimen, hair preservation success rates were 74.5% in scalp cooling system and 71.2% in chemical cooling cap group and demonstrated good tolerability. The chemical group showed significantly lower anxiety scores and better QoL.

CONCLUSIONS: Cooling therapies effectively improved CIA. Scalp cooling showed superior early efficacy during anthracycline treatment, while chemical cooling provided better psychological outcomes and QoL benefits. Disease-free survival (DFS) was comparable between groups.

CLINICAL TRIAL REGISTRATION: NCT03711877 on 26 November 2021.}, } @article {pmid41957230, year = {2026}, author = {Vickery, J and Peerenboom, R and Siddiqui, F and Joy, JA and Prabu, SS and Arber, DA and Gurbuxani, S and Biernacka, A and Venkataraman, G}, title = {Hematolymphoid neoplasms involving the breast: A single institution clinicopathologic study of 59 patients.}, journal = {Annals of hematology}, volume = {105}, number = {5}, pages = {}, pmid = {41957230}, issn = {1432-0584}, } @article {pmid41949735, year = {2026}, author = {Chen, JH and Wanis, KN and Rahman, M and Gianchandani, A and Bedrosian, I and Tamirisa, N and Yi, M and Raghavendra, A and Singh, P and Teshome, M and Sun, S and Kuerer, H and Hunt, KK and Meric-Bernstam, F and Adesoye, T}, title = {Implications for Sentinel Lymph Node Biopsy Omission in Patients with Early-Stage Node-Negative HR+/HER2- Breast Cancer Undergoing Mastectomy.}, journal = {Annals of surgical oncology}, volume = {}, number = {}, pages = {}, pmid = {41949735}, issn = {1534-4681}, support = {P30 CA016672/GF/NIH HHS/United States ; T32 CA 009599/GF/NIH HHS/United States ; }, abstract = {INTRODUCTION: The SOUND and INSEMA trials have demonstrated the non-inferiority of sentinel lymph node (SLN) biopsy (SLNB) omission in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) early-stage breast cancer (BC) with negative axillary ultrasound undergoing breast-conserving therapy (BCT). We evaluated SLNB positivity rates and treatment characteristics among patients undergoing BCT versus mastectomy.

METHODS: Patients with cT1N0M0 HR+/HER2- unifocal invasive ductal carcinoma with negative axillary ultrasound undergoing upfront BCT + radiation therapy (RT) or mastectomy +/- RT were included (2010-2023). Clinicopathologic characteristics, treatment, and patient outcomes were compared by surgery type.

RESULTS: Among 1506 patients, the median age was 59 years (interquartile range [IQR] 51-67). In total, 78.2% (1178) underwent BCT and 21.8% (328) underwent mastectomy. The mastectomy cohort was significantly younger and had larger and higher-grade tumors (age 55.7 vs. 60.8; grade 3: 20.1 vs. 12.5%, both p < 0.001). Rates of positive SLNs were similar in BCT and mastectomy cohorts (7.6 vs. 8.2%, p = 0.684). Among the mastectomy cohort, 10.1% received RT and 28.1% received chemotherapy, with higher rates in patients with positive SLNs (RT: 51.8 vs. 6.31%, chemotherapy: 76.5 vs. 22.5%, both p < 0.0001). At a median follow up time of 25.3 months (IQR 13.2-58.9), three (0.2%) had axillary recurrences (two after mastectomy) and seven (0.46%) had distant recurrences (two after mastectomy).

CONCLUSIONS: Among patients with cT1N0M0 HR+/HER2- disease and negative AUS who underwent SLNB, early recurrence rates were low regardless of surgery type. Given that nodal status affects the use of RT after mastectomy, further research investigating the omission of SLNB in this cohort is warranted.}, } @article {pmid41944070, year = {2026}, author = {Li, N and Taherdangkoo, K and Baatsch, IM and Guduru, T and Meng, Q and Li, S and Zhou, Y and Li, X and Zhu, M and Polczer, S and Geissler, C and Briem, E and Megens, RTA and Na, H and Kumbrink, J and Richter, D and Li, Y and Jethwa, C and Bartelt, A and Döring, Y and von Hundelshausen, P and Enard, W and Weber, C and Nazari-Jahantigh, M and Schober, A}, title = {Mir147 Limits the Contribution of Non-Foamy Macrophages to Atherosclerosis.}, journal = {Circulation}, volume = {}, number = {}, pages = {}, doi = {10.1161/CIRCULATIONAHA.125.077821}, pmid = {41944070}, issn = {1524-4539}, abstract = {BACKGROUND: Hypercholesterolemia and a high-fat diet promote 2 macrophage subtypes involved in atherosclerosis by inducing lipid droplet accumulation in foamy macrophages (FMs) and inflammatory activation in non-foamy macrophages (NFMs). MicroRNAs are key regulators of macrophage function; for instance, miR-10a-5p reduces atherosclerosis and improves mitochondrial health in FMs, whereas miR-155-5p accelerates atherosclerosis by impairing efferocytosis. miR-147-3p is upregulated by inflammatory stimuli in macrophages and in atherosclerotic lesions, suggesting a role in NFMs.

METHODS: The role of miR-147-3p in myeloid cells, with or without enhanced green fluorescent protein expression, on atherosclerosis was examined in Apoe[-/-]Mir147[flox/flox]LysMCre[+] mice. Using live-plaque 4D confocal imaging, we assessed lipid droplets, caspase-3 activation, apoptotic DNA, cholesterol crystal (CC) formation, and mitochondrial function. We also imaged macrophage migration, phagocytosis of apoptotic DNA, and the formation of tubular membrane extensions. We tested mitochondrial function in live-plaque tissue by Seahorse assay. GFP-tagged Argonaute 2 immunoprecipitation combined with prime RNA sequencing was performed using atherosclerotic aortas from Apoe[-/-]LSL-tAgo2/Mir147[flox/flox]LysMCre[+] and control mice. The effect of the galectin-3 inhibitor GB1107 was studied using 4D live-plaque imaging.

RESULTS: Unlike FMs, NFMs are primarily located in the plaque core and show higher miR-147-3p levels in both mouse and human atherosclerosis. Knocking out Mir147 in myeloid cells increases atherosclerosis, with enhanced CC formation and apoptotic DNA accumulation in necrotic cores. Removing Mir147 reduces mitochondrial activity and elevates caspase-3 activity in NFMs, but not in FMs, and lowers the spare respiratory capacity of plaque macrophages. Moreover, deleting Mir147 impairs NFM uptake of apoptotic DNA, increases extracellular apoptotic DNA, and promotes CC formation. Additionally, Mir147 deficiency in NFMs induces caspase-3 activation in endothelial cells, facilitating the transendothelial extension of FM projections. The Lgals3 transcript, encoding galectin-3, was reduced in the tagged Argonaute 2 immunoprecipitate after Mir147 knockout. A miR-147-3p binding site in the Lgals3 3'-UTR was functionally confirmed. GB1107 treatment reversed the Mir147 knockout effect in macrophages.

CONCLUSIONS: miR-147-3p reduces atherosclerosis by suppressing the harmful effects of NFMs on endothelial cells and by enhancing their clearance of apoptotic DNA through targeting galectin-3. Increasing miR-147-3p levels might thus slow the expansion of the necrotic core and reduce atherothrombosis caused by NFM-induced endothelial damage.}, } @article {pmid41944473, year = {2026}, author = {Wieland, J}, title = {[Differentiating crises in people with intellectual disabilities].}, journal = {Tijdschrift voor psychiatrie}, volume = {68}, number = {3}, pages = {131-134}, pmid = {41944473}, issn = {0303-7339}, mesh = {Humans ; *Intellectual Disability/psychology/therapy ; *Mental Health Services ; *Crisis Intervention ; }, abstract = {BACKGROUND: Crises in people with intellectual disabilities often occur at the intersection of mental health care (MHC) and intellectual disability care (IDC). Different actors and crisis regulations with their own definitions and agreements make appropriate care challenging. Effective collaboration between MHC and IDC is essential but often not structurally organized.

AIM: To distinguish between different types of crises in order to promote shared perceptions and a common language between MHC and IDC. This will improve the coordination of interventions and make cooperation between professionals more effective.

METHOD: Based on clinical experience and scientific background, I propose a model with four types of crises: contextual crisis, somatic crisis, overburdening, and psychiatric crisis.

RESULTS: Better differentiation between different types of crises can be advantageous for people with intellectual disabilities. It ensures a shared perception and common language across domains, leading to better task distribution and cooperation between the various professionals involved.

CONCLUSION: Better differentiation of crises can improve collaboration between MHC and IDC. This model provides tools for joint crisis management and can further improve care in the future.}, } @article {pmid41945372, year = {2026}, author = {Yan, X and Xie, Y and Liu, M and Zhu, W and Huo, L}, title = {Incidental Detection of a CAIX-avid Breast Invasive Ductal Carcinoma on 68Ga-NY104 PET/CT During Evaluation of a Suspected Renal Mass.}, journal = {Clinical nuclear medicine}, volume = {}, number = {}, pages = {}, doi = {10.1097/RLU.0000000000006375}, pmid = {41945372}, issn = {1536-0229}, support = {UHB12582//Peking Union Medical College Hospital Talent Cultivation Program (Category D)/ ; }, abstract = {68Ga-NY104 is a novel tracer targeting carbonic anhydrase IX (CAIX) with promising diagnostic efficacy for clear cell renal cell cancer. We present a 55-year-old woman with a suspected left renal mass who underwent 68Ga-NY104, showing no significant uptake in the renal mass but incidentally revealing an intense uptake nodule in the left breast. Subsequent 18F-FDG PET/CT revealed mild renal mass and intense breast nodule uptake. Postoperative pathology confirmed the renal mass as benign angiomyolipoma and the breast nodule as invasive ductal carcinoma. This case highlights the inclusion of primary breast cancer in the differential diagnosis of extra-renal CAIX-avid lesions.}, } @article {pmid41939465, year = {2026}, author = {Sun, Y}, title = {Low-grade osteosarcoma after radiotherapy for breast cancer: a case report and literature review.}, journal = {Frontiers in oncology}, volume = {16}, number = {}, pages = {1758269}, pmid = {41939465}, issn = {2234-943X}, abstract = {OBJECTIVE: To investigate the clinicopathological characteristics, diagnostic strategies and clinical management of primary low-grade osteosarcoma of the breast occurring after radiotherapy for breast cancer.

METHODS: We report a rare case of primary low-grade osteosarcoma of the breast in a 69-year-old female patient with a history of breast cancer radiotherapy, and review the relevant literature to summarize its clinicopathological features, aiming to improve clinicians' and pathologists' recognition and diagnostic capability for this rare disease.

RESULTS: The patient was diagnosed with left breast invasive ductal carcinoma (pT2N0M0, Luminal A type) 12 years ago and underwent breast-conserving surgery followed by postoperative radiotherapy and adjuvant chemotherapy. She presented with a recurrent mass at the original radiotherapy site. Following mastectomy and comprehensive pathological evaluation, the final diagnosis was primary low-grade osteosarcoma of the breast. She then underwent a modified radical mastectomy and has been followed up for 22 months with no signs of local recurrence or distant metastasis to date. Primary osteosarcoma of the breast is rare, typically high-grade, and is associated with a poor prognosis and high recurrence rate. Primary low-grade osteosarcoma is exceptionally rare, with only sporadic case reports suggesting a potentially more favorable prognosis compared to its high-grade counterpart. Its bland histological appearance can lead to misdiagnosis or underdiagnosis, and no standardized treatment protocols have been established for this disease.

CONCLUSION: Core needle biopsy of radiation-induced low-grade osteosarcoma of the breast is prone to misdiagnosis due to limited sampling and bland histological morphology; comprehensive pathological evaluation of surgical specimens combined with a specific immunohistochemical panel (SATB2, MDM2, β-catenin) is key to a definitive diagnosis. Mastectomy is a reasonable primary treatment option for this rare tumor, and long-term standardized follow-up is necessary. This case report supplements the clinical and pathological data on radiation-induced low-grade osteosarcoma of the breast, and provides a reference for the diagnosis and treatment of this disease.}, } @article {pmid41939568, year = {2026}, author = {Sriram, A and Polhemus, L and Rodriguez, W and Singh, D and Kafaie, J}, title = {Opsoclonus-Myoclonus-Ataxia Syndrome Related to Pembrolizumab Treatment for Invasive Ductal Carcinoma: A Case Report.}, journal = {Cureus}, volume = {18}, number = {3}, pages = {e104726}, pmid = {41939568}, issn = {2168-8184}, abstract = {Immune checkpoint inhibitors (ICIs) such as pembrolizumab have become integral to the treatment of various metastatic malignancies. However, their use is associated with a growing spectrum of immune-related adverse events, including rare neurological complications. This report adds to the limited existing literature on ICI-associated opsoclonus-myoclonus-ataxia syndrome (OMAS) and highlights the importance of prompt recognition and multidisciplinary management of such cases. We present a case of a 67-year-old female who presented with rapid, chaotic eye movements, truncal ataxia, and full-body myoclonus two months after beginning a combined immunotherapy and chemotherapy regimen of paclitaxel, carboplatin, and pembrolizumab for triple-negative invasive ductal carcinoma. The case highlights pembrolizumab, an ICI targeting the programmed death-1 receptor, as a cause of adult-onset OMAS. In our discussion, we expand upon the mechanism of action of ICIs, notably the immune pathways underlying their use. We follow this with how this immunotherapy causes damage to peripheral tissues, focusing on the neurological side effects. We finish by discussing currently implemented treatment options for patients who experience these adverse events, and future directions in the field of autoimmune and paraneoplastic neurology. This case describes the onset of OMAS following pembrolizumab therapy in a patient with triple-negative breast cancer, a rare but clinically significant adverse event. As ICIs are increasingly used, clinicians must remain vigilant for uncommon neurological immune-related adverse events. Early recognition and immunosuppressive treatment can mitigate long-term sequelae. This case underscores the need for further research and interdisciplinary awareness in the evolving field of autoimmune and paraneoplastic neurology.}, } @article {pmid41939661, year = {2026}, author = {Abarca Ruiz, JW and Suárez Caicedo, MN and Redroban Tufino, EJ and Arteaga Morocho, EA and Corella Sanguil, PH}, title = {Acute Pancreatitis as the Initial Presentation of Metastatic Breast Cancer Due to Malignant Hypercalcemia: A Case Report.}, journal = {Cureus}, volume = {18}, number = {3}, pages = {e104627}, pmid = {41939661}, issn = {2168-8184}, abstract = {Hypercalcemia-induced acute pancreatitis is a rare condition, most commonly associated with primary hyperparathyroidism or advanced malignancies, and represents a metabolic emergency. We report the case of a 63-year-old woman who presented with severe epigastric abdominal pain, constipation, and episodes of disorientation. Laboratory tests revealed elevated pancreatic enzymes and severe hypercalcemia. Acute pancreatitis secondary to hypercalcemia was diagnosed, and normal parathyroid hormone (PTH) levels excluded primary hyperparathyroidism. The presence of anemia, thrombocytopenia, and multiple lytic bone lesions initially suggested multiple myeloma; however, this diagnosis was ruled out due to the absence of monoclonal gammopathy. Further imaging revealed an irregular right breast mass with axillary lymphadenopathy, classified as BI-RADS 5. Tumor markers were markedly elevated, and core needle biopsy confirmed human epidermal growth factor receptor 2 (HER2)-positive invasive ductal carcinoma with bone metastases. Despite intensive treatment with intravenous hydration and zoledronic acid, neurological deterioration occurred; hence, after 25 days of hospitalization, the patient was discharged for home-based palliative care at the family's request. This case highlights the importance of considering metastatic malignancies, particularly breast cancer, in patients with pancreatitis of unclear etiology and severe hypercalcemia.}, } @article {pmid41941530, year = {2026}, author = {Musamba, J and Chisompola, D and Mwansa, P and Kamvuma, K and Liweleya, S and Masenga, SK}, title = {Correlates of Ki-67 proliferation index in a cohort of women with suspected breast cancer in Lusaka, Zambia.}, journal = {PLOS global public health}, volume = {6}, number = {4}, pages = {e0005752}, doi = {10.1371/journal.pgph.0005752}, pmid = {41941530}, issn = {2767-3375}, abstract = {Ki-67 is a key biomarker of tumor proliferation in breast cancer, yet its clinical correlates in this population, where disease is often detected at earlier stages, remain underexplored. This study aimed to identify factors independently associated with high Ki-67 expression among women investigated for suspected breast cancer at Unilabs Laboratory, Lusaka, Zambia. A retrospective cross-sectional analysis was conducted on 208 women suspected of having breast cancer through a laboratory-based screening program in Lusaka, Zambia (2019-2024). Demographic, clinical, and pathology data were extracted from laboratory records. Ki-67 expression, as the outcome variable, was dichotomized as low (<20%) or high (>20%). Variables significant in bivariate analysis (p < 0.05) were included in a multivariable logistic regression model to identify correlates of high Ki-67 expression. The median age was 48 years (IQR: 40-63), and 46.2% (n = 96) exhibited high Ki-67 expression. In bivariate analysis, younger age, invasive ductal carcinoma, right breast involvement, progesterone receptor (PR) positivity threshold ≥10%, non-Quick Score scoring methods, and lack of fluorescence in situ hybridization (FISH) testing were associated with high Ki-67. However, in adjusted multivariable models, only older age (>41 years, aOR: 0.43-0.46, p < 0.05), PR positivity threshold ≥10% (aOR: 6.14-6.38, p < 0.05), and use of non-Quick Score scoring methods (aOR: 10.5-14.9, p ≤ 0.002) remained significantly associated with high Ki-67, while other factors lost statistical significance after controlling for confounders. In this diagnostic cohort from Zambia, nearly half of women with breast cancer exhibited high Ki-67 expression, reinforcing its relevance even in early detection settings. The study identified younger age (≤40 years), higher PR positivity threshold, and alternative scoring methods as independent correlates of high Ki-67, highlighting the importance of standardized biomarker assessment. Future studies should consider a prospective study design incorporating molecular subtyping to enhance the clinical interpretation of Ki-67 in similar populations.}, } @article {pmid41930855, year = {2026}, author = {Corso, G and Andreon, C and La Vecchia, C and Bottazzoli, EI and Abruzzese, G and Favilla, K and Citterio, O and Spoldi, E and Di Silvestre, S and De Scalzi, AM and Polizzi, A and Meduri, E and Trapani, D and Nicosia, L and Pesapane, F and Bossi, D and Brogi, E and Shen, S and Mukhtar, R and Criscitiello, C and Veronesi, P and Gandini, S and Magnoni, F and Curigliano, G}, title = {Invasive lobular and ductal breast cancers: a systematic review and metanalysis in association with BRCA1/2 mutation status.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {239}, number = {}, pages = {116692}, doi = {10.1016/j.ejca.2026.116692}, pmid = {41930855}, issn = {1879-0852}, abstract = {BACKGROUND: Invasive lobular breast carcinoma (ILC) differs from invasive ductal breast carcinoma (IDC) with respect to genetic alterations and risk factors. We aimed to quantify differences in the prevalence of germline BRCA1/2 mutations between these two patients' populations.

MATERIALS AND METHODS: We conducted a systematic literature search to extract data on the association between BRCA1/2 mutation status and breast cancer (BC) histological subtype (ILC and IDC). Summary odds ratios (SOR) and 95% CI were calculated using random effects univariate and bivariate models and between-study heterogeneity investigated through meta-regression and subgroup analyses.

RESULTS: Twelve studies, published between 1998 and 2025, were considered, including 8004 BC women. BRCA1 mutations were significantly less frequent in patients with ILC than IDC (SOR=0.32, 95%CI (0.16-0.65)) whereas no association was found overall for BRCA2 (SOR=1.28, 95%CI (0.95-1.72)). The difference between the association with BRCA1 and BRCA2 was statistically significant (p-value<0.001). There was no indication of publication bias in BRCA1 (Egger's and Begg's test p-value=0.23, 0.12). The between study heterogeneity was 29% in BRCA1 and 0% in BRCA2. Excluding papers with high risk of bias, BRCA2 mutations were more frequent in patients with ILC than in IDC (SOR=2.56, 95%CI (1.15-5.7)). This association was primarily driven by the bivariate random-effects model, which accounts for the correlation between BRCA1 and BRCA2 estimates.

CONCLUSIONS: In studies with lower risk of bias, germline BRCA2 mutations were more frequent in patients with ILC than IDC. Conversely, BRCA1 mutations are more frequently observed in IDC, particularly among younger patients and those with a positive family history of BC.}, } @article {pmid41931334, year = {2026}, author = {Wang, X and Xiao, X and Yang, A and Zeng, S and Chen, W and Chen, Y and Cui, S and Huang, Z and Zeng, Y and Huang, X}, title = {Correlation between quantitative DCE-MRI and pathologic complete response in patients with invasive ductal carcinoma undergoing neoadjuvant systemic therapy.}, journal = {Medicine}, volume = {105}, number = {14}, pages = {e48122}, doi = {10.1097/MD.0000000000048122}, pmid = {41931334}, issn = {1536-5964}, support = {Grant No. 2021B1026//Special Funds for Social Public Welfare and Basic Research in Zhongshan City/ ; }, mesh = {Humans ; Female ; Middle Aged ; Retrospective Studies ; *Neoadjuvant Therapy/methods ; *Magnetic Resonance Imaging/methods ; *Breast Neoplasms/pathology/diagnostic imaging/drug therapy/therapy ; *Carcinoma, Ductal, Breast/pathology/diagnostic imaging/drug therapy/therapy ; Adult ; Contrast Media/pharmacokinetics ; Aged ; Treatment Outcome ; ROC Curve ; Pathologic Complete Response ; Dynamic Contrast Enhanced Magnetic Resonance Imaging ; }, abstract = {This study aimed to determine the associations between pretreatment quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) pharmacokinetic (PK) parameters, post-neoadjuvant systemic therapy (NST) MRI features, and pathologic complete response (pCR) in patients with invasive ductal carcinoma (IDC). Twenty-eight consecutive IDC patients who received NST were retrospectively reviewed. All patients underwent MRI at 3 time points: before NST; after 2 cycles of NST; and before surgery. Continuous and categorical variables were compared between pCR and non-pCR groups using the Mann-Whitney U test and Fisher exact test, respectively, with HER2 status adjusted in PK parameter analyses. Partial correlation assessed associations between MRI features and pCR. Select PK parameters were further evaluated using Firth's penalized-likelihood regression, controlling for covariates. Receiver operating characteristic (ROC) analysis was performed to evaluate predictive performance. Significant differences were detected between groups regarding HER2-positive, luminal B subtype, Miller-Payne, and postoperative lymph node metastasis (P < .05). Pretreatment peritumoural extravascular extracellular volume (Ve), post-NST shrinkage pattern, and residual disease were significantly different between the groups (P < .05). Partial correlation analysis indicated a positive association between the peritumoural flux rate constant (Kep) and pCR (P < .05). Regression analysis identified the peritumoural Kep as a factor influencing the pCR with an area under the curve of 0.756 (95% CI = 0.564-0.947). Our preliminary findings suggested an association between the pCR and pretreatment peritumoural PK parameters, highlighting the potential value of the peritumoural region. These results require further validation in larger prospective studies.}, } @article {pmid41742173, year = {2026}, author = {Wu, Z and Cheng, Y and Lin, S and Hu, Q and Fu, X and Li, Z and Qin, G and Li, H}, title = {Trimethylamine N-oxide as a potential biomarker for predicting axillary lymph node metastasis in breast cancer: a retrospective study.}, journal = {World journal of surgical oncology}, volume = {24}, number = {1}, pages = {}, pmid = {41742173}, issn = {1477-7819}, support = {20211800904582//Dongguan Science and Technology of Social Development Program/ ; }, abstract = {BACKGROUND: Axillary lymph node (ALN) metastasis is a critical prognostic factor in breast cancer, but current assessment methods have limitations. Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, has been implicated in tumor progression, though its role in breast cancer remains unclear.

METHODS: This retrospective study analyzed TMAO levels in breast tissue from benign breast nodules (BBN, n = 10), ductal carcinoma in situ (DCIS, n = 10), and invasive ductal carcinoma (IDC, n = 10). A cohort of 97 treatment-naive IDC patients (26 ALN + , 71 ALN −) was further evaluated. TMAO concentrations were quantified via ELISA, and associations with clinicopathological features were assessed using logistic regression and ROC analysis.

RESULTS: TMAO levels were significantly higher in IDC (113.9 ± 16.36 ng/g) than in DCIS (82.29 ± 13.84 ng/g, p < 0.01) or BBN (76.09 ± 10.32 ng/g, p < 0.001). ALN + patients exhibited elevated TMAO (210.92 ± 82.09 ng/g) versus ALN − (122.99 ± 48.23 ng/g, p < 0.001). Multivariable analysis identified TMAO (OR = 1.022, 95% CI: 1.009–1.031), T-stage (T1 vs T2, OR = 1.201, 95% CI: 1.019–2.169), and axillary ultrasound positivity (OR = 6.993, 95% CI: 1.099–45.455) as independent predictors. A combined model (TMAO + T-stage + ultrasound) improved predictive accuracy (AUC = 0.915; 95% CI: 0.838–0.992).

CONCLUSION: TMAO levels correlate with breast cancer progression and ALN metastasis, demonstrating potential as a biomarker. Further studies are needed to validate its clinical utility and mechanistic role.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12957-026-04251-4.}, } @article {pmid41923005, year = {2026}, author = {Wang, L and Dong, C and Wang, H and Yang, L and Zhang, C and Wang, M and Wang, Q and Xu, Q}, title = {Evaluating the predictive value of dynamic contrast-enhanced MRI and six diffusion models for prognostic factors in mass-type invasive ductal carcinoma of the breast.}, journal = {BMC medical imaging}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12880-026-02308-0}, pmid = {41923005}, issn = {1471-2342}, support = {20221336//the Medical Science Research Project of Hebei/ ; ZF2024116//2024 Government-Funded Clinical Medicine Outstanding Talents Training Program/ ; }, } @article {pmid41926512, year = {2026}, author = {Li, J and Li, S and Li, C and Chen, Z and Ding, Y}, title = {Prosthetic Loosening in a Total Hip Arthroplasty Patient After Breast Cancer Chemotherapy and Hormonal Therapy: A Case Report.}, journal = {Drug, healthcare and patient safety}, volume = {18}, number = {}, pages = {543323}, doi = {10.2147/DHPS.S543323}, pmid = {41926512}, issn = {1179-1365}, abstract = {BACKGROUND: Studies have shown that there are a lot of risk factors that could cause periprosthetic osteolysis and aseptic loosening, threatening the life-span of the hip prosthesis. Breast cancer is one of the most frequent malignancy in women. However, the use of breast cancer chemotherapy and hormonal therapy has been shown to significantly elevate the risk of osteoporosis. Chemotherapy can systematically suppress the anabolism of various organs, ultimately leading to bone metabolism dysfunction and osteolysis. Aromatase inhibitors (AI) function by inhibiting the conversion of androgens to estrogen, thereby reducing systemic estrogen levels, which is essential for maintaining bone mass; however, prolonged estrogen deprivation can lead to osteoporosis, which has been proven to pose a significant threat to the survival of hip implants.

CASE PRESENTATION: In this case, the patient suffered hip joint tuberculosis and took intertrochanteric osteotomy procedure at age 24. Seventeen years after, she took Total Hip Arthroplasty (THA). She then undertook chemotherapy and hormonal therapy for breast invasive ductal carcinoma (BI-RADS category III), 1 year after her primary THA. Three years later, she was diagnosed with aseptic loosening of her hip prosthesis. A summary and analysis of her treatment were conducted.

CONCLUSION: Breast cancer chemotherapy and hormonal therapy might be a threat to the stability of THA prosthesis. More attention should be paid when a Total Hip Arthroplasty patient received chemotherapy and hormonal therapy. Further research is needed to fully understand the impact of breast cancer treatments, as current therapies like hormonal therapy can increase the risk of osteoporosis and fractures.}, } @article {pmid41918804, year = {2026}, author = {Aldawood, M and Alamoudi, MK and Alsaleh, AA and Alharbi, N and Huwaizi, S and Alroshody, R and Ali, R and Almeer, R and Matou-Nasri, S}, title = {Methylglyoxal-derived glycated albumin enhances the stemness potential of invasive ductal carcinoma-derived breast cancer stem-like cell line KAIMRC1.}, journal = {Oncology letters}, volume = {31}, number = {5}, pages = {186}, pmid = {41918804}, issn = {1792-1082}, abstract = {Type 2 diabetes mellitus (T2DM) is a risk factor for breast cancer (BC) development and recurrence due to multifactorial mechanisms, including the generation of glycated proteins under hyperglycemic conditions. Emerging evidence indicates that hyperglycemia promotes the formation and expansion of BC stem-like cells (BCSC), contributing to worse outcomes in patients with T2DM. To support early detection and personalized therapy, there is an urgent need to identify novel biomarkers that specifically target BCSCs in patients with T2DM. The present study examined the effects of glycated albumin (GA) on the cellular functions of KAIMRC1, a naturally immortalized BCSC line derived from invasive ductal carcinoma (IDC), the primary breast carcinoma developed in patients with T2DM. Cells were subjected to in vitro assays, including soft agar colony formation, real-time monitoring of cell proliferation, motility and invasion through a reconstituted basement membrane using the xCELLigence system and western blotting. A triple-negative BC cell line was used as a comparator. Aldehyde dehydrogenase (ALDH) activity was quantified using a biochemical assay. As expected, KAIMRC1 cells exhibited high ALDH activity, a characteristic feature of cancer stem-like cells (CSCs). GA induced dose-dependent increases in KAIMRC1 cell proliferation, motility, invasion and colony formation and was associated with elevated levels of the oncoprotein phosphorylated-ERK1/2, the receptor for advanced glycation end products (RAGE) and the stemness-associated proteins OCT3/4 and vimentin. GA-treated KAIMRC1 cells showed notable invasive capacity despite slow proliferation, consistent with known metastatic potential of quiescent CSCs. Conversely, unglycated albumin had no detectable biological effects except for an anti-mitogenic response at high concentration. Bioinformatics analyses showed that vimentin mRNA was upregulated in patients with BC and DM and was associated with a poor prognosis in patients with BC. RAGE neutralization attenuated GA-induced vimentin upregulation. Altogether, these findings show that GA exerts pro-tumorigenic effects in IDC-derived CSCs and upregulates vimentin protein expression via RAGE, highlighting the GA-RAGE axis as a potential therapeutic target and supporting vimentin as a promising prognostic marker for invasive BC in patients with DM.}, } @article {pmid41920176, year = {2026}, author = {Liberman, L and Harel, E and Gilboa, Y}, title = {Sensory Processing Disorders and Emotional Distress Among Young Children Exposed to Traumatic Events.}, journal = {The American journal of occupational therapy : official publication of the American Occupational Therapy Association}, volume = {80}, number = {3}, pages = {}, doi = {10.5014/ajot.2026.051402}, pmid = {41920176}, issn = {0272-9490}, mesh = {Humans ; Child ; Male ; Female ; Cross-Sectional Studies ; Child, Preschool ; Israel/epidemiology ; *Psychological Distress ; *Sensation Disorders/psychology ; *Terrorism/psychology ; Surveys and Questionnaires ; *Stress Disorders, Post-Traumatic/psychology ; }, abstract = {IMPORTANCE: Sensory processing disorders have been found mostly among school-age children exposed to traumatic events or after maltreatment. Therefore, it is important to examine sensory processing and emotional distress among young children exposed to traumatic events after a collective terror attack.

OBJECTIVE: To examine the correlation between sensory processing patterns and emotional distress among young children exposed to traumatic events after a terror attack.

DESIGN: Cross-sectional design with purposive criterion sampling.

SETTING: Community.

PARTICIPANTS: Thirty-seven children ages 2 to 7 yr, residents of the Gaza envelope (the populated areas in the Southern District of Israel within 4.3 mi of the Gaza Strip border) in Israel, who were directly affected by the events that followed the October 7, 2023, terror attack.

OUTCOMES AND MEASURES: Demographic questionnaire, the Pediatric Emotional Distress Scale (PEDS), and the Sensory Profile 2.

RESULTS: Participants scored significantly higher than the cutoff scores for PEDS Total Score and the Anxious/Withdrawn, Fearful, and Acting Out subscales. Almost half the participants showed sensory processing patterns that were scored as "more" or "much more" than others, with sensory avoidance and sensitivity being the most prevalent. Significant correlations were found between most of the emotional distress and sensory processing patterns.

CONCLUSIONS AND RELEVANCE: Sensory processing difficulties frequently occurred and were significantly correlated with emotional distress among young children exposed to traumatic events. Occupational therapy practitioners working with children with sensory processing difficulties play a role in addressing the environmental and regulatory needs of young children affected by trauma. Plain-Language Summary: This study examined how young children ages 2 to 7 years were affected by the traumatic events after the October 7, 2023, terror attack in Israel. It focused on the correlation between emotional distress and sensory processing. Emotional distress refers to strong negative feelings that may affect how a child behaves. Among young children, it may show up as fear, anxiety or acting out. Sensory processing is how children notice, interpret, and respond to things they see, hear, touch, taste, or feel. Some children are overly sensitive and can be easily overwhelmed by sights, sounds, or textures. Others may not notice sensations that most people do, some may seek extra stimulation, and some may avoid certain sensations. The study included 37 children living near the Gaza border who directly experienced traumatic events. The results showed that many had high levels of emotional distress and sensory processing difficulties, especially sensitivity and avoidance. Emotional distress and sensory processing were correlated. The findings suggest that early childhood trauma can affect how children feel and respond to inputs in daily life. Occupational therapy practitioners can help these children by supporting their sensory needs to improve their participation in daily activities.}, } @article {pmid41907633, year = {2026}, author = {Xu, A and Weng, X and Zheng, J and Cui, Q and He, G and Cheng, Y and Jiang, H and Wei, M and Zhang, S}, title = {Exploring the recurrence and metastasis of breast invasive ductal carcinoma based on machine learning and survival analysis.}, journal = {Frontiers in oncology}, volume = {16}, number = {}, pages = {1734379}, pmid = {41907633}, issn = {2234-943X}, abstract = {OBJECTIVE: Invasive ductal carcinoma (IDC), the predominant histopathological subtype comprising about 80% of breast malignancies, continues to pose a significant clinical challenge due to frequent recurrence. Existing relapse prediction models remain limited in accuracy and generalizability. This study aimed to construct and validate machine learning-based models for predicting 5-year (short- to medium term) recurrence and metastasis risk in IDC, based on recurrence-free survival (RFS) analysis.

METHODS: A total of 640 IDC cases diagnosed between January 2017 and December 2019 were enrolled, data were partitioned into three sets: the training set (n = 303) from Fudan University Shanghai Cancer Center; the validation set (n = 217) from Shaoxing Central Hospital; and the test set (n = 120) from Zhejiang Cancer Hospital. Independent prognostic factors were identified through univariate and multivariate Cox regression analyses. Three predictive strategies were implemented: evaluating recurrence risk, distinguishing local from distant recurrence, and identifying metastatic sites. Light Gradient Boosting Machine (LGBM), XGBoost (XGB), Random Forest (RF), k-Nearest Neighbor (KNN), Neural Network (NN), and Support Vector Machine (SVM) were trained and validated.

RESULTS: The median follow-up duration was 5.7 years. Multivariate Cox regression analyses identified multiple factors significantly associated with RFS, including the rad-score, Ki-67 index, lymph node metastasis, tumor histological grade, and breast cancer family history in first- or second-degree relatives (all p < 0.05). In contrast, age, menopausal status, and molecular subtype showed no significant association with recurrence risk in this cohort (p = 0.987, p = 0.987, and p = 0.960, respectively). The clinical-radiomic nomogram demonstrated strong in predictive IDC recurrence. The XGBoost model demonstrated robust and consistent predictive performance across all cohorts, achieving AUCs of 0.842, 0.848, and 0.912 on the training, validation, and test sets, respectively. On the independent test set, the model attained an accuracy of 93.8%, sensitivity of 96.3%, and specificity of 79.6%.Furthermore, density plots of the radiomic score and Ki-67 index effectively differentiated between local recurrence, bone metastasis, and metastases to other organs. Patients with lymph node metastasis and high histological grade demonstrated a higher frequency of metastases to distant organs, accounting for most cases and emphasizing the contrast with local recurrence and bone metastasis. Patients with a breast cancer family history displayed a distinct pattern of bone metastasis.

CONCLUSION: This study underscores the utility of machine learning models in forecasting recurrence and metastatic behavior in IDC. The clinical-radiomic nomograms proved valuable for individualized surgical and therapeutic decision-making in IDC patients.}, } @article {pmid41907708, year = {2024}, author = {Kaufman, P and O'Meara, KE and Hawrelak, J}, title = {Preventing chemotherapy-induced diarrhea and microbiota imbalances with prebiotics and probiotics in breast cancer treatment: A case report.}, journal = {Gut microbes reports}, volume = {1}, number = {1}, pages = {2379475}, pmid = {41907708}, issn = {2993-3935}, abstract = {Breast cancer (BC) is the second most common cancer in women in the United States. Of those diagnosed, 40-80% will undergo chemotherapy. Adverse effects of chemotherapy are chemotherapy-induced diarrhea (CID) and gut microbiota dysregulation. CID can lead to dehydration, metabolic acidosis, malnutrition, and gut dysbiosis. Antidiarrheal medications are the standard treatment of care; however, this has been shown to further contribute to gut dysbiosis, is not always effective in controlling diarrhea, and can lead to rebound constipation with the potential of pathogenic bacterial overgrowth. In this case report, we describe the experience of a patient-centered, personalized intervention with pre- and probiotics to preserve the microbiota and prevent CID. A 57-year-old postmenopausal female with BC undergoing adriamycin-cyclophosphamide (AC) and taxol-cyclophosphamide (TC) chemotherapies for invasive ductal carcinoma under the care of a cancer team wanted to refrain from using loperamide and instead use nutritional interventions and supplementation for preventing CID and maintaining gut health. This case report is a narrative report of the observed outcomes of one patient with BC after taking specific prebiotics and probiotics. The outcomes included the prevention of CID and other gastrointestinal adverse effects, and maintaining microbiota alpha-diversity, butyrate producing genera, and Bifidobacterium populations while inhibiting the overgrowth of Proteobacteria pathogenic bacteria.}, } @article {pmid41909112, year = {2026}, author = {Park, A and Lugo-Rodriguez, V and Diaz, KF}, title = {Epidermal inclusion cyst after breast reduction mammoplasty.}, journal = {Radiology case reports}, volume = {21}, number = {6}, pages = {2482-2484}, pmid = {41909112}, issn = {1930-0433}, abstract = {We report a case of a 74-year-old female with left breast multicentric invasive ductal carcinoma status post left mastectomy with reconstruction and right breast symmetrizing reduction mammoplasty presenting with a new asymmetry of the right breast that was found to be an epidermal inclusion cyst (EIC) upon core needle biopsy. The aim of the case report is to characterize the pathogenesis of EIC as well as its clinical and imaging features. This benign entity is of significance due to its malignant potential to squamous cell carcinoma.}, } @article {pmid41909317, year = {2026}, author = {Sophabmixay, AO and Obuch, JC}, title = {Breast Cancer Metastasis to the Gastrointestinal Tract After Nine Years of Remission: A Case Report.}, journal = {Cureus}, volume = {18}, number = {2}, pages = {e104194}, pmid = {41909317}, issn = {2168-8184}, abstract = {Gastrointestinal (GI) metastasis from breast cancer is rare and more commonly associated with invasive lobular carcinoma than invasive ductal carcinoma (IDC). Diagnosis of GI metastases secondary to breast cancer is difficult because patients may have long disease-free intervals or present with non-specific symptoms. We present a case of a 55-year-old patient with high-grade IDC in nine-year remission after bilateral mastectomy, axillary node dissection, reconstruction, and adjuvant chemoradiation who presented with recurrent abdominal pain and progressive, cholestatic liver enzyme elevation. Imaging and endoscopic evaluations demonstrated hepatic and duodenal lesions and biliary strictures. Biopsy confirmed the diagnosis of recurrent Stage IV IDC with metastasis to the duodenum, liver, lymph nodes, and spine. The patient received palliative systemic therapy and survived three years after recurrence diagnosis. Our case emphasizes that metastasis of IDC to the GI tract can occur after prolonged remission and that cholestatic liver enzyme elevation with new hepatic or biliary abnormalities should prompt consideration of metastatic recurrence in patients with a prior history of breast cancer.}, } @article {pmid41913016, year = {2026}, author = {Shern, TP and Holt, LR and Lloyd, K and Daly, AE and Gadd, MA and Verdial, FC and Kwait, RM and Specht, MC and Smith, BL and Ozmen, T}, title = {Economic and Health System Impact of Implementing the SOUND Trial Approach in Early-Stage Breast Cancer.}, journal = {Annals of surgical oncology}, volume = {}, number = {}, pages = {}, pmid = {41913016}, issn = {1534-4681}, abstract = {BACKGROUND: Axillary management in early-stage breast cancer is increasingly shifting toward de-escalation. While sentinel lymph node biopsy (SLNB) remains standard, evidence suggests axillary ultrasound (AUS) may safely replace SLNB in selected patients. The SOUND trial demonstrated noninferior oncologic outcomes with AUS-based staging among clinically node-negative patients with small (≤ 2 cm), unifocal invasive breast cancers and negative preoperative AUS. However, the economic and health system impact of implementing this strategy in routine practice remains unclear.

PATIENTS AND METHODS: We conducted a retrospective cohort analysis of 221 SOUND-eligible patients who underwent breast-conserving surgery with SLNB at four affiliated hospitals between January and June 2023. Costs were modeled using 2025 Medicare reimbursement rates, comparing the observed SLNB pathway with a theoretical AUS-only approach. Estimates included procedural, anesthesia, pathology, and complication-related costs, analyzed from both hospital and patient perspectives.

RESULTS: Total estimated hospital costs were $1192,159.56 for SLNB versus $111,825.65 for AUS-only staging, a 90.6% reduction. Mean patient out-of-pocket costs decreased similarly (from $1078.88 to $101.20 per patient). SLNB added an average of 15.1 min of operative time and increased pathology workload owing to lymph node processing.

CONCLUSIONS: In SOUND-eligible patients, axillary staging with ultrasound alone provides substantial reductions in cost, operative time, and resource utilization while supporting a less invasive, value-based approach to breast cancer care. Together with existing evidence, these findings support broader implementation of the SOUND strategy in appropriately selected populations, particularly postmenopausal patients over 50 years undergoing breast-conserving surgery for cT1N0, ER-positive, HER2-negative invasive ductal carcinoma with a negative AUS.}, } @article {pmid41723509, year = {2026}, author = {Kim, S and Woo, S and Song, YM and Jhung, K and Choi, J and Yang, YH and Kwack, YS and Kim, Y}, title = {Reducing social isolation in schools: a social network analysis of the HOPE bullying prevention program.}, journal = {Child and adolescent psychiatry and mental health}, volume = {20}, number = {1}, pages = {}, pmid = {41723509}, issn = {1753-2000}, support = {AMHIR22A01//National Center for Mental Health/ ; }, abstract = {BACKGROUND: School bullying is a public health concern, disproportionately affecting socially isolated students. Peer network position strongly influences vulnerability to victimization. This study examined the effectiveness of a Korean school-based bullying prevention program, HOPE, using social network analysis (SNA).

METHODS: From an initial intervention cohort of 275 students, a total of 204 students (112 boys, 92 girls) who completed both pre- and post-intervention measures across nine classrooms were included in the final analysis (attrition rate: 25.8%). In-degree centrality (IDC), defined as the number of close-friend nominations received from peers, was measured before and after the intervention as the primary outcome. SNA was conducted at baseline and post-intervention to capture changes in peer network structures. Secondary analysis examined psychosocial characteristics of students with low baseline IDC to identify factors associated with isolation and victimization.

RESULTS: Following the HOPE program, IDC scores for previously isolated students were observed to increase. Post-intervention networks showed greater density, reflecting improved peer acceptance and social integration. Students with low baseline IDC were more likely to report elevated anxiety and lower self-esteem, underscoring their vulnerability to exclusion. Post-intervention network displayed greater density and inclusiveness with fewer students at risk of marginalization.

CONCLUSION: The HOPE program was associated with enhanced social integration and promoted supportive classroom networks. By reshaping peer dynamics, the intervention may be linked to reduced isolation and strengthened protective relationships for vulnerable children. These findings underscore the utility of SNA in evaluating bullying prevention efforts and suggest that network-based approaches can provide valuable insights into how programs promote resilience and reduce bullying risk.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13034-026-01032-5.}, } @article {pmid41903363, year = {2026}, author = {Tiberghien, ME and Blanc-Lapierre, A and Saib, S and Neveu, M and Mascarel, AM and Bocquet, F and Doutriaux-Dumoulin, I and Geffroy, D}, title = {Performance of contrast-enhanced spectral mammography for sizing breast invasive ductal carcinoma with an in situ component.}, journal = {Surgical oncology}, volume = {66}, number = {}, pages = {102409}, doi = {10.1016/j.suronc.2026.102409}, pmid = {41903363}, issn = {1879-3320}, } @article {pmid41896221, year = {2026}, author = {Yanushko, D and Pichot, A and Vincent, A and Keime, C and Laverny, G and Metzger, D}, title = {HIF1 inhibition targets tumoral and myeloid cells, and is a promising therapy for metastatic castration-resistant prostate cancer.}, journal = {Cell death & disease}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41419-026-08590-8}, pmid = {41896221}, issn = {2041-4889}, support = {EQU201903007800//Fondation pour la Recherche Médicale (Foundation for Medical Research in France)/ ; }, abstract = {Metastatic prostate cancer (PCa) remains lethal due to limited effective therapies. PTEN and TP53 are commonly mutated tumor suppressors in metastatic PCa, yet the molecular and cellular mechanisms driving aggressiveness and treatment resistance are not fully understood. We have previously shown that mice with both Pten and Trp53 inactivation in prostate luminal cells at adulthood develop aggressive intraductal prostate carcinoma (IDC) and liver metastases. By combining single-cell and spatial transcriptomics, along with flow cytometry and immunohistochemical analyses, we now reveal that prostatic tumors of such mice are hypoxic and progress within a complex immune microenvironment, including neutrophils, TREM2[+] macrophages, and CCR2[+] myeloid cells. Moreover, we uncovered that genetic Hif1a inactivation in prostate luminal cells or pharmacological inhibition of HIF1 signaling in Pten/Trp53[(i)pe-/-] mice does not prevent IDC formation or epithelial plasticity driven by Trp53 loss, but impairs neutrophil recruitment. In addition, HIF1 inhibition reduces CCR2[+] myeloid cell infiltration. Importantly, targeting these immune cells sensitizes tumors to androgen deprivation and reduces the size of liver metastatic niches. Moreover, pharmacological HIF1 inhibition not only overcomes castration resistance, but also eliminates metastatic niches, offering a more effective approach than direct myeloid cell blockade. Thus, HIF1 targeting emerges as a promising therapy for metastatic castration-resistant PCa.}, } @article {pmid41897239, year = {2026}, author = {Silva, RMD and Soper, MS and Martins, LC and Sousa, IR and Neves, JH and Soares, DRA and Maciel, CEA and Santos, GPD and Oliveira, AR and Cardona, IOS and Pereira, SB and Santos, MAD and Pille, A and Maccari, JG and Mutlaq, MP and Nasi, LA and Wolf, JM}, title = {Improvements in Timely Care and Patient-Reported Outcomes for Breast Cancer: A Seven-Year Southern Brazilian Cohort Analysis.}, journal = {Healthcare (Basel, Switzerland)}, volume = {14}, number = {6}, pages = {}, doi = {10.3390/healthcare14060786}, pmid = {41897239}, issn = {2227-9032}, abstract = {Background/Objective: Breast cancer is one of the leading diseases affecting the Brazilian population and is often diagnosed at advanced stages. Due to its heterogeneity, treatment involves multiple therapeutic modalities, such as chemotherapy, hormone therapy, immunotherapy, and radiotherapy. The aim of this study was to characterize the profile of patients undergoing treatment for breast cancer in a private hospital in southern Brazil, and to assess the physical and psychological effects associated with different therapeutic modalities. Methods: An ambidirectional longitudinal cohort study was conducted from September 2018 to December 2024, incorporating retrospective data since 2013. Clinical and therapeutic data were collected, and Patient-Reported Outcome Measures (PROMs) using the QLQ-C30 Summary Score (QLQ-BR23, FACT-ES, BREAST-Q, LMC21) and Symptom Global Score questionnaires were analyzed using mixed-effects models to evaluate physical, emotional, cognitive, social, and overall quality-of-life domains, as well as body image. The temporal trend of time-to-treatment was assessed via linear regression. Results: Among 871 individuals evaluated, 98.4% were female, and invasive ductal carcinoma was the predominant histological type (75.1%). Radiotherapy was one of the most frequently used treatment modalities (39.2%), while immunotherapy had the lowest usage rate (2.7%). A significant reduction in the time between diagnosis and initiation of treatment was observed from 2013 to 2024 (from 21.0 to 10.9 days; p < 0.01), reflecting improvements in healthcare services. Mixed-effects models for PROMs indicated significant improvements across all assessed domains (p < 0.01) over the 48-month follow-up, despite a median follow-up of 22 months. Conclusions: High-quality and timely oncological care provided to breast cancer patients in a private hospital in southern Brazil demonstrates the implementation of a dynamic, agile, and human-centered care model, contributing to improved clinical and patient-reported outcomes validated by robust longitudinal analysis.}, } @article {pmid41899990, year = {2026}, author = {Wen, W and Qin, J and Chang, Q}, title = {Semi-Supervised Graph Attention Network for Screw Pump Fault Diagnosis: Revealing the Dynamic Coupling of Multi-Source Information.}, journal = {Entropy (Basel, Switzerland)}, volume = {28}, number = {3}, pages = {}, doi = {10.3390/e28030338}, pmid = {41899990}, issn = {1099-4300}, abstract = {The screw pump is a critical device for elevating downhole petroleum to the surface, and screw pump failure can significantly disrupt the production of oil wells. Due to the complex structure of the screw pump, the same pump fault can cause different changes in the monitoring parameters, and different faults can also cause the same parameter change. In consequence of the complexity, it requires a large amount of labeled data for a diagnosis model to achieve fault diagnosis of a screw pump in practical application. Aiming for this kind of condition, we discovered the dynamic coupling effect between multi-source information through detailed research on the collected data of screw pumps. To fully leverage the information dynamic coupling (IDC) effect, a semi-supervised learning graph attention network (SSL-GAT) fault diagnosis method is proposed. This approach integrates the semi-supervised learning framework and graph attention neural network for the fault diagnosis of a screw pump. The experimental validation of the SSL-GAT method demonstrates its outstanding performance in screw pump fault diagnosis.}, } @article {pmid41889414, year = {2026}, author = {Ding, JS and Zhang, M and Zhou, F}, title = {Case Report: A primary breast collision tumor composed of myeloid sarcoma and invasive ductal carcinoma.}, journal = {Frontiers in oncology}, volume = {16}, number = {}, pages = {1788294}, pmid = {41889414}, issn = {2234-943X}, abstract = {Collision tumors, characterized by the coexistence of distinct malignant neoplasms within the same anatomical site, are rare in the breast. We present a case of a 53-year-old woman with an incidentally discovered palpable mass in the upper inner quadrant of the left breast. Preoperative hematological evaluation was unremarkable. Comprehensive imaging evaluation, including ultrasound, mammography, MRI, and PET-CT, was suggestive of malignancy. A preoperative core needle biopsy was performed but yielded limited material, with pathology suggestive of possible invasive ductal carcinoma, necessitating definitive surgical excision for diagnosis. Following breast-conserving surgery and sentinel lymph node biopsy, histopathological and immunohistochemical analysis revealed a collision tumor composed of myeloid sarcoma (MS) and invasive ductal carcinoma (IDC), the latter exhibiting a triple-negative phenotype (ER-, PR-, HER2-), with no lymph node metastasis. This case highlights the clinicopathological and imaging features of this rare entity and underscores the integral role of multimodal imaging, thorough pathological evaluation, multidisciplinary collaboration, and the limitations of biopsy in heterogeneous lesions in diagnosis and management.}, } @article {pmid41890485, year = {2026}, author = {Rajbongshi, H and Gogoi, M and Goswami, S and Duara, BK}, title = {Diagnostic Role of Shear Wave Elastography for Differentiating Benign and Malignant Breast Lesions With Histopathological Examination (HPE) Correlation.}, journal = {Cureus}, volume = {18}, number = {2}, pages = {e104103}, pmid = {41890485}, issn = {2168-8184}, abstract = {Breast cancer is a leading cause of mortality worldwide, with invasive ductal carcinoma being the most common malignant tumor. Ultrasonography (USG) is the initial imaging modality for breast lesions, but its low specificity often necessitates invasive histopathological examination (HPE). Shear wave elastography (SWE) is a novel technique that assesses tissue stiffness non-invasively, providing promising results in differentiating benign and malignant breast lesions. This study evaluates the diagnostic accuracy of SWE combined with B-mode USG in characterizing breast lesions and correlates findings with HPE results. A hospital-based prospective observational study was conducted on 50 female patients aged 18 years and above with breast lesions categorized as Breast Imaging-Reporting and Data System (BI-RADS) 3 or higher. SWE demonstrated a sensitivity of 72.72%, a specificity of 85.71%, and a diagnostic accuracy of 80%, highlighting its potential to reduce unnecessary biopsies. This study concludes that SWE is a valuable adjunct to conventional USG for breast lesion evaluation.}, } @article {pmid41894312, year = {2026}, author = {Mohamed, Z and Abdulkarim, A and Abdullah, AR and Al-Azab, M and Baklola, M}, title = {Molecular subtypes of breast cancer in Libyan women and their clinicopathological associations: A retrospective observational study from eastern Libya.}, journal = {Medicine}, volume = {105}, number = {13}, pages = {e48215}, doi = {10.1097/MD.0000000000048215}, pmid = {41894312}, issn = {1536-5964}, mesh = {Humans ; Female ; Libya/epidemiology ; Retrospective Studies ; *Breast Neoplasms/pathology/epidemiology/genetics/classification ; Middle Aged ; Adult ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Receptors, Progesterone/metabolism ; Receptors, Estrogen/metabolism ; Aged ; Ki-67 Antigen/metabolism ; }, abstract = {Breast cancer (BC) is the most commonly diagnosed cancer among women globally, with significant regional variations in its molecular subtypes, clinical presentation, and management. Despite advancements in oncology, limited data exist on the molecular and clinical characteristics of BC in Libya. This study aims to analyze the prevalence of molecular subtypes, clinicopathological features, and treatment patterns among Libyan women with BC at Tobruk Medical Center. This retrospective observational study included BC patients diagnosed between January 2019 and December 2020 at Tobruk Medical Center. Demographic, clinical, pathological, and treatment-related data were extracted from medical records. Molecular subtyping was based on immunohistochemical assessment of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and Ki-67. Statistical analyses were performed using SPSS version 28 (IBM Corp., Armonk). Among 115 patients analyzed, the median age at diagnosis was 46 years. Invasive ductal carcinoma accounted for 89.6% of cases, with grade II tumors being the most common (69.6%). Luminal B was the predominant molecular subtype (67.8%), followed by luminal A (14.8%), HER2-enriched (10.4%), and triple-negative BC (7.0%). Advanced-stage diagnoses (stage III and IV) were observed in 57.4% of cases. Hormone receptor positivity was detected in 82.6%, and HER2 positivity in 25.2% of cases. This study highlights the high prevalence of advanced-stage BC and the predominance of the aggressive luminal B subtype in Libya. Targeted early detection programs and improved treatment access are urgently needed to address these challenges.}, } @article {pmid41884195, year = {2026}, author = {Akter, KM and Das, S and Alam, MI and Bhuiyan, AMR and Alam, A and Chowdhury, MK}, title = {Palliative Management of Advanced Breast Carcinoma Complicated by Myiasis: First Case Report From Bangladesh.}, journal = {Clinical medicine insights. Case reports}, volume = {19}, number = {}, pages = {11795476261429282}, pmid = {41884195}, issn = {1179-5476}, abstract = {Invasive ductal carcinoma (IDC) is the most common subtype of breast cancer. While malignant wounds are known to predispose patients to secondary infections, the co-occurrence of cutaneous myiasis in breast carcinoma remains rare. We report the first documented case of wound myiasis in a patient with advanced breast carcinoma in Bangladesh. A 52-year-old woman with HER2-positive IDC of the right breast, previously treated with mastectomy, chemotherapy, and radiotherapy in a tertiary care hospital of Dhaka, presented to the Department of Palliative Medicine at Bangladesh Medical University with severe chest wall pain, facial swelling, and a foul-smelling ulcerated wound on her right chest wall on mastectomy site, infested with live maggots. The patient had advanced stage 4 disease with extensive skin and bony metastasis, stage 3 lymphedema, and a Palliative Performance Scale score of 30%, indicating an estimated survival of 8 to 41 days. Approximately 650 larvae were removed over 3 days through manual extraction and irrigation using saline, metronidazole, and turpentine, followed by occlusive dressing with petroleum gauze. She was treated with morphine, flucloxacillin, ivermectin, and albendazole, which resulted in significant symptomatic relief. This case highlights the complex intersection of advanced malignancy, socioeconomic deprivation, poor hygiene, and parasitic infestation. Palliative care played a critical role in pain relief, wound management, and preserving dignity in her final days. This report underscores the importance of early recognition and integrated management of malignant wound myiasis, particularly in resource-constrained environments. It also draws attention to the broader psychosocial impacts of such conditions and the essential role of end-of-life care in mitigating suffering.}, } @article {pmid41885729, year = {2026}, author = {Lee, ZJO and Gudi, MA and Tan, PH and Kong, TY and Lim, GH}, title = {Localized Breast Amyloidosis in a Previously Treated Breast: A Case Report and Literature Review.}, journal = {International journal of surgical pathology}, volume = {}, number = {}, pages = {10668969261428044}, doi = {10.1177/10668969261428044}, pmid = {41885729}, issn = {1940-2465}, abstract = {Breast amyloidosis is a rare disorder that can mimic malignancy, particularly in patients with a history of breast cancer. We describe a 61-year-old woman with a history of left breast invasive ductal carcinoma who developed an enlarging mass at the mastectomy site eight years post-treatment. Imaging suggested recurrence; however, biopsies revealed Congo red-positive amyloid deposits with admixed necrosis, fibrosis, and inflammation, with no evidence of recurrent carcinoma or lymphoproliferative disease. Mass spectrometry identified only amyloid signature proteins, with no specific amyloid fibril protein or subtype detected, and in the absence of systemic involvement, supporting a diagnosis of localized degenerative amyloidosis possibly related to prior treatment. This not only represents a novel etiopathological category of post-treatment degenerative amyloidosis but also highlights the importance of Congo red staining and mass spectrometry in the evaluation of ambiguous post-treated lesions to prevent misdiagnosis and overtreatment.}, } @article {pmid41880302, year = {2026}, author = {Nath, S and Illa, SK and Worku, D and Mukherjee, S and Mukherjee, A and Yata, VK}, title = {Composite selection signal analysis: Uncovering candidate genes and quantitative trait loci in Indian sheep breeds.}, journal = {PloS one}, volume = {21}, number = {3}, pages = {e0344299}, doi = {10.1371/journal.pone.0344299}, pmid = {41880302}, issn = {1932-6203}, mesh = {Animals ; *Quantitative Trait Loci ; Polymorphism, Single Nucleotide ; India ; Breeding ; *Selection, Genetic ; Sheep/genetics ; }, abstract = {Selective pressures, both natural and artificial, have significantly influenced the genomic architecture of domesticated sheep. Understanding their underlying molecular mechanisms is critical for developing efficient breeding programs to conserve and improve economically important traits in native breeds. In this study, we analysed high-density 50K SNP data from three Indigenous sheep breeds: Chanthangi (CHA, n = 29), Garole (GAR, n = 24), and Deccani (IDC, n = 26), each native to diverse climatic regions of India. We implemented a novel SNP-based de-correlated composite of multiple signals (DCMS) statistic, which integrates p-values from five selection metrics viz., FST, H1, H12, Tajima's D, and nucleotide diversity (π) into a unified measure. The SNP-based DCMS approach offers finer resolution and complements window-based methods by enabling more precise localisation of selection signals and candidate genes. Multiple testing correction was applied at a False Discovery Rate (FDR) threshold of <5% to detect significant genomic regions. Comprehensive gene and quantitative trait loci (QTL) annotation and enrichment analysis of these regions were also performed for each breed. The DCMS analysis identified 21, 10, and 14 novel and breed-specific putative genes in the Chanthangi, Garole, and Deccani breeds, respectively, as well as 10, 28, and 13breed-specific QTL regions. The identified genes and QTLs are associated with diverse phenotypic traits, including growth and muscle development (CNTNAP5, DOCK3), reproduction (TCERG1L, BUB1, UNC5C, C2CD5, BBX), wool trait (TPPP3, P2RY6, FGF10, POU2F1, FAM168A), disease resistance (MTSS1, B4GALNT3), environment adaptation (TRMT12, MAPKAPK3), domestication (LRRC36). The QTLs identified are associated with body conformation (body measurements and bone area), production (milk fat yield), reproduction (total lambs born), disease resistance (hemonchus resistance, foot rot, and pneumonia susceptibility), and health (platelet count and entropion). Our SNP-based DCMS method enabled high-resolution detection of breed-specific selection signatures. It facilitated the discovery of both known and novel genomic regions, candidate genes, and QTLs unique to Indian sheep breeds. This comprehensive approach provides valuable insights into the molecular mechanisms underlying economically important traits and offers a robust foundation for targeted genetic improvement and conservation of indigenous sheep breeds.}, } @article {pmid41881711, year = {2026}, author = {Li, H and Wang, Z}, title = {Molecular Subtype Dictates Survival Outcomes in Encapsulated Papillary Carcinoma of the Breast: A Propensity Score-Matched SEER Analysis Supporting Treatment De-Escalation.}, journal = {Clinical breast cancer}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.clbc.2026.02.012}, pmid = {41881711}, issn = {1938-0666}, abstract = {BACKGROUND: Encapsulated papillary carcinoma (EPC) is a rare breast malignancy. Controversy persists over its classification and whether its prognosis stems from histology or biology. This study clarified the role of molecular subtypes in EPC prognosis and evaluated treatment de-escalation feasibility.

PATIENTS AND METHODS: EPC and contemporary invasive ductal carcinoma (IDC) patients (2010-2019) were identified from the surveillance, epidemiology, and end results (SEER) database. A 1:1 propensity score matching (PSM) balanced baseline characteristics, including age, grade, stage, and molecular subtype. Breast cancer-specific survival (BCSS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression.

RESULTS: We included 165 EPC and 247,581 IDC patients. EPC patients were significantly older with lower grade tumors, less nodal involvement, and higher HR+/HER2- proportions (89.7% vs. 71.1%, P < .001). Before matching, EPC showed superior BCSS (P = .044). After PSM (n = 165 per group), no significant differences were observed in BCSS (P = .207) or OS (P = .733) between groups. Subgroup analysis of HR+/HER2- patients yielded consistent results. Chemotherapy usage was low (10.3%) in EPC with excellent outcomes; radiotherapy was an independent protective factor for survival.

CONCLUSION: EPC's favorable prognosis is primarily driven by its molecular profile (HR+/HER2-) rather than histology. After subtype adjustment, EPC survival is equivalent to IDC. Findings support chemotherapy omission for most EPC patients while emphasizing radiotherapy for local control.}, } @article {pmid41873263, year = {2026}, author = {Agrawal, UK and Jaiswal, S}, title = {Invasive Apocrine Carcinoma in a Young Female With Triple Hormone Receptor Positivity: A Case Report.}, journal = {Cureus}, volume = {18}, number = {2}, pages = {e103977}, pmid = {41873263}, issn = {2168-8184}, abstract = {Apocrine carcinoma (AC) of the breast is a rare histological subtype, classically characterized by androgen receptor (AR) positivity with estrogen receptor (ER) and progesterone receptor (PR) negativity. We report the case of a 35-year-old premenopausal woman who presented with a five-month history of a left retroareolar breast lump associated with intermittent serous nipple discharge. Clinical examination and breast imaging revealed a suspicious lesion, and core needle biopsy suggested invasive ductal carcinoma. The patient underwent nipple-sparing breast conservation surgery with axillary clearance. Histopathological examination demonstrated invasive AC, modified Bloom-Richardson grade 1, without lymphovascular invasion or nodal metastasis. Immunohistochemistry revealed an unusual triple hormone receptor-positive profile (ER-positive, PR-positive, AR-positive), with human epidermal growth factor receptor 2 (HER2) negativity and a low Ki-67 proliferative index. Adjuvant treatment included combination chemotherapy, radiotherapy, and dual hormonal therapy with tamoxifen and an AR inhibitor. This case highlights the diagnostic and therapeutic challenges of hormone receptor-positive AC and underscores the importance of comprehensive immunohistochemical profiling for individualized management.}, } @article {pmid41866577, year = {2026}, author = {Arshad, M and Abdullah, AR and Ismail, F and Yahaya, A and Tan, GC and Chia, SL and Salleh, MSM and Pezzella, F and Tan, KL}, title = {Complete NUB1 depletion in ER - negative breast cancer progression in paired primary-metastatic cases: a case series.}, journal = {Journal of medical case reports}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13256-026-05939-7}, pmid = {41866577}, issn = {1752-1947}, support = {FRGS/1/2019/SKK15/USIM/03/1//Fundamental Research Grant Scheme (FRGS)/ ; }, abstract = {BACKGROUND: NEDD8 ultimate buster 1 is an interferon-inducible tumor suppressor increasingly recognized as a prognostic biomarker in breast cancer. Low cytoplasmic expression correlates with aggressive disease, yet little is known about its dynamics between primary and metastatic estrogen-receptor-negative tumors.

OBJECTIVE: The objective of this report is to compare NEDD8 ultimate buster 1 expression in paired estrogen-receptor-negative primary and metastatic breast cancer tissues, clarifying its role in tumor progression.

CASE PRESENTATION: Two postmenopausal Caucasian women, patient A (ID: 14,024, aged 58 years) and patient B (ID: 20,996, aged 54 years), both diagnosed with estrogen-receptor-negative, human epidermal growth factor receptor 2-negative, grade III invasive ductal carcinoma, underwent NEDD8 ultimate buster 1 immunohistochemical analysis on matched primary breast tumors and corresponding metastatic lymph nodes. Both primary tumors exhibited high nuclear but low cytoplasmic NEDD8 ultimate buster 1, shifting to complete loss in metastases. The patient with higher primary cytoplasmic NEDD8 ultimate buster 1 had longer relapse-free and overall survival.

CONCLUSION: Loss of NEDD8 ultimate buster 1 in metastases may signal a transition from hypoxia-driven nuclear localization to unchecked metastatic progression. These findings highlight NEDD8 ultimate buster 1 as a potential prognostic marker and therapeutic stratifier, warranting larger studies to confirm its mechanistic and clinical relevance.}, } @article {pmid41867707, year = {2026}, author = {Khuu, C and Malek, M and Conlon, SG and Wadey, GP and Trasviña-Arenas, CH and David, SS}, title = {MUTYH cancer-associated variants within the interdomain connector differentially impact glycosylase activity and cellular DNA repair.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.03.03.709415}, pmid = {41867707}, issn = {2692-8205}, abstract = {The base excision repair (BER) glycosylase MUTYH initiates repair of 8-oxo-7,8-dihydroguanine (OG): adenine (A) mispairs to prevent G to T transversion mutations. Inherited biallelic mutations in MUTYH are correlated with the cancer pre-disposition syndrome MUTYH -associated polyposis (MAP) and contribute to an increased lifetime risk of colorectal cancer. Over 1,000 germline and somatic MUTYH variants have been reported that are associated with MAP and other cancers, but for most the functional impact is unknown. Herein, we examined a subset of cancer-associated variants (CAVs) localized in the interdomain connector (IDC), which links the N-terminal adenine excision and C-terminal OG recognition domains via its zinc linchpin motif and serves as a hub for downstream repair interactions. In vitro assays measuring glycosylase activity, lesion affinity, and AP endonuclease stimulation revealed no substantial defects relative to wild-type MUTYH. In contrast, a newly optimized mammalian cell assay revealed some IDC variants exhibit reduced repair. These results suggest that some variants disrupt steps downstream of adenine excision, whereas others impair lesion recognition and base excision. This work underscores the value of independent functional assays for accurately assessing variant dysfunction and classification. Analysis of MUTYH variants highlights the complexity of the roles of MUTYH in preserving genomic integrity.}, } @article {pmid41865649, year = {2026}, author = {Kuang, Y and Zheng, Y and Li, G and Du, Y and Jia, C and Wu, T and Diao, X and Wu, R}, title = {Prediction of recurrence-free survival in patients with invasive ductal carcinoma of the breast on the basis of clinicopathological, conventional ultrasound and contrast-enhanced ultrasound imaging characteristics.}, journal = {Clinical radiology}, volume = {96}, number = {}, pages = {107256}, doi = {10.1016/j.crad.2026.107256}, pmid = {41865649}, issn = {1365-229X}, abstract = {AIM: This study aimed to incorporate clinicopathological, conventional ultrasound (US) and contrast-enhanced US (CEUS) imaging features to establish a predictive model for evaluating recurrence-free survival (RFS) in patients with invasive ductal carcinoma (IDC) of the breast.

MATERIALS AND METHODS: Patients confirmed with IDC in our hospital between 2016 and 2020 were retrospectively analysed. We performed Cox regression analyses based on the clinicopathological and USdata to identify independent factors. A nomogram model was constructed and verified to predict the 1-, 3-, and 5-year RFS. Nomogram performance, calibration, and clinical applicability were evaluated with the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis.

RESULTS: A total of 377 patients were included and divided into training group (n=226) and validation group (n=151). Axillary lymph node burden, oestrogen receptor status, colour Doppler flow imaging blood flow, maximum length diameter on CEUS, and perfusion defects were independent risk factors for poor RFS. The AUC values of nomogram model were 0.876, 0.823, and 0.753 in the training group and 0.731, 0.763, and 0.714 in the validation group. The calibration curves exhibited good concordance between the predicted survival probabilities and the actual values.

CONCLUSION: The nomogram, which integrates clinicopathological and US features, serves as a supplementary prognostic tool for IDC patients. It offers individualised risk stratification to support clinical decision-making, potentially minimising interventions for low-risk patients and prioritising monitoring for high-risk cases, while complementing traditional staging systems.}, } @article {pmid41863187, year = {2026}, author = {Cazenave, MG and Mahiou, K and Elahi, L and Maumy, L and Pauly, L and Guillot, E and Miailhe, G and Pouget, N and Benoit, L and Trotin, M and Bonneau, C}, title = {SENOPAUSE: Evaluation of an ASCO-Derived Clinical Proxy for Axillary Risk Stratification in a Retrospective Cohort.}, journal = {Clinical breast cancer}, volume = {26}, number = {4}, pages = {37-43}, doi = {10.1016/j.clbc.2026.02.013}, pmid = {41863187}, issn = {1938-0666}, abstract = {BACKGROUND: Sentinel lymph node biopsy (SLNB) omission is increasingly considered in carefully selected postmenopausal patients with low-risk, early-stage breast cancer. However, the prevalence of occult nodal disease and wether nodal information alters adjuvant management remain key concerns in real-world implementation.

METHODS: We conducted a retrospective, two-center observational study using an institutional REDCap database. Consecutive patients treated surgically between 2023 and 2024 were screened and a strict proxy of ASCO eligibility criteria for SLNB omission was applied (postmenopausal; HR-positive/HER2-negative; invasive ductal carcinoma; T0 to T1; grade 1 to 2; no neoadjuvant therapy). The primary outcome was the prevalence of pN1 disease within the ASCO-eligible cohort. Secondary outcomes included adjuvant chemotherapy use, whole-breast radiotherapy (WBRT), and availability of genomic testing.

RESULTS: Among 662 screened patients, 211 met all ASCO proxy eligibility criteria. Occult nodal involvement was observed in 20/211 patients (9.5%, pN1). Adjuvant chemotherapy was administered in 10/211 patients (4.7%), while WBRT was delivered in 203/211 (95.7%). Genomic testing was available in 17/211 patients (8.1%) and was predominantly low-risk among those tested (13/17, 76%). Within the pN1 subgroup (n = 20), chemotherapy was administered in 4/20 patients (20%), and genomic testing was available in 8/20 (40%).

CONCLUSION: In a real-world cohort meeting strict ASCO proxy criteria, approximately 1 in ten patients had occult pN1 disease, yet chemotherapy use remained uncommon and WBRT was near-universal. These findings suggest nodal status may have limited impact on downstream adjuvant treatment escalation in highly selected low-risk luminal breast cancers.}, } @article {pmid41858527, year = {2026}, author = {Çetin Tunçez, H and Adibelli, ZH and Havvat, N and Kocatepe Çavdar, D and Altın, L and Bozer, A}, title = {Radiological and Histopathological Predictors of Survival in Neuroendocrine Differentiated Breast Cancer: A Comparative Analysis with NS-IDC.}, journal = {Breast cancer (Dove Medical Press)}, volume = {18}, number = {}, pages = {569083}, pmid = {41858527}, issn = {1179-1314}, abstract = {PURPOSE: This study aims to compare the radiological and immunohistochemical (IHC) features of neuroendocrine differentiated breast cancer (NEBC) with those of non-specific invasive ductal carcinoma (NS-IDC) and to examine the prognostic relevance of these features, including their association with overall survival (OS).

PATIENTS AND METHODS: Patients with histopathologically confirmed NEBC between 2015 and 2022 were retrospectively identified. Inclusion criteria were availability of preoperative mammography, ultrasonography, and magnetic resonance imaging (MRI), along with complete clinical records; patients with missing data were excluded. A randomly selected NS-IDC cohort from the same institutional database served as the comparison group. Histopathology was the reference standard. Imaging was reassessed by two breast radiologists, and pathological specimens were reviewed by an experienced breast pathologist. Statistical analyses were performed using IBM SPSS 26.0, with significance set at p < 0.05.

RESULTS: Eighty-five patients (44 NEBC, 41 NS-IDC) were included. Compared with NS-IDC, NEBC more frequently demonstrated rapid initial enhancement and late washout on MRI (p=0.001 and p=0.009, respectively), and higher progesterone reseptor (PR) expression (p=0.037). Five-year OS did not differ significantly between groups (p = 0.858). Multivariate analysis revealed that the presence of ductal carcinoma in situ (DCIS), T stage, and T2 hyperintensity on MRI emerged as independent predictors of mortality (p = 0.006, p = 0.003, and p = 0.028, respectively).

CONCLUSION: Although NEBC exhibits distinct MRI characteristics and a predominantly hormone-positive IHC profile, survival outcomes were comparable to those of NS-IDC. Notably, T2 hyperintensity on MRI was the strongest imaging feature associated with poorer survival, suggesting a potential role in future prognostic stratification. The modest sample size, prognostic interpretations should be viewed as exploratory. Larger prospective studies are needed to validate these findings.}, } @article {pmid41859720, year = {2026}, author = {Amei, C and Satake, T and Kamisaka, K and Yoshino, R and Noto, M and Taki, K and Tachibana, G and Tsukura, K and Kobayashi, K and Nagai, F and Onoda, S and Matsui, K}, title = {Hemiabdominal Deep Inferior Epigastric Perforator Flap Banking for Contralateral Occult Breast Cancer.}, journal = {Plastic and reconstructive surgery. Global open}, volume = {14}, number = {2}, pages = {e7448}, pmid = {41859720}, issn = {2169-7574}, abstract = {The deep inferior epigastric perforator (DIEP) flap is the gold standard in autologous breast reconstruction. Because abdominal tissue is limited to a single use, metachronous contralateral breast cancer reconstruction frequently necessitates an alternative donor site, raising concerns about symmetry and additional scarring. We propose using a hemi-DIEP flap for the initial reconstruction while preserving the unused contralateral hemi-flap subcutaneously in the abdominal region for future use. The patient is a 69-year-old woman diagnosed with invasive ductal carcinoma of the right breast. The patient underwent a nipple-sparing mastectomy with sentinel lymph node biopsy, followed by immediate breast reconstruction using a hemi-DIEP flap. The unused hemi-DIEP flap was denuded and stored subcutaneously in the lower abdominal region. The abdominal donor site healed with only mild midline thickening, without bulging or cosmetic deformity, resulting in an appearance comparable to a standard DIEP flap harvest. For high-risk patients with contralateral breast cancer, this approach provides a promising autologous breast reconstruction alternative that reduces donor-site morbidity while ensuring optimal symmetry and tissue quality.}, } @article {pmid41861529, year = {2026}, author = {Kim, Y and Lim, J and Kwak, B}, title = {Phenotypic profiles for anticancer drug responses using tumor spheroids.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {198}, number = {}, pages = {119237}, doi = {10.1016/j.biopha.2026.119237}, pmid = {41861529}, issn = {1950-6007}, abstract = {Phenotypic drug discovery enables the evaluation of anticancer drug responses without requiring prior knowledge of molecular targets. Tumor spheroids more accurately recapitulate in vivo tumor architecture compared to conventional monolayer cultures but currently lack standardized drug evaluation criteria. In this study, we fabricated uniform and drug evaluation-optimized tumor spheroids using triple-positive (ER+, PR+, HER2 +) invasive ductal carcinoma cells. Anticancer drugs used in breast cancer were administered at clinically relevant plasma concentrations. We propose drug response evaluation parameters including spheroid size change, morphological features (surface cell size and convexity), and optical transmittance monitored during drug treatment and throughout a defined post exposure observation period. These optical image-based analytical features showed consistent correlations with the respective mechanisms of molecular action and the associated drug response. This study establishes a phenotype-based evaluation system for breast cancer chemotherapy using tumor spheroids, offering a reference model for drug evaluation. Moreover, it proposes quantifiable evaluation parameters for drug screening and provides reference data for assessing investigational compounds, thereby enhancing the utility of spheroids in phenotypic anticancer drug discovery.}, } @article {pmid41852361, year = {2026}, author = {Malick, A and Lebwohl, B and Green, PHR and Lagana, SM and Krishnareddy, S}, title = {Development of Celiac Disease After Immunotherapy: A Case Series.}, journal = {Gastro hep advances}, volume = {5}, number = {4}, pages = {100891}, pmid = {41852361}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: Celiac disease results from a complex immune response to gluten in genetically susceptible individuals. It has been noted to occur with immune checkpoint inhibitor therapies and other novel therapies in prior case reports. In this case series, we report 3 cases of celiac disease in patients receiving therapy for psoriasis, breast cancer, and renal cell carcinoma.

METHODS: Three cases of celiac disease occurring in patients after novel medications were identified by gastroenterologists at a tertiary care center. Informed consent was obtained from all 3 patients. Medical history and clinical data were obtained by review of the electronic medical record.

RESULTS: Celiac disease developed in 3 patients after initiating biologic therapy: a 21-year-old female with psoriasis receiving ixekizumab (interleukin-17 antagonist) and risankizumab (interleukin-23 antagonist); a 49-year-old female with invasive ductal carcinoma of the breast after pertuzumab (human epidermal growth factor receptor 2 antagonist); and an 82-year-old male taking cabozantinib (multityrosine kinase inhibitor) for renal cell carcinoma.

CONCLUSION: We have identified 3 cases of celiac disease that presented after initiating new immune-modulating medications. It is important to consider celiac disease and nonceliac villous atrophy in the differential for diarrhea developing during or after a new therapy as it heavily impacts management and may eliminate the need for alternate therapies that include steroid courses, cessation of therapy, or even gluten-free diet.}, } @article {pmid41853427, year = {2026}, author = {Camejo, N and Amarillo, D and Castillo, C and Olguin, C and Navas, M and Mendez, M and Duran, A and Firpo, Y and Gordienko, T and Herrera, G and Alonso, I and Krygier, G}, title = {Clinical Characteristics and Long-Term Outcomes of Young Women With Breast Cancer: A Multicenter Study From Uruguay.}, journal = {Cureus}, volume = {18}, number = {2}, pages = {e103645}, pmid = {41853427}, issn = {2168-8184}, abstract = {BACKGROUND: Breast cancer in women aged ≤40 years is uncommon but clinically challenging, often associated with aggressive pathological features and advanced-stage diagnosis. In Latin America, real-world data on long-term outcomes in this population remain limited. This study aimed to describe clinicopathological characteristics, treatment patterns, and survival outcomes of young women with breast cancer treated in Uruguay.

METHODS: We conducted a multicenter retrospective cohort study including women aged 18-40 years diagnosed with invasive breast cancer between 2006 and 2024 at two public referral centers. Clinical, pathological, and treatment data were collected from medical records. Overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan-Meier analysis.

RESULTS:  A total of 267 patients were included (mean age at diagnosis, 34.8 years). Invasive ductal carcinoma was the predominant histology (85.8%), with a high proportion of grade III tumors (39.3%). The most common biological subtype was luminal (48.8%), followed by HER2-positive (27.7%) and triple-negative disease (17.2%). Stage II disease was most frequent (40.4%), while 28.7% of patients presented with stage III disease. Modified radical mastectomy was the most commonly performed surgical procedure (38.2%). Most patients received surgery, radiotherapy, and systemic therapy according to recurrence risk. With a median follow-up of 52.3 months, estimated OS was 84.8% at 5 years and 80.9% at 10 years. Survival outcomes differed significantly according to clinical stage but not biological subtype.

CONCLUSIONS:  Young women with breast cancer in Uruguay frequently present with aggressive tumor features and advanced disease at diagnosis. Nevertheless, when managed within a multidisciplinary framework and treated according to current standards of care, long-term survival outcomes are favorable and comparable to international reports. These findings underscore the importance of early detection strategies and equitable access to guideline-based care in middle-income countries.}, } @article {pmid41840060, year = {2026}, author = {Yang, J and Li, Y and Luo, S and Wang, J and Duan, Y}, title = {Decoding clone evolution in HER2 amplified breast cancer through single-cell and spatial transcriptomics analysis of copy number variations.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-44476-7}, pmid = {41840060}, issn = {2045-2322}, support = {82403484//National Natural Science Foundation of China/ ; }, } @article {pmid41841690, year = {2026}, author = {Chawla, B and Jatia, S and Sloan, D and Eduful, J and Mendoza, H and McClear, CA and Tran, J and Csankovszki, G}, title = {Condensin IDC has a Functional ATPase That is Required for X-Chromosome Dosage Compensation in C. elegans.}, journal = {Genetics}, volume = {}, number = {}, pages = {}, doi = {10.1093/genetics/iyag072}, pmid = {41841690}, issn = {1943-2631}, abstract = {Dosage compensation (DC) in C. elegans utilizes a condensin complex that resembles mitotic condensins, but differs by one subunit, DPY-27. DPY-27 replaces SMC-4, one of the Structural Maintenance of Chromosome (SMC) proteins that is responsible for hydrolyzing ATP, required for condensation of DNA and other mitotic condensin functions. To understand if the ATPase function is required in DC, we first demonstrated that DPY-27 is capable of hydrolyzing ATP in vitro. Then, we used CRISPR/Cas9-mediated genome editing to generate an ATPase mutation in dpy-27. Although the mutant protein is expressed and it is incorporated into the condensin IDC complex, this mutation results in a loss of DC. Specifically, we found that without ATPase function, DPY-27 containing condensin IDC has reduced capacity to bind DNA, condense the X chromosomes, and facilitate H4K20me1 enrichment on the X-chromosomes. Our results suggest that condensin IDC, like mitotic condensins, uses ATP hydrolysis to perform its functions, making C. elegans DC a model for how activities attributed to mitotic condensins can be used to regulate gene expression.}, } @article {pmid41835638, year = {2026}, author = {Mainer, S and Lachmayr, H and Lemon, B and Killorin, W}, title = {Breast Cancer Metastasis with a Ureteral Obstruction and Bladder Mass.}, journal = {Cureus}, volume = {18}, number = {2}, pages = {e103428}, pmid = {41835638}, issn = {2168-8184}, abstract = {Breast cancer is the most common cause of cancer mortality in females globally, and a significant proportion of patients develop metastatic disease. Common metastatic sites of breast cancer include bone, lung, liver, and brain. Secondary neoplasms (metastases from other primary sites) represent a minority of all malignant bladder tumors In this report, we describe a case of breast cancer metastasis with ureteral obstruction and bladder mass in a 60-year-old African-American female. For over a decade, this patient was asymptomatic and had been under surveillance following bilateral radical mastectomy for invasive ductal carcinoma (IDC) with adjuvant chemoradiotherapy. Unrelated imaging revealed an incidental finding of right hydronephrosis. Subsequent cystoscopy revealed a bladder mass obstructing the right ureteral orifice. Transurethral resection of a bladder tumor and ureteral stent placement were performed, and the pathology findings favored metastatic breast cancer. The details of the case are intended to help further knowledge of urinary bladder metastases. This case is unusual in that the patient was asymptomatic, her breast cancer type is associated with a lower incidence of bladder metastases, and the bladder was the solitary location of metastasis.}, } @article {pmid41835700, year = {2026}, author = {Oshita, G and Oura, S}, title = {Invasive Ductal Carcinoma of the Breast With an Uncommon Widespread Thick Hyperechoic Pattern: A Case Report.}, journal = {Cureus}, volume = {18}, number = {2}, pages = {e103491}, pmid = {41835700}, issn = {2168-8184}, abstract = {A 77-year-old woman visited our hospital due to a palpable breast mass. Mammography only showed a focal asymmetric density. In addition to one normal-sized lymph node with a punctate hyperechoic pattern, ultrasound showed widespread, thick hyperechoic areas with indistinct margins and adjacent hypoechoic areas. The hypoechoic areas had both an irregular shape and focal internal punctate high echoes on grayscale ultrasound, as well as blood inflow on Doppler ultrasound. Magnetic resonance imaging (MRI) of the mass showed weak high signals on fat-suppressed T2-weighted images and slow initial enhancement followed by persistent enhancement on dynamic studies, highly suggesting the hyperechoic areas to have abundant fat components. Core needle biopsy pathologically showed cancer cells with fat invasion. The patient, therefore, underwent mastectomy and axillary dissection. Postoperative pathological study showed cancer cells spreading in 25-mm sizes in the fat tissue, with microvoids around cancer cell clusters, and two metastatic lymph nodes. Immunostaining of the tumor showed estrogen receptor positivity (Allred score 7), progesterone receptor negativity, human epidermal growth factor receptor type 2 equivocality (fluorescence in situ hybridization (FISH) negative), and a Ki-67 labeling index of 35%. The patient has been well on adjuvant endocrine therapy without any events for three years. A diagnostic physician should note that microvoids just around cancer cell clusters may make the internal echoes of the metastatic lymph node high, and widespread cancer infiltration into the fat tissue generates an uncommon, widespread, thick hyperechoic pattern.}, } @article {pmid41836045, year = {2026}, author = {Masuda, Y and Aoki, M and Tanaka, M and Koga, Y and Eto, K and Yoshinaga, Y and Sato, T}, title = {Necrosis of a Metastatic Axillary Lymph Node in Breast Cancer Possibly Induced by Fine-Needle Aspiration Cytology: A Case Report.}, journal = {Case reports in oncology}, volume = {19}, number = {1}, pages = {349-355}, doi = {10.1159/000550529}, pmid = {41836045}, issn = {1662-6575}, abstract = {INTRODUCTION: Axillary lymph node metastasis is a major prognostic factor for breast cancer. In rare cases, metastatic lesions may undergo necrosis.

CASE PRESENTATION: A 69-year-old woman with a history of rheumatoid arthritis and ovarian tumor surgery was diagnosed with right-sided breast cancer (cT1N1M0) following abnormal screening mammography. Core needle biopsy revealed invasive ductal carcinoma (estrogen receptor: >95%, progesterone receptor: <1%, human epidermal growth factor receptor 2: 2+ [fluorescence in situ hybridization-negative], MIB-1: 18%). Fine-needle aspiration (FNA) cytology of an enlarged axillary lymph node confirmed metastasis. Mastectomy and axillary dissection were performed approximately 3 months after the FNA procedure without preoperative treatment, suggesting a temporal relationship between aspiration and subsequent necrosis. Histopathological analysis revealed no viable cancer cells in the lymph nodes but uniform eosinophilic necrosis with partial epithelial-like structures in one node. Immunohistochemistry showed positivity for epithelial membrane antigen, AE1/AE3, estrogen receptor, and GATA3, and histiocytes surrounding the necrotic area were positive for cluster of differentiation 68 and 163. These findings suggested that the metastatic carcinoma had undergone necrosis, likely triggered by FNA. The Oncotype DX score was 33; however, the patient chose endocrine therapy alone. No recurrence has been observed at the time of writing, 18 months after surgery.

CONCLUSION: This case highlights a rare instance of necrosis in a metastatic lymph node, possibly induced by FNA. Immunohistochemistry is essential to confirm the diagnosis and avoid misinterpretation as a granulomatous or infectious process.}, } @article {pmid41836257, year = {2026}, author = {Fedeli, F and Bistika, M and Ascione, F and Marangelo, A and Guzzi, FL and Schrader, J and Harris, AG and Pellegata, NS}, title = {Anti-secretory and anti-proliferative actions of next-generation dual subtype 2 and 5 somatostatin receptor ligands in neuroendocrine tumor models.}, journal = {Frontiers in oncology}, volume = {16}, number = {}, pages = {1766563}, doi = {10.3389/fonc.2026.1766563}, pmid = {41836257}, issn = {2234-943X}, abstract = {INTRODUCTION: First-generation somatostatin receptor ligands (SRLs) mainly target SSTR2, whereas neuroendocrine tumors (NETs) often express multiple SSTR subtypes, frequently SSTR5. Dual SSTR2/SSTR5 targeting may enhance anti-hormonal and antiproliferative effects. We evaluated five novel dual SSTR2/SSTR5 agonists (SMTR-001 to SMTR-005) in preclinical NET models to assess their anti-secretory and anti-proliferative effects in representative preclinical NET models.

METHODS: The human insulinoma-derived NT-3 cell line and the murine AtT-20 corticotroph cell line, both expressing SSTR2 and SSTR5, were treated with 1-50 nM of the novel SRLs or reference agents (octreotide, pasireotide). Insulin and ACTH secretion were quantified by ELISA and cell viability was measured after 72 h (AtT-20) or 5 days (NT-3). A putative lead compound, SMTR-002, was further tested in 3D spheroid cultures of NT-3 cells. Intracellular cAMP modulation was evaluated after forskolin stimulation in AtT-20 cells.

RESULTS: In NT-3 cells, all dual SRLs inhibited insulin secretion (-65% to -95%), with SMTR-002, SMTR-004, and SMTR-005 showing significantly greater inhibition than octreotide at 10 nM. Each compound also reduced cell proliferation (-30% to -44%). In 3D cultures of NT-3 cells, SMTR-002 reduced insulin secretion to a degree comparable to octreotide but, unlike octreotide, significantly decreased cell proliferation. In AtT-20 cells, four novel SRLs significantly reduced ACTH secretion (-11% to -69%), with SMTR-001 and SMTR-004 showing efficacy comparable to pasireotide. SMTR-002 and SMTR-003 demonstrated the greatest antiproliferative effects (-53% and -48% at 10 nM). In AtT-20 cells, SMTR-002 also suppressed forskolin-induced cAMP accumulation more strongly than reference SRLs.

CONCLUSION: Dual SSTR2/SSTR5 agonists exhibit antisecretory and antiproliferative activity in NET models that was similar or even superior to reference SRLs. These findings support their further development as next-generation SRLs for SSTR2/5-expressing tumors.}, } @article {pmid41831716, year = {2026}, author = {Hornuss, D and Mathé, P and Giesen, R and Escolà-Vergé, L and Isler, B and Bartoletti, M and Lamy, B and Wagner, D and Kern, WV and Rieg, S and , }, title = {Possible quality indicators for clinical infectious diseases consultations - results from a hybrid Delphi-nominal group approach and scenario study.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2026.03.006}, pmid = {41831716}, issn = {1469-0691}, abstract = {SCOPE: Infectious diseases consultation (IDC) services contribute to optimized infection management and are associated with improved outcomes, particularly in difficult-to-treat infections. However, there is uncertainty on how IDC should best be performed, reported, and communicated to achieve optimal impact and adherence. This consensus paper aims to provide structured expert consensus guidance on possible quality indicators (QIs) for IDC activities and reports.

METHODS: A systematic literature review was performed but yielded no pertinent findings. Based on experience in clinical practice, the authors proposed 30 potential QIs in four major IDC domains. A Delphi-based anonymous online survey among ID specialists and clinical microbiologists was conducted with two evaluation rounds. QIs were evaluated on 5-point Likert scales (-2, -1, 0, +1, +2). Five possible QIs were additionally evaluated using scaling bars (from 0: only focused assessment/basic evaluation to 10: complete assessment/detailed evaluation). Consensus for a QI was reached when ≥ 80% of the responses showed a strong agreement (+2) in the first round and when ≥ 80% of responses showed a strong agreement (+2) or ≥ 85% agreement for +1 or +2 on the Likert in the second round. Three clinical case scenarios were included to estimate the time required for IDC. Additionally, options for (automated) preparation and artificial intelligence (AI) support for IDC reports were assessed.

The survey was completed by 51 IDC experts of 17 different countries in the first round and by 26 experts of 10 countries in the second round. Consensus was reached for 25 possible QIs categorized in four major domains (history and risk factors, bedside assessment, recommendations, and reporting), emphasizing a thorough conduct and documentation of IDC activities. Required time for IDC ranged from 35 minutes for simple or follow-up consultations to 55 minutes for complex cases. Almost half of 20 IDC procedures were judged as amenable to benefit from automation and AI support. This consensus paper proposes a comprehensive set of possible QIs for IDC services. The integration of these indicators may standardize evaluation, enhance the effectiveness of IDC, and facilitate international benchmarking. Further research is required to validate these QIs in diverse clinical settings and explore the integration of AI tools in clinical workflows.}, } @article {pmid41825963, year = {2026}, author = {Westbrook, JI and McMullan, RD and Fitzpatrick, E and Merchant, A and Wiggins, M and Aryal, N and Raban, MZ and Gardo, A and Lapointe, C and Williams, P and Li, L}, title = {Is independent double-checking superior to single-checking in medication administration error detection? A randomised controlled simulation trial.}, journal = {BMJ quality & safety}, volume = {}, number = {}, pages = {}, doi = {10.1136/bmjqs-2025-019743}, pmid = {41825963}, issn = {2044-5423}, abstract = {BACKGROUND: Double-checking of medication administration is a safety practice used in hospitals around the world. Independence is recommended as the key to effectiveness. Independent double-checking (IDC) requires each nurse to separately check the five rights (eg, right drug, dose). There is no empirical evidence that IDC is more effective in error detection than a single-nurse check.

OBJECTIVES: To compare the effectiveness of IDC versus single-checking in detecting medication errors during administration, assess the time required and explore factors influencing performance, including nurse experience and social dynamics.

METHODS: A multicentre randomised controlled simulation trial with 82 nurses from two paediatric hospitals. Forty-one 2-hour simulations each involved two nurses exposed to single-checking and IDC conditions administering medication sets containing embedded errors. Condition order and medication sets were randomised. Primary outcomes were error detection and time taken. Multivariable models compared primary outcomes by condition. Secondary analyses examined the influence of nurse experience and social loafing, defined as reduced individual performance when working in pairs. Social loafing was assessed by comparing error detection performance when nurses single-checked with error detection in the role of first checker in IDC.

RESULTS: Across 1160 dose administrations with 640 error detection opportunities, nurses detected 72.2% (95% CI 68.6 to 75.5) of errors. Overall, IDC yielded an 11% higher error detection rate than single-checking (adjusted incident rate ratio (aIRR): 1.11, 95% CI 1.01 to 1.21; p=0.02; 77.7% (95% CI 72.9 to 81.9) for IDC vs 66.3% (95% CI 60.9 to 71.4) for single checks). However, this benefit was limited to experienced nurses. Among early career nurses (<5 years clinical experience), IDC produced no significant improvement in error detection (aIRR: 0.98, 95% CI 0.86 to 1.11; p=0.7; IDC 67.0% (95% CI 57.3 to 75.4) vs single checking 73.0% (95% CI 63.6 to 80.7) error detection). In contrast, experienced nurses showed a 26% improvement in error detection with IDC (aIRR 1.26, 95% CI 1.11 to 1.44; p<0.001; IDC 82.5% (95% CI 77.0 to 86.8) vs single-checking 63.2% (95% CI 56.5 to 69.4)). Evidence of social loafing was observed, particularly among early career nurses whose error detection performance was 26.0% higher when single-checking compared with their performance in the role of first checker in IDC. IDC required significantly more time per medication set (mean difference 4.96 min (95% CI 2.10 to 7.83; p<0.001)).

CONCLUSIONS: IDC improved error detection for experienced nurses, but not for early career nurses. Given its inconsistent benefits, resource demands and susceptibility to social loafing, IDC may be unsuitable as a universal safety strategy. Strengthening single-checking competence and supporting clinical judgement may offer a more effective, scalable approach to improving medication safety.}, } @article {pmid41825139, year = {2026}, author = {Icht, M and Tayar, M and Mikulincer, M and Taitelbaum-Swead, R and Ben-David, BM}, title = {Parent-therapist therapeutic alliance - a neglected factor in pediatric speech-language intervention: A longitudinal study.}, journal = {Journal of communication disorders}, volume = {121}, number = {}, pages = {106637}, doi = {10.1016/j.jcomdis.2026.106637}, pmid = {41825139}, issn = {1873-7994}, abstract = {BACKGROUND: The therapeutic alliance (TA) has been widely used to explain variations in psychotherapy, but its role in pediatric speech-language therapy remains underexplored.

AIMS: This longitudinal study examined whether the TA between speech-language therapists (SLTs) and parents of children undergoing speech-language intervention predicted therapeutic outcomes and whether it moderated the effects of parental psychological factors.

METHODS: Forty-one parents of children aged 3-12 years and 12 SLTs participated in a 12-week intervention. SLTs rated child disorder severity at onset, TA after two sessions, and therapeutic outcomes at completion. At the onset of therapy, parents completed measures of caregiving style, perceptions of their child, and child-related emotions. Hierarchical regression models assessed predictors of therapeutic outcomes, and moderation analyses tested interactions between TA and parental variables.

RESULTS: Background variables explained 18% of the variance in therapeutic outcomes. Adding parental psychological variables increased the explained variance to 40%, and including TA significantly increased it to 50%. Stronger TA predicted better therapeutic outcomes, while greater disorder severity, compulsive caregiving, and highly positive parental perceptions of the child predicted poorer outcomes. Importantly, the moderation analysis indicated that a strong TA buffered the negative impact of compulsive caregiving on therapeutic outcomes.

CONCLUSIONS: Findings underscore the role of early parent-SLT alliance in promoting therapeutic success and mitigating the negative effects of intrusive parenting. Clinicians should prioritize building a strong TA with parents and address parental psychological factors as part of pediatric speech-language therapy. Future research should include parent-reported alliance and independent outcome measures, in longitudinal multi-informant designs.}, } @article {pmid41823999, year = {2026}, author = {Mercado-Evans, V and Levett, K and Diwan, AH and Huttenbach, Y}, title = {Radiation-Induced Angiosarcoma of the Breast With Diffuse GATA-3 Positivity: A Possible Diagnostic Pitfall.}, journal = {The American Journal of dermatopathology}, volume = {}, number = {}, pages = {}, doi = {10.1097/DAD.0000000000003270}, pmid = {41823999}, issn = {1533-0311}, abstract = {Radiation-induced angiosarcomas of the breast are rare malignancies that carry a poor prognosis. Expected immunohistochemical profiles reflect vascular differentiation: CD31 and ERG positivity, with variable CD34 positivity. GATA-3 is a transcription factor important for mammary gland development, playing a role in ductal epithelial cell differentiation. It serves as an important immunohistochemical marker of breast-origin carcinomas and is not associated with angiosarcomas. We report a case of an 83-year-old woman with breast radiation-induced angiosarcoma, which displayed diffuse GATA-3 positivity, which has not been previously reported in the literature. The patient had a history of inflammatory carcinoma of the left breast (histologically a high-grade invasive ductal carcinoma of no special type) treated with lumpectomy and radiation therapy. Ten years later, she presented with skin thickening and 3 tender nodules (ranging from 0.6 to 2 cm) confined to the left breast skin. Biopsy showed a high-grade, epithelioid dermal neoplasm with abundant hemorrhage. The tumor was diffusely positive for GATA-3, CD31, and ERG, with focal CD34 positivity. Strong and diffuse MYC positivity with an increased Ki-67 proliferative index was also demonstrated. CK5/6, AE1/AE3, MOC-31, CK5/6, CK7, ER, PR, S100, Melan A, and synaptophysin were all negative. The histopathologic features and immunohistochemical profile were consistent with radiation-induced angiosarcoma. With this case, we highlight a diffusely positive GATA-3 staining pattern in radiation-induced angiosarcoma of the breast, which has not been previously documented. Awareness of this potential staining pitfall is essential for arriving at the correct diagnosis particularly when recurrent or metastatic high-grade carcinoma is a diagnostic consideration.}, } @article {pmid41822488, year = {2026}, author = {Song, C and Quan, Y and Shan, Y and Chen, Y and Du, J and Li, K and Li, N}, title = {Prognostic significance and regulatory role of ACOT7 in the tumor immune microenvironment of breast invasive ductal carcinoma: a multi-omics analysis.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1735908}, pmid = {41822488}, issn = {1664-3224}, mesh = {Humans ; *Tumor Microenvironment/immunology/genetics ; Female ; *Breast Neoplasms/immunology/genetics/mortality/pathology/metabolism ; Prognosis ; *Carcinoma, Ductal, Breast/immunology/genetics/mortality/pathology/metabolism ; Gene Expression Regulation, Neoplastic ; *Biomarkers, Tumor/genetics ; Protein Interaction Maps ; *Thiolester Hydrolases/genetics/metabolism ; Computational Biology/methods ; Gene Expression Profiling ; Kaplan-Meier Estimate ; Multiomics ; }, abstract = {BACKGROUND: Invasive Ductal Carcinoma (IDC), which is the most common histological subtype of breast cancer, is highly aggressive and progresses rapidly. Acyl-CoA thioesterase 7 (ACOT7) is a key regulator of cell survival, the cell cycle, and lipid and glucose metabolism. However, the mechanism of ACOT7 in IDC is still unclear. Our study aims to investigate the clinical significance of ACOT7 in IDC.

METHODS: A comparative analysis of ACOT7 expression in IDC and matched normal tissues was performed using the limma R package on datasets from GEO and TCGA. Prognostic evaluation was conducted using Kaplan-Meier survival curves from the Kaplan-Meier plotter. Furthermore, a protein-protein interaction (PPI) network of ACOT7 was constructed by GeneMANIA, and the correlation between ACOT7 expression and the level of tumor immune infiltration was explored via the TIMER database. In order to further analyze the biological functions of ACOT7, we performed Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and Gene Set Enrichment Analysis (GSEA) using the clusterProfiler package. To validate this, we profiled ACOT7 mRNA expression across clinical samples (tumor and adjacent normal) and in vitro models (cell lines) via Real-Time quantitative Polymerase Chain Reaction (RT-qPCR).

RESULTS: Bioinformatic analysis of public databases revealed that ACOT7 mRNA expression was significantly upregulated in IDC patients compared to normal tissues. Elevated ACOT7 expression was associated with poorer overall survival, a finding further validated in cell lines and clinical tissue samples. Furthermore, ACOT7 transcriptional levels showed a significant correlation with the degree of tumor immune infiltration. Functional enrichment analysis indicated that ACOT7 is primarily involved in cancer-related regulation, autoimmune diseases, and multiple metabolic pathways.

CONCLUSION: Our study indicates that elevated ACOT7 expression is a significant marker of adverse clinical outcomes. This effect it likely mediated through the remodeling of the tumor immune microenvironment and the reprogramming of metabolic pathways, which collectively fuel the malignant procession of IDC. These results provide a solid theoretical foundation for targeting ACOT7 as both a prognostic biomarker and a potential therapeutic target in IDC.}, } @article {pmid41821903, year = {2026}, author = {Liu, Y and Duan, X and Zheng, Z and Cheng, G and Zhang, X and Zhao, J}, title = {Case Report: long-term survival of a male patient with breast cancer complicated by lung adenocarcinoma treated with individualized therapy.}, journal = {Frontiers in oncology}, volume = {16}, number = {}, pages = {1780512}, pmid = {41821903}, issn = {2234-943X}, abstract = {Male breast cancer (MBC) is a rare malignant tumor with unique clinical characteristics, accounting for only approximately 1% of all breast cancer cases. Although its pathological features are similar to those of female breast cancer (FBC), significant differences exist in the clinical manifestations, diagnosis, and prognosis of MBC. This article reports a case of a male patient with stage IV lung cancer complicated by invasive ductal carcinoma of the breast, which is extremely rare in MBC. The particularity of this case lies in the sequential occurrence of two malignant tumors, highlighting the importance of early identification of MBC to improve the overall prognosis of patients. Through detailed analysis of this case, we found that the potential pathogenic mechanism of MBC needs further investigation, and clinicians must maintain a high degree of vigilance when evaluating patients with existing malignant tumors to promptly identify potential coexisting tumors. We call for enhanced awareness of MBC in clinical practice to achieve early diagnosis and treatment, thereby improving patient survival rates.}, } @article {pmid41821026, year = {2026}, author = {Möser, C and Prystupa, K and Schön, M and Yurchenko, I and Bódis, KB and Huttasch, M and Michelotti, F and Kupriyanova, Y and Schrauwen-Hinderling, V and Granata, C and Bönhof, GJ and Strom, A and Herder, C and Dörr, D and Trenkamp, S and Heilmann, G and Bobrov, P and Straßburger, K and Szendroedi, J and Cramer, M and Polzin, A and Jung, C and Kelm, M and Burkart, V and Wagner, R and Roden, M and Zaharia, OP}, title = {Cohort profile: The DIabetes and ST-segment Elevation Myocardial Infarction (DISTEMI) Study.}, journal = {Cardiovascular diabetology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12933-026-03097-0}, pmid = {41821026}, issn = {1475-2840}, abstract = {BACKGROUND: Humans with type 2 diabetes and/or metabolic dysfunction-associated steatotic liver disease (MASLD) are at higher risk of ST-segment elevation myocardial infarction (STEMI) and worse prognosis. However, mechanisms, prognostic factors and risk subtypes in humans with STEMI and (pre)diabetes with or without MASLD, are not fully understood.

METHODS: The DIabetes and ST-segment Elevation Myocardial Infarction (DISTEMI) study is a prospective longitudinal cohort study, recruiting humans with different degrees of glucose tolerance after recent STEMI. This cohort study has the primary objective to detect changes in glycemia and insulin sensitivity derived from the oral glucose tolerance test (OGTT) and their relationships to cardiac function. Secondary objectives address tissue-specific insulin sensitivity and organ function, focusing on adipose tissue, liver and heart. Exploratory objectives comprise multiomic analyses and measures of mitochondrial function and quality of life. At 2 and 12 months after STEMI, participants undergo comprehensive cardiometabolic phenotyping (OGTT, modified Botnia clamp-test, magnetic resonance imaging/spectroscopy/elastography, high-resolution respirometry). Magnetic resonance-based techniques are employed to assess cardiovascular function and structure, adipose tissue distribution, skeletal muscle and hepatic lipid deposition and fibrosis, and hepatic energy metabolism. Exploratory analyses include multiomics of blood, urine, and stool samples. Multiomics analyses shall allow detecting biomarkers for stratification of cardiovascular disease risk. Currently, 100 participants have been included in DISTEMI, of whom 29% have type 2 diabetes.

CONCLUSION: The DISTEMI study integrates comprehensive cardiometabolic phenomic with multiomic profiling to identify cardiometabolic STEMI subtypes and predictors of outcomes, and to improve precision risk stratification and targeted prevention.

TRIAL REGISTRATION: NCT05046483.}, } @article {pmid41819611, year = {2026}, author = {Wobker, SE and Williamson, SR and Kenigsberg, A and Muthusamy, S and Smith, SC}, title = {Intraductal histiocytes as a simulant of intraductal carcinoma of the prostate.}, journal = {American journal of clinical pathology}, volume = {165}, number = {3}, pages = {}, doi = {10.1093/ajcp/aqag004}, pmid = {41819611}, issn = {1943-7722}, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/diagnosis ; Retrospective Studies ; Aged ; Middle Aged ; *Histiocytes/pathology ; Diagnosis, Differential ; Immunohistochemistry ; *Carcinoma, Ductal/pathology/diagnosis ; Aged, 80 and over ; *Carcinoma, Intraductal, Noninfiltrating/pathology/diagnosis ; }, abstract = {OBJECTIVE: Contemporary reporting guidelines require assessment for intraductal carcinoma of the prostate (IDC-P), given its recognition as an adverse prognostic factor. While several benign and malignant mimickers of intraductal carcinoma have been reported and studied, the potential for intraductal aggregates of histiocytes to simulate or complicate assessment of this process has not been addressed in the literature.

METHODS: The authors performed a retrospective multi-institutional review of challenging prostate lesions in which intraductal histiocytic aggregates simulated involvement by IDC-P. Pathology reports and slides were reviewed by 3 fellowship-trained genitourinary pathologists, and clinicopathologic features, immunohistochemistry use, and relative difficulty of the diagnosis were assessed.

RESULTS: A total of 47 cases of intraductal histiocytes simulating IDC-P were identified, including 27 needle biopsy, 9 transurethral resection, and 6 radical prostatectomy cases. Overall, 19 cases showed histiocytic aggregates in cases with carcinoma, while 28 occurred in otherwise benign settings. Immunohistochemistry was performed in 14 cases for resolution of the diagnosis. When categorized by the authors in terms of difficulty of the diagnosis, 20 of 47 cases were considered "moderate" or "difficult."

CONCLUSIONS: Based on their solid appearance spanning an intact duct, aggregates of histiocytes within prostatic ducts may closely simulate IDC-P. Given the prognostic significance of IDC-P, this potential pitfall merits consideration and targeted use of immunohistochemistry in challenging cases.}, } @article {pmid41818097, year = {2026}, author = {Potu, SR and Gumdal, V and Koppaka, D and Natti, HS and Rapole, PS and Syed, TAH}, title = {Clinicopathological Spectrum and Biomarker Profile of Male Breast Cancer: A Retrospective Study from a Tertiary Care Center in South India.}, journal = {The Journal of the Association of Physicians of India}, volume = {74}, number = {3}, pages = {56-58}, doi = {10.59556/japi.74.1427}, pmid = {41818097}, issn = {0004-5772}, mesh = {Humans ; *Breast Neoplasms, Male/pathology/therapy/diagnosis/metabolism ; Retrospective Studies ; Male ; India/epidemiology ; Middle Aged ; Adult ; Aged ; *Biomarkers, Tumor/metabolism ; Tertiary Care Centers ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Neoplasm Staging ; }, abstract = {INTRODUCTION: Male breast cancer (MBC) accounts for <1% of breast malignancies yet often presents at advanced stages, particularly in low- and middle-income countries where awareness is limited. This study sought to define the clinicopathological spectrum, biomarker profile, and treatment outcomes of MBC in a South Indian tertiary cancer center.

OBJECTIVES: To analyze the demographic features, clinical presentation, pathological characteristics, biomarker distribution, treatment modalities, and outcomes of MBC cases managed at our center between 2019 and 2025.

MATERIALS AND METHODS: We retrospectively analyzed all male patients with histologically confirmed breast carcinoma managed between 2019 and 2025 at ESIC Medical College and Hospital, Hyderabad. Demographic, clinical, pathological, biomarker, and treatment data were retrieved from hospital records and supplemented by follow-up contact.

RESULTS: A total of 15 patients (mean age 60 years, range 31-74) were identified. Median delay from symptom onset to diagnosis was 6 months. All presented with a retroareolar mass, frequently accompanied by nipple retraction or skin changes. Most patients had advanced disease: Stage III (n = 9, 60.0%) and Stage IV (n = 4, 26.7%). Invasive ductal carcinoma was universal. Hormone receptor positivity was seen in 80%, HER2 positivity in 40%, and a triple-positive phenotype in 26.7%. Treatment strategies were stage- and biomarker-driven: 86.7% underwent surgery, endocrine therapy was prescribed for all HR+ cases, HER2-directed therapy was delivered when feasible, and CDK4/6 inhibitors were used in selected advanced HR+ tumors. At last follow-up, 9 patients (60%) remained alive with disease control, while 2 succumbed to progression.

CONCLUSION: MBC in this cohort was characterized by delayed diagnosis, advanced presentation, and a high prevalence of HER2-positive tumors. Multimodality, biomarker-guided therapy achieved durable control in many patients, underscoring the urgent need for awareness initiatives, earlier detection, and equitable access to targeted therapies in India.}, } @article {pmid41817646, year = {2026}, author = {Khattak, A and Khan, S and Nauman, F and Sabeen, I and Khan, A}, title = {Association of genetic variation in TLR4 and TLR9 genes with susceptibility to invasive ductal breast carcinoma.}, journal = {Molecular biology reports}, volume = {53}, number = {1}, pages = {}, pmid = {41817646}, issn = {1573-4978}, } @article {pmid41817380, year = {2026}, author = {Kane, BL and Gouldman, KP and Yu, JL}, title = {Characterizing inspiratory duty cycle compensation to flow limited breathing during drug-induced sleep endoscopy in obstructive sleep apnea.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {}, number = {}, pages = {}, doi = {10.1152/japplphysiol.01076.2025}, pmid = {41817380}, issn = {1522-1601}, support = {UL1TR002378//HHS | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; KL2TR002381//HHS | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; 11-SRG-24//Sleep Research Society (SRS)/ ; }, abstract = {Rationale: Inspiratory duty cycle (IDC), the fraction of inspiratory time relative to total breath duration, serves as an adaptive response to flow limited ventilation in obstructive sleep apnea (OSA). IDC compensation remains incompletely characterized in the context of OSA pathophysiology. We studied the relationship of IDC and flow-limited breathing in OSA during drug induced sleep endoscopy (DISE). Methods: Eighty-two adults with OSA underwent DISE with continuous positive airway pressure (CPAP) titration. Airflow (VI), tidal volume (TV), and IDC were measured across varying levels of flow-limited breathing. Airway collapsibility was assessed by pharyngeal opening (Popen) and critical closing pressures (Pcrit). IDC compensation was quantified as the slope of IDC versus normalized TV (%PopenTV), representing the degree of IDC increase to declining ventilation. Patients were classified as high versus low IDC compensators based on this slope metric and differences in Popen and Pcrit were compared between groups. Results: As CPAP increased from flow-limited to non-flow-limited breathing, IDC decreased by 20% while TV and ventilation more than doubled. IDC compensation varied among subjects with stronger compensators exhibiting higher airway collapsibility (Popen = 10.2 vs. 8.2cmH2O; p = 0.01, Pcrit = 4.2 vs. 3.0cmH2O; p = 0.03). Conclusions: IDC compensation reflects a physiological response that helps maintain ventilation under flow-limited conditions. Greater airway collapsibility was associated with stronger IDC compensation, reflecting the capacity of the respiratory system to tolerate increased mechanical load. DISE provides a unique experimental platform to quantify ventilatory timing responses, advancing our mechanistic understanding of respiratory compensation in OSA.}, } @article {pmid41815159, year = {2026}, author = {Liu, J and Li, X and Li, Z and Zhang, R and Li, X and Feng, K and Zhang, W and He, J and Zhang, H}, title = {Development and validation of a ferroptosis-related gene signature for prognostic prediction and therapeutic target identification in invasive lobular carcinoma.}, journal = {Translational cancer research}, volume = {15}, number = {2}, pages = {105}, pmid = {41815159}, issn = {2219-6803}, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) accounts for 15% of breast cancers and presents challenges such as chemotherapy resistance and poorer survival outcomes compared to other subtypes. While often managed similarly to invasive ductal carcinoma (IDC), ILC requires tailored approaches due to its distinct biology. Ferroptosis, an iron-dependent form of cell death, shows potential in overcoming therapeutic resistance but remains unexplored in ILC. This study aimed to identify ferroptosis-related molecular subtypes, develop a robust gene signature using machine learning, construct an integrated prognostic model, and uncover potential therapeutic targets for ILC.

METHODS: This study integrated data from a total of 490 patients with ILC across four datasets from The Cancer Genome Atlas (TCGA), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), and Gene Expression Omnibus (GEO). The TCGA cohort was utilized for model development, while the remaining cohorts served for independent external validation. ILC samples were classified into two subtypes based on the expression levels of ferroptosis-related genes via consensus clustering. The associations between the subtypes and the tumor microenvironment (TME), biological function, and mutation were assessed. A ferroptosis-related gene signature (FRGS) was developed using the integration of machine learning. A prediction model was subsequently constructed by combining the FRGS with clinical features. Sensitivity analysis and molecular docking were used to identify potentially effective targets and drugs.

RESULTS: We identified two ferroptosis-related subtypes and found that Cluster 2 had increased immune cell infiltration. By integrating machine learning, we identified 10 hub biomarkers of ILC and developed a FRGS. The FRGS was proven to be an independent risk factor for overall survival. Combining the FRGS with clinical features, a stable and superior ILC prognostic model was constructed. Sensitivity analysis and molecular docking revealed that KLRB1 and SERPINB5 are hypothesis-generating targets and that rapamycin and AZD5582 are hypothesis-generating drug candidates for the treatment of ILC.

CONCLUSIONS: By integrating multi-omics analysis, machine learning and molecular docking, we established a robust prognostic model for ILC, revealed two distinct ferroptosis-related molecular subtypes, and identified potential therapeutic targets and candidate drugs. These findings may help advance the development of personalized medicine and targeted therapies for ILC.}, } @article {pmid41814294, year = {2026}, author = {Ding, H and Dong, Z}, title = {A novel multimodal framework integrating pathomics, deep learning, and machine learning for breast cancer histological grades classification.}, journal = {Diagnostic pathology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13000-026-01769-9}, pmid = {41814294}, issn = {1746-1596}, } @article {pmid41809087, year = {2026}, author = {Matsutani, T and Nishiwaki, N and Kakishita, T and Kobatake, T and Ohta, K and Hato, S}, title = {Ascitic Fluid Cytology Provides Diagnostic Clues in a Case of Gastric Metastasis from Invasive Lobular Carcinoma of the Breast.}, journal = {Surgical case reports}, volume = {12}, number = {1}, pages = {}, pmid = {41809087}, issn = {2198-7793}, abstract = {INTRODUCTION: Breast cancer metastasis to the gastrointestinal tract is rare, and invasive lobular carcinoma (ILC) shows a higher propensity for dissemination than invasive ductal carcinoma. Accurate diagnosis is often challenging because of nonspecific clinical and pathological findings.

CASE PRESENTATION: A 53-year-old woman presented to our hospital with a diagnosis of gastric cancer discovered during gastrointestinal cancer screening. Fourteen years earlier, she had undergone a right mastectomy for ILC and subsequently received treatment for local recurrence and bone metastasis. The gastric lesion was initially diagnosed as primary gastric cancer, and adjuvant chemotherapy was administered after gastrectomy. However, postoperative ascites gradually worsened. Five years after gastrectomy, cytological examination of the ascites revealed tumor cells positive for GATA3 and estrogen receptor, and negative for E-cadherin, leading to a diagnosis of peritoneal metastasis from breast cancer.ILC is characterized by a loss of E-cadherin and diffuse metastatic patterns, including peritoneal and gastric involvement. This case highlights the diagnostic difficulty of differentiating primary gastric cancer from metastatic breast cancer. Although tumor markers and imaging suggested gastric cancer recurrence, cytological examination revealed otherwise. Ascitic fluid cytology is essential for definitive diagnosis, emphasizing its diagnostic value for patients with ambiguous gastric lesions and a history of breast cancer.

CONCLUSIONS: Metastasis should be considered in the differential diagnosis of patients with prior breast cancer presenting with gastric lesions. Ascitic fluid cytology can be a useful adjunct for an accurate diagnosis, guiding appropriate treatment, and avoiding unnecessary interventions.}, } @article {pmid41804625, year = {2025}, author = {Vasari, L and Špoljarić Carević, S and Tomić Babić, L and Bakula, M}, title = {A Rare Case of Paraneoplastic Raynaud's Phenomenon and Uveal Melanoma.}, journal = {Acta dermatovenerologica Croatica : ADC}, volume = {33}, number = {2}, pages = {89-91}, pmid = {41804625}, issn = {1847-6538}, mesh = {Humans ; *Melanoma/complications/diagnosis ; *Raynaud Disease/etiology/diagnosis ; Middle Aged ; Female ; Uveal Melanoma ; *Uveal Neoplasms/complications/diagnosis ; *Paraneoplastic Syndromes ; }, abstract = {Raynaud's phenomenon (RP) presents as acral skin pallor, cyanosis, and erythema, usually after cold exposure or emotional stress. Symptoms of RP affect 3-5% of the general population, with the incidence four times higher in women than in men. Paraneoplastic RP is extremely rare and is thought to involve plasma hyperviscosity and blood hypercoagulability, which are present in patients with malignant diseases. Paraneoplastic RP often presents abruptly and, besides changes in skin color, it includes erosions, ulcerations, and necrosis, resulting in severe pain. We present a case of a 62-year-old female patient who suddenly developed symptoms of RP, characterized by periodic skin pallor without erosions or associated pain in all fingers, lasting 10-15 minutes after cold exposure. She was diagnosed with uveal melanoma three months prior and was also in a 14-year remission from invasive ductal carcinoma. Investigations confirmed positive antinuclear antibodies (ANA) with PCNA (proliferating cell nuclear antigen) and myositis-specific antibodies including anti-Jo, anti-mitochondrial antibody (AMA-M2), and anti-benzylpenicilloyl antibody (BPO).}, } @article {pmid41804392, year = {2026}, author = {Meyer, MS and Goodson, M and Eggert-Cichocki, SR and Frimodig, B and Sawan, H and Zakaria, K}, title = {Bannwarth Syndrome in a Patient With Early-Stage Breast Cancer: An Atypical Manifestation of Lyme Neuroborreliosis.}, journal = {Cureus}, volume = {18}, number = {2}, pages = {e103078}, pmid = {41804392}, issn = {2168-8184}, abstract = {Neurological symptoms in breast cancer patients can arise from metastasis, medication side effects, or underlying neurodegenerative conditions. When imaging is inconclusive, the more uncommon immune-mediated neuropathies should be considered. Guillain-Barré syndrome and Lyme neuroborreliosis are two immune-mediated conditions that share neurological findings. This case involves a 72-year-old Caucasian female who presented with early-stage invasive ductal carcinoma with neuroendocrine features and gradual bilateral upper extremity weakness and paresthesia. Surgery was uncomplicated, but in the subacute postoperative period, the patient developed progressive worsening of neck and scapular pain, left upper extremity weakness, right-hand paresthesia, and decreased right-hand dexterity. Cervical spine MRI and CT scans of the head and neck areas were insignificant. Leukocytosis, mild hyponatremia, and elevated C-reactive protein were found on laboratory workup. The initial differential diagnosis included paraneoplastic syndromes; however, given the inconclusive imaging, immune-mediated neuropathies, including Lyme neuroborreliosis, were prioritized. A lumbar puncture established the diagnosis of Lyme neuroborreliosis presenting as Bannwarth syndrome, also known as lymphocytic meningoradiculitis. Acute or subacute neurological decline in oncology patients should prompt consideration of paraneoplastic and infectious immune-mediated neurological disorders. Despite its rarity in the United States, Bannwarth syndrome should be considered as a paraneoplastic neuropathy mimic, especially with inflammatory cerebrospinal fluid findings.}, } @article {pmid41800043, year = {2026}, author = {Zhong, S and Xu, H and Ye, X and Xu, Y and Fan, Z}, title = {Co-existence of fibroadenoma, intraductal carcinoma and invasive ductal carcinoma in the unilateral breast mass: a case report and literature review.}, journal = {Frontiers in oncology}, volume = {16}, number = {}, pages = {1727815}, pmid = {41800043}, issn = {2234-943X}, abstract = {BACKGROUND: Fibroadenoma is the most common benign breast tumor. However, the coexistence of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) within single breast fibroadenomas is rare.

CASE DESCRIPTION: A 71-year-old woman presented with a palpable mass in her left breast, and she had a history of right-side breast cancer, which had been treated 16 years ago. Invasive ductal carcinoma was confirmed through core needle biopsy. She subsequently underwent left breast mastectomy with sentinel lymph node biopsy. Postoperative pathological examination revealed two fibroadenomas: the larger one coexisted with IDC and focal DCIS, and the small one coexisted with high-grade DCIS. Immunohistochemical analysis showed positive expression of estrogen receptor (ER) and progesterone receptor (PR), but negative expression of Her-2, demonstrating a Luminal B1 subtype (clinical stage IA). She had completed the adjuvant chemotherapy and currently received endocrine therapy. No recurrence was found during the follow-up examinations.

CONCLUSION: Coexistence of fibroadenoma, DCIS and IDC in unilateral breast mass is rare, highlighting the importance of comprehensive preoperative evaluation, optimal surgical strategy and accurate histopathological examination.}, } @article {pmid41796902, year = {2026}, author = {El-Merahbi, R and Karagiannakou, V and Kardinal, R and Seep, L and Lindner, R and Jäckstein, MY and Hildebrand, S and Hasic, M and Korkmaz, E and Jha, AK and Krokidi, AT and Dyar, K and Meissner, F and Grein, S and Heeren, J and Klingenspor, M and Pfeifer, A and Hasenauer, J and Wachten, D and Herzig, S and Georgiadi, A}, title = {Endothelial ADGRF5(GPR116) governs vascular adaptation required for sustained thermogenic remodeling of brown adipose tissue.}, journal = {Molecular metabolism}, volume = {}, number = {}, pages = {102346}, doi = {10.1016/j.molmet.2026.102346}, pmid = {41796902}, issn = {2212-8778}, abstract = {OBJECTIVE: Brown adipose tissue (BAT) dissipates energy via non-shivering thermogenesis, but durable thermogenic benefit requires sustained cold remodeling that stabilizes a cold-adapted tissue state. While most studies have focused on adipocyte-intrinsic pathways that drive acute activation, how stromal niche cells-particularly the vasculature-sense and coordinate long-term adaptation remains poorly defined. Because GPCRs are key sensors of extracellular and neurohumoral cues, we mapped GPCR expression across mouse and human BAT at single-nucleus resolution and identified adhesion GPCRs as a prominent family enriched in vascular cells, with endothelial ADGRF5(GPR116) emerging as a leading candidate regulator.

METHODS: Single-nucleus RNA sequencing of mouse and human BAT was used to map GPCR expression across cell types. Global, inducible endothelial-specific, and adipocyte-specific ADGRF5(GPR116) knockout mouse models were each challenged with acute and prolonged cold exposure. Endothelial and adipocyte states were analyzed using single-nucleus RNA sequencing transcriptional profiling, functional vascular assays, and cell-cell communication modeling.

RESULTS: Endothelial deletion of ADGRF5(GPR116) impaired the ability of mice to sustain thermogenesis during prolonged cold exposure, whereas adipocyte-specific deletion did not affect thermogenic capacity in vivo. Loss of endothelial ADGRF5(GPR116) did not alter endothelial cell abundance, but induced endothelial transcriptional reprogramming characterized by disrupted quiescent remodeling programs, shifts in endothelial state with EndMT-like features, and context-dependent alterations in barrier-associated pathways, occurring in the absence of immune cell infiltration or overt fibrosis. Adipocyte reclustering revealed a failure to acquire a fully cold-adapted thermogenic state, with thermogenically inefficient programs and adrenergic hyporesponsiveness, despite preserved sympathetic input. CellChat and NicheNet analyses predicted altered endothelial-derived paracrine signaling capable of reshaping adipocyte identity.

CONCLUSION: Endothelial ADGRF5(GPR116) is a critical regulator of vascular adaptation during sustained cold exposure and supports full acquisition of the thermogenic adipocyte state through endothelial identity and paracrine signaling.}, } @article {pmid38523415, year = {2024}, author = {Seth, A and Slama, EM}, title = {Delayed Diagnosis of Inflammatory Breast Cancer Presenting as Acute Mastitis in a Patient One Month Postpartum.}, journal = {The American surgeon}, volume = {90}, number = {7}, pages = {1925-1927}, doi = {10.1177/00031348241241736}, pmid = {38523415}, issn = {1555-9823}, mesh = {Humans ; Female ; Adult ; *Mastitis/diagnosis/etiology ; *Inflammatory Breast Neoplasms/diagnosis ; *Delayed Diagnosis ; *Postpartum Period ; Diagnosis, Differential ; Acute Disease ; }, abstract = {Inflammatory breast cancer (IBC) is a rare yet aggressive form of invasive ductal carcinoma, with a poor prognosis and decreased 5-year survival rates. Characteristic findings for IBC include rapid onset of breast edema, peau d'orange appearance, and involvement of the breast skin. Additionally, diagnosis is confirmed with a skin punch biopsy. With such nonspecific features, IBC can be mistaken for benign etiologies, causing delays in diagnosis and treatment. This patient is a 44-year-old woman presenting with left breast swelling while concurrently breastfeeding. Following antibiotic treatment but no symptom resolution, the patient was referred out for further follow-up. Despite multiple imaging studies, suggesting benign findings, clinical suspicion prompted continued evaluation and finally diagnosis of triple-negative inflammatory breast cancer with distant metastases. Further awareness of the presentation of IBC and its mimicking of other disease processes such as mastitis is paramount to earlier detection and improved outcomes in future patients.}, } @article {pmid28507543, year = {2017}, author = {Lapko, N and Zawadka, M and Polosak, J and Worthen, GS and Danet-Desnoyers, G and Puzianowska-Kuźnicka, M and Laudanski, K}, title = {Long-term Monocyte Dysfunction after Sepsis in Humanized Mice Is Related to Persisted Activation of Macrophage-Colony Stimulation Factor (M-CSF) and Demethylation of PU.1, and It Can Be Reversed by Blocking M-CSF In Vitro or by Transplanting Naïve Autologous Stem Cells In Vivo.}, journal = {Frontiers in immunology}, volume = {8}, number = {}, pages = {401}, pmid = {28507543}, issn = {1664-3224}, abstract = {The duration of post-sepsis long-term immune suppression is poorly understood. Here, we focused on the role of monocytes (MO) as the pivotal cells for long-term regulation of post-sepsis milieu. Lost ability of MO to adapt is seen in several acute conditions, but it is unclear for how long MO aberrancy post-sepsis can persist. Interestingly, the positive feedback loop sustaining secretion of macrophage-colony stimulation factor (M-CSF) can persist even after resolution of sepsis and significantly alters performance of MO. Here, we investigated the activation of M-CSF, and it as critical regulator of PU.1 in mice surviving 28 days after sepsis. Our primary readout was the ability of MO to differentiate into dendritic cells (DCs; MO→iDC) in vitro since this is one of the critical processes regulating a successful transition from innate to acquired immunity. We utilized a survival modification of the cecal ligation and puncture (CLP) model of sepsis in humanized mice. Animals were sacrificed 28 days after CLP (tCLP+28d). Untouched (CONTR) or sham-operated (SHAM) animals served as controls. Some animals received rescue from stem cells originally used for grafting 2 weeks after CLP. We found profound decrease of MO→iDC in the humanized mice 28 days after sepsis, demonstrated by depressed expression of CD1a, CD83, and CD209, diminished production of IL-12p70, and depressed ability to stimulate T cells in mice after CLP as compared to SHAM or CONTR. In vitro defect in MO→iDC was accompanied by in vivo decrease of BDCA-3[+] endogenous circulating DC. Interestingly, post-CLP MO had persistent activation of M-CSF pathway, shown by exaggerated secretion of M-CSF, activation of PU.1, and demethylation of SPII. Neutralization of the M-CSF in vitro reversed the post-CLP MO→iDC aberration. Furthermore, transplantation of naïve, autologous stem cell-derived MO restored CLP-deteriorated ability of MO to become DC, measured as recovery of CD1a expression, enhanced production of IL-12p70, and ability of IL-4 and GM-CSF MO to stimulate allogeneic T cells. Our results suggest the role of epigenetic mediated M-CSF aberration in mediating post-sepsis immune system recovery.}, } @article {pmid26197043, year = {2015}, author = {Laudanski, K and Qing, M and Oszkiel, H and Zawadka, M and Lapko, N and Nowak, Z and Worthen, GS}, title = {Ketamine affects in vitro differentiation of monocyte into immature dendritic cells.}, journal = {Anesthesiology}, volume = {123}, number = {3}, pages = {628-641}, doi = {10.1097/ALN.0000000000000783}, pmid = {26197043}, issn = {1528-1175}, mesh = {Anesthetics, Dissociative/*pharmacology ; Cell Differentiation/*drug effects/physiology ; Cells, Cultured ; Dendritic Cells/*drug effects/metabolism ; Dose-Response Relationship, Drug ; Humans ; Inflammation Mediators/metabolism ; Ketamine/*pharmacology ; Monocytes/*drug effects/metabolism ; }, abstract = {BACKGROUND: Monocytes (MOs) have the unique ability to differentiate into immature dendritic cells (iDCs) (MO→iDC) under the influence of interleukin-4 and granulocyte-monocyte colony-stimulating factor (IL-4&GM-CSF). In this study, the authors investigated the influence of ketamine on the process of MO→iDC.

METHODS: iDCs were cultured from MO obtained from 36 subjects in the presence of IL-4 and GM-CSF and ketamine at 100, 10, and 1 μg/ml for 5 days. In some of the experiments, the authors used nonspecific N-methyl-D-aspartate (NMDA) receptor antagonist MK-801, NMDA, or a neutralizing antibody for transforming growth factor β (TGFβ). The expression of surface markers and functional assays were used to assess the effect of ketamine on IL-4&GM-CSF-stimulated MO. IL-4&GM-CSF-stimulated MO's supernatants were assessed for cytokine levels.

RESULTS: Ketamine at 10 μg/ml, and higher concentrations, diminished the expression of CD1a on IL-4&GM-CSF-stimulated MO and retarded both their ability to process DQ ovalbumin and mixed lymphocyte reaction stimulation. The addition of ketamine to IL-4&GM-CSF-differentiated MO resulted in the persistent expression of CD14 and unchanged expression of CD86 and CD206. The phagocytic abilities of IL-4&GM-CSF-differentiated MO were not changed by ketamine. MK-801, a nonselective NMDA agonist, mimicked ketamine's effect on MO→iDC differentiation. Adding exogenous NMDA to IL-4&GM-CSF-stimulated MO in the presence of ketamine partially restored the level of CD1a. TGFβ was elevated in supernatants of IL-4&GM-CSF-stimulated MO in the presence of ketamine. Adding neutralizing TGFβ antibody or TGFβR1 blocker (SB431542) resulted in the full recovery of MO→iDC, despite the presence of ketamine.

CONCLUSIONS: Ketamine diminishes the process of MO→iDC in vitro. This is mediated via NMDA-dependent mechanisms and TGFβ.}, } @article {pmid41795152, year = {2026}, author = {Hibino, T and Kato, M and Tsuzuki, T and Nishikimi, T and Kimura, T and Komatsu, T and Hattori, K and Naito, Y and Sano, Y and Inoue, S and Matsuo, K and Sano, T and Kimura, T and Zennami, K and Ishida, S and Matsukawa, Y and Akamatsu, S}, title = {Total Positive Margin Length as a Novel Prognostic Indicator After Radical Prostatectomy.}, journal = {International journal of urology : official journal of the Japanese Urological Association}, volume = {33}, number = {3}, pages = {e70395}, doi = {10.1111/iju.70395}, pmid = {41795152}, issn = {1442-2042}, mesh = {Humans ; Male ; *Prostatectomy/methods ; *Prostatic Neoplasms/surgery/pathology/blood ; Retrospective Studies ; *Margins of Excision ; Middle Aged ; Aged ; Prognosis ; *Neoplasm Recurrence, Local/pathology/epidemiology/blood ; Neoplasm Grading ; *Prostate/pathology/surgery ; Risk Assessment ; Prostate-Specific Antigen/blood ; }, abstract = {OBJECTIVES: Positive surgical margins (PSMs) are associated with biochemical recurrence (BCR) following radical prostatectomy (RP). However, their prognostic significance varies, and not all patients with PSMs experience recurrence. This study aimed to evaluate whether detailed analysis of margin characteristics could improve postoperative risk stratification.

METHODS: We retrospectively reviewed 1003 patients who underwent RP without neoadjuvant or adjuvant therapy. PSMs were categorized according to total PSM length (≤ 5 mm vs. > 5 mm), maximum PSM length (≥ 3 mm vs. < 3 mm), primary Gleason pattern (pGP) at PSM (pGP3 vs. pGP4-5), multifocality (single vs. multiple), and location (apex-only vs. others). Other pathological factors analyzed pathological T/N stage, ISUP grade group, and intraductal carcinoma of the prostate (IDC-P).

RESULTS: PSMs were present in 377 patients (37%), Total PSM length was 5.0 (0.1-66) mm and pGP3 was more common in apex-only PSMs. pGS, IDC-P, and PSM status were significant predictors of BCR in the entire cohort. Among margin parameters, total PSM length and pGP at the PSM were the strongest predictors. In organ-confined disease with PSM, BCR risk was significantly stratified into three groups based on total PSM length > 5 mm and pGP4-5 at the margin (0, 1, or 2; p < 0.001).

CONCLUSIONS: A risk classification incorporating total PSM length and pGP at the margin improves postoperative prognostic stratification for localized prostate cancer with PSMs. In cases with multiple PSMs, total PSM length may be more informative than the maximum PSM length European Association of Urology recommended.}, } @article {pmid41777936, year = {2026}, author = {Tashima, Y and Araki, Y and Araki, S and Tahara, Y and Tanaka, F}, title = {Exceptional and Durable Complete Response to Ado-Trastuzumab Emtansine in HER2-Positive Metastatic Breast Cancer: A Case Report.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e102669}, pmid = {41777936}, issn = {2168-8184}, abstract = {Ado-trastuzumab emtansine (T-DM1) is an established treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have previously received trastuzumab-based therapy. However, complete and durable responses to T-DM1 are uncommon, and long-term complete remission has rarely been reported. We report the case of a 72-year-old woman with HER2-positive metastatic breast cancer who achieved a sustained complete response following T-DM1 therapy. The patient was initially diagnosed with left breast invasive ductal carcinoma with axillary and abdominal lymph node metastases. She received first-line chemotherapy with trastuzumab, pertuzumab, and docetaxel, followed by maintenance anti-HER2 therapy and surgery for local disease control. During maintenance therapy, chest wall recurrence with rib and mediastinal lymph node involvement was detected. Re-biopsy confirmed persistent HER2 overexpression. After progression on endocrine therapy, T-DM1 was initiated. Marked tumor regression was observed on CT imaging three months after initiation of T-DM1, and complete radiological remission has been maintained for more than five years with continuous T-DM1 treatment. Adverse events were limited to mild liver dysfunction, and no clinically significant thrombocytopenia occurred. This case may represent an exceptional response to T-DM1 and highlights the potential for durable complete remission in selected patients with HER2-positive metastatic breast cancer. Further investigation is warranted to identify predictive factors for exceptional responses and to determine optimal treatment duration.}, } @article {pmid41745694, year = {2026}, author = {Shin, SU and Jang, M and Yun, B and Cho, SM and Choi, YY and Kim, B and Kim, MJ and Kim, SM}, title = {Comparison of Clinical Performance Between Digital Breast Tomosynthesis and MammouS-N.}, journal = {Tomography (Ann Arbor, Mich.)}, volume = {12}, number = {2}, pages = {}, pmid = {41745694}, issn = {2379-139X}, support = {Ministry of Science and ICT, Ministry of Trade, Industry and Energy, Ministry of Health & Wel-fare, and Ministry of Food and Drug Safety, Project Number: RS-2020-KD000001//Sun Mi Kim/ ; 06-2024-0049 from SNUBH Research Fund.//Sun Mi Kim/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology ; Middle Aged ; Aged ; Adult ; Prospective Studies ; *Ultrasonography, Mammary/methods ; *Mammography/methods ; Breast/diagnostic imaging/pathology ; Magnetic Resonance Imaging/methods ; }, abstract = {Background/Objectives: We compared the visibility of breast cancer using the newly developed standing automated breast ultrasound system (MammouS-N) and digital breast tomosynthesis (DBT), and identified factors influencing lesion visibility. Methods: We prospectively enrolled 100 women (mean age: 51.6 years; range: 26-76 years) who were diagnosed with breast cancer and were scheduled to undergo DBT between January and July 2024. They underwent DBT and an ultrasound on the same day. Two radiologists evaluated the visibility scores (0-5) of lesions corresponding to biopsy-confirmed breast cancers identified using magnetic resonance imaging. The Wilcoxon signed-rank test was used to compare the visibility scores of cancers identified on DBT and/or MammouS-N images. Results: Among the 100 women, invasive ductal carcinoma was the most common malignancy (73%). DBT findings included negative findings (7%), masses (46%), masses with calcification (29%), calcifications only (15%), and architectural distortions (3%). On MammouS-N ultrasound, most lesions were classified as masses (93%), whereas 7% were non-mass lesions. For Reviewer 1, MammouS-N demonstrated significantly higher visibility scores (higher scores: 26 on MammouS-N, seven on DBT; equal scores: 67, z = -3.234, p = 0.001). For Reviewer 2, the two modalities showed no significant difference in visibility (higher scores: 27 on MammouS-N, 28 on DBT, equal scores: 45, z = -0.040, p = 0.968). Noncalcified lesions that were obscured on DBT were better visualized on MammouS-N (p < 0.001) by both reviewers. Conclusions: MammouS-N holds promise as an imaging modality complementary to DBT in women with dense breast tissue, particularly for non-calcified lesion detection.}, } @article {pmid41795110, year = {2026}, author = {Karkeabadi, N and Omranipour, R and Nozheh, A and Farazmand, B and Esmaeilian, S}, title = {Invasive lobular carcinoma of the breast with multifocal gastrointestinal, ovarian, and peritoneal metastases: a case report.}, journal = {Journal of medical case reports}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13256-026-05952-w}, pmid = {41795110}, issn = {1752-1947}, abstract = {BACKGROUND: Invasive lobular carcinoma of the breast exhibits distinct biological behavior and metastatic patterns compared with invasive ductal carcinoma, with a recognized tendency to involve unusual sites such as the gastrointestinal tract, peritoneum, and ovaries. These metastases are often clinically occult and may mimic primary gastrointestinal or gynecologic malignancies, leading to delayed diagnosis.

CASE PRESENTATION: We report the case of a 43-year-old Iranian woman with estrogen receptor-positive invasive lobular carcinoma who developed sequential multifocal metastases to the stomach, ovaries, peritoneum, rectum, and jejunum over a 9-year disease course. Initial biochemical progression, manifested by a rising serum cancer antigen 15-3 level, preceded overt radiologic or endoscopic findings. Gastric metastasis was confirmed by biopsy 6 years after primary treatment. Despite negative pelvic imaging, bilateral salpingo-oophorectomy revealed occult ovarian and peritoneal metastases. Subsequent rectal and small-bowel involvement were diagnosed following new gastrointestinal symptoms. The patient was managed with multiple lines of systemic therapy and remains under active treatment with disease confined to the abdominal cavity.

CONCLUSION: This case highlights the insidious metastatic behavior of invasive lobular carcinoma and the limitations of conventional imaging in detecting gastrointestinal and ovarian involvement. Persistent or unexplained gastrointestinal symptoms and rising tumor markers in patients with a history of invasive lobular carcinoma should prompt consideration of metastatic disease and early histopathological evaluation.}, } @article {pmid41787481, year = {2026}, author = {Diallo, A and Aman, NA and Traore, B and Coulibaly, ZI and Kouacou, BFA and Nzi, MR and Doukoure, B and Diomande, MI}, title = {Interest of PD-L1 in the management of triple negative breast cancers in Ivorian patients.}, journal = {BMC women's health}, volume = {26}, number = {1}, pages = {}, pmid = {41787481}, issn = {1472-6874}, abstract = {BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that does not express hormonal receptors and Her2. Its prevalence is high and varies from 30 to 41% in the Ivory Coast. For decades, chemotherapy has remained the only systematic treatment choice; however, the current availability of programmed death-ligand 1 (PD-L1) immunohistochemistry provides benefits for immune checkpoint inhibitors. The purpose of the study aimed to determine the prevalence of PD-L1 and its relationship with specific prognostic features for better survival of TNBC patients in the Ivory Coast.

METHODS: A 10-month prospective study included 132 patients diagnosed with TNBC. The paraffin blocks were subjected to PD-L1 immunohistochemistry. The Chi-Square Test was used to evaluate the correlations between PD-L1 status and prognostic parameters.

RESULTS: The mean age at diagnosis was 46.6 ± 12.9 years. 62.9% of the study population were premenopausal. The predominant histological type was invasive ductal carcinoma of no special type (95.5%) at the advanced stage of grade II (59.1%) and III (27.3%). There was an abundant inflammatory stroma (67.4%). 20.5% of TNBC patients were PD-L1 positive. PD-L1 status was significantly associated with the breast imaging-reporting and data system (BIRADS) scoring (p = 0.0362) and Nottingham grade (p = 0.0049). However, there was no association between PD-L1 expression and menopausal status (p = 0.1771), sex (p = 0.3030), inflammatory stroma (p = 0.0803), tumor necrosis (p = 0.0571), and histological type (p = 0.2037).

CONCLUSION: 20.5% of TNBC patients expressed PD-L1. This study highlights a significant association between PDL-1 expression and the BIRADS scoring and the Nottingham grade. The present study could help to select patients who would be likely to benefit from anti-PD-L1 immunotherapy for better clinical outcomes in the Ivory Coast.}, } @article {pmid41776715, year = {2026}, author = {De Coster, I and Leroux-Roels, I and Withanage, K and Suykens, L and D'Onofrio, V and Leroux-Roels, G and van Damme, P and Ciarlet, M and Adams, EM and Rida, W and Wen, J and MacDonald, M and Price, J and Kanesa-Thasan, N}, title = {A first-in-human Phase 1/1b randomized trial evaluating the safety and immunogenicity of a respiratory syncytial virus (RSV) virus-like particle subunit vaccine (IVX-121) in healthy young and older adults.}, journal = {Human vaccines & immunotherapeutics}, volume = {22}, number = {1}, pages = {2633021}, pmid = {41776715}, issn = {2164-554X}, mesh = {Humans ; Middle Aged ; Male ; Female ; Aged ; Adult ; *Respiratory Syncytial Virus Vaccines/immunology/adverse effects/administration & dosage ; Antibodies, Viral/blood ; *Respiratory Syncytial Virus Infections/prevention & control/immunology ; Adolescent ; Young Adult ; Vaccines, Subunit/immunology/administration & dosage/adverse effects ; Adjuvants, Immunologic/administration & dosage ; *Respiratory Syncytial Virus, Human/immunology ; *Immunogenicity, Vaccine ; *Vaccines, Virus-Like Particle/immunology/administration & dosage/adverse effects ; Injections, Intramuscular ; Aluminum Hydroxide/administration & dosage ; Antibodies, Neutralizing/blood ; Healthy Volunteers ; Double-Blind Method ; }, abstract = {Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease in all age groups, with substantial burden in older adults. Here, we report the safety and immunogenicity of IVX-121, an investigational virus-like particle vaccine against RSV. This Phase 1/1b trial (EudraCT number: 2020-003633-38) randomized 90 healthy young (18-45 y of age; Phase 1) and 130 older adults (60-75 y of age; Phase 1b) to receive a single intramuscular injection of IVX-121 at low (25 µg), medium (75 µg), or high (250 µg) dose, with/without the adjuvant aluminum hydroxide (Al[OH]3), or placebo. Outcomes were assessed through Day 180. Older adult participants who had received IVX-121 or placebo could continue into an extension study in which safety was assessed for an additional 6 months before receiving IVX-121 (75 µg, unadjuvanted, open-label) on Day 365; safety and immunogenicity were assessed up to Day 546. Adverse reactions were generally mild, and there were no vaccine-related serious adverse events. All IVX-121 dose levels and formulations boosted preexisting RSV neutralizing antibody (nAb) responses. Although not statistically powered to compare treatment groups, there was no clear dose response and the adjuvant Al(OH)3 did not appear to improve immunogenicity. For both age groups, IVX-121 induced nAbs against RSV A and B, which remained above baseline levels for at least 6 months. A second dose of IVX-121 in older adults elicited a modest increase in nAbs against RSV A but not RSV B. Overall, IVX-121 had a favorable safety profile and induced immune responses against RSV in young and older adults.}, } @article {pmid41776559, year = {2026}, author = {Siddique, H and Khan, A and Salomon, I and Hashmi, AH}, title = {Unusual metastasis of breast cancer to the paranasal sinuses: a case report.}, journal = {Journal of medical case reports}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13256-026-05870-x}, pmid = {41776559}, issn = {1752-1947}, abstract = {BACKGROUND: Breast cancer is the most common malignancy in women, with invasive ductal carcinoma being the predominant subtype. Although metastases commonly affect the bones, liver, lungs, and brain, involvement of the paranasal sinuses is exceedingly rare and poses significant diagnostic challenges.

CASE PRESENTATION: A 70-year-old postmenopausal woman from Pakistan with a history of left-sided mastectomy and chemotherapy for invasive ductal carcinoma presented with an altered sensorium, aphasia, and reduced oral intake. Imaging revealed an aggressive, destructive lesion in the left frontal sinus, ethmoid air cells, and posterior parietal bone. Biopsy confirmed metastasis from the primary breast carcinoma. The patient received palliative radiotherapy and supportive care owing to her preference to avoid invasive interventions. Despite management, her condition progressively deteriorated, and she succumbed 2 years later. Paranasal sinus metastases are uncommon and often mimic rhinosinusitis, leading to a delayed diagnosis. Breast cancer metastasis to this region underscores the unpredictability of metastatic spread even years after the initial diagnosis. Management focuses on symptom control because surgical intervention is typically limited by anatomical constraints and the patient's overall health.

CONCLUSION: This case highlights the importance of maintaining a high index of suspicion for atypical metastatic sites in survivors of breast cancer. Multidisciplinary approaches and patient-centered care are critical for optimizing quality of life in advanced disease stages.}, } @article {pmid41773136, year = {2026}, author = {Aydrose, A and Elsdaig, HE and Abdalla, A and Abdalla, M and Alsadig, F and Ahmed, T and Abdallah, E and Alagha, A and Yousif, T}, title = {Breast Cancer During Pregnancy and Lactation: A Five-Year Retrospective Study in Sudan.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e102646}, pmid = {41773136}, issn = {2168-8184}, abstract = {Introduction Breast cancer diagnosed during pregnancy or within the first year postpartum is termed pregnancy-associated breast cancer (PABC), and it is the most common malignancy occurring during pregnancy. Objective The objective of this study was to investigate the characteristics of breast cancer patients diagnosed during pregnancy and lactation at Wad-Madani Teaching Hospital, Sudan, from 2017 to 2022. Methods A retrospective, cross-sectional study was conducted, screening 2,151 breast cancer patients. After applying age and menopausal status exclusions, 33 patients (2.69% of eligible patients) who experienced symptom onset during pregnancy or lactation were included. Data on demographics, clinical presentation, risk factors, receptor status, and histopathology were collected from hospital records. Results The most common clinical presentation was a palpable breast lump (31/33, 93.9%), followed by breast pain (12/33, 36.4%) and skin changes or ulceration (10/33, 30.3%). Inflammatory features were present in 11 patients (33.3%). Obesity (9/33, 27.3%) and early menarche (10/33, 30.3%) were prevalent risk factors. Histopathological analysis revealed invasive ductal carcinoma (IDC) in 28 patients (84.8%). Regarding receptor status, 21 patients (63.6%) were estrogen/progesterone receptor (ER/PR)-negative, and 24 patients (72.7%) were human epidermal growth factor-2 (HER2)-negative. Conclusion Physiological changes during pregnancy and lactation complicate breast cancer detection and diagnosis. These findings underscore the need for heightened clinical suspicion, early investigation of breast symptoms, and a multidisciplinary approach to improve outcomes in this patient population.}, } @article {pmid41772273, year = {2026}, author = {Metser, U and Dayes, IS and Parpia, S and Eisen, AF and Hodgson, N and Cil, TD and George, R and Blanchette, P and Arnaou, A and Chan, A and Levine, MN}, title = {Prospective study on [18]F-FDG PET-CT for staging locally advanced invasive lobular breast carcinoma.}, journal = {British journal of cancer}, volume = {}, number = {}, pages = {}, pmid = {41772273}, issn = {1532-1827}, support = {none//Cancer Care Ontario (Action Cancer Ontario)/ ; none//Cancer Care Ontario (Action Cancer Ontario)/ ; none//Cancer Care Ontario (Action Cancer Ontario)/ ; none//Cancer Care Ontario (Action Cancer Ontario)/ ; none//Cancer Care Ontario (Action Cancer Ontario)/ ; none//Cancer Care Ontario (Action Cancer Ontario)/ ; none//Cancer Care Ontario (Action Cancer Ontario)/ ; none//Cancer Care Ontario (Action Cancer Ontario)/ ; none//Cancer Care Ontario (Action Cancer Ontario)/ ; none//Ontario Ministry of Health and Long-Term Care (ministère de la Santé et des Soins de longue durée" into: Ministère de la Santé et des Soins de Longue Durée)/ ; none//Ontario Ministry of Health and Long-Term Care (ministère de la Santé et des Soins de longue durée" into: Ministère de la Santé et des Soins de Longue Durée)/ ; none//Ontario Ministry of Health and Long-Term Care (ministère de la Santé et des Soins de longue durée" into: Ministère de la Santé et des Soins de Longue Durée)/ ; none//Ontario Ministry of Health and Long-Term Care (ministère de la Santé et des Soins de longue durée" into: Ministère de la Santé et des Soins de Longue Durée)/ ; none//Ontario Ministry of Health and Long-Term Care (ministère de la Santé et des Soins de longue durée" into: Ministère de la Santé et des Soins de Longue Durée)/ ; none//Ontario Ministry of Health and Long-Term Care (ministère de la Santé et des Soins de longue durée" into: Ministère de la Santé et des Soins de Longue Durée)/ ; none//Ontario Ministry of Health and Long-Term Care (ministère de la Santé et des Soins de longue durée" into: Ministère de la Santé et des Soins de Longue Durée)/ ; none//Ontario Ministry of Health and Long-Term Care (ministère de la Santé et des Soins de longue durée" into: Ministère de la Santé et des Soins de Longue Durée)/ ; none//Ontario Ministry of Health and Long-Term Care (ministère de la Santé et des Soins de longue durée" into: Ministère de la Santé et des Soins de Longue Durée)/ ; }, abstract = {PURPOSE: Patients with locally advanced breast cancer (LABC) undergo staging tests. In the absence of metastases, they may receive combined modality therapy with curative intent. A randomised controlled trial (RCT) in patients with locally advanced breast cancer (LABC) compared staging using 18F-FDG PET-CT versus the usual CT chest/abdomen and bone scan, with the primary outcome being upstaging to Stage 4. Because of concern regarding the lower FDG-avidity of invasive lobular breast cancer (ILBC) compared to invasive ductal cancer (IDC), patients with ILBC were not eligible for the RCT.

METHODS: A prospective cohort study in patients with ILBC and TNM stage III or IIb (T3N0) was conducted contemporaneously to the RCT. Consenting patients from six regional cancer centres in Ontario all underwent whole body 18F-FDG PET-CT, CT with contrast of the chest/abdomen, and a bone scan. The primary endpoint was upstaging to stage IV. (ClinicalTrials.gov identifier: NCT02751710).

RESULTS: Between December 2016 and April 2022, 41 patients with ILBC were enroled: 38 undergoing all three imaging tests. Five patients (13.2%) were upstaged due to distant disease; all had positive PET-CT scans. Among these five patients, two were positive on both CT and bone scan, two on either CT or bone scan, and one on neither. Six of 38 (15.8%) primary ILBC tumours lacked [18]FDG uptake and the mean standard uptake value was 4.4 (3.2).

CONCLUSION: In this cohort, 18F-FDG PET-CT detected all cases of metastatic spread.}, } @article {pmid41769367, year = {2026}, author = {Abe, M and Saito, F and Honma, N and Tamaki, Y and Goto, M and Fukutake, K and Sonobe, S and Katagiri, Y and Shibayama, T and Ogata, H}, title = {Invasive Lobular Carcinoma of the Male Breast With BRCA2 Mutation.}, journal = {Case reports in pathology}, volume = {2026}, number = {}, pages = {3580444}, pmid = {41769367}, issn = {2090-6781}, abstract = {Male breast cancer (MBC) is a rare condition, accounting for < 1% of all breast cancer cases. Reports of bilateral synchronous MBC are even more uncommon. Although lobular carcinoma is generally absent in the male mammary gland, a few cases of lobular carcinoma in MBC have been documented, comprising 1%-2% of all MBC cases. A man in his 80s presented to our hospital with a mass on his left nipple. After detailed examination, he was diagnosed with invasive ductal carcinoma of the left breast and invasive lobular carcinoma of the right breast. Because he had a family history of breast cancer, he underwent genetic testing and was found to have a BRCA2 gene mutation (c.331_347delinsC [p.Asn111Leufs∗5]). Simultaneous surgery was performed for bilateral breast cancer. Although drug therapy and radiation therapy were recommended after the operation, the patient was under observation due to his advanced age. A brief literature review is presented in this section.}, } @article {pmid41768803, year = {2025}, author = {Roy, B and Rathore, R and Singhal, S and Halder, S and Singh, N}, title = {Vaginal Neoplasm in a Breast Cancer Survivor.}, journal = {JNMA; journal of the Nepal Medical Association}, volume = {63}, number = {286}, pages = {433-435}, pmid = {41768803}, issn = {1815-672X}, mesh = {Humans ; Female ; *Vaginal Neoplasms/secondary/drug therapy/diagnosis/pathology/diagnostic imaging ; Cancer Survivors ; Paclitaxel/therapeutic use ; Middle Aged ; *Triple Negative Breast Neoplasms/pathology/therapy ; Positron Emission Tomography Computed Tomography ; *Breast Neoplasms/pathology/therapy ; Mastectomy, Modified Radical ; Magnetic Resonance Imaging ; Antineoplastic Agents, Phytogenic/therapeutic use ; }, abstract = {According to GLOBOCAN 2022 data, Carcinoma breast is the second most common malignancy worldwide after lung and ranks 4[th] in mortality worldwide. Breast cancer can metastasize to various organs. The incidence of vaginal metastasis in carcinoma breast is 1-2%. Here we present a patient with post menopausal bleeding with vaginal mass. She had a history of Triple negative carcinoma left breast 3 years back, treated by Modified Radical Mastectomy followed by chemo radiotherapy. Vaginal biopsy was suggestive of a metastatic carcinoma breast. MRI and PET CT showed isolated vaginal growth. Due to poor performance status and multiple medical comorbidities, decision was taken to treat her with single agent Paclitaxel 3weekly until disease progression. This case report points out the necessity for thorough gynaecological examination in a cancer survivor, either via clinical examination, routine PAP smear or imaging.}, } @article {pmid41768223, year = {2026}, author = {Sklar, K}, title = {Ureteric Injury From an Indwelling Catheter in the Context of an Undiagnosed Duplex Ureter in a Labouring Woman: A Case Report.}, journal = {Cureus}, volume = {18}, number = {2}, pages = {e104410}, pmid = {41768223}, issn = {2168-8184}, abstract = {Indwelling urinary catheter (IDC) insertion is routine in obstetric practice and is considered low risk. Inadvertent ureteric catheterisation is rare and has been reported only in a few patients with complex backgrounds, mainly neurogenic bladder. This report describes a case of iatrogenic ureteric injury secondary to IDC insertion in an otherwise well woman, who was later found to have an undiagnosed duplex renal collecting system. Interestingly, an antenatal ultrasound in this case detected a fetal duplex renal collecting system. The case describes a woman in her thirties in spontaneous labour who had an IDC inserted due to concurrent epidural analgesia. She was noted to have minimal urine output after IDC insertion. She required an emergency caesarean section for a prolonged second stage and fetal tachycardia, and the bladder was noted to be oedematous and high during entry. Further imaging with computerized tomography following the caesarean section demonstrated the duplex collecting system with evidence of ureteric rupture of the lower pole moiety. The IDC was seen to be malpositioned, passing into the left ureter. The patient then required emergency cystoscopy with stent insertion. This case highlights a rare but serious complication related to routine IDC insertion. Consideration of maternal imaging when fetal renal anomalies are detected may be useful in diagnosing maternal duplex systems; however, current evidence does not support this practice.}, } @article {pmid41768114, year = {2026}, author = {AiErken, N and Wang, X and Zhang, M and Lei, K and Ling, Y and Yang, L}, title = {Clinical outcomes and aesthetic satisfaction of the lateral thoracic artery perforator (LTAP) flap in immediate oncoplastic breast reconstruction following breast-conserving surgery.}, journal = {JPRAS open}, volume = {48}, number = {}, pages = {1016-1024}, pmid = {41768114}, issn = {2352-5878}, abstract = {To investigate the clinical application, aesthetic outcomes, and patient satisfaction of the lateral thoracic artery perforator (LTAP) flap for immediate breast reconstruction following breast-conserving surgery (BCS) in breast cancer patients. Twenty-eight breast cancer patients (aged 33-65 years, mean 48.75 ± 7.481 years) treated between August 2023 and December 2024 were enrolled. Tumor diameters ranged from 1.05 to 2.80 cm (mean 1.50 ± 0.32 cm), with pathological types including invasive ductal carcinoma (25 cases), invasive lobular carcinoma (2 cases), and phyllodes tumor (1 case). All underwent LTAP flap reconstruction. Aesthetic outcomes and patient satisfaction were assessed using the BREAST-Q BCT module version 2.0, with data analyzed via SPSS 23. No postoperative complications occurred. All patients completed the BREAST-Q survey, with median (IQR) scores of 100 (42) for breast satisfaction and 76 (19) for physical well-being of the chest. The LTAP flap achieves favorable aesthetic outcomes and high patient satisfaction for immediate breast reconstruction after BCS, with good safety.}, } @article {pmid41764344, year = {2026}, author = {Williams, AE and Hoffmann, EJ and Inman, DR and Gari, MK and Zhou, C and Burkel, BM and Haidar, N and Pan, Y and Halambeck, M and Moore, BN and Wisinski, KB and McGregor, SM and Kerr, SC and Arendt, LM and Ponik, SM}, title = {Obesity and breast density enhance immune exclusion in the primary tumor microenvironment and promote breast cancer metastasis.}, journal = {Oncogene}, volume = {}, number = {}, pages = {}, pmid = {41764344}, issn = {1476-5594}, support = {R01CA179556, R01CA206458, U54CA268069//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R01CA179556, R01CA227542//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P30CA014520//University of Wisconsin Carbone Cancer Center (UW Carbone Cancer Center)/ ; P30CA014520//University of Wisconsin Carbone Cancer Center (UW Carbone Cancer Center)/ ; GT1453//Howard Hughes Medical Institute (HHMI)/ ; R25GM083252//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, abstract = {Recent epidemiological studies suggest that breast density and obesity together increase breast cancer risk. Although these risk factors have been explored individually, little is known about how they combine to alter the tumor immune microenvironment (TIME) and promote disease progression. To address this gap, we developed a murine model of both risk factors. Spatial analysis of the TIME revealed macrophages and T-cells predominantly localized in the stroma of both risk factor groups, indicating an immune exclusion phenotype. Mice with dual risk factors had significantly increased lung metastasis. To establish the human relevance of this model, we interrogated the TIME in biopsies from 158 patients with invasive ductal carcinoma and 10 years of follow-up data. We found that patients with both risk factors had the highest incidence of metastasis (45%). Furthermore, spatial immune profiling revealed exacerbated stromal localization of macrophages and T-cells in the dual risk factor group that progressed to metastasis. Overall, we uncovered an immune exclusion phenotype in metastatic breast cancer patients with obesity and breast density, and we present a relevant murine model that parallels human disease. The murine model will enable future investigation into therapies that intercept the mechanisms by which dual risk factors modulate the TIME.}, } @article {pmid41764072, year = {2026}, author = {Hass, D and Madsen, AN and da Silva-Buttkus, P and Kjølbye, AL and Støy, S and Nøhr-Meldgaard, J and Sandahl, TD and Hrabě de Angelis, M and Jorgensen, R and Rohm, M and van de Bunt, M}, title = {Lipidated Interleukin-22 Reduces Body Weight And Spares Lean Mass In Mice By A Novel Gut Acting Mechanism Additive To GLP-1 Agonism.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2026.02.041}, pmid = {41764072}, issn = {1525-0024}, abstract = {The prevalence of metabolic diseases, including obesity and type 2 diabetes, continues to rise. Although GLP-1 receptor agonists (GLP-1RAs) now provide the first effective treatment options for patients with obesity, many still fail to reach their target weight. Interleukin (IL)-22 has emerged as a promising therapeutic due to its ability to modulate key metabolic factors. This study evaluated the potential of a novel long-acting lipidated IL-22 analogue as a complementary treatment to GLP-1RAs in mouse models. Lipidated IL-22 induced up to 20% weight reduction as a monotherapy and up to 40% in combination with GLP-1RAs, demonstrating additive efficacy. Lipidated IL-22 preserved lean body mass with less than half the lean mass loss of GLP-1RAs or caloric restriction. Glycemic control was also enhanced, with lipidated IL-22 normalizing blood glucose, and improving insulin sensitivity independent of food intake. Mechanistically, lipidated IL-22 enhanced intestinal secretion of anorectic factors like PYY and doubled fecal energy loss through reduced intestinal calorie absorption. These findings demonstrate the novel intestinal mechanisms of action of lipidated IL-22 and its additive potential to GLP-1RA treatment. Therefore, lipidated IL-22 is strongly positioned as a novel anti-obesity treatment that can address critical unmet needs in the treatment of metabolic diseases.}, } @article {pmid41760667, year = {2026}, author = {Swellam, M and Ramadan, A and Sobeih, ME and Bakr, NM}, title = {Clinical impact of the methylation status of SMAD4 and AKR1B1 genes in a liquid biopsy sample as a prognostic marker for breast cancer.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {}, pmid = {41760667}, issn = {2045-2322}, mesh = {Humans ; Female ; *DNA Methylation ; *Breast Neoplasms/genetics/pathology/mortality/diagnosis ; *Smad4 Protein/genetics ; *Biomarkers, Tumor/genetics ; Middle Aged ; Prognosis ; Adult ; Liquid Biopsy ; Aged ; ROC Curve ; Kaplan-Meier Estimate ; Gene Expression Regulation, Neoplastic ; Aldehyde Reductase ; }, abstract = {The role of DNA methylation in the prognosis of breast cancer, particularly concerning small mothers against decapentaplegic 4 (SMAD4) and aldo-keto reductase family 1 member B1 (AKR1B1), remains largely unexplored. This study aimed to investigate the clinical role of SMAD4 and AKR1B1 methylation as noninvasive prognostic biomarkers in breast cancer. The study included 140 individuals. The patients were stratified into two groups based on their diagnostic investigation: women diagnosed with cancer in breast (N = 80) and cases with benign lesions in breast (N = 30). Additionally, a group of subjects considered as healthy served as the control group (N = 30). Methylation levels of SMAD4 and AKR1B1 were quantified using the Methyl II quantitative PCR system. The methylation specificity and sensitivity were examined through performing a receiver operating characteristic (ROC) curve analysis. The association of the methylation of investigated patterns with breast cancer clinical features and response to treatment was also examined. Survival patterns were assesed using Kaplan-Meier analyses. The outcomes revealed that hypermethylation of SMAD4 and AKR1B1 was upregulated in cancerous patients relative to the benign group and healthy subjects. Based on the values of the area under the curve (AUC) (0.945 and 0.935, respectively) for SMAD4 and AKR1B1, both markers demonstrated superior diagnostic accuracy, surpassing conventional biomarkers for instance cancer antigen 15 - 3 (CA 15 - 3; AUC = 0.698) as well as carcinoembryonic antigen (CEA; AUC = 0.537). Remarkably, SMAD4 and AKR1B1 hypermethylation exhibited a significant association with invasive duct carcinoma (IDC), particularly in early stages, high grades, and cases with lymph node metastasis. A significant difference was observed in methylation status concerning both items and treatment response. Additionally, survival outcomes indicated that hypermethylation of SMAD4 and AKR1B1 was associated with worse DFS and OS. In conclusion, SMAD4 and AKR1B1 methylation may serve as significant epigenetic markers affecting breast cancer prognosis, potentially indicating more aggressive disease and poorer outcomes in these patients.}, } @article {pmid41760005, year = {2026}, author = {Li, P and Wu, S and Ma, H and Ji, W and Wang, Y and Wang, L and Dai, Y}, title = {Occult metastasis of hormone receptor-positive breast cancer to the ovary: A case report and literature review.}, journal = {Medicine}, volume = {105}, number = {9}, pages = {e47830}, pmid = {41760005}, issn = {1536-5964}, support = {L2024-QCY-ZYYJJQ-270//Xianyang Municipal Science and Technology Bureau/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/therapy ; Adult ; *Ovarian Neoplasms/secondary/therapy/surgery ; *Carcinoma, Ductal, Breast/secondary/pathology/therapy ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; }, abstract = {RATIONALE: Breast cancer is the most common malignancy among women worldwide. It typically metastasizes to the bone, lungs, and liver, while ovarian involvement is relatively uncommon. This report aims to illustrate the clinical features, diagnostic approach, and treatment strategies for this rare type of metastasis through a case study, thereby enhancing clinicians' awareness and management capabilities.

PATIENT CONCERNS: A 32-year-old premenopausal woman presented with a palpable nodule in the left breast. Comprehensive diagnostic evaluation, including mammography, ultrasonography, contrast-enhanced computed tomography, and core needle biopsy, confirmed invasive ductal carcinoma, classified as Luminal A subtype (estrogen receptor/progesterone receptor-positive, human epidermal growth factor receptor 2-negative).

DIAGNOSES: Invasive ductal carcinoma of the left breast (pT3N3M1, stage IV) with ovarian metastasis.

INTERVENTIONS: The patient received 6 cycles of docetaxel/doxorubicin/cyclophosphamide chemotherapy (docetaxel, doxorubicin, and cyclophosphamide), followed by left modified radical mastectomy with axillary lymph node dissection, achieving R0 resection. Laparoscopic bilateral adnexectomy was also performed for ovarian ablation. Final pathology confirmed metastatic breast carcinoma in the ovaries.

OUTCOMES: The patient successfully achieved surgical tumor reduction, recovered well postoperatively, and showed no clinical evidence of disease progression.

LESSONS: This case highlights the distinct characteristics of ovarian metastases in HR+/HER2- breast cancer and their critical importance in differential diagnosis, particularly in distinguishing them from primary gynecologic tumors. For patients with a history of breast cancer, the presence of pelvic lesions should prompt consideration of metastatic potential to guide appropriate comprehensive treatment.}, } @article {pmid41759689, year = {2026}, author = {Guo, Y and Moalem-Taylor, G and Shivdasani, MN and Fridman, GY and Aplin, FP}, title = {Safety assessment of a soft metal-free silicone peripheral nerve cuff implanted in rat models of neuropathic and inflammatory pain.}, journal = {The journal of pain}, volume = {42}, number = {}, pages = {106232}, doi = {10.1016/j.jpain.2026.106232}, pmid = {41759689}, issn = {1528-8447}, abstract = {Peripheral nerve stimulation offers a promising alternative to pharmacological treatments for chronic pain, and recent advances in direct current stimulation enable selective inhibition of nociceptive activity. However, the safety of direct current delivery systems, particularly soft, metal-free nerve cuffs, remains poorly characterized under pathological conditions. This study evaluated the safety and biocompatibility of a silicone tripolar cuff for ionic direct current delivery in naïve rats and rodent models of neuropathic (spared nerve injury) and inflammatory (complete Freund's adjuvant) pain. The cuff was implanted around the sciatic nerve and evaluated through behavioral testing (von Frey and Hargreaves), magnetic resonance imaging, and immunohistochemistry of the sciatic nerve, dorsal root ganglia, and spinal cord. In naïve cohorts, both short- and long-term implantation did not alter behavior outcomes, and neither disease model showed worsening of pain sensitivity. Across implanted groups, markers associated with immune activation and fibrotic encapsulation were upregulated. Notably, only the implanted spared nerve injury cohort exhibited additional pathological changes, including T cell infiltration in the sciatic nerve and dorsal root ganglia, elevated satellite glial and astrocytic responses, and significant interaction between injury and implantation. Demyelination and C-fiber loss were observed in spared nerve injury cohort irrespective of cuff placement, consistent with baseline injury-driven pathology. These findings indicate that the soft, metal-free cuff is well tolerated in healthy and inflammatory pain conditions but may exacerbate local inflammation and tissue changes when implanted near nerve injury. This supports its potential use in chronic pain management when implantation is distal to local injury site. PERSPECTIVE: This study provides the first comprehensive safety assessment of a soft, metal-free nerve cuff for iDC delivery in healthy and pathological pain models. This work advances iDC as a potential treatment for chronic pain, and helps identify pathological conditions in which invasive cuff implantation could exacerbate existing nerve injury.}, } @article {pmid41759049, year = {2026}, author = {Borges, P and Costa, V and Spencer, HB and Leite-Silva, P and Furtado, S and Barbosa, C and Pereira, C and Dos-Santos-Silva, I and Santos, LL}, title = {Breast Cancer in Cape Verde: Clinical-Molecular Profile and Impact of an International Treatment Partnership.}, journal = {JCO global oncology}, volume = {12}, number = {}, pages = {e2500258}, doi = {10.1200/GO-25-00258}, pmid = {41759049}, issn = {2687-8941}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/therapy/pathology/mortality/epidemiology ; Adult ; Aged ; Retrospective Studies ; Aged, 80 and over ; }, abstract = {PURPOSE: Breast cancer (BC) is becoming a significant public health issue in Cape Verde. Understanding the profile of BC cases is crucial for improving patient outcomes and guiding public health initiatives. This study aimed to investigate the clinical and pathologic characteristics, treatment approaches, and outcomes of BC cases diagnosed and treated at Agostinho Neto University Hospital between January 2015 and July 2021 following implementation of an international treatment partnership.

METHODS: A retrospective analysis was conducted on 158 female patients with BC diagnosed during the study period. Data were collected on patient demographics, tumor characteristics, treatment protocols, and survival outcomes. Immunohistochemistry was performed on a subset of 114 patients to identify molecular subtypes. Descriptive statistics were used to summarize all variables. Overall survival was analyzed, and log-rank tests were performed to formally compare the survival curves and assess the statistical significance of any observed differences. Cox proportional hazard models were used to determine the independent effect of sociodemographic factors and clinical characteristics.

RESULTS: The median age at diagnosis was 52.5 years, with patients ranging from 28 to 91 years. Most patients resided on Santiago Island. Invasive ductal carcinoma was the most common type, found in 93% of cases. Over half of the tumors were poorly differentiated, and 57% were diagnosed at advanced stages (III and IV). Subtype distribution mirrored sub-Saharan patterns, with 24% triple negative and 11% human epidermal growth factor receptor 2 positive. Among patients with potentially curable BC, 61.4% received adequate therapy that followed the National Comprehensive Cancer Network (NCCN) Harmonized Guidelines for sub-Saharan Africa (SSA), including radiotherapy treatment, although this was performed abroad. The median follow-up calculated by reverse Kaplan-Meier was 33.7 months (IQR, 20.5-52.8 months). Patients treated according to stage-appropriate and phenotype-specific recommendations achieved better outcomes (79.9% 3-year survival).

CONCLUSION: This study emphasizes the importance of early diagnosis and adoption of the NCCN Harmonized Guidelines for SSA. Access to radiotherapy abroad, necessitated by the absence of local radiotherapy facilities, was correlated with improved survival. These findings underscore the feasibility of improving outcomes in low-resource settings through standardized treatment frameworks.}, } @article {pmid41756704, year = {2026}, author = {Ebrahimian, S and Soleimani Varaki, S and Zabihi, F}, title = {Breast Fibromatosis in a Patient With a History of Treated Breast Cancer: A Case Report.}, journal = {Clinical case reports}, volume = {14}, number = {3}, pages = {e72054}, pmid = {41756704}, issn = {2050-0904}, abstract = {Desmoid tumors are benign mesenchymal neoplasms that originate from muscular fasciae and aponeuroses. Breast involvement is exceptionally rare, accounting for less than 0.2% of all breast tumors. A 41-year-old woman with a history of right-sided invasive ductal carcinoma (IDC) diagnosed in 2022 underwent breast-conserving surgery (BCS) and axillary lymph node dissection (ALND), followed by adjuvant chemotherapy, radiotherapy, and daily tamoxifen (20 mg). The tumor measured 3.5 cm at its greatest dimension, was grade 2, estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, HER2 negative, and had a Ki-67 proliferation index of 25%. Histologic examination revealed a cribriform growth pattern without associated ductal carcinoma in situ (DCIS) or lymphovascular invasion (LVI), and one of nine axillary lymph nodes was positive for metastasis. In 2023, a total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed for ovarian suppression. During routine surveillance in 2024, a new mass was detected at the 2 o'clock position in the right breast. Two core needle biopsies performed over 6 months confirmed fibromatosis. Ongoing tumor enlargement and severe pain, despite radiotherapy, led to a wide local excision. Breast fibromatosis can closely mimic carcinoma both clinically and radiologically, and histologic analysis remains essential for definitive diagnosis. Complete surgical excision with negative margins remains the treatment of choice.}, } @article {pmid41756134, year = {2026}, author = {Napolitano, G and Napolitano, R and Coppola, R and Ragone, A and Kafeel, S and Palmiero, G and Lombardi, A and Casaretta, G and Giannatiempo, R and Caraglia, M and Naviglio, S and Sapio, L}, title = {Monocyte distribution width in breast cancer: Results from a retrospective exploratory pilot study.}, journal = {Molecular and clinical oncology}, volume = {24}, number = {3}, pages = {21}, pmid = {41756134}, issn = {2049-9469}, abstract = {Despite the therapeutic breakthroughs achieved over the years, breast cancer (BC) continues to rank as the deadliest tumor among women worldwide. Therefore, prevention and screening programs remain crucial for the successful recovery of patients with BC. Monocyte distribution width (MDW) is a novel hematological parameter provided along with the complete blood count by DxH haematology analyzers. Variations in MDW have been associated with diagnostic and prognostic significance in sepsis, viral infections and other inflammation-related diseases. However, the potential role of MDW remains largely unknown in malignant disorders, including BC. Using a retrospective approach, patients with BC were included in the present study to examine the MDW levels at diagnosis in relation to controls. MDW was also assessed with respect to the histopathological features of BC. Either Welch's t-test or Brown-Forsythe and Welch ANOVA were used to estimate significance, while receiver operating characteristic curves and the area under the curve were used to evaluate the overall performance of MDW in BC. MDW levels were higher in patients with BC than in controls (P<0.0001), while no changes were recorded in the absolute monocytes count. With respect to the histopathological features, an elevated MDW was typically detected in BC presenting as invasive ductal carcinoma (P=0.0002), and expressing either estrogen (P<0.0001) or progesterone receptors (P<0.0001). Higher MDW levels were also observed in patients with BC scoring as grade III, as well as in those presenting lymph node involvement (N1-3), suggesting a possible association with the progression of BC. Overall, the present retrospective exploratory pilot study proposed MDW as a possible biomarker in BC, indicating future perspectives for the diagnosis, stratification and prognosis of this deadly disease.}, } @article {pmid41755041, year = {2026}, author = {Yeo, J and Kwon, Y}, title = {High-Sensitive Microwave Humidity Sensor Using Polyvinyl Alcohol/Carboxymethyl Cellulose (PVA/CMC) Composites.}, journal = {Sensors (Basel, Switzerland)}, volume = {26}, number = {4}, pages = {}, pmid = {41755041}, issn = {1424-8220}, support = {2023-0279//Daegu University/ ; }, abstract = {This study investigates the humidity sensing characteristics of microwave sensors coated with polyvinyl alcohol/carboxymethyl cellulose (PVA/CMC) composites with different weight percentages. The microwave sensor has a band-stop filter characteristic and consists of a microstrip transmission line with an interdigital capacitor-defected ground structure (IDC-DGS). To evaluate performance, PVA/CMC composites were prepared in 100/0 (pure PVA), 90/10, 80/20, 60/40, and 0/100 (pure CMC) weight percentages. The humidity sensing capability of the IDC-DGS-based microwave sensors coated with the PVA/CMC composites with different weight percentages was compared by measuring the variations in the resonant frequency and magnitude level of the transmission coefficient. The relative humidity (RH) was changed from 40% to 90% with increments of 10% at a temperature around 25 °C. The experimental results demonstrate that the humidity sensing capability of the microwave sensor in terms of the variations in the resonant frequency and magnitude level of the transmission coefficient increased as the weight percentage of CMC content increased. Pure CMC shows enhanced humidity sensing performance compared to gelatin and PVA in terms of the percent relative frequency shift and effective relative permittivity.}, } @article {pmid41753930, year = {2026}, author = {Griep, G and Bovadilla, RG and Gomes, LG and Cartagena, LQ and Rehder, GP and Serrano, ALC}, title = {2D and 3D Interdigital Capacitors and Bias Tees Technologies on MnM Interposer for mmWave Applications.}, journal = {Micromachines}, volume = {17}, number = {2}, pages = {}, pmid = {41753930}, issn = {2072-666X}, support = {2023/17414-4; 2022/13645-9 and 0001//FAPESP and CAPES/ ; }, abstract = {This paper presents two capacitors fabricated using the metallic nanowire membrane (MnM) interposer technology operating at mmWaves. Standard 2D interdigital capacitors (IDCs) are designed to operate up to 70 GHz, which presents a straightforward and non-complex fabrication. In comparison, this work also proposes an improved device that is more compact and exhibits large capacitance density, as high-performance vias enable the realization of high-depth capacitors. The fabrication process of 3D devices presents advanced maturity and innovation as it takes advantage of the porous nature of the interposer material to overcome the device complexity, and is also described in detail. Both capacitor types are modeled by a numerical lumped-element model that also considers parasitics. The 3D capacitors were successfully fabricated and characterized up to 70 GHz, displaying capacitance values between 30 fF and 160 fF and self-resonant frequencies in good agreement with mmWave applications. The quality factor of these devices, measured at 40 GHz, lies between 16 and 4, and the superficial capacitance density is between 4 pF/mm[2] and 8 pF/mm[2], showing that these devices are indeed promising for mmWave applications. These devices present considerably larger capacitance density compared to 2D traditional capacitors fabricated on the high-performance substrate, highlighting the advantage of 3D fabrication using nanowire growth. In addition, thin-film resistances are simulated and fabricated, projecting their functions as an RF-choke in a bias tee configuration using Ti thin film sputtering deposition step that is also part of the capacitors fabrication.}, } @article {pmid41753610, year = {2026}, author = {Rodas-Pazmiño, K and Pazmiño-Gómez, B and Cagua-Montaño, L and Valle-Asan, S and Acosta-Farías, M and Fajardo-Aguilar, PJ and Romoleroux-Gutiérrez, P and Jiménez-Gurumendy, A and Andaluz-Guamán, S and Rodas-Neira, E}, title = {Strain-Specific microRNA Reprogramming of Human Dendritic Cells by Probiotic and Commensal Escherichia coli Outer Membrane Vesicles.}, journal = {Microorganisms}, volume = {14}, number = {2}, pages = {}, pmid = {41753610}, issn = {2076-2607}, abstract = {Outer membrane vesicles (OMVs) are tractable, cell-free microbial outputs that can shape innate immune programs. Here, we compared OMVs from the probiotic Escherichia coli Nissle 1917 (EcN) and the commensal strain ECOR12 in a paired within-donor model of human monocyte-derived dendritic cells (Mo-DCs) (N = 20). In the core integrated arm, Mo-DCs were exposed to iDC control, EcN OMVs, or ECOR12 OMVs (10 µg/mL, 24 h) and profiled for maturation markers (CD14, CD83, CD209), cytokines (IL-6, TNF-α, IL-10), and a targeted miRNA panel (miR-155-5p, let-7i-3p, miR-146b-5p, miR-29a-5p). Both OMV types promoted maturation (increased CD83 and reduced CD14), but generated distinct cytokine-miRNA configurations, with ECOR12 tending toward an IL-10-high profile and EcN toward higher IL-6/TNF-α tendencies. Multivariate integration separated conditions into reproducible, strain-specific immune fingerprints, supporting the key take-home that probiotic versus commensal E. coli OMVs imprint distinguishable coordinated response states in human DCs. In an extended phenotyping arm, ECOR63 OMVs were evaluated by ELISA and flow cytometry only and were not included in miRNA profiling or integrated PCA due to unavailable matched miRNA measurements.}, } @article {pmid41751080, year = {2026}, author = {Zhang, Y and Xu, Q and Chen, W and Fan, S and Hu, Y and Deng, X and Zhong, G and Luo, K and Chai, M and Zhong, H and Li, W and Hu, F and Wang, S and Liu, S}, title = {Evidence for Paternal Mitochondrial DNA Leakage in Diploid Hybrid Fish Lineages.}, journal = {Animals : an open access journal from MDPI}, volume = {16}, number = {4}, pages = {}, pmid = {41751080}, issn = {2076-2615}, support = {YLS-2025-ZY01011//Yuelushan Laboratory Breeding Program/ ; 2023YFD2400203//National Key R&D Program of China/ ; 32373119//National Natural Science Foundation of China/ ; 32293252//National Natural Science Foundation of China/ ; 2023TJ-N02//Youth Science and Technology Talents Lifting Project of Hunan Province/ ; CARS-45//the earmarked fund for China Agriculture Research System/ ; D20007//111 Project/ ; }, abstract = {Distant hybridization induces genomic instability in offspring, driving the occurrence of gene recombination and mutation. Analysis of the genomic genetic composition can be used to infer the genetic evolutionary relationships between species. Based on the improved diploid carp (IDC) and the improved diploid scattered mirror carp (IDMC) lineages derived from distant hybridization between female common carp and male blunt snout bream, this study analyzed the genetic variation in their mitochondrial genomes to investigate the impact of distant hybridization on mitochondrial DNA (mtDNA) structural variation. Analysis of complete mitochondrial genome sequence structure and composition revealed subtle structural divergence across generations in both the IDC and IDMC lineages. Analysis of the protein-coding gene sequence structure demonstrated mitochondrial genome structure instability in nascent hybrid diploid lineages. Yet, subsequent self-crossing significantly narrowed the range of structural variation within each lineage. Furthermore, analysis of the genetic variation in the mitochondrial genome sequence structure revealed that paternal base insertions occurred in both F1 lineages, accompanied by mutations predominantly consistent with those in crucian carp. The results of this study also indicated that the strictness of the paternal mtDNA elimination mechanism varied significantly among polymorphic individuals across different generations of the hybrid lineages, reflecting the randomness of paternal leakage.}, } @article {pmid41750424, year = {2026}, author = {Suigo, L and Lanzini, A and Straniero, V and Margolin, W}, title = {Mechanistic Insights into the Antimicrobial Effect of Benzodioxane-Benzamides Against Escherichia coli.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {15}, number = {2}, pages = {}, pmid = {41750424}, issn = {2079-6382}, support = {GM131705/GM/NIGMS NIH HHS/United States ; }, abstract = {Background/Objectives: The bacterial cell division machinery is emerging as an attractive target for antimicrobial compounds. FtsZ, a highly conserved essential division protein, is the target for a number of small molecules such as benzamides. Recent studies show that benzodioxane-benzamides (BDOBs) are among the most potent inhibitors of FtsZ function in Gram-positive bacteria, although their ability to inhibit Gram-negative FtsZ, in particular Escherichia coli FtsZ, has been more controversial. Methods: Here, we use genetic and cytological methods to demonstrate that FtsZ of efflux pump-disabled E. coli can be efficiently targeted by BDOBs. Results: We show that engineered mutants and spontaneous variants map in or near the interdomain cleft (IDC) of FtsZ that confers resistance to BDOBs, similar to previous results with Gram-positive FtsZs. We also uncover spontaneous extragenic mutants that can confer high levels of resistance to at least one potent BDOB, including a mutant that encodes a novel hyperfission variant of the essential cell division protein FtsW. Conclusions: Our evidence indicates that as with Gram-positive bacteria, the IDC of Gram-negative bacterial FtsZ is directly targeted by BDOBs, provided efflux pumps are disabled. We also conclude that FtsZ-independent factors can influence the effect of BDOBs on E. coli cell division, including activation of division septum synthesis.}, } @article {pmid41749909, year = {2026}, author = {Ultimescu, F and Ardeleanu, C and Ginghina, O and Mardare, M and Zamfir, M and Puscasu, AI and Bondoc, I and Vacarasu, AB and Antoniu, T and Hudita, A and Galateanu, B and Gales, L and Serban, E and Liscu, HD and Ionescu, AI and Ceausu, M and Olinca, MV}, title = {From Static to Dynamic: Adaptive Molecular Subtyping in Treated Breast Cancers-Evidence from Single-Center Retrospective Cohort Study.}, journal = {Cancers}, volume = {18}, number = {4}, pages = {}, pmid = {41749909}, issn = {2072-6694}, abstract = {Background/Objective: Breast cancer (BC) management has traditionally relied on static clinicopathologic and immunohistochemical biomarkers (hormone receptor status, HER2 expression, and proliferative activity assessed at diagnosis). However, these biomarkers are typically evaluated at a single time point and may not reflect therapy-induced molecular evolution. This study evaluates whether longitudinal molecular profiling before and after treatment better characterizes tumor dynamics and provides clinically actionable insights into treatment response, resistance, and prognosis. Methods: Thirty-two patients with invasive breast carcinoma were analyzed using histopathology, immunohistochemistry, tissue-based next-generation sequencing, and plasma circulating tumor DNA (ctDNA) analysis. Paired tumor tissue and plasma samples were collected before and after treatment when available. Changes in biomarker expression, molecular subtype, and genomic alterations were assessed to characterize molecular plasticity under therapeutic pressure. Results: The cohort had a median age of 54 years (range 29-86), predominantly invasive ductal carcinoma (>85%), and high-grade disease. Hormone receptor-positive tumors accounted for 78.1%. Molecular subtypes were Luminal A (34.4%), Luminal B HER2- (40.6%), Luminal B HER2+ (6.3%), HER2-enriched (6.3%), and triple-negative breast cancer (12.5%). Initial tissue sequencing identified PI3K/AKT pathway alterations in 28.1% of cases. Post-treatment analyses revealed substantial molecular discordance, including progesterone receptor loss (33.3%), HER2 status changes (33.3%), and Ki67 variability (77.8%). Plasma ctDNA analysis was informative in 53.1% of patients and identified additional clinically relevant alterations, including FGFR1 amplification and BRCA1/2 variants not detected in tissue. Conclusions: BC molecular profiles are dynamic and frequently altered by therapy. Longitudinal molecular assessment reveals clinically actionable changes overlooked by static subtyping, supporting a dynamic model of molecular classification, highlighting the potential value of adaptive molecular subtyping to improve treatment stratification and resistance monitoring.}, } @article {pmid41748602, year = {2026}, author = {Ativi, WX and Chen, W and Kwao, L and Ayivi, W and Sam, F and Alqahtani, A and Gu, YH and Al-Antari, MA}, title = {CMAF-Net: cross-modal attention fusion with information-theoretic regularization for imbalanced breast cancer histopathology.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-32794-1}, pmid = {41748602}, issn = {2045-2322}, support = {U22B2061//National Natural Science Foundation of China/ ; RGP2/314/45//Deanship of Scientific Research, King Khalid University, Saudi Arabia/ ; IITP-2025-RS-2024-00437191//Institute of Information & Communications Technology Planning & Evaluation (IITP) - Information Technology Research Center (ITRC), Ministry of Science and ICT, Republic of Korea/ ; IITP-2025-RS-2024-00437191//Institute of Information & Communications Technology Planning & Evaluation (IITP) - Information Technology Research Center (ITRC), Ministry of Science and ICT, Republic of Korea/ ; }, abstract = {Breast cancer diagnosis from histopathology images remains challenging due to two intertwined factors: severe class imbalance, where malignant cases represent a small minority of samples, and the need to integrate discriminative features across multiple spatial scales. Existing methods typically address imbalance and multi-scale fusion separately, leading to biased or redundant representations. We propose CMAF-Net, a theoretically grounded architecture that unifies information bottleneck principles with margin-based learning to jointly tackle these challenges. CMAF-Net employs a dual-branch CNN-Transformer backbone fused through a Cross-Modal Attention Fusion block, which implements temperature-controlled attention and redundancy minimization to preserve complementary local and global features. At the classification level, we introduce an Adaptive Class-Balanced Focal Loss that operationalizes margin theory under imbalance, enforcing larger margins for minority classes while dynamically adapting to feature distributions. Extensive experiments on the IDC dataset show that CMAF-Net achieves 94.92% sensitivity and 95.52% balanced accuracy, outperforming state-of-the-art baselines by up to 8.6% on malignant detection. Under extreme 99:1 imbalance, CMAF-Net maintains 76.45% sensitivity, demonstrating graceful degradation where competing methods fail catastrophically. Cross-dataset evaluation on BreakHis confirms robust zero-shot transfer across four magnifications with average sensitivity of 95.61%. Ablation studies and information-theoretic analyses validate the contributions of each component, while computational profiling shows CMAF-Net achieves superior accuracy-efficiency trade-offs compared to prior fusion networks. Beyond breast cancer, our framework establishes a principled template for information-theoretic fusion under class imbalance, with implications for rare disease detection, clinical decision support, and broader multi-modal learning tasks.}, } @article {pmid41741671, year = {2026}, author = {Lee, KH and Yang, Y and Heo, J and Kim, JH}, title = {Optimization of enhancement-mode MIS-GaN HEMT with dual channel for simple process using TCAD simulation.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-41105-1}, pmid = {41741671}, issn = {2045-2322}, abstract = {A metal-insulator-semiconductor (MIS) GaN high electron mobility transistor (HEMT) utilizing a dual-channel structure is demonstrated for enhancement-mode (E-mode) operation using the Synopsys Sentaurus™ technology computer-aided design (TCAD) simulator. The MIS dual-channel HEMT (IDC-HEMT) employs two AlGaN/GaN heterojunction layers to form two two-dimensional electron gas (2DEG) layers. Electrons in the lower 2DEG layer induce a continuous negative bias body effect on the upper channel, shifting the threshold voltage (Vth) in the positive direction and enabling E-mode operation. This structure achieves E-mode operation without requiring additional complex fabrication steps, such as the precise etching processes used in recessed gate or p-GaN gate designs. The 2DEG sheet density in the upper 2DEG of the MIS single-channel HEMT (ISC-HEMT) and IDC-HEMT are 5.49 × 10[12] cm[- 2] and 3.43 × 10[12] cm[- 2], respectively, while the lower 2DEG in the IDC-HEMT has sheet density of 0.76 × 10[12] cm[- 2], all obtained in the access region with a gate and drain bias of 0 V. Due to the reduced 2DEG sheet density in the upper 2DEG, the proposed IDC-HEMT exhibits degraded performance in on-resistance (Ron), with values 28.7 Ω∙mm, respectively, compared to the ISC-HEMT, which has and a Ron of 22.7 Ω mm. However, the Vth of the ISC-HEMT is - 1.41 V, while that of the IDC-HEMT is 0.25 V, demonstrating a significant positive shift of 1.66 V. This confirms that the proposed IDC-HEMT can operate in E-mode.}, } @article {pmid41740233, year = {2026}, author = {Martín-Quesada, AI and Martín-Abreu, C}, title = {Advances in the management of metastatic lobular breast cancer: Current evidence and emerging treatments.}, journal = {Seminars in oncology}, volume = {53}, number = {2}, pages = {152466}, doi = {10.1016/j.seminoncol.2026.152466}, pmid = {41740233}, issn = {1532-8708}, abstract = {Invasive lobular carcinoma (ILC) comprises ∼10%-15% of breast cancers and is characterized by loss of the cell-adhesion molecule E-cadherin (encoded by CDH1), discohesive growth, predominant estrogen receptor (ER) positivity, low-to-intermediate proliferation, and atypical metastatic spread to bone and gastrointestinal/peritoneal sites. Diagnostic assessment is often challenging owing to diffuse infiltration, frequently yielding non-measurable disease per response evaluation criteria in solid tumors (RECIST). Molecularly, ILC is enriched for phosphoinositide 3-kinase (PI3K) activation and harbors emerging vulnerabilities-such as ROS1 synthetic lethality in CDH1-deficient tumors and fibroblast growth factor receptor 1 (FGFR1)/bromodomain and extra-terminal (BET) dependencies-now under study. Because metastatic ILC remains underrepresented in trials, systemic therapy often mirrors invasive ductal carcinoma (IDC). This short communication synthesizes current evidence to distinguish shared from plausibly lobular-specific signals; highlights near-term opportunities-including antibody-drug conjugates (ADCs), oral selective ER degraders (SERDs), and selective use of immunotherapy in an immune-enriched subset with higher tumor-infiltrating lymphocytes (TILs) and PD-L1; and outlines trial-design adaptations-such as incorporating 18F-fluoroestradiol PET (FES-PET)-to improve representation and interpretability in metastatic ILC research.}, } @article {pmid41737064, year = {2026}, author = {Verma, P and Khurana, R and Kumar, S and Poojari, A and Rastogi, M and Agarwal, N and Gandhi, AK and Bharati, A and Mittal, K and Srivastava, S}, title = {Evaluation of Patterns of Recurrences in Patients With Breast Carcinoma: Are We Treating the Right Volumes, or Does the Tumor Biology Play the Role?.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e102214}, pmid = {41737064}, issn = {2168-8184}, abstract = {Purpose The study's purpose is to evaluate the patterns of locoregional recurrences (LRRs) in women with breast cancer treated with curative intent surgery with conventional postoperative radiation therapy and to assess whether LRRs are mainly related to clinical target volume (CTV) coverage, tumor biology, or both. Materials and methods This was a retrospective observational study conducted between 2016 and 2023; 151 patients with histopathologically proven infiltrating ductal carcinoma (IDC) of the breast were included in the study. After modified radical mastectomy or breast-conserving surgery (BCS) with axillary dissection or sentinel lymph node biopsy, based on the indications, patients also received regional nodal irradiation (RNI). Patients were treated with 50 Gy in 25 fractions with an additional 10-16 Gy boost in 5-8 fractions in BCS patients by conventional field border-based plans on the linear accelerator. Patients who developed LRRs were studied and mapped for patterns of recurrences and compared with the Radiation Therapy Oncology Group (RTOG) guidelines of CTV delineation. All cases of bilateral breast cancer were excluded. In all cases, regional RNI, including supraclavicular and axillary lymph node irradiation, was done, while internal mammary chain (IMN) irradiation was done in 19% of cases only. Results Median follow-up was 60 months. Of 151 patients, 15 (10%) developed LRRs. When compared to the index population, 40% of the patients in the recurrence group had triple-negative breast carcinoma versus 35.1% in the index population group, and 27% in the recurrence group were human epidermal growth factor receptor 2 (HER2)-positive versus 17% in the index group. Five-year LRR-free survival, distant metastasis-free survival, and overall survival were 90.07%, 82.79%, and 89.41%, respectively. Most of the patients with recurrences had aggressive biological features with IDC grade 3 tumors in 10/15 (67%), >4 node-positive disease in 15/15 (100%), triple-negative tumors in 6/15 (40%), and HER2neu 3+ disease in 4/15 (26.67%) (three out of the four patients had taken one year of anti-HER2 therapy also). Lymphovascular invasion was observed in 10/15 cases (67%). In 10 (67%) cases, LRRs were diagnosed simultaneously as the metastatic disease, while five (33%) patients presented with distant metastases secondarily. Chest wall (local) recurrences occurred in 12 (80%) cases, which also had a marginal failure, i.e., at the posterior border of RTOG volumes; 13 (87%) regional recurrences were observed in 11 patients; of these, seven (53.8%) recurrences occurred in the supraclavicular fossa. Four (31%) recurrences occurred inside the RTOG level III axilla, and two (15%) recurrences occurred inside the RTOG volume in the IMN. Of all 13 regional recurrences, only 3/13 (23%) regional recurrences occurred outside RTOG CTV, while 10 (77%) recurrences occurred inside RTOG volumes. Conclusion Our study showed that LRRs predominantly occurred in patients with aggressive tumor biology. Approximately 70% of failures were covered inside RTOG volumes, which indicates that if RTOG volume-directed planning had been used for radiation treatment in such high-risk patients, these geographical misses could have been avoided. Adopting RTOG guidelines for volume delineation in high-risk cases with aggressive histology might be beneficial. However, further follow-up and meticulous documentation of the recurrences are needed to improve their understanding.}, } @article {pmid41735610, year = {2026}, author = {Sadeghi, M and Ghaderi, A and Mousavi, P and Sabetian, S and Ramezani, A and Haghshenas, MR}, title = {FN1 as a key gene in modulating the integrin cell surface pathway in breast cancer.}, journal = {Medical oncology (Northwood, London, England)}, volume = {43}, number = {4}, pages = {}, pmid = {41735610}, issn = {1559-131X}, support = {4000409//deputy of Research in the Hormozgan University of Medical Sciences, Bandar Abbas, Iran./ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/metabolism/pathology ; *Fibronectins/genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/genetics ; DNA Methylation ; *Integrins/metabolism/genetics ; Antigens, CD/genetics ; *Carcinoma, Ductal, Breast/genetics/pathology/metabolism ; Promoter Regions, Genetic ; Middle Aged ; Cadherins ; }, abstract = {Breast carcinoma represents the most prevalent form of invasive neoplasia among the female population globally, and is distinguished by its molecular heterogeneity by significant genomic instability. The discipline of bioinformatics provides essential tools for the identification of novel biomarkers and enhances the prospects for subsequent experimental investigations. Differentially expressed messenger RNAs were assembled by employing datasets sourced from the Gene Expression Omnibus repository. Intersection of DEGs and proteins involving in the integrin cell surface interactions were done. Ce-RNA network were constructed and Functional analysis were done. Protein expression analysis, methylation and, Correlation analysis as well as drug sensitivity analysis for the hub genes were performed. The expression of FN1 were evaluated using Real-Time PCR for 45 invasive ductal carcinoma breast tissues and adjacent normal samples. We found FN1, CDH1, COMP, SPP1 and ITGA7 to act in integrin cell surface interactions. The Ce-RNA network consisted of 126 nodes and 192 edges which the network nodes were significantly enriched in known cancer pathways. Protein expressions of FN1, CDH1, COMP was upregulated while ITGA7 were downregulated. The methylation levels in ITGA7 and SPP1 promoter regions were significantly altered across all stages compared to normal. In contrast, FN1 and CDH1 promoter regions exhibited dysregulation only in stage 3 relative to normal. A correlation study identified five positive and three negative gene correlations. Altered expression of FN1, SPP1, CDH1, and ITGA7 in breast cancer enhanced cancer cell susceptibility to specific pharmacological molecules. FN1 expression was markedly higher in breast cancer tissues compared to non-cancerous tissues, showing a threefold increase (p < 0.0001). Both early-stage and advanced-stage cancers showed higher FN1 levels (p = 0.002, p = 0.01). Additionally, FN1 was higher in lower histological grade tissues (p = 0.0002). In ROC curve analysis with limited stage III samples, FN1 showed potential for diagnosing IDC, achieving an AUC of 0.82. We identified FN1 as a highly connected component of integrin cell-surface interactions in breast cancer and provide hypothesis-generating associations with drug sensitivity; these findings require further protein-level validation and functional testing before translational application.}, } @article {pmid41730259, year = {2026}, author = {Dupont, AC and Farges, M and Chapelle, B and Cancel, M and Ribeiro, MS}, title = {From One Cancer to Two: [[18]F]FES PET/CT Redirected Diagnosis and Therapy in a Metastatic Breast Cancer Patient.}, journal = {Clinical nuclear medicine}, volume = {}, number = {}, pages = {}, doi = {10.1097/RLU.0000000000006386}, pmid = {41730259}, issn = {1536-0229}, abstract = {A 59-year-old woman with an ulcerated right breast lesion was diagnosed with ER-positive invasive ductal carcinoma. Staging [[18]F]FDG PET/CT revealed intense uptake in the breast, axillary nodes, a large hypermetabolic pulmonary mass, mediastinal lymphadenopathies, and bone lesions. Because of this metabolic pattern, [[18]F]FES PET/CT was performed, demonstrating [[18]F]FES-avid bone metastases but no uptake in the lung mass. Biopsy confirmed a BRAF V600E-mutated lung adenocarcinoma. [[18]F]FES PET/CT proved crucial in differentiating synchronous primary malignancies from metastatic spread and guiding targeted therapy with dabrafenib-trametinib.}, } @article {pmid41727395, year = {2026}, author = {Javed, A and Dreyer, J and Cassidy, D and Amin, S}, title = {Metastatic lobular breast cancer masquerading as achalasia.}, journal = {VideoGIE : an official video journal of the American Society for Gastrointestinal Endoscopy}, volume = {11}, number = {2}, pages = {41-45}, pmid = {41727395}, issn = {2468-4481}, abstract = {BACKGROUND AND AIMS: A 64-year-old woman with stage IV breast cancer taking exemestane presented with weight loss of 10 to 15 pounds and dysphagia of 3 to 6 months in duration. Upper endoscopy and positron emission tomography/computed tomography did not reveal a pathologic diagnosis. Esophageal manometry was suggestive of achalasia. The patient was referred for an esophageal peroral endoscopic myotomy (E-POEM) procedure. We aim to describe a rare finding encountered during submucosal dissection in an E-POEM that may result in an incomplete, aborted, technically challenging, or ineffective procedure.

METHODS: An E-POEM using a posterior approach is our preferred method. E-POEM was planned in the standard fashion. A mucosotomy followed by submucosal injection and dissection was performed, with plan for an extended circular and full-thickness myotomy of the lower esophageal sphincter.

RESULTS: During submucosal dissection, atypical yellow-brown tissue was encountered within the submucosal tunnel. This was initially thought to be related to fibrosis from severe achalasia. In total, 3 tunnels were created with eventual abortion of the procedure because this abnormal tissue was found 3 to 4 cm proximal to the esophagogastric junction in each tunnel. This tissue was biopsied, and all tunnels were closed without any postprocedural adverse event. Pathology demonstrated metastatic lobular breast cancer.

CONCLUSIONS: Invasive lobular breast cancer has a propensity to spread to the GI tract as compared with other forms of cancer such as invasive ductal carcinoma. Endoscopists who perform E-POEM who encounter difficulty expanding the submucosal plane during E-POEM should keep malignancy and metastatic disease in mind as a rare cause of pseudoachalasia, even in the absence of nondiagnostic pre-peroral endoscopic myotomy evaluation.}, } @article {pmid41726015, year = {2026}, author = {Nupur, N and Mohanty, M and Panda, K and Mohanty, NR and Dash, S}, title = {Diagnostic Accuracy of the BI-RADS, Using Both Mammograms and Sonograms, in Distinguishing Between Benign and Malignant Breast Masses.}, journal = {Indian journal of surgical oncology}, volume = {17}, number = {2}, pages = {462-468}, pmid = {41726015}, issn = {0975-7651}, abstract = {UNLABELLED: The American College of Radiology (ACR) created the Breast Imaging Reporting and Data System, or BI-RADS, to standardize the way radiologists report mammography, ultrasound, and MRI findings. This study aimed to compare the diagnostic accuracy of combined mammography and sonography with that of mammography alone in differentiating malignant from benign breast masses. This 3-year, hospital-based cross-sectional study included female patients presenting with breast lumps. Diagnostic accuracy metrics, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy, were calculated with histopathology as the gold standard. This study evaluated 590 female patients with breast lumps (mean age 46.3 years), identifying 330 benign and 260 malignant cases. Fibroadenoma and invasive ductal carcinoma were the most common diagnoses. Patient age and body mass index (BMI) were significantly correlated with diagnosis, with an increased incidence of malignancy in the older and higher BMI groups, unlike fertility status; and, crucially, combining mammography with ultrasonography significantly enhanced breast lesion detection. This combined approach increased the sensitivity from 94.62% to 99.23% and the specificity from 86.67% to 90.91%. Consequently, both the PPV (84.83% to 89.58%) and NPV (95.33% to 99.34%) improved, resulting in an overall increase in diagnostic accuracy from 90.17% to 94.58%. This study revealed that combining mammography and sonography significantly improves the diagnostic accuracy for palpable breast masses, especially in differentiating between benign and malignant lesions. Integrating both imaging techniques into standard practice will lead to early diagnosis of malignant lesions and help avoid unnecessary biopsies for benign lesions.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13193-025-02432-3.}, } @article {pmid41724602, year = {2026}, author = {Tao, J and Niu, Z and Zhou, M and Zhao, J and Xiao, M and Zhu, Q}, title = {Viscoelastic Mechanical Properties Assessed by Ultrasound Correlates with Tumor Proliferation in Invasive Ductal Breast Cancer: A Preliminary Study.}, journal = {Ultrasound in medicine & biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ultrasmedbio.2026.01.016}, pmid = {41724602}, issn = {1879-291X}, abstract = {OBJECTIVE: Ultrasound-based viscoelastic imaging enables the real-time characterization of tissue properties. In this study, we aimed to investigate the correlation between viscoelastic mechanical properties and tumor proliferation in invasive ductal breast cancer (IDC).

METHODS: This prospective study consecutively enrolled patients with IDC during October 2024 and January 2025. All patients underwent preoperative shear-wave elastography (SWE) and ultrasound-based viscoelastic imaging. The viscoelastic mechanical properties (viscosity coefficients [Vmax and Vmean] and dispersion coefficients [Dmax and Dmean]) and SWE (Emax) were measured within the tumor and in a 1-mm peritumoral region (Vtmax, Vtmean, et al.). Patients were stratified into high (Ki-67 ≥ 14%) and low (Ki-67 < 14%) proliferation groups. Viscoelastic mechanical properties and SWE between groups were compared.

RESULTS: Among the 124 female patients with IDC, 94 exhibited high Ki-67 expression while 30 had low Ki-67 expression. No significant differences were observed in SWE-based elasticity between the two groups (p > 0.05). Vmean and Vtmean were lower in the high Ki-67 group (1.1 [0.7-1.7] vs. 1.5 [1.0-2.3], p = 0.020; 1.3 [0.8-1.8] vs. 1.7 [1.1-2.4], p = 0.026, respectively). Using Vmean ≤ 1.2 Pa·s as cutoff value, a significantly higher proportion of high Ki-67 expression was found (64.9% vs. 35.1%, p = 0.016).

CONCLUSION: Viscoelastic mechanical properties, rather than traditional SWE elasticity, correlated with Ki-67 expression in IDC. A lower Vmean may be correlated with higher proliferative activity, potentially serving as a non-invasive imaging biomarker. These findings support further exploration of ultrasound-based viscoelastic imaging for the assessment of tumor microenvironment heterogeneity.}, } @article {pmid41721009, year = {2026}, author = {Sengupta, A and Saha, P and Chakraborty, R and Maiti, AK and Chakraborty, S and Datta, A and Datta, AS}, title = {Breast cancer: taxonomy, distribution analysis, risk factors, predictive biomarkers, and modern treatment method.}, journal = {Apoptosis : an international journal on programmed cell death}, volume = {31}, number = {3}, pages = {}, pmid = {41721009}, issn = {1573-675X}, } @article {pmid41719937, year = {2026}, author = {Westermann, S and Bennühr, BC and Fumo, AR and Rohm, M and Hiller, K}, title = {Muscle-immune metabolic crosstalk: shared pathways in cachexia and exercise.}, journal = {Current opinion in biotechnology}, volume = {98}, number = {}, pages = {103455}, doi = {10.1016/j.copbio.2026.103455}, pmid = {41719937}, issn = {1879-0429}, abstract = {Skeletal muscle and the immune system continuously exchange metabolites and signals that are essential for homeostasis. Disruption of this communication, such as during infection, inflammation, or cancer, triggers cachexia, a severe wasting syndrome characterized by altered amino acid flux, mitochondrial dysfunction, and systemic energy imbalance. By contrast, regular exercise activates overlapping pathways but directs them toward regeneration and hypertrophy, supported by controlled cytokine release and metabolite exchange. This review outlines the metabolic reprogramming that underlies muscle-immune crosstalk in cachexia and exercise, emphasizing how identical mediators, including interleukin-6, can promote either catabolism or adaptation depending on context. Understanding these shared yet divergent pathways opens avenues for therapeutic strategies that target metabolism and immune-metabolic communication.}, } @article {pmid41718582, year = {2026}, author = {Gilchrist, FJ and Clayton, S and Carroll, WD}, title = {Saving money but costing lives: the lack of integrated dose counters on pressurised metered dose inhalers.}, journal = {Expert opinion on drug delivery}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/17425247.2026.2636180}, pmid = {41718582}, issn = {1744-7593}, abstract = {INTRODUCTION: Pressurized metered dose inhalers (pMDIs) are used to deliver treatment to individuals with respiratory diseases. Whilst the technology within pMDIs has not significantly changed in the last 25 years, some changes in legislation and supply have taken place. These have been driven by pragmatism, cost and most recently concerns about the environmental impact of the propellants used within their manufacture. A major issue affecting patients in most countries, is the large number of pMDIs without an integrated dose counter (IDC). This makes it difficult or impossible for patients to monitor the number of remaining doses.

AREAS COVERED: This article will review how pMDIs work, their environmental impact and the adverse clinical effects of not having an IDC. It will also look at the scale and cost of the issue as well as ways in which individuals can safely assess if their pMDI is empty of medication.

EXPERT OPINION: We conclude there is an urgent need for IDCs on short acting beta agonist (SABA) pMDIs to be made mandatory as this is likely to reduce asthma exacerbations and deaths. Whilst waiting for this to happen, patients should be shown how to weigh their SABA canister to identify when it needs to be replaced.}, } @article {pmid41713211, year = {2026}, author = {Esteban-Burgos, AA and Molina-Mérida, R and Granero-Moya, N and Iribarne-Durán, LM and Montoya-Juárez, R and López-Morales, M}, title = {[Identification of palliative needs, complexities and other clinical variables in complex chronic patients in primary care in Andalusia: INCO-Pal study].}, journal = {Atencion primaria}, volume = {58}, number = {5}, pages = {103469}, pmid = {41713211}, issn = {1578-1275}, abstract = {OBJECTIVE: To describe palliative care needs, case and palliative complexity, frailty, prognosis, and other relevant clinical variables in complex chronic patients (CCPs) attended in Primary Care in Andalusia.

DESIGN: Descriptive, cross-sectional, multicentre study. SITE: Primary care centres in the eight provinces of Andalusia.

PARTICIPANTS: 179 CCPs randomly selected by case management nurses trained in the use of assessment tools.

INTERVENTIONS: Sociodemographic and clinical variables were collected, and validated tools were applied: NECPAL-ICO-CCOMS© for palliative needs, Frágil-VIG for frailty, ICCa for case complexity, IDC-Pal for palliative complexity, and the PROFUND and PPI indices to estimate prognosis.

MAIN MEASUREMENTS: The mean age was 80.59 (±9.764) years, and 54.7% were women. Forty-two point five per cent met NECPAL criteria for advanced PCC. The mean frailty was 0.37 (±0.166). Forty-one point three per cent were classified as complex cases (ICCa) and 26.3% presented high palliative complexity (IDC-Pal). The one-year mortality risk was 45-50% (PROFUND), with an estimated mean survival of 135days (PPI).

RESULTS: Statistically significant differences (P≤0,05) were found in tool scores by sex, presence of cognitive impairment, and caregiver availability. Significant correlations were observed between frailty, complexity, and prognosis.

CONCLUSIONS: A high proportion of CCPs in Primary Care in Andalusia present palliative needs, frailty, and clinical and social complexity, with a limited life expectancy. These findings evidence the need for systematic comprehensive assessments to identify early patients requiring specific palliative care and to optimize the use of health and social care resources.}, } @article {pmid41710858, year = {2026}, author = {Czyz, S and Marszal, W and Marszal, R}, title = {From Prophylactic Screening to Definitive Treatment: A Case Report of Breast Cancer in a Young Woman.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e101722}, pmid = {41710858}, issn = {2168-8184}, abstract = {This article presents the case of a 39-year-old woman with a positive family history of breast cancer (her family member had left breast cancer, cT4N2M0, non-luminal human epidermal growth factor receptor 2 (HER2)-positive). During routine prophylactic ultrasonographic examination, a breast mass was detected, which, on further diagnostics, turned out to be an invasive ductal carcinoma of the left breast. The stage of the disease was determined as pT1cN1mic(sn), Nottingham Histologic Grade 3 (NHG 3). The patient was subjected to surgical treatment, which involved left mastectomy with simultaneous removal of the axillary sentinel lymph node. Subsequently, adjuvant chemotherapy was administered, including a "dose-dense" regimen with the use of doxorubicin and cyclophosphamide, followed by treatment with paclitaxel. During chemotherapy, complications related to the implantation of a vascular port occurred, which resulted in its removal before the completion of treatment. After the completion of chemotherapy, breast reconstruction was performed. During the entire treatment process, extended genetic diagnostics were performed, which did not demonstrate the presence of pathogenic gene mutations. The treatment was completed, and the patient remains under continuous care of the oncology outpatient clinic.}, } @article {pmid41710445, year = {2026}, author = {Seifert, L and Guignard, B and Létocart, A and Regaieg, MA and Guimard, A and Chollet, D and Carmigniani, R and Pouleau, N and Charentus, A and Leprêtre, PM}, title = {Stroke Rate and Arm Coordination Management in Swimming in A Double Paralympic Triathlete Champion.}, journal = {Journal of sports science & medicine}, volume = {25}, number = {1}, pages = {211-220}, pmid = {41710445}, issn = {1303-2968}, mesh = {Humans ; *Swimming/physiology ; Energy Metabolism/physiology ; Oxygen Consumption ; Male ; *Arm/physiology ; *Athletic Performance/physiology ; Lactic Acid/blood ; Adult ; *Sports for Persons with Disabilities/physiology ; Biomechanical Phenomena ; *Para-Athletes ; Competitive Behavior/physiology ; *Motor Skills/physiology ; }, abstract = {The 2024 Paris Paralympic triathlon required swimming with and against the current which requested to adapt stroke mechanics. To understand how a Paralympic triathlete champion might adapt his stroke mechanics under varying current conditions, this study aimed to 1) determine the range and optimal stroke rate (SR) and index of coordination (IdC); 2) examine the flexibility of SR, IdC and associated total energy expenditure. The para triathlete performed two front crawl tests: 10 times 25m incremented in swimming speed (S), from which S-SR and S-IdC relationships have been modelled to detect two regimes of functioning and the most effective SR; then, 6 times 50 m at the speed of the 800 m freestyle using 6 different SR conditions: spontaneous SR (SRs), SRs imposed by tempo trainer, SRs+3, SRs+6, SRs-3 and SRs-6 cycles. Total energy expenditure was computed from post-exercise oxygen uptake and blood lactate measurements. In test 1, the highest effective SR equals 44 cycle.min[-1], which corresponds to the preferred SR in 800 m freestyle competition. In test 2, the para triathlete struggled to perform the high SR conditions, which was associated to higher total energy expenditure; conversely, the para triathlete naturally decreased SR. It is advised to modulate SR around the preferred SR to optimise efficiency under varying current conditions.}, } @article {pmid41708931, year = {2026}, author = {Pujol, N and Gal, J and Gautier, M and Rizzi, Y and Courtault-Deslandes, F and Schiappa, R and Hannoun-Levi, JM}, title = {Second Ipsilateral Breast Cancer Event: True Recurrence, New Primary, or True Recurrence Like? : Breast Cancer Local Recurrence.}, journal = {Annals of surgical oncology}, volume = {}, number = {}, pages = {}, pmid = {41708931}, issn = {1534-4681}, abstract = {BACKGROUND: In the case of a second ipsilateral breast cancer event (2[nd] iBCE) after breast-conserving treatment (BCT), tumor histology and topography are used to distinguish between true recurrence (TR) and new primary (NP). This study aimed to address the lack of data to accurately define TR and NP.

METHODS: Patients experiencing a second iBCE with a second BCT (lumpectomy + brachytherapy) were retrospectively analyzed. Histology (type, grade, hormone receptor [HR], human epidermal growth factor receptor 2 [HER2] status) and second iBCE topography were used to determine TR and NP. Oncologic outcomes of TR and NP were compared by cumulative incidence rate of second local relapse (CI-2[nd] LR), distant metastasis disease (CI-DMD), disease-free survival (DFS), and overall survival (OS). A systematic literature review was performed.

RESULTS: From September 2000 to January 2024, 113 patients met the inclusion criteria (76 TR patients, 37 NP patients). The median age was 52.1 years for the first and 65.4 years for the second iBCE. The median interval between the two breast surgeries (TIS1S2) was 149.3 months. The second iBCE occurred at a distance from the first iBCE (82.3%), was invasive ductal carcinoma (83.2%), and had a luminal profile (92%). With a median follow-up period of 78.9 months, CI-2[nd] LR was 4%, CI-DMD was 8%, DFS was 87%, and OS was 90%. No significant difference in oncologic outcome was observed between TR and NP (CI-2[nd] LR: 3 vs 6% [p = 0.9]/CI-DMD: 9 vs 5% [p = 0.6]/OS: 90 vs 91% [p = 0.5]).

CONCLUSION: This study suggests that TR and NP dichotomy based on tumor histology and topography does not necessarily support TR therapeutic consequences. In case of late TR, a second BCT could be carefully discussed for patients who wish to preserve their breast.}, } @article {pmid41707646, year = {2026}, author = {Cheng, Y and Wan, L and Huang, E and Zheng, B and Ding, X and Tan, S and Ma, G and Li, W and Chu, C and Wu, T and Chen, S and Zhuang, J and Na, R and Chen, Z and Teng, G and Zhang, D and Ju, S and Chen, M and Xu, B}, title = {A conserved eIF1A[+] luminal cell-centered hypoxic and "cold" tumor microenvironment promotes pan-subtype prostate cancer progression.}, journal = {Cell reports. Medicine}, volume = {7}, number = {2}, pages = {102619}, pmid = {41707646}, issn = {2666-3791}, mesh = {Male ; Humans ; *Prostatic Neoplasms/pathology/metabolism/genetics ; *Tumor Microenvironment ; Disease Progression ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; Animals ; Cell Line, Tumor ; Mice ; }, abstract = {Prostate cancer (PCa) is a malignancy with high heterogeneity arising from tumor microenvironment and histological subtypes. Identifying conserved progression drivers within such heterogeneity is essential for improving clinical outcomes. Using imaging mass cytometry, this study analyzes 38 proteins across paracancerous tissue and four histological subtypes: low-grade prostate acinar adenocarcinoma (LgPAC), high-grade PAC (HgPAC), intraductal carcinoma (IDC), and ductal adenocarcinoma (DAC). Results reveal that eIF1A is overexpressed in high-risk subtypes including HgPAC, IDC, and DAC and correlates with poor prognosis. In luminal cells, EIF1A knockdown and the translation inhibitor homoharringtonine (HHT) both suppress HIF-1α translation and tumor growth, while promoting infiltration of anticancer immune cells including PD-1[-] T cells and CD163[-] macrophages. Clinically, neoadjuvant HHT combined with androgen deprivation therapy reduces hypoxia and enhances immune cell infiltration, as shown by single-cell RNA sequencing. Collectively, this work defines conserved molecular features across PCa subtypes, providing promising insights for clinical management. This study was registered at Clinicaltrials.gov (NCT06834321).}, } @article {pmid41703656, year = {2026}, author = {Bekai, C and Stirling, M}, title = {Metastatic breast cancer presenting with dyspeptic symptoms: a case report.}, journal = {Journal of medical case reports}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13256-026-05864-9}, pmid = {41703656}, issn = {1752-1947}, abstract = {BACKGROUND: Breast cancer is among the most commonly diagnosed malignancies worldwide. While distant metastases typically involve the bone, lung, liver, and brain, metastasis to the gastrointestinal tract is uncommon and occurs disproportionately in invasive lobular carcinoma (ILC). The clinical presentation is often nonspecific, which can delay diagnosis. This case presents the synchronous diagnosis of both primary breast cancer and gastric metastasis.

CASE PRESENTATION: A 78-year-old woman presented with chronic belching, dyspepsia, and intermittent melena. Initial treatment and improvement with proton pump inhibitor therapy, suggested a primary gastrointestinal disorder. However, gastric biopsy confirmed metastatic invasive lobular carcinoma, and subsequent imaging revealed diffuse bony metastases.

CONCLUSIONS: This case highlights the synchronous diagnosis of gastric metastases originating from invasive lobular carcinoma with its associated diagnostic complexities and the limitations of traditional imaging modalities in detecting such metastases. Early recognition and accurate diagnosis are crucial for guiding appropriate treatment and improving patient outcomes. Therefore, we present a case that suggests considering breast cancer metastasis in the differential diagnosis for patients presenting with nonspecific gastrointestinal symptoms, even in the absence of breast-related complaints, is a reasonable clinical approach.}, } @article {pmid41702510, year = {2026}, author = {Vu, ATT and Shrestha, P and Le Thi, TH and Giri, A and Pham, KY and Nguyen, TTK and Cho, J and Kweon, S and Lee, NK and Hong, IS and Kwon, TK and Kang, JS and Jeong, JH and Yook, S}, title = {Protein corona-guided delivery of dextran-PLGA NPs for enhanced dendritic cell uptake, maturation and improved cancer immunotherapy.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {392}, number = {}, pages = {114733}, doi = {10.1016/j.jconrel.2026.114733}, pmid = {41702510}, issn = {1873-4995}, abstract = {The formation of a protein corona (PC) significantly influences the behavior of nanoparticles (NPs) in biological fluids; however, its impact on immune modulation and therapeutic efficacy has not been completely understood. The dextran coating of NPs has demonstrated promising effects, including complement system activation and enhanced immune cell uptake. The stimulator of interferon genes (STING) pathway plays a vital role in coordinating innate and adaptive immunity, making STING agonists attractive candidates for cancer immunotherapy. In this study, we developed dextran-coated PLGA nanoparticles loaded with SR717 (Dex-PLGA@SR717 NPs) for enhanced uptake by immature dendritic cells (iDCs) and for promoting tumor-targeted immune activation. Following incubation with human serum (HS), Dex-PLGA NPs formed a PC enriched in the complement component C3, which resulted in superior cellular internalization compared with uncoated PLGA NPs. The significant role of Dex-PLGA@SR717 NPs in promoting iDC maturation and enhancing antigen presentation was confirmed through in vitro studies. This facilitated robust T cell activation and cytotoxicity against B16F10 melanoma cells. Biodistribution analysis revealed preferential accumulation of Dex-PLGA@SR717 NPs in immune-related organs, such as the spleen and lymph nodes, further supporting their immunostimulatory potential. In a murine tumor model, intravenous administration of Dex-PLGA@SR717 NPs (10 mg/kg SR717) was observed to effectively suppressed tumor growth by eliciting a potent antitumor immune response. These findings highlight the potential of Dex-PLGA@SR717 NPs as a promising immunotherapeutic nanoplatform for enhancing dendritic cell-mediated cancer treatment.}, } @article {pmid41695362, year = {2026}, author = {Li, S and Huang, T and Feng, M and Deng, M and Chen, X and Li, X and Mo, D}, title = {HER-2 overexpressing breast cancer during pregnancy: a case report and literature review.}, journal = {Frontiers in oncology}, volume = {16}, number = {}, pages = {1725927}, pmid = {41695362}, issn = {2234-943X}, abstract = {BACKGROUND: Breast cancer during pregnancy (PrBC) is rare but increasingly reported due to delayed childbearing, widespread assisted reproduction, and younger onset of breast cancer. Among these, HER2-overexpressing subtypes pose particular clinical challenges in balancing effective oncologic control with fetal safety. It requires a delicate balance between optimizing maternal oncologic outcomes and ensuring fetal safety.

CASE PRESENTATION: We report the case of a 33-year-old woman diagnosed with HER-2 overexpressing invasive ductal carcinoma of the right breast at 16 weeks of gestation. Driven by a strong desire to continue the pregnancy, the patient, in consultation with a multidisciplinary team, opted for neoadjuvant chemotherapy. From 17 to 31 weeks' gestation, she received four cycles of epirubicin and cyclophosphamide, followed by one cycle of nab-paclitaxel, achieving a partial response. At 37 weeks, she underwent a successful vaginal delivery, giving birth to a healthy female infant. Postpartum, she continued her neoadjuvant treatment with three cycles of nab-paclitaxel plus dual anti-HER2 therapy (trastuzumab and pertuzumab). After completing the full neoadjuvant regimen, she underwent breast-conserving surgery, and pathology confirmed a complete response. Her postoperative treatment included adjuvant dual anti-HER2 therapy and whole-breast radiotherapy. At the last follow-up (18 months post-delivery), the mother showed no signs of recurrence, and the child exhibited normal growth and neurodevelopment.

CONCLUSIONS: This case demonstrates that with careful multidisciplinary planning and individualized treatment strategies, it is feasible to achieve both successful maternal oncologic control and the delivery of a healthy baby in patients with HER-2 overexpressing breast cancer during pregnancy. This case contributes valuable evidence to the management of this complex clinical scenario.}, } @article {pmid41694167, year = {2026}, author = {Eren, A and Karatay, E and Durur-Subasi, I}, title = {The Role and Feasibility of Automated Breast Ultrasound in the Evaluation of Male Breast Disease: Workflow Efficiency and Imaging Spectrum.}, journal = {Cureus}, volume = {18}, number = {2}, pages = {e103467}, pmid = {41694167}, issn = {2168-8184}, abstract = {Traditional hand-held ultrasonography (HHUS) suffers from inherent limitations, including operator dependency, lack of reproducibility, and long acquisition times in busy clinical settings. Automated breast ultrasound (ABUS) addresses these drawbacks by providing standardized, three-dimensional, and operator-independent imaging that separates acquisition from interpretation. While the diagnostic performance of ABUS has been extensively validated for supplemental screening in females with dense breast tissue, its specific application in the male population remains an unexplored frontier in the literature. Objective The objective of this study was to evaluate the diagnostic value, workflow advantages, and imaging spectrum of ABUS in male breast diseases based on a large-scale, single-center experience. Methods This retrospective study included 85 male patients (mean age: 36.6 ± 13.7 years) who underwent ABUS between April 2023 and February 2025. Inclusion criteria focused on symptomatic patients and those requiring high-risk screening or follow-up. Recall rates, complementary imaging frequency, and the Breast Imaging Reporting and Data System or BI-RADS categories were analyzed. Results Breast pain (53 cases, 62.4%) was the most common symptom, and gynecomastia (29 cases, 34.1%) was the most frequent finding. The recall rate for secondary HHUS was 1.2% (1 case). Three biopsies revealed one lipoma, one invasive ductal carcinoma, and one papillary carcinoma. Conclusion ABUS provides a standardized, reproducible evaluation of male breast diseases with minimal recall and optimized workflow efficiency. It serves as a promising adjunct to standard imaging protocols, particularly in younger males where avoiding radiation is preferable, and offers a unique anatomical plane (C-plane).}, } @article {pmid41685202, year = {2026}, author = {Wake, H and Watanabe, K and Tanami, H}, title = {Surgical Management of Breast Cancer Adjacent to a Calcified Ventriculoperitoneal Shunt: A Case Report.}, journal = {Surgical case reports}, volume = {12}, number = {1}, pages = {}, pmid = {41685202}, issn = {2198-7793}, abstract = {INTRODUCTION: Breast cancer arising in tissue adjacent to a ventriculoperitoneal (VP) shunt is exceptionally rare, and there is little guidance on how to manage the shunt hardware during oncologic surgery in such cases.

CASE PRESENTATION: The patient was a 46-year-old woman with a history of intellectual disability and hydrocephalus. She had undergone VP shunt placement via the left chest wall for hydrocephalus during childhood. Decades later, she was admitted to our hospital for the examination and treatment of left breast cancer. Imaging studies revealed a tumor in the left nipple, with the shunt catheter passing as close as 12 mm from the tumor. During radical mastectomy for breast cancer, it became clear that preserving the catheter was not feasible. Consequently, the shunt catheter was rerouted, and both the left breast and the catheter were removed as a single unit. Pathological findings of a resection specimen revealed invasive ductal carcinoma pT2N1M0, pStage IIB. Although the catheter had been positioned very closely to the tumor, no cancer progression was observed along the catheter.

CONCLUSIONS: The present case is noteworthy for describing a rare case of mastectomy for breast cancer involving repositioning of an ipsilateral catheter. Included in this report is a review of past studies.}, } @article {pmid41685010, year = {2026}, author = {Purohit, T and Sahu, S and Dandekar, M and Verma, D}, title = {Expression of PTEN and p53 and Their Clinicopathological Correlation in Breast Cancer.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e101323}, pmid = {41685010}, issn = {2168-8184}, abstract = {BACKGROUND: Breast cancer is one of the most common malignancies in women and is a major cause of cancer-related mortality. Alterations in the expression of tumor suppressor genes such as PTEN and p53 may influence tumor behavior and prognosis. This study aimed to evaluate the immunohistochemical expression of PTEN and p53 in breast carcinoma and analyze their association with clinicopathological parameters.

METHODS: A cross-sectional study was conducted on 50 histologically confirmed female breast carcinoma cases. Immunohistochemistry (IHC) for PTEN and p53 was performed using standard protocols. PTEN expression was assessed based on cytoplasmic and nuclear staining intensity and categorized as positive or negative. p53 expression was evaluated as nuclear positivity and categorized similarly. Statistical analysis was done using standard significance tests.

RESULTS: The mean patient age was 49.8 years. The most common histologic subtype was infiltrating ductal carcinoma (IDC). Loss of PTEN expression was found in most of the cases and was associated with higher tumor grade and lymph node metastasis. Most cases exhibited p53 overexpression, which showed trends toward an association with higher tumor grade, premenopausal status, and lymph node positivity. An inverse relationship was noted between PTEN loss and p53 positivity.

CONCLUSIONS: PTEN loss and p53 overexpression were frequent in breast carcinoma and correlated with aggressive tumor features. Combined assessment of these biomarkers may provide prognostic value and support therapeutic decision-making in breast cancer.}, } @article {pmid41684983, year = {2026}, author = {Sikandar, F and Zahid, S and Basit Ali, A and Younas, A and Mani Tripathi, K and Fatima, P and Fatima, F}, title = {Clinicopathological Characteristics and Postoperative Outcomes of Patients Undergoing Modified Radical Mastectomy: A Retrospective Study.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e101373}, pmid = {41684983}, issn = {2168-8184}, abstract = {Background Breast cancer remains the most common malignancy among women worldwide and a leading cause of cancer-related mortality, particularly in developing countries where delayed presentation and limited screening facilities persist. Objective The objective of this study is to evaluate the clinicopathological profile and short-term (30-day) postoperative outcomes of patients with breast cancer undergoing modified radical mastectomy (MRM) in a resource-limited tertiary care setting while exploring factors that may influence surgical complications. Methods This retrospective observational study included 210 female patients who underwent MRM between January 2022 and December 2024. Demographic, clinical, histopathological, perioperative, and 30-day postoperative outcome data were extracted from hospital records and analyzed using SPSS version 26.0 (IBM Corp., Armonk, NY). Results The mean age was 51.4 ± 10.2 years, with 63.8% of patients being postmenopausal. Invasive ductal carcinoma was the predominant histological subtype (89.5%). Most patients presented with locally advanced disease (stage IIIC, 60%), and axillary lymph node involvement was observed in 65.7%. Estrogen receptor (ER) positivity was noted in 62.9%, progesterone receptor (PR) positivity in 57.1%, human epidermal growth factor receptor 2 (HER2/neu) overexpression in 25.7%, and triple-negative breast cancer in 17.1% of cases. The mean operative time was 115 ± 25 minutes, and the mean blood loss was 210 ± 60 mL. Postoperative complications occurred in 27.6% of patients, most commonly seroma formation (16.2%). No 30-day postoperative mortality was observed. Conclusion Modified radical mastectomy remains a safe and effective surgical option for breast cancer management in resource-limited settings, providing acceptable morbidity and reliable short-term outcomes, particularly among patients presenting with advanced disease.}, } @article {pmid41681766, year = {2026}, author = {Hunt, E and Davis, M and Hou, W and Bains, H and Darby, T and Hou, J and Chung, J and Hadidchi, R and Duong, TQ and Maldjian, T}, title = {Analysis of Neutrophil/Lymphocyte Ratio as a Potential Biomarker Stratified by Breast Cancer Histologic Subtype.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {3}, pages = {}, pmid = {41681766}, issn = {2075-4418}, abstract = {Background/Objectives: Breast cancer is the most common cancer in women. The neutrophil/lymphocyte ratio (NLR) is an emerging biomarker from peripheral blood that has been associated with breast cancer prognosis in some studies; however, some studies fail to demonstrate an association. We stratified breast cancer patients into invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) cohorts to evaluate if any meaningful association could be found in either cohort between NLR and mortality. Additionally, no prior studies have examined the relationship between NLR and background parenchymal enhancement (BPE) on breast MRI, an imaging feature linked to increased breast cancer risk and a potential imaging prognostic biomarker, so we examined the relationship between BPE and NLR in the two cohorts. Methods: This retrospective study included 794 breast cancer patients who had either IDC or ILC. Radiologists' MRI reports and their BI-RADS categorization of BPE (1 = minimal, 2 = mild, 3 = moderate, 4 = marked) were extracted and recorded. The NLR was calculated from blood counts obtained prior to treatment. Tumor characteristics were also recorded. Results: For patients with ILC, NLR was found to be associated with mortality. Additionally, patients with ILC and a high BPE had a significantly higher mean NLR compared to all other groups, including low BPE groups and all IDC groups. Conclusions: There is potential value in using NLR, a readily available blood biomarker, in models predicting prognosis in ILC patients.}, } @article {pmid41676265, year = {2026}, author = {Liu, XH and Fan, MZ and Lin, L and Bai, YY and Zhang, M}, title = {Ultrasonographic features and inflammatory status associated with tumor size in breast invasive ductal carcinoma.}, journal = {American journal of translational research}, volume = {18}, number = {1}, pages = {207-221}, pmid = {41676265}, issn = {1943-8141}, abstract = {OBJECTIVES: This study explored how ultrasound features relate to tumor size and inflammatory markers in invasive ductal carcinoma (IDC) patients.

METHODS: We retrospectively reviewed 218 female IDC patients. Based on the largest diameter of the tumor, patients were split into two groups: those with tumors ≤ 2 cm and those with tumors > 2 cm. We gathered data from conventional ultrasound (CUS), contrast-enhanced ultrasound (CEUS), and virtual touch tissue imaging quantification (VTIQ), along with blood-based inflammation indicators like neutrophil count and C-reactive protein (CRP) levels. Group comparisons were done using univariate analysis, and Spearman correlation was used to examine relationships between tumor size and other variables.

RESULTS: Larger tumors were more frequently located in the upper outer quadrant (60.71% vs 41.03%, P = 0.035) and showed richer blood flow (73.57% vs 53.85%, P = 0.003). By CEUS, larger tumors were more likely to show high enhancement (90% vs 78.21%, P = 0.017) and expanded enhancement range (82.86% vs 70.51%, P = 0.034). VTIQ results showed that SWV max (P = 0.033), SWV peritumoral average (peri-avg) (P = 0.010), and SWVR max/min (P = 0.009) were significantly increased in the larger tumor group. Correlation analysis showed that tumor size was significantly correlated with the above elastic parameters (P < 0.05). For inflammation, CRP was significantly increased in the larger tumor group (P < 0.001) and positively correlated with tumor size (r = 0.249, P = 0.0002); neutrophils were also correlated with SWV peri-avg (r = 0.158, P = 0.019) (P < 0.05).

CONCLUSIONS: Tumor size in IDC patients is not only related to their ultrasonographic features but also reflects their inflammatory status.}, } @article {pmid41674992, year = {2026}, author = {Zheng, Q and Jin, Z and You, J and Wang, Y and Zhu, H and Xu, J and Liang, T and Pei, S}, title = {A nomogram to predict disease-free survival in patients with residual triple-negative breast cancer after neoadjuvant chemotherapy based on clinicopathological and sonographic features.}, journal = {Translational cancer research}, volume = {15}, number = {1}, pages = {56}, pmid = {41674992}, issn = {2219-6803}, abstract = {BACKGROUND: Patients with triple-negative breast cancer (TNBC) who failed to achieve pathological complete response after neoadjuvant chemotherapy (NAC) may have a poorer prognosis. This study aimed to explore the factors associated with the adverse outcomes of these patients, and to develop a nomogram model for predicting disease-free survival (DFS).

METHODS: Patients diagnosed with TNBC at our institution between 2013 and 2022 were retrospectively evaluated. Clinicopathological and sonographic features associated with DFS were identified through multivariate Cox regression analysis to establish a nomogram model. The predictive performance of the nomogram model was assessed using receiver operating characteristic (ROC) curves and calibration curves.

RESULTS: A total of 103 TNBC patients with residual lesions following NAC were included in this study, with 15 cases (14.6%) experiencing DFS events. Multivariate analysis revealed that the pathological type of non-invasive ductal carcinoma [hazard ratio (HR) =7.741, 95% confidence interval (CI): 1.928-31.081, P=0.004], lymph node involvement (HR =3.455, 95% CI: 1.152-10.359, P=0.027), and the presence of a hyperechoic halo on ultrasound images (HR =4.43, 95% CI: 1.164-16.852, P=0.029) were independent prognostic factors associated with poor DFS. Patients with multiple risk factors exhibited worse survival outcomes. The areas under the ROC curve for predicting 2-, 3-, 4-, and 5-year DFS rates in the nomogram model were 0.767, 0.786, 0.785, and 0.739, respectively. The calibration curves demonstrated excellent consistency between the nomogram-predicted and actual survival probabilities.

CONCLUSIONS: Our study developed a nomogram model to predict poor survival outcomes in TNBC patients with residual lesions after NAC, which may provide guidance for treatment strategies in high-risk populations.}, } @article {pmid41673677, year = {2026}, author = {Baena, JC and Cabrera-Salcedo, SC and Carrera Suárez, Y and Biancha-Vasco, JM and Rios-Serna, LJ and García-Mantilla, MD and Estrada-Schweineberg, M and Victoria Hincapie, JS and Toro-Pedroza, A and Garcia-Robledo, JE and Cañas, CA and Ortiz-Guzman, J and Loukanov, A}, title = {The avatar principle: exosomal dynamics guiding tumor adaptation and next-generation therapeutic strategies.}, journal = {Journal of nanobiotechnology}, volume = {24}, number = {1}, pages = {159}, pmid = {41673677}, issn = {1477-3155}, mesh = {*Exosomes/metabolism ; Humans ; *Neoplasms/therapy/immunology ; Tumor Microenvironment ; Immunotherapy/methods ; Animals ; Receptors, Chimeric Antigen ; Avatar ; }, abstract = {Exosomes are nanoscale extracellular vesicles that transfer proteins, nucleic acids, and lipids, reflecting the state of their parent cells. A persistent scientific challenge is that tumor-derived exosomes (TDEs) facilitate immune evasion, remodel the tumor microenvironment, and create premetastatic niches, intensifying tumor aggressiveness and undermining therapeutic efficacy, ultimately narrowing treatment options to palliative strategies in advanced settings. Yet their dual roles as suppressive agents and potential therapeutic tools remain poorly integrated within current cancer immunotherapy frameworks. This review examines the molecular mechanisms underlying TDE-mediated immune suppression and therapeutic resistance, while also highlighting engineering strategies to exploit or counteract exosome biology. Exosomes derived from chimeric antigen receptor (CAR) T cells preserve antigen specificity and cytotoxic components without the risks of uncontrolled proliferation or cytokine release, offering a safer class of cell free immunotherapies. Advances in genetic engineering, hybrid vesicle design, and nanotechnology have extended exosome applications to the delivery of CRISPR/Cas systems, chemotherapeutic agents, immunoregulatory RNAs, and vaccines, with liposome or nanoparticle integration enhancing targeting and efficacy. Remaining obstacles include the lack of standardized protocols, scalability issues in production, and unresolved regulatory frameworks. Drawing on The Art of War, exosomes can be envisioned as avatars of strategy, discreet messengers capable of undermining host defenses while simultaneously carrying the potential to redirect immunity against the tumor. By embodying both deception and counterattack, they illustrate the capacity to penetrate hidden barriers and redefine the therapeutic battlefield, opening new horizons for precision cancer immunotherapy.}, } @article {pmid41672380, year = {2026}, author = {He, W and Jiang, Y and Jiang, B and Tang, Y and Zeng, L and Luo, L and Liao, X and Wu, S and Tan, Y and Li, Y}, title = {RTN4IP1 drives breast tumorigenesis: Molecular mechanisms linking elevated expression to enhanced proliferation, suppressed apoptosis, and therapeutic resistance.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1872}, number = {5}, pages = {168181}, doi = {10.1016/j.bbadis.2026.168181}, pmid = {41672380}, issn = {1879-260X}, abstract = {Abnormal expression of RTN4IP1 is implicated in diverse pathologies, including malignant tumors, yet its role in breast cancer (BC) remains insufficiently defined. This study integrated TCGA-based bioinformatics analysis with experimental validation to characterize RTN4IP1-related phenotypes. RTN4IP1 mRNA and protein levels were elevated in BC tissues compared to normal breast tissue, with higher expression correlating with advanced T/N stages, HER2 positivity, aggressive PAM50 subtypes, and lower PR/ER status. Clinically, increased RTN4IP1 expression was more frequent in Black/African American patients, postmenopausal women, and invasive ductal carcinoma cases. Elevated expression was also linked to poorer overall survival in both the TNBC and HER2-positive subgroups. Functional assays showed that RTN4IP1 silencing was accompanied by reduced proliferation, increased apoptosis, and inhibited xenograft growth in MCF-7 and MDA-MB-453 models, whereas overexpression exhibited the opposite pattern. RTN4IP1 expression was further linked to features of the tumor immune microenvironment and to differential responses to Tamoxifen and Paclitaxel; inhibition of RTN4IP1 was associated with greater drug sensitivity, while overexpression coincided with reduced response. Together, these findings indicate that RTN4IP1 is closely associated with BC progression, prognosis, and treatment response, supporting its potential relevance as a biomarker and a candidate target for further investigation.}, } @article {pmid41669457, year = {2026}, author = {Ogunlade, SB and Wang, L and Maimone, S and Robinson, KA and Moran, KM and Leon, A and Morozov, AP and Nwachukwu, CT and Letter, HP}, title = {Mammogram-based AI risk assessment in patients with dense breasts undergoing supplemental molecular breast imaging.}, journal = {Quantitative imaging in medicine and surgery}, volume = {16}, number = {2}, pages = {123}, pmid = {41669457}, issn = {2223-4292}, abstract = {BACKGROUND: Image-based artificial intelligence (AI) risk models can estimate short-term breast cancer risk directly from mammograms and may outperform traditional questionnaire-based tools. However, risk stratification remains particularly challenging in women with dense breasts who do not otherwise meet high-risk criteria. At our institutions, molecular breast imaging (MBI) is used as supplemental screening for this population. This study evaluated the performance and clinical utility of a mammography-based AI risk model (iCAD ProFound AI[®] Risk) in predicting short-term breast cancer risk among women with dense breasts undergoing MBI.

METHODS: This retrospective IRB-approved study included 416 non-actionable (BI-RADS category 1 or 2) screening digital breast tomosynthesis mammograms (BI-RADS C-D density) obtained from 2018 to 2023, all followed by MBI within one year. The cohort comprised 70 cancer cases (16.8%) and 346 (83.2%) non-cancer controls. Mammograms were retrospectively processed using the ProFound AI[®] Risk model to generate 1-year risk and density scores. Tyrer-Cuzick and Gail model scores were computed for comparison. Group differences were assessed using t-tests and effect sizes, and model discrimination was evaluated with ROC analysis using area under the curve (AUC), sensitivity, specificity, and 95% confidence intervals (CIs).

RESULTS: Across the full cohort, mean AI risk scores were higher in cancer cases than controls (0.41±0.35 vs. 0.37±0.21), although this difference was not statistically significant (P=0.239; Cohen's d=0.23). Subgroup analyses demonstrated progressively stronger discriminatory performance with increasing breast density. The greatest separation was observed in women with extremely dense breasts (category D), where the AI model achieved an AUC of 0.75 (95% CI: 0.61-0.89; P=0.049), with 69.3% sensitivity and 61.1% specificity at a threshold of 0.14. Effect size in this group was the largest (d=0.41). In contrast, traditional models showed limited and non-significant discrimination across all density categories, with AUC values ranging from 0.54 to 0.63. When stratified by cancer subtype, the AI model produced significantly higher risk scores in invasive lobular carcinoma (ILC) compared with controls (0.69±0.46 vs. 0.41±0.32; P=0.048; d=0.56). Although differences in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) were not significant, risk scores trended higher for cancer cases. A similar pattern of increasing AI-estimated risk was observed with higher tumor grade, with the strongest separation seen in grade 2 cancers (P=0.089).

CONCLUSIONS: Although overall differences between cancer and non-cancer groups were not statistically significant, the mammography-based AI risk model demonstrated meaningful and statistically significant discrimination in women with extremely dense breasts, outperforming both Tyrer-Cuzick and Gail models. The AI model also showed better separation in ILC and in higher-grade tumors. These findings support the role of image-based AI tools in refining risk assessment in women for whom mammography is least effective and in guiding more targeted use of supplemental MBI screening.}, } @article {pmid41669308, year = {2025}, author = {Mohammadizadeh, F and Naraki, T and Vafaei, M}, title = {The Frequency of PD-L1 Marker Expression in ER Positive, PR Positive, HER2 Negative Invasive Breast Carcinomas, and Its Correlation with Clinicopathological Factors Affecting Prognosis.}, journal = {Advanced biomedical research}, volume = {14}, number = {}, pages = {153}, pmid = {41669308}, issn = {2277-9175}, abstract = {BACKGROUND: The aim of this study was to investigate the expression of the PD-L1 marker in ER-positive, PR-positive, and HER2-negative breast carcinoma and examine its correlation with clinicopathological factors that affect prognosis in these patients.

MATERIALS AND METHODS: This cross-sectional descriptive-analytical study was conducted on paraffin-embedded tissue blocks from 50 invasive breast carcinoma patients. PD-L1 immunohistochemical staining was performed, and samples were examined to assess the membranous staining of tumor cells with the PD-L1 marker. ER, PR, and HER2 results were obtained from the pathology reports. The tumor proliferative index was divided into two groups: low proliferative index (<14%) and high proliferative index (= or >14%), based on the percentage of tumor cell nuclei with positive staining.

RESULTS: PD-L1 expression was negative in 44 (88%) and positive in 6 samples (12%). There was no significant difference in the mean age, tumor grade, and tumor proliferative index between the two groups (P value > 0.05). All positive PD-L1 samples belonged to the IDC tumor subtype with a mean tumor size of 6.33 ± 6.41 cm. In the negative PD-L1 group, 88.6% were IDC, 4.5% were ILC, and 6.8% were mixed tumor subtypes, with a mean tumor size of 2.79 ± 1.54 cm. Tumor subtype, tumor size, and axillary lymph node status showed no significant difference between the two groups (P value > 0.05).

CONCLUSION: According to the results of this study, there is no relationship between the PD-L1 expression and well-known clinicopathological prognostic factors in ER-positive, PR-positive, and HER2-negative invasive breast carcinomas.}, } @article {pmid41669107, year = {2026}, author = {Kawachi, K and Tang, X and Kasajima, R and Katayama, K and Yamaguchi, R and Yamaguchi, K and Furukawa, Y and Imoto, S and Miyano, S and Yoshioka, E and Washimi, K and Okubo, Y and Sato, S and Yokose, T and Miyagi, Y}, title = {Case Report: Mixed ductal-lobular carcinoma consisting of invasive lobular carcinoma with a glycogen-rich clear cell pattern and elevated tumor mutation burden.}, journal = {Frontiers in oncology}, volume = {16}, number = {}, pages = {1741727}, pmid = {41669107}, issn = {2234-943X}, abstract = {BACKGROUND: Mixed ductal-lobular carcinoma (MDL) of the breast exhibits considerable molecular complexity. The pathways leading to the glycogen-rich clear cell morphology of the breast tumors, and its clinical relevance, currently remain unclear. Herein, we report a case of MDL, predominantly composed of invasive lobular carcinoma with a glycogen-rich clear cell pattern (gILC), accompanied by classic invasive lobular carcinoma and invasive ductal carcinoma (IDC).

CASE PRESENTATION: A 70-year-old woman presented with a 3.5 cm mass in the left breast, for which total mastectomy was performed. The pathological diagnosis was MDL predominantly comprising gILC. Tissue samples from the gILC and IDC areas were subjected to whole-exome and RNA sequencing. The gILC region had a higher tumor mutation burden than the IDC. Three stop-gain single nucleotide variations (SNVs) in CDH1, SETD2, and USP9 and two nonsynonymous SNVs in PIK3CA were identified in the gILC region, whereas only two nonsynonymous SNVs in SMAD4 and PIK3CA were identified in the IDC region. Phylogenetic analysis revealed a common ancestor of gILC and IDC, sharing a pathogenic PIK3CA p.H1047L mutation. Reduced SETD2 protein and H3K36me3 levels and the DNA mismatch repair-microsatellite instability-associated mutational signatures SBS6 and SBS26 were uniquely demonstrated in gILC. Further, a structural variant involving HNF1B and elevated HNF1B transcript levels was detected in gILC. The predominant gILC component was estrogen receptor-positive. Adjuvant endocrine therapy was administered postoperatively, and the patient currently remains disease-free at 51 months.

CONCLUSION: In this case, the gILC and IDC components of an MDL shared a common origin, but exhibited marked genomic divergence. This experience also shows that SETD2 functional impairment may underlie gILC hypermutation, while HNF1B overexpression could contributes to a glycogen-rich clear cytoplasm. Overall, this case emphasizes the complexity of MDL with gILC, and highlights the need for further studies to clarify the underlying molecular mechanisms and their prognostic implications.}, } @article {pmid41663430, year = {2026}, author = {Singareeka Raghavendra, A and Liu, DD and Pasyar, S and Damodaran, S and Shen, Y and Mouabbi, JA and Barcenas, CH and Tripathy, D}, title = {Prevalence of HER2-low status and outcomes in early-stage HER2-negative breast cancer.}, journal = {NPJ breast cancer}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41523-026-00901-8}, pmid = {41663430}, issn = {2374-4677}, abstract = {HER2-low breast cancer (IHC 1+ or 2+ without HER2 gene amplification) is a distinct and understudied subtype. In a cohort of 14,593 early-stage breast cancer patients treated at MD Anderson from 2006 to 2019, 60.4% were HER2-low. Multivariable analysis showed HER2-low status was independently associated with race, histologic subtype, higher nuclear grade and stage, and estrogen receptor (ER) positivity. Among 2464 patients receiving neoadjuvant chemotherapy, HER2-low status was not linked to pathologic complete response (pCR), overall survival (OS), or disease-free survival (DFS) compared to HER2-0 tumors. Factors predicting pCR included nuclear grade III, stage I, invasive ductal carcinoma, lower ER/PR expression, and absence of lymphovascular invasion (LVI). Patients with TNBC had significantly higher pCR rates (31.9%) than those with luminal type (2.2%, p < 0.0001). Longer OS and DFS were associated with non-White race, lower stage and grade, negative LVI, and higher ER/PR levels. These findings confirm HER2-low status is common but not independently prognostic for response or survival.}, } @article {pmid41660331, year = {2026}, author = {Freire-Figueroa, IA and Vargas-Ardila, PA and Castaño-Rodríguez, I and Rojas-Romero, LO}, title = {Hypertrophic olivary degeneration mimicking tumor recurrence after brainstem radiosurgery: A diagnostic pitfall in neuro-oncology.}, journal = {Surgical neurology international}, volume = {17}, number = {}, pages = {42}, pmid = {41660331}, issn = {2229-5097}, abstract = {BACKGROUND: Hypertrophic olivary degeneration (HOD) is a rare trans-synaptic degeneration of the inferior olivary nucleus resulting from disruption of the dentato-rubro-olivary pathway, also known as the Guillain- Mollaret triangle. Unlike most degenerative processes, it produces olivary hypertrophy rather than atrophy. In oncology patients with prior posterior fossa or brainstem involvement, this condition can simulate tumor recurrence or radiation necrosis, leading to unnecessary interventions if unrecognized.

CASE DESCRIPTION: A 38-year-old woman with a history of human epidermal growth factor receptor 2-positive invasive ductal carcinoma of the breast and previously treated brainstem metastasis presented with progressive right facial paresthesias and gait instability. Neurological examination revealed dysmetria, impaired rapid alternating movements, and gait ataxia without motor or sensory deficits. Magnetic resonance imaging (MRI) demonstrated a nodular enhancing pontine lesion due to the treated metastatic lesion and a new enlargement involving the rostral aspect of the left central tegmental tract with associated hypertrophic change of the inferior olivary nucleus, consistent with unilateral HOD. Magnetic resonance spectroscopy and perfusion imaging excluded neoplastic recurrence. A multidisciplinary neuro-oncology board concluded that the findings were secondary to radiation-induced tract injury. The patient continued maintenance chemotherapy and received symptomatic management and rehabilitative therapy, with serial MRI showing stability.

CONCLUSION: HOD should be considered in patients with prior brainstem surgery or radiotherapy who develop delayed cerebellar signs and characteristic MRI findings. Recognizing its benign and self-limited nature is crucial to prevent misdiagnosis as tumor recurrence and avoid unnecessary oncologic or surgical interventions. Integration of advanced MRI techniques and multidisciplinary evaluation allows precise diagnosis and tailored management, ensuring appropriate treatment and long-term follow-up.}, } @article {pmid41660202, year = {2026}, author = {López-Ponce-de-León, JD and Muñoz-Ordoñez, JA and Toro-Pedroza, A and Arango-Ibanez, JP and Azcarate-Rodriguez, V and Naranjo-Ramírez, MC and León-Giraldo, H and Largo, J and Carrillo-Gomez, D and Arteaga-Tobar, AA and Escalante-Forero, M and Olaya, P and Florez, N and Olaya, N and Rivera-Muñoz, EL and Barbosa-Rengifo, MM and Nativi-Nicolau, J and Gómez-Mesa, JE}, title = {Survival in Adult Patients Undergoing Heart Transplantation 1995-2024: A Report of the RETRAC Registry.}, journal = {Global heart}, volume = {21}, number = {1}, pages = {7}, pmid = {41660202}, issn = {2211-8179}, mesh = {Humans ; Male ; *Heart Transplantation/mortality ; Female ; Middle Aged ; *Registries ; Survival Rate/trends ; Adult ; *Heart Failure/surgery/mortality ; Colombia/epidemiology ; Retrospective Studies ; Aged ; Follow-Up Studies ; }, abstract = {BACKGROUND: Heart transplantation (HT) remains the definitive treatment for advanced heart failure that is refractory to both medical and invasive therapies. Although global registries offer extensive data on survival outcomes, there is a relative paucity of information regarding HT outcomes in Latin America (LATAM), particularly in Colombia.

METHODS: This study analyzed adult patients who underwent HT between 1995 and 2024, using data obtained from an institutional HT registry (RETRAC) in Cali, Colombia. Survival outcomes were evaluated using Kaplan-Meier curves and Cox proportional hazards models.

RESULTS: We included 260 patients who underwent HT in this 29-year cohort from a LATAM country. The median age at transplantation was 51 years, and 77.7% were male. The primary etiologies were idiopathic/dilated cardiomyopathy (IDC) (41.3%), ischemic cardiomyopathy (IC) (27.0%), and valvular heart disease (VHC) (9.7%). The most prevalent comorbidities were hypertension (HTN) (48.3%), diabetes mellitus (DM) (18.9%), and chronic kidney disease (CKD) (13.1%). The overall median survival following HT was 7.4 years. One-year survival was 74.6% (n = 194), five-year survival was 56.9% (n = 147), and ten-year survival was 46.9% (n = 122). Survival differed significantly by age and sex, with patients aged <40 years demonstrating the highest median survival (8.4 years) and those aged ≥60 years the lowest (2.2 years) (p = 0.038). The 40- to 49-year age group exhibited the most pronounced reduction in survival; however, this effect was attenuated after adjustment. Among patients under 40 years, females had significantly higher mortality compared to males (p = 0.0078), with younger males exhibiting better survival. Additionally, patients transplanted between 2016 and 2020 had higher survival rates. CKD was identified as a significant independent risk factor for increased mortality (hazard ratio (HR) = 1.79; 95% CI: 1.15-2.79; p = 0.01).

CONCLUSIONS: HT patients in Colombia exhibit demographic and clinical profiles comparable to global cohorts; however, they demonstrate lower survival rates and poorer clinical outcomes compared to international registries, such as the International Society for Heart and Lung Transplantation registry. Nonetheless, clinical outcomes are more favorable than those reported in other studies from the LATAM region. CKD emerged as a significant independent predictor of mortality. These findings highlight the need for region-specific strategies aimed at improving HT outcomes in LATAM.}, } @article {pmid41658570, year = {2025}, author = {Wang, Z and Bai, C and Zhang, N and Han, Z and Dong, H and Liu, S and Meng, J and Zhang, C}, title = {Predicting histological grade in invasive ductal carcinoma of the breast: a radiomics-based machine learning model using DCE-MRI.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1593075}, pmid = {41658570}, issn = {2234-943X}, abstract = {OBJECTIVES: To investigate the feasibility analysis of predicting the pathological differentiation grade of breast invasive ductal carcinoma based on DCE-MRI imaging histology.

METHODOLOGY: 198 patients with breast invasive ductal carcinoma who underwent preoperative enhanced MRI were retrospectively collected from January 2019 to October 2024.According to Nottingham histologic grading, 108 cases were divided into a high-grade group and 90 cases into an intermediate-low-grade group, which were randomly divided into 148 cases of the training group and 50 cases of the validation group according to a 3:1 ratio. The 3D slicer software was applied to extract the image histological features of the region of interest, and five models, namely, decision tree, Gaussian plain Bayes, logistic regression, random forest, and AdaBoost, were constructed by filtering the features with intragroup correlation coefficients and the minimum absolute contraction and selection operators. Compare the area under the work characteristic curve of subjects in the validation group and select the best model. The performance of the best model validation group was evaluated, the clinical usability of the best model was examined using decision curves, and the accuracy of the predictive model was visualized using calibration curves.

RESULTS: After rigorous stability and redundancy screening, 22 key radiomics features were selected from DCE-MRI images. Multiple machine learning models trained based on these features were evaluated for their predictive performance on the validation set. The logistic regression model achieved the highest AUC value of 0.795 (95% confidence interval: 0.664-0.927), outperforming other models such as random forest (AUC = 0.700), Gaussian naive Bayes (AUC = 0.700), AdaBoost (AUC = 0.718), and decision tree (AUC = 0.587). Consequently, the logistic regression model was ultimately selected as the optimal model.

CONCLUSION: The DCE-MRI radiomics model based on Logistic Regression can non-invasively and effectively predict the histological grade of IDC preoperatively, offering valuable potential for supporting individualized clinical decision-making.}, } @article {pmid41652023, year = {2026}, author = {Khodadadi AghGhaleh, M and Abedian, R and Zarghami, R and Fotuhi Siahpirani, A and Gharaghani, S}, title = {ConvAHKG: Action-based hybrid knowledge graph with a dual-channel convolutional approach for drug repurposing.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {}, pmid = {41652023}, issn = {2045-2322}, abstract = {Drug repurposing efficiently identifies new applications for already approved drugs at reduced time and cost. ConvAHKG, an action-based hybrid knowledge graph approach, is proposed to improve the prediction of drug-disease associations by leveraging biological relationships among drugs, proteins, and diseases. AHKG is designed to integrate both drug and disease features to provide a comprehensive framework. To represent these relationships, Word2Vec embeddings are used to capture the semantic similarities among entities, and a novel dual-channel 1D convolutional neural network (IDC_Conv1D) is introduced for the classification of drug-disease pairs. This architecture is specifically intended to handle the complexity and heterogeneity of biological data. Furthermore, to address the significant class imbalance present in drug-disease datasets, a weighted binary cross-entropy loss function was introduced that assigns higher penalties to minority-class misclassifications, resulting in improved predictive performance. ConvAHKG outperforms state-of-the-art models, with an AUC of 0.9836 and an AUPRC of 0.9686. To validate its practical utility, we applied ConvAHKG to study non-small cell lung cancer (NSCLC). The framework identified promising therapeutic candidates for NSCLC, including Trastuzumab, and molecular docking analyses demonstrated strong binding interactions for an additional predicted but experimentally unvalidated compound, further supporting its potential as a novel treatment option. All data and code used in this study are available at https://github.com/Marzieh-Khodadadi/ConvAHKG .}, } @article {pmid41649045, year = {2026}, author = {Nafissi, N and Mahadevan, A and Chiao, E and Rijal, N and Parajuli, R}, title = {Triple Negative Breast Cancer With Choroidal Metastasis Responsive to Sacituzumab Govitecan and Radiation Therapy.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {9}, number = {2}, pages = {e70462}, pmid = {41649045}, issn = {2573-8348}, mesh = {Humans ; Female ; *Triple Negative Breast Neoplasms/pathology/therapy ; Middle Aged ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration & dosage ; *Immunoconjugates/therapeutic use ; *Choroid Neoplasms/secondary/therapy ; *Camptothecin/analogs & derivatives/therapeutic use/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Carcinoma, Ductal, Breast/therapy/secondary ; Treatment Outcome ; }, abstract = {BACKGROUND: Orbital metastases are rare in patients with breast cancer. However, medical management of orbital metastases is limited by the inability of treatment options to penetrate the blood-brain barrier. In patients with triple negative breast cancer (TNBC), these treatment options are further limited. Sacituzumab govitecan, an antibody-drug conjugate, has emerged as a promising agent for metastatic TNBC. However, to date, patients with central nervous system (CNS) disease have been excluded from corresponding clinical trials, making the efficacy of sacituzumab govitecan in patients with orbital metastases unclear.

CASE: A 61-year-old female was initially diagnosed with a left breast hormone receptor positive invasive ductal carcinoma, receiving neoadjuvant chemotherapy with doxorubicin, cyclophosphamide, and docetaxel and a partial mastectomy. Several years later, the patient presented with a cough and was subsequently diagnosed with metastatic triple negative breast cancer with hepatic, osseous, and right supraclavicular and thoracic nodal metastases. Concurrently, the patient noted floaters in her vision, later found to be consistent with orbital metastases. The patient received radiation therapy to both eyes and was started on Sacituzumab govitecan. Following cycle 1, the ophthalmic exam showed a dramatic decrease in the size of choroidal metastases.

CONCLUSION: This case report documents the first case of orbital metastases successfully treated with radiation therapy and sacituzumab govitecan. As such, this case highlights the importance of sacituzumab govitecan as a potentially effective option for TNBC patients with CNS disease. Further studies and real-world data are needed to investigate the efficacy of combined radiotherapy and sacituzumab govitecan toward ocular metastases.}, } @article {pmid41646442, year = {2026}, author = {Lyu, X and Mao, F}, title = {Rectal metastasis in a patient with long-term breast cancer: a rare case report with literature review.}, journal = {Frontiers in oncology}, volume = {16}, number = {}, pages = {1597103}, pmid = {41646442}, issn = {2234-943X}, abstract = {Gastrointestinal (GI) metastases from breast cancer are uncommon, with rectal involvement being particularly rare. Here, we present a case of a 55-year-old female with a history of bilateral breast cancer who developed rectal metastasis seven years after initial diagnosis. The patient was initially diagnosed in 2017 with left breast invasive ductal carcinoma (IDC) and right breast ductal carcinoma in situ (DCIS). Despite receiving comprehensive treatment, including modified radical mastectomy, chemotherapy, radiotherapy, and endocrine therapy, she experienced multiple metastases involving the bones, lymph nodes, and pleura. In 2024, she presented with new bowel symptoms, and colonoscopy revealed rectal wall thickening with stenosis. Biopsy confirmed metastatic breast cancer with immunohistochemistry showing GATA3(+), CDX2(-), and loss of hormone receptor expression compared to the primary tumor. This case underscores the importance of considering gastrointestinal metastasis in breast cancer patients with bowel symptoms, even years after initial treatment. We also review the literature regarding the literature on the diagnosis, treatment, and prognosis of breast cancer rectal metastasis.}, } @article {pmid41641105, year = {2026}, author = {Nobile, I and Tessitore, A and Palumbo, M and Boccia, D and Mignogna, C and Bifulco, G and Della Corte, L}, title = {A case report of a mammary gland type adenocarcinoma of the vulva in a patient with a concomitant breast cancer: a diagnostic challenge.}, journal = {Frontiers in oncology}, volume = {16}, number = {}, pages = {1716250}, pmid = {41641105}, issn = {2234-943X}, abstract = {We describe the case of a 68-year-old woman who presented with a 4-cm ulcerated lesion in the left paraclitoral area. Imaging revealed increased FDG uptake at the vulvar lesion and multiple skeletal sites but no suspicious inguinal lymphadenopathy, while breast imaging showed a 30-mm BI-RADS 5 lesion in the upper outer quadrant of the left breast. Core biopsies confirmed two distinct primaries: an invasive ductal carcinoma of the breast and an eccrine ductal-type adenocarcinoma of the vulva arising from anogenital mammary-like glands. A bone biopsy demonstrated metastatic breast carcinoma. The patient underwent radical anterior vulvectomy with bilateral sentinel lymph node biopsy; final pathology confirmed a well-differentiated, adenocarcinoma of mammary-gland type of the vulva (pT1bN0) with negative margins. Because of breast metastases, systemic therapy with ribociclib and letrozole was initiated but later discontinued owing to therapy-related acute myeloid leukemia. At 9-month follow-up, no recurrence of the vulvar disease was observed. This report highlights one of the very few documented instances of synchronous mammary-like vulvar carcinoma and breast carcinoma. It underscores the diagnostic complexity of the case and emphasizes the importance of an individualized, multidisciplinary approach tailored to tumor biology, staging, and patient comorbidities.}, } @article {pmid41639449, year = {2026}, author = {Li, X and Lebeaupin, C and Kadianaki, A and Druelle-Cedano, C and Vesper, N and Rennert, C and Huguet-Pradell, J and Gomez Ramos, B and Fan, C and Piecyk, RS and Zizmare, L and Ramadori, P and Li, L and Frick, L and Qiu, M and Zhang, C and Martins Nascentes Melo, L and Ranvir, VP and Shen, P and Hanselmann, J and Kosla, J and Fernández-Vaquero, M and Vucur, M and Baskaran, P and Bao, X and Coleman, OI and Tang, Y and Cetin, M and Chen, Z and Jang, I and Del Prete, S and Rahbari, M and Zhang, P and Pham, TV and Hou, Y and Sun, A and Gu, L and Kim, LC and Rothermel, U and Heide, D and Ali, A and Gallage, S and Talvard-Balland, N and Piqué-Gili, M and Gris-Oliver, A and Bevilacqua, A and Schlicker, L and Duffey, A and Unger, K and Szydlowska, M and Hetzer, J and Odom, DT and Machauer, T and Bucci, D and Sant, P and Lee, JH and Rösler, J and Meckelmann, SW and Schreck, J and Murray, S and Simon, MC and Nahnsen, S and Schulze, A and Ho, PC and Jugold, M and Breuhahn, K and Mallm, JP and Schirmacher, P and Roth, S and Rahbari, N and Tschaharganeh, DF and Roessler, S and Goeppert, B and Bengsch, B and Andrieux, G and Boerries, M and Malek, NP and Prinz, M and Weber, A and Zeiser, R and Tamayo, P and Bronsert, P and Kurowski, K and Thimme, R and Yuan, D and Carretero, R and Luedde, T and Pinyol, R and Hartmann, FJ and Karin, M and Tasdogan, A and Trautwein, C and Mall, M and Hofmann, M and Llovet, JM and Haller, D and Kaufman, RJ and Heikenwälder, M}, title = {Activated ATF6α is a hepatic tumour driver restricting immunosurveillance.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {41639449}, issn = {1476-4687}, abstract = {Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related mortality and there are limited therapies[1]. Although endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are implicated in HCC, the involvement of the UPR transducer ATF6α remains unclear[2]. Here we demonstrate the function of ATF6α as an ER-stress-inducing tumour driver and metabolic master regulator restricting cancer immunosurveillance for HCC, in contrast to its well-characterized role as an adaptive response to ER stress[3]. ATF6α activation in human HCC is significantly correlated with an aggressive tumour phenotype, characterized by reduced patient survival, enhanced tumour progression and local immunosuppression. Hepatocyte-specific ATF6α activation in mice induced progressive hepatitis with ER stress, immunosuppression and hepatocyte proliferation. Concomitantly, activated ATF6α increased glycolysis and directly repressed the gluconeogenic enzyme FBP1 by binding to gene regulatory elements. Restoring FBP1 expression limited ATF6α-activation-related pathologies. Prolonged ATF6α activation in hepatocytes triggered hepatocarcinogenesis, intratumoural T cell infiltration and nutrient-deprived immune exhaustion. Immune checkpoint blockade (ICB)[4] restored immunosurveillance and reduced HCC. Consistently, patients with HCC who achieved a complete response to immunotherapy displayed significantly increased ATF6α activation compared with those with a weaker response. Targeting Atf6 through germline ablation, hepatocyte-specific ablation or therapeutic hepatocyte delivery of antisense oligonucleotides dampened HCC in preclinical liver cancer models. Thus, prolonged ATF6α activation drives ER stress, leading to glycolysis-dependent immunosuppression in liver cancer and sensitizing to ICB. Our findings suggest that persistently activated ATF6α is a tumour driver, a potential stratification marker for ICB response and a therapeutic target for HCC.}, } @article {pmid41625393, year = {2026}, author = {Sugiyama, E and Suzuki, R and Takano, J and Tokuyama, Y and Morikawa, A and Nishimura, K and Ishihara, K}, title = {A Case of Invasive Ductal Carcinoma with Axillary Skip Metastasis Confined to the Interpectoral (Rotter's) Lymph Node.}, journal = {Surgical case reports}, volume = {12}, number = {1}, pages = {}, pmid = {41625393}, issn = {2198-7793}, abstract = {INTRODUCTION: Axillary skip metastasis is a rare phenomenon in breast cancer and is defined as metastasis to level II or III lymph nodes without involvement of level I nodes. Interpectoral (Rotter's) nodes are situated between the pectoralis major and minor muscles and may occasionally be overlooked during sentinel node (SN) mapping. Reports of isolated interpectoral node metastases are rare. Here, we present a unique case of breast cancer with isolated interpectoral node involvement despite a negative sentinel lymph node, underscoring the clinical implications of preoperative imaging and surgical planning.

CASE PRESENTATION: A 69-year-old woman was referred to our hospital after an abnormality was detected by mammography. MRI demonstrated a 20-mm enhancing breast mass located in the deep portion of the upper outer quadrant, along with a strongly enhancing 6-mm interpectoral lymph node; no suspicious axillary level I nodes were identified. The patient underwent a mastectomy with sentinel and interpectoral node biopsies. The SN was negative, whereas the interpectoral node was positive, prompting axillary dissection. Histology confirmed a 15-mm invasive ductal carcinoma, with only the interpectoral node being positive among the 12 dissected nodes. Immunohistochemistry showed an ER-positive, PgR-positive, and HER2-negative status. The patient was started on adjuvant endocrine therapy. Her postoperative course was uneventful and she remained disease-free at 54 months of follow-up.

CONCLUSIONS: This extraordinarily rare case of axillary skip metastasis limited to the interpectoral node emphasizes the potential for false-negative SN biopsies. Careful review of preoperative images, particularly MRI images, is crucial to avoid understaging. Awareness of interpectoral node involvement may help guide appropriate treatment strategies for selected patients.}, } @article {pmid41624813, year = {2026}, author = {Inamdar, V and Shaila, SG}, title = {Automated Segmentation and Analysis of Histopathological Breast Cancer Images for Enhanced IDC Diagnosis and Assessment Using MobileNetV2+U-Net With Label Propagation.}, journal = {International journal of breast cancer}, volume = {2026}, number = {}, pages = {5948413}, pmid = {41624813}, issn = {2090-3170}, abstract = {Breast cancer remains the most common cancer type among women, with invasive ductal carcinoma (IDC) responsible for almost 80% of cases. The exact histopathological segmentation of IDC is the premise of diagnosis, but manual observation of hematoxylin and eosin (H&E) stained slides is very time-consuming and results in interobserver variability. This work presents an automated IDC segmentation method with a lightweight hybrid deep learning framework by integrating U-Net with a MobileNetV2 encoder and a label propagation refinement module. This hybrid model leverages MobileNetV2's efficient depth-wise-separable convolutions for feature extraction, U-Net's encoder-decoder precision for boundary localization, and the label propagation step enhances spatial smoothness and anatomical consistency. Experiments are conducted on the BACH 2018 and BreakHis datasets at multiple magnification levels (40×, 100×, and 200×). The model reaches a precision of 94.85%, Dice coefficient of 94.63%, F1-score of 94.56%, and AUC of 94.65% on the BACH dataset and a precision of 93.87%, Dice of 94.24%, F1-score of 94.18%, and AUC of 93.93% on the BreakHis dataset. The proposed model surpasses several state-of-the-art techniques such as CNN and transformer-based models, including DeepLabV3, Mask R-CNN, Swin-UNet, and ViT-Histo. Cross-dataset validation yields a Dice of 92.10% and AUC of 93.70% from BACH → BreakHis, confirming robustness under domain shifts. Explainable AI analyses using Grad-CAM and SHAP confirmed accurate localization of diagnostically relevant regions. The proposed hybrid model of MobileNetV2 + U-Net with label propagation presents a computationally efficient and clinically reliable solution toward real-time, AI-assisted breast cancer histopathology.}, } @article {pmid41618616, year = {2026}, author = {Buñay, J and Record, M and de Medina, P and Ayadi, S and Pucheu, L and Colacios, C and Ségui, B and Höring, M and Liebisch, G and Martin, H and Poirot, M and Silvente-Poirot, S}, title = {The Phospholipid Bis(monoacylglycero)Phosphate Confers Antitumour Immunogenicity to Exosomes Secreted by Dendrogenin A, Which Activates Its Biosynthesis in Tumour Cells.}, journal = {Journal of extracellular vesicles}, volume = {15}, number = {2}, pages = {e70225}, pmid = {41618616}, issn = {2001-3078}, support = {PLBio 20-160//Institut National Du Cancer/ ; //Equipe labellisée par la Ligue Nationale Contre le Cancer/ ; //Institut National de la Santé et de la Recherche Médicale/ ; //Centre National de la Recherche Scientifique/ ; //Université de Toulouse/ ; }, mesh = {*Exosomes/metabolism/immunology ; Animals ; Mice ; *Monoglycerides/metabolism ; Humans ; *Lysophospholipids/metabolism ; Dendritic Cells/immunology/metabolism ; Cell Line, Tumor ; Mice, Inbred C57BL ; Female ; *Antineoplastic Agents/pharmacology ; }, abstract = {Dendrogenin A (DDA) is a cholesterol-derived antitumour metabolite that promotes the secretion of immunogenic antitumour exosomes (DDA-sEV) enriched in bis(monoacylglycero)phosphate (BMP). BMP is a phospholipid specific to late endosomes and lysosomes, where it plays a crucial role in lipid degradation, regulates the fate of endosomal cholesterol, and contributes to intraluminal vesicle formation. Dysregulation of BMP biosynthesis is associated with multiple diseases. Here, we show that the DDA/LXRβ complex activates the transcription and activity of phospholipase D (PLD) and CLN5, two enzymes involved in BMP biosynthesis. Inhibition of PLD in DDA-treated tumour cells reduces BMP levels in DDA-sEV, impairs their release, and their antitumour immune activity. Blocking BMP on DDA-sEV with a specific antibody abolishes their antitumour reponse, prevents the recruitment of activated dendritic cells (DC) and T cells into tumours, and decreases mouse survival. This blockade also impairs DDA-sEV uptake by immature DC (iDC) and hinders DC maturation and Th1 T cell activation. Notably, neutralising the BMP-presenting receptor on iDC inhibits DDA-sEV uptake and DC maturation. Treatment of iDC with free BMP induces their functional maturation, confirming BMP as a key immune activator. Furthermore, BMP-containing DDA-sEV enhance the efficacy of anti-PD-1 therapy in melanoma. Targeting LXRβ with DDA represents an innovative strategy to stimulate anticancer immunity by increasing BMP levels in tumours and sEV.}, } @article {pmid41617450, year = {2026}, author = {Demirors, B and Ahmed, SH and Grace, K and Jimenez, PB and Bowers, JC and Mahesh, VA and Yadav, A and Manaise, HK and Chiriboga, G and Brock, LF and Popp, R and Merly, AA and Gabriel, E}, title = {Geographic Variations in Demographics, Socioeconomic Status, and Stage at Diagnosis Among Hormone Receptor-positive Invasive Ductal Carcinoma: An NCDB Analysis (2004-2020).}, journal = {Anticancer research}, volume = {46}, number = {2}, pages = {811-817}, doi = {10.21873/anticanres.17989}, pmid = {41617450}, issn = {1791-7530}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/epidemiology/pathology/diagnosis/metabolism ; *Carcinoma, Ductal, Breast/pathology/epidemiology/diagnosis/metabolism ; Neoplasm Staging ; Aged ; Cross-Sectional Studies ; *Social Class ; Male ; Receptors, Progesterone/metabolism ; Receptors, Estrogen/metabolism ; United States/epidemiology ; Adult ; Databases, Factual ; }, abstract = {BACKGROUND/AIM: Although hormone receptor-positive (HR+) invasive ductal carcinoma (IDC) is the most common breast cancer subtype, there is limited evidence describing how demographic and clinical features vary across U.S. regions. Understanding geographic disparities is essential for improving screening and treatment planning. To examine regional variations in demographic, socioeconomic status (SES), and stage-at-diagnosis characteristics among U.S. patients with HR+ IDC.

PATIENTS AND METHODS: This cross-sectional study used data from the National Cancer Database (NCDB) for patients diagnosed with HR+ IDC between 2004 and 2020. Patients were categorized into 6 U.S. geographic regions: Northeast, Southeast, Midwest, Southwest, Mountain, and Pacific, based on the Commission on Cancer facility location. Descriptive and comparative analyses evaluated age, sex, race and ethnicity, insurance type, income, urban-rural residence, and American Joint Committee on Cancer stage.

RESULTS: Among 136,280 patients (mean age, 64.4 years; 98.8% female), racial and SES composition differed significantly across regions. Black patients comprised 19.5% of the Southeast cohort and 18.1% of the Southwest cohort, compared with 2.9% in the Mountain region. The Asian population was highest in the Pacific (13.1%). Low-income households (<$63,000) were most prevalent in the Southwest (74.7%) and Southeast (69.5%), while the Pacific region had the highest proportion of higher-income households (46.4%) and metropolitan residents (94.3%). Stage III-IV disease at diagnosis occurred most often in the Southwest (17.6%) and least in the Northeast (14.0%).

CONCLUSION: Significant variation exists in the demographic and SES profile of patients with HR+ IDC, corresponding to differences in stage at diagnosis, and BC-related overall outcomes. These disparities likely reflect inequities in screening access, SES, and healthcare infrastructure, underscoring the need for region-specific public health strategies. Targeted regional interventions and equitable screening expansion are warranted to reduce geographic disparities and improve overall BC-related outcomes.}, } @article {pmid41613558, year = {2025}, author = {Xu, M and Liu, K and Zhang, S and Li, H and Zhang, R and Xu, C and Yuan, J and Wu, Y and Wu, D and Chen, X and Qu, J}, title = {Time-dependent diffusion MRI for noninvasive molecular subtype differentiation and biological correlation in breast cancer: emphasizing the emerging three-tier HER2 classification.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1739008}, pmid = {41613558}, issn = {2234-943X}, abstract = {BACKGROUND: Breast cancer is a heterogeneous disease, and accurate subtype characterization is essential for guiding personalized treatment. In particular, HER2-low tumors have recently emerged as a distinct clinical entity with potential responsiveness to novel HER2-targeted therapies. However, reliable noninvasive imaging methods to identify these subgroups remain lacking.

PURPOSE: To evaluate the potential of time-dependent diffusion MRI (Td-dMRI) in differentiating breast cancer molecular subtypes and to investigate its correlation with immunohistochemical biomarkers, particularly the newly established three-tier HER2 classification.

MATERIALS AND METHODS: In this retrospective study, female patients with untreated invasive ductal carcinoma underwent 3T breast MRI including Td-dMRI between June 2023 and October 2024. A custom protocol combining oscillating gradient spin-echo (OGSE) and pulsed gradient spin-echo (PGSE) sequences enabled diffusion sampling at multiple diffusion times and frequencies. Microstructural parameters-cellularity, extracellular and intracellular diffusivity (Dex, Din), cell diameter, intracellular volume fraction (fin), and intracellular water residence time (τin)-were estimated using a Bayesian model based on a joint multicompartmental framework. Molecular subtypes (Luminal A/B, HER2-enriched, triple-negative [TN]) and HER2 expression levels (HER2-zero, HER2-low, HER2-positive) were determined via IHC and fluorescence in situ hybridization (FISH). Quantitative Td-dMRI metrics were compared across subtypes and correlated with ER, PR, HER2, and Ki-67 status using ANOVA, Kruskal-Wallis, and ROC curve analysis.

RESULTS: This study included 71 female participants (mean age, 51.3 ± 10.2 years). Multiple Td-dMRI parameters varied significantly across molecular and HER2 subtypes. ADC50Hz was significantly higher in Luminal A compared to Luminal B (P = 0.003). HER2-enriched tumors showed higher ADC values and cell diameters but lower cellularity compared to Luminal B (P< 0.05). ER- and PR- tumors had higher ADCs, cell diameters, and Din, with lower cellularity than positive counterparts. Din effectively distinguished TN from non-TN cancers (AUC = 0.710). For HER2 stratification, ADC30ms distinguished HER2-zero from HER2-low tumors with high accuracy (AUC = 0.898), and cell diameter and cellularity were most effective for differentiating HER2-low from HER2-positive tumors (AUC = 0.770). No significant Td-dMRI differences were observed for Ki-67.

CONCLUSION: ADC30ms most effectively distinguished HER2-zero from HER2-low tumors, while microstructural parameters such as cellularity and cell diameter moderately differentiated HER2-low from HER2-positive cancers. These results support the potential of Td-dMRI as a complementary imaging biomarker for subtype characterization, although findings were limited by small subgroup sizes and the single-center design.}, } @article {pmid41608229, year = {2026}, author = {Zhu, L and Li, J and Yang, L and Li, T and Zhang, P and Li, P and Hong, Y}, title = {Multiple gastrointestinal metastases in de novo invasive ductal carcinoma of the breast: A case report and literature review.}, journal = {SAGE open medical case reports}, volume = {14}, number = {}, pages = {2050313X261417159}, pmid = {41608229}, issn = {2050-313X}, abstract = {Gastrointestinal tract (GIT) metastases occur in only 0.6% of metastatic breast cancer cases, with invasive lobular carcinoma being the predominant histological subtype. Synchronous GIT metastases at the time of invasive ductal carcinoma (IDC) diagnosis are exceptionally uncommon. We report a case of de novo IDC presenting with synchronous, multifocal metastases in the stomach and colon. The diagnosis was prompted by significantly elevated tumor markers and confirmed via endoscopic examination and biopsy. This case underscores the rarity of GIT metastases, particularly in IDC, and highlights the critical need for a high index of suspicion in the face of markedly elevated tumor markers, even without gastrointestinal symptoms. While contrast-enhanced computed tomography has limited sensitivity for detecting small GIT lesions, endoscopic biopsy with immunohistochemical analysis remains the gold standard for diagnosis. Accompanying this report is a systematic literature review on breast cancer metastases to the GIT.}, } @article {pmid41608012, year = {2025}, author = {Aragão, JA and Amaral, JV and Sant'Anna Aragão, IC and Sant'Anna Aragão, FM and Reis, FP}, title = {Early Diagnosis of Male Breast Cancer: A Case Report and Literature Review.}, journal = {Cureus}, volume = {17}, number = {12}, pages = {e100241}, pmid = {41608012}, issn = {2168-8184}, abstract = {Male breast cancer (MBC) is a rare neoplasm, and this rarity underscores the critical importance of awareness and appropriate screening. This study presents a case of male breast cancer (MBC) in a 64-year-old patient to enhance understanding of this rare and frequently underdiagnosed neoplasm. A 64-year-old man presented with a palpable mass in the left breast. Imaging revealed bilateral gynecomastia and a highly suspicious 4.3-cm Breast Imaging Reporting and Data System (BI-RADS) 5 nodule with nipple retraction. Biopsy confirmed histologic grade III invasive ductal carcinoma. Immunohistochemistry showed positivity for hormone receptors (Estrogen Receptor (ER) 90%, Progesterone Receptor (PR) 50%) and was negative for Human Epidermal Growth Factor Receptor 2 (HER2). Following left mastectomy, the patient experienced postoperative complications, including a contralateral hematoma and a persistent seroma. Oncotype diagnosis (DX) testing indicated a low chemotherapy benefit, leading to adjuvant therapy with tamoxifen. Pathologic tumor stage pT1c and pathologic nodal status pN0, confirmed by sentinel lymph node biopsy, indicated early-stage disease. The complexity of MBC underscores the critical importance of early diagnosis. The prompt detection of the suspicious mass, culminating in effective early-stage treatment, proved crucial to this patient's favorable prognosis, in contrast to the common trend of delayed diagnoses and their less promising outcomes. Accordingly, strengthening public awareness and professional training is essential to optimize management and improve outcomes in men with breast cancer.}, } @article {pmid41605726, year = {2026}, author = {Liu, Y and Hu, S and Munot, S and Konofagou, EE}, title = {3-D Handheld Harmonic Motion Imaging System for Breast Tumor Assessment: A Clinical Feasibility Study.}, journal = {Ultrasound in medicine & biology}, volume = {52}, number = {4}, pages = {870-881}, doi = {10.1016/j.ultrasmedbio.2026.01.001}, pmid = {41605726}, issn = {1879-291X}, mesh = {Humans ; *Breast Neoplasms/diagnostic imaging ; Feasibility Studies ; Female ; *Elasticity Imaging Techniques/instrumentation/methods ; *Imaging, Three-Dimensional/methods/instrumentation ; Phantoms, Imaging ; *Ultrasonography, Mammary/methods/instrumentation ; Reproducibility of Results ; Breast/diagnostic imaging ; Equipment Design ; Transducers ; }, abstract = {OBJECTIVE: Harmonic motion imaging (HMI) is a displacement-based ultrasound elastography that simultaneously induces and tracks oscillatory on-axis motion using focused ultrasound and imaging transducers. Single transducer (ST)-HMI was recently developed to perform harmonic excitation and tracking using 1-D imaging arrays and electronic steering to exclude redundant raster-scanning. However, ST-HMI is limited to 2D imaging. This study develops 3-D-HMI with a handheld system.

METHODS: Harmonic radiation force (200 or 400 Hz) was generated using row or column elements of a row-column array (RCA), with resulting displacements estimated using the same elements for focused transmission and the remaining orthogonal elements in receive, interleaved between excitation pulses.

RESULTS: The proposed method was first validated in phantoms with stiff (Young's moduli: 22, 31, 44 and 56 kPa in 5.3-kPa background) or soft (5.1 kPa in 18.6-kPa background) inclusions (n = 12, diameters: 2.2-13.2 mm) mimicking malignant and benign tumors. The 3-D estimated normalized displacement detected all inclusions, including the smallest at 2 mm, and was found to be inversely proportional to the Young's modulus ratio of inclusions to background. 3-D HMI displacement maps of human breast tumors (n = 5) were reconstructed, including fibroadenoma (FA, n = 1) and invasive ductal carcinoma (IDC, n = 4), among which two were residual diseases after up to 12 wk of neoadjuvant chemotherapy.

CONCLUSION: 3-D-HMI was hereby described and found to be feasible, accurate and time-efficient volumetric mapping of relative stiffness. The proposed method increases the clinical potential of HMI to assess the mechanical properties of entire tumor volumes in a typical handheld manner, as in conventional breast sonography.}, } @article {pmid41605126, year = {2026}, author = {Watanabe, R and Miura, N and Kikugawa, T and Saika, T and Haffner, MC and Nelson, PS}, title = {Molecular pathology of rare histologic variants and treatment-resistant lineages of prostate cancer.}, journal = {Urologic oncology}, volume = {44}, number = {4}, pages = {110987}, doi = {10.1016/j.urolonc.2025.110987}, pmid = {41605126}, issn = {1873-2496}, abstract = {Rare histological variants of prostate cancer-including ductal adenocarcinoma, intraductal carcinoma of the prostate (IDC-P), neuroendocrine carcinoma, basal cell/adenoid cystic carcinoma, squamous cell carcinoma, sarcomatoid carcinoma, and stromal tumors-exhibit highly diverse biological behaviors and distinct molecular features. Accurate pathological recognition is essential, as these entities frequently diverge from conventional acinar adenocarcinoma in morphology, genomic alterations, therapeutic responsiveness, and clinical outcomes. Intraductal carcinoma of the prostate (IDC-P) and ductal adenocarcinoma often display genomic instability and aggressive clinical behavior, including enrichment for homologous recombination repair (HRR) defects and hypoxia-related pathways. Neuroendocrine subtypes, including de novo and treatment-related NEPC as well as double-negative prostate cancer (DNPC), are characterized by androgen receptor (AR) independence, RB1/TP53 loss, low prostate-specific antigen (PSA) production, and poor prognosis, reflecting lineage plasticity under therapeutic pressure. Other rare tumors-such as basal cell carcinoma/adenoid cystic carcinoma, squamous cell carcinoma, and stromal tumors (STUMP and prostatic stromal sarcoma)-demonstrate unique pathological patterns and limited responsiveness to standard systemic therapies, underscoring the importance of tailored diagnostic and management strategies. This review integrates the histopathological, molecular, and emerging spatial transcriptomic insights across this spectrum of rare and treatment-resistant prostate cancer subtypes. By highlighting shared mechanisms such as genomic instability, androgen receptor (AR) pathway bypass, and microenvironmental remodeling, we outline key diagnostic considerations and evolving therapeutic implications relevant to precision oncology.}, } @article {pmid41602403, year = {2025}, author = {Han, H and Liu, J and Wang, C and Yang, M and Liu, J and Sun, P}, title = {Trastuzumab deruxtecan (DS-8201) plus bevacizumab for HER2-low metastatic breast cancer with malignant pleural effusion: a case report and literature review.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1694553}, pmid = {41602403}, issn = {2234-943X}, abstract = {INTRODUCTION: HER2-low breast cancer has emerged as a distinct molecular subtype with unique biological features and therapeutic significance. Trastuzumab deruxtecan, an antibody-drug conjugate, has shown promising efficacy in both HER2-high and HER2-low disease.

CASE DESCRIPTION: We report the case of a 69-year-old woman with a 17-year history of breast cancer, initially diagnosed in 2007 with invasive ductal carcinoma and lymph node metastasis. After multiple lines of systemic therapy, the disease progressed with dynamic reduction of HER2 expression from 3+ to 1+, ultimately confirming HER2-low advanced breast cancer. Recurrent malignant pleural effusion became the predominant manifestation, severely impairing quality of life.

INTERVENTION AND OUTCOMES: DS-8201 monotherapy was initiated but failed to control pleural effusion. Sequential combinations of DS-8201 with intrapleural cisplatin and then intrapleural bevacizumab were attempted, with only the latter yielding significant benefit. The regimen was subsequently optimized to intravenous DS-8201 plus bevacizumab, resulting in rapid symptom relief, substantial reduction of pleural effusion, and sustained disease control. At the latest follow-up, the patient achieved 18 months of stable disease with improved quality of life and no severe adverse events.

CONCLUSION: To our knowledge, this is the first reported case of DS-8201 plus bevacizumab for HER2-low metastatic breast cancer with malignant pleural effusion. This case highlights the potential of this regimen as a promising therapeutic option for patients with limited alternatives.}, } @article {pmid41599740, year = {2026}, author = {Besli, N and Ercin, N and Tokocin, M and Boluk, SE and Cakmak, RK and Ozdogan, K and Aktokmakyan, TV and Toprak, M and Ercan, G and Beker, M and Celik, U and Capkinoglu, E and Tutar, Y}, title = {Carvacrol Selectively Induces Mitochondria-Related Apoptotic Signaling in Primary Breast Cancer-Associated Fibroblasts.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {1}, pages = {}, pmid = {41599740}, issn = {1424-8247}, support = {123C141//Scientific and Technological Research Council of Turkey/ ; }, abstract = {Background/Objectives: Cancer-associated fibroblasts (CAFs) are key stromal mediators of breast tumor progression and therapy resistance. Carvacrol, a dietary monoterpenic phenol, exhibits antiproliferative activity in cancer cells, but its effects on primary human breast CAFs remain unclear. This study aimed to determine whether carvacrol selectively induces mitochondria-related apoptotic signaling in breast CAFs while sparing normal fibroblasts (NFs). Methods: Primary fibroblast cultures were established from invasive ductal carcinoma tissues (CAFs, n = 9) and nonmalignant breast tissues (NFs, n = 5) and validated by α-SMA and FAP immunofluorescence. Cells were exposed to 400 μM carvacrol. Apoptosis was assessed by TUNEL assay and BAX/BCL-XL Western blotting. Changes in signaling pathways were evaluated by analyzing PPARα/NF-κB, sirtuin (SIRT1, SIRT3), autophagy-related markers (LAMP2A, p62), and matrix metalloproteinases (MMP-2, MMP-3). In silico molecular docking and 100-ns molecular dynamics simulations were performed to examine interactions between carvacrol and caspase-3 and caspase-9. Results: Carvacrol induced a pronounced, time-dependent apoptotic response in CAFs, with TUNEL-based viability declining to approximately 10% of control levels by 12 h and a marked increase in the BAX/BCL-XL ratio. In contrast, NFs exhibited minimal TUNEL positivity and no significant change in BAX/BCL-XL. In CAFs, but not NFs, carvacrol reduced PPARα expression and NF-κB nuclear localization, increased SIRT1 and SIRT3 levels, selectively suppressed MMP-3 while partially normalizing MMP-2, and altered autophagy-related markers (decreased LAMP2A and accumulation of p62), consistent with autophagic stress and possible impairment of autophagic flux. Computational analyses revealed stable carvacrol binding to caspase-3 and caspase-9 with modest stabilization of active-site loops, supporting caspase-dependent, mitochondria-related apoptosis. Conclusions: Carvacrol selectively targets breast cancer-associated fibroblasts by inducing mitochondria-related apoptotic signaling while largely sparing normal fibroblasts. This effect is accompanied by coordinated modulation of PPARα/NF-κB, sirtuin, autophagy, and MMP pathways. These findings support further evaluation of carvacrol as a microenvironment-directed adjunct in breast cancer therapy.}, } @article {pmid41592189, year = {2026}, author = {Baboli, KM and Salehiazar, S and Tran, T}, title = {Encapsulated Papillary Carcinoma of the Breast: Two Cases with Literature Review and Molecular Insights.}, journal = {Rhode Island medical journal (2013)}, volume = {109}, number = {2}, pages = {7-10}, pmid = {41592189}, issn = {2327-2228}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/genetics/diagnosis/therapy/surgery ; Middle Aged ; Adult ; *Carcinoma, Papillary/pathology/genetics/diagnosis/therapy/surgery ; Class I Phosphatidylinositol 3-Kinases/genetics ; Mastectomy, Segmental ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; }, abstract = {INTRODUCTION: Encapsulated papillary carcinoma (EPC) of the breast is a rare subtype of breast cancer, accounting for 0.5-2% of cases, and typically affects postmenopausal women. Characterized by well-circumscribed lesions lacking peripheral and central myoepithelial cells, EPC is associated with favorable prognosis due to its indolent behavior and high hormone receptor positivity. However, its potential association with ductal carcinoma in situ (DCIS) or invasive carcinoma necessitates thorough diagnostic evaluation.

CASE PRESENTATION: This study presents two cases of EPC-one in a 57-year-old and the other in a 39-year-old female-each with focal DCIS and strong estrogen and progesterone receptor expression. Both patients underwent breast-conserving surgery and were managed with hormone therapy.

CONCLUSION: Histopathological and immunohistochemical analyses confirmed the EPC diagnosis, and molecular insights revealed common mutations, particularly in the PIK3CA gene. This report underscores the importance of integrating clinical, histological, and molecular findings to guide diagnosis and management of EPC, which, despite its low invasive potential, shares genetic features with invasive ductal carcinoma.}, } @article {pmid41591602, year = {2026}, author = {Alshuaibi, H and Neduvanchery, S and Fitzpatrick, SG and Bhattacharyya, I and Islam, MN}, title = {Intraductal Salivary Gland Neoplasms of the Oral Cavity: A Retrospective Case Series with Emphasis on Newly Described Entities.}, journal = {Head and neck pathology}, volume = {20}, number = {1}, pages = {16}, pmid = {41591602}, issn = {1936-0568}, mesh = {Humans ; *Salivary Gland Neoplasms/pathology ; Retrospective Studies ; Female ; Male ; Middle Aged ; Aged ; Adult ; Aged, 80 and over ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; }, abstract = {PURPOSE: Intraductal salivary gland tumors represent a distinct and intriguing subset of salivary gland neoplasms, characterized by their origin within the ductal epithelium. These tumors encompass a wide range from benign entities such as intraductal papilloma to the malignant forms such as intraductal carcinoma (IDC). IDC often present as well-circumscribed mass due to their intraductal growth pattern, thereby mimicking benign neoplasms and posing diagnostic challenges. Recent advances have led to the molecular characterization of IDC, which may have been previously unrecognized or misclassified. This study aims to perform a comprehensive retrospective analysis of intraductal oral salivary gland neoplasms with a focus on reviewing newly described entities.

MATERIALS AND METHODS: Following institutional review board approval, archival biopsy records from 2000 to 2024 were reviewed for cases diagnosed as salivary ductal papilloma or IDC. Additional cases previously classified as papillary cystadenoma or adenocarcinoma, not otherwise specified, were re-evaluated for features consistent with IDC. Cases suspected of IDC were subjected to immunohistochemical analysis for p63, S100, and mammaglobin expression.

RESULTS: Thirty-five benign intraductal neoplasms were identified, which included sialadenoma papilliferum (SP) (n = 18, 31.40%), DP (n = 12, 34.30%), and inverted ductal papilloma (n = 5, 14.30%). The mean age of benign lesions was 66.5, with a slight male predominance. Most benign cases occurred on the buccal mucosa (n = 18, 51.4%). A total of seven IDC cases were identified, comprising three low-grade apocrine, two intercalated-like, one mixed phenotype, and one high-grade apocrine type. The mean age of the IDC cases was 58.6 years with a female predominance (n = 4, 66%), and most frequently occurred on the palate (n = 3, 42%).

CONCLUSION: Intraductal salivary gland neoplasms present diagnostic challenges due to their overlapping clinical and histologic features. Understanding of the characteristic morphologic and immunophenotypic profile of IDC is essential for accurate diagnosis and appropriate patient management.}, } @article {pmid41587557, year = {2026}, author = {De Coster, I and AbdelGhany, M and Sarakinou, E and Fineschi, C and Marchetti, E and La Gaetana, R and Nigro, S and Carducci, M and Massai, L and Conti, V and Rossi, O and Luna Cilio, G and Serry-Bangura, A and Tessitore, P and Van Damme, P and Withanage, K and Micoli, F and Berlanda Scorza, F and Rondini, S and Nakakana, UN and Kumar Arora, A}, title = {Safety and immunogenicity of a conjugate vaccine candidate against Salmonella enterica serovars Typhi and Paratyphi A in healthy adults in Europe: a phase 1 randomised controlled trial.}, journal = {The Lancet. Infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/S1473-3099(25)00730-3}, pmid = {41587557}, issn = {1474-4457}, abstract = {BACKGROUND: Enteric fever caused by Salmonella enterica serovars Typhi and Paratyphi A remains a major concern. No vaccines are licensed against Salmonella Paratyphi A. We aimed to assess the safety and immunogenicity of an investigational conjugate vaccine against Salmonella Typhi and Paratyphi A (Vi-CRM197+O:2-CRM197).

METHODS: In this observer-masked, randomised, controlled, dose-escalation, single-centre, phase 1 trial done during Nov 28, 2022, to April 2, 2024, at the Centre for Evaluation of Vaccination in Belgium, healthy adults (aged 18-50 years) were randomly assigned (2:1 or 2:2:1 across different steps using sealed envelopes following a randomisation schedule generated by an independent statistician) to receive two intramuscular doses (on day 1 and day 169) of one of four Vi-CRM197+O:2-CRM197 formulations (low dose or full dose, with or without aluminium hydroxide) or a control vaccine (Vi capsular polysaccharide vaccine and diphtheria toxoid-tetanus toxoid-acellular pertussis vaccine for first and second dose). The primary outcome was vaccine safety (solicited events during 7 days and unsolicited adverse events during 28 days after vaccination, serious adverse events [SAEs], and adverse events or SAEs leading to study withdrawal or withholding of further study intervention administration from day 1 to day 197, and deviations from normal or baseline laboratory test values 7 days after vaccination). Secondary outcomes included long-term vaccine safety (SAEs and adverse events or SAEs leading to study withdrawal from day 197 to day 337), and immunogenicity, including anti-Vi and anti-O:2 IgG antibody geometric mean concentrations and geometric mean ratios (GMRs) by ELISA, and seroresponses (percentages of participants with anti-Vi IgG concentrations ≥4·3 μg/mL and ≥2·0 μg/mL; ≥4-fold anti-O:2 IgG concentration increase from baseline) at day 1 (as applicable), day 29, day 169, day 176, and day 197. Safety analyses were done on the solicited safety set, unsolicited safety set, and the exposed set. The primary immunogenicity analysis was done on the per-protocol set defined by timepoint. The trial is registered with ClinicalTrials.gov (NCT05613205) and gsk-studyregister.com (205480), and is completed.

FINDINGS: 96 participants were randomly assigned, 12 to each low-dose group, 24 to each full-dose group, and 24 to the control group. The incidence of solicited administration-site events (mostly pain) ranged from six (50% [95% CI 21·1-78·9]) of 12 participants in the low-dose without aluminium hydroxide group to 23 (96% [78·9-99·9]) of 24 in the full-dose with aluminium hydroxide group, versus 22 (92% [73·0-99·0]) of 24 in the control group. Solicited systemic events (mostly fatigue, headache, and myalgia) ranged from eight (67% [34·9-90·1]) of 12 in the low-dose groups to 20 (83% [62·6-95·3]) of 24 in the full-dose with aluminium hydroxide group, versus 21 (88% [67·6-97·3]) of 24 in the control group. The incidence of unsolicited adverse events (mostly nasopharyngitis) ranged from seven (58% [27·7-84·8]) of 12 in the low-dose without aluminium hydroxide group to ten (83% [51·6-97·9]) of 12 in the low-dose with aluminium hydroxide group, versus 14 (58% [36·6-77·9]) of 24 in the control group. Most safety laboratory results were within reference ranges. No SAEs occurred. After dose 1 (ie, at day 29), full-dose without aluminium hydroxide and full-dose with aluminium hydroxide induced the highest anti-Vi IgG responses (GMR 53·01 [95% CI 31·94-87·99] and 31·55 [18·74-53·11], respectively) versus control (4·50 [2·93-6·90]). Full-dose without aluminium hydroxide and low-dose without aluminium hydroxide induced the highest anti-O:2 IgG responses after dose 1 (GMR 162·61 [91·17-290·04] and 114·19 [44·83-290·86], respectively), versus control (1·27 [1·02-1·60]). 89-100% and 82-100% of participants (lowest percentages for low-dose with aluminium hydroxide) had anti-Vi IgG ≥4·3 μg/mL at day 29 (in initially seronegative participants) and ≥4-fold anti-O:2 IgG increase from baseline, respectively, versus 13 (54% [95% CI 32·8-74·4]) and one (4% [0·1-21·1]) of 24 participants in the control group, respectively. The second dose did not boost the responses.

INTERPRETATION: Vi-CRM197+O:2-CRM197 formulations did not raise safety concerns and showed immunogenicity with a single dose, supporting further clinical assessment of the full-dose without aluminium hydroxide in target populations (infants and older age groups) in endemic regions.

FUNDING: Wellcome Trust.}, } @article {pmid41585001, year = {2026}, author = {Yoneda, H and Shimizu, Y and Bae, Y and Osako, T and Ogiya, A}, title = {A 21-Year-Old Female with Invasive Breast Cancer within a Benign Phyllodes Tumor.}, journal = {Surgical case reports}, volume = {12}, number = {1}, pages = {}, pmid = {41585001}, issn = {2198-7793}, abstract = {INTRODUCTION: Although breast cancer occurring within a phyllodes tumor (PT) has been reported, it is extremely rare in young patients. Herein, we describe a case of breast cancer complicated by a PT in a 21-year-old female.

CASE PRESENTATION: A 21-year-old female was referred to our hospital with a rapidly growing breast mass and suspected PT. Mammography revealed a well-defined, high-density mass. Ultrasonography revealed a blood-flow-rich hypoechoic mass with multiple slit structures, and MRI revealed a heterogeneous high signal on T2 weighted image with some diffusion restriction. A core needle biopsy revealed fibroepithelial lesions, and the lack of stromal changes suggested a high possibility of fibroadenoma. Based on the clinical and imaging findings, we considered the possibility of the PT being more than borderline malignant and planned tumor resection with a safety margin. The postoperative pathology revealed a benign PT complicated by invasive ductal carcinoma, with a predominance of intraductal carcinoma.

CONCLUSIONS: We report the case of a 21-year-old female with breast cancer occurring within a PT. The presence of cancer was difficult to predict preoperatively based on the patient's young age and imaging findings.}, } @article {pmid41584599, year = {2025}, author = {Garcia-Robledo, JE and Cabrera-Salcedo, S and Brandauer, AM and Romano, F and Rengifo-Martinez, J and Toro-Pedroza, A and Victoria, JS and Rios-Serna, LJ and Loukanov, A and Cardona, AF and Genovese, P and Baena, JC}, title = {Engineering the next generation of CAR T- cells: precision modifications, logic gates and universal strategies to overcome exhaustion and tumor resistance.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1698442}, pmid = {41584599}, issn = {2234-943X}, abstract = {Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment landscape of hematologic malignancies, delivering durable remissions in diseases previously associated with poor outcomes. However, translating this success to solid tumors has proven challenging due to antigen heterogeneity, limited tumor infiltration, immunosuppressive tumor microenvironments, and progressive T-cell exhaustion. In response, next-generation CAR T-cell platforms have emerged that integrate advances in receptor architecture, intracellular signaling, and programmable control systems to enhance specificity, persistence, and safety. This review comprehensively examines recent innovations in CAR T-cell engineering, including optimization of extracellular binding domains, hinge and transmembrane modifications, fine-tuning of intracellular signaling motifs, and the incorporation of alternative protein scaffolds. We discuss logic-gated strategies such as synNotch receptors, inducible ON-switch CARs, inhibitory CARs, and modular adaptor systems that enable context-dependent activation and reduce off-tumor toxicity. In parallel, we explore approaches aimed at overcoming T-cell dysfunction through intrinsic checkpoint rewiring, cytokine armoring, and epigenetic reprogramming to sustain antitumor activity in hostile microenvironments. The development of allogeneic and off-the-shelf CAR T-cell products derived from healthy donors, induced pluripotent stem cells, natural killer cells, γδ T cells, and macrophages is also reviewed, highlighting strategies to mitigate graft-versus-host disease and host immune rejection while enabling scalable manufacturing. Finally, we address current translational bottlenecks related to immunogenicity, regulatory complexity, and production logistics, and outline future directions for integrating Boolean logic circuits, safety switches, and automated GMP-compliant processes. Collectively, these advances position next-generation CAR T-cell therapies as programmable and adaptable immunotherapeutic platforms with the potential to extend durable clinical benefit beyond hematologic cancers into solid tumors.}, } @article {pmid41581331, year = {2026}, author = {Nori Cucchiari, J and Di Naro, F and Migliaro, G and Baldi Giorgi, SE and Pugliese, F and Amadori, T and Bicchierai, G and De Benedetto, D and Bellini, C and Vidali, S and Vanzi, E and Boeri, C and Lamagna, V and Miele, V and Susini, T}, title = {Cryoablation for Treatment of Early-Stage Breast Cancer: Efficacy and Quality of Life Assessment.}, journal = {Clinical breast cancer}, volume = {26}, number = {2}, pages = {70-79}, doi = {10.1016/j.clbc.2025.12.004}, pmid = {41581331}, issn = {1938-0666}, mesh = {Humans ; Female ; *Cryosurgery/methods/adverse effects ; *Quality of Life ; *Breast Neoplasms/surgery/pathology ; Prospective Studies ; Aged, 80 and over ; Aged ; Neoplasm Staging ; Treatment Outcome ; Follow-Up Studies ; *Carcinoma, Ductal, Breast/pathology/surgery ; Mammography ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most common cancer among women. There has been growing interest in less invasive techniques for the treatment of breast lesions, with cryoablation emerging as promising option. We aimed to assess the safety and efficacy of cryoablation for the treatment of breast cancer tumor subtypes 12 months post-treatment.

METHODS: This single-center prospective study included patients with biopsy-proven BC who underwent ultrasound-guided-cryoablation treatment during 2021-2023. Locoregional staging was performed using ultrasound and contrast-enhanced mammography (CEM). Follow-up included ultrasound at 1-, 3-, 6- and 12-months with additional CEM and biopsy at 12-months. Rate of complete ablation, tumor size and quality of life (QoL) were assessed. Primary endpoint was absence of residual tumor for BC at 12-month post cryoablation.

RESULTS: Thirthy-six female patients (mean age, 84.5±6.7 years) with 39 biopsy-proven tumors (mean size 15.3±7.5 mm) underwent cryoablation. No device-related unexpected adverse events were reported. The 39 BCs were early-stage luminal A or B, invasive ductal carcinoma (IDC) or IDC + ductal carcinoma in situ. Complete ablation rates for BC ≤ 15 mm and BC >15 mm were 100% and 84.6%, respectively; Cryoablation positively impacted patient QoL as assessed by validated questionnaires.

CONCLUSIONS: With improved QoL, cryoablation emerges as a promising, safe, and effective treatment option for low-risk breast cancer.

DISCLAIMER/PUBLISHER'S NOTE: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.}, } @article {pmid41579313, year = {2026}, author = {Scherer, C and Fung, V and Anzellini, D and Osti, MF and Doridot, V and Muracciole, X and Nappa, M and Mesurolle, B and Loganadane, G}, title = {Real world experience of intraoperative radiation therapy (IORT) during lumpectomy for early-stage breast cancer: retrospective data from a single large institutional observational study.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {33}, number = {2}, pages = {426-435}, pmid = {41579313}, issn = {1880-4233}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/radiotherapy/surgery/mortality/therapy ; Middle Aged ; Aged ; *Mastectomy, Segmental/methods ; Retrospective Studies ; Aged, 80 and over ; Radiotherapy, Adjuvant/methods ; Intraoperative Care/methods ; Sentinel Lymph Node Biopsy ; *Carcinoma, Ductal, Breast/pathology/radiotherapy/surgery ; Neoplasm Recurrence, Local/epidemiology ; Follow-Up Studies ; Neoplasm Staging ; }, abstract = {BACKGROUND: We report outcomes of patients who received intraoperative radiation therapy (IORT) using 50 kV after lumpectomy and sentinel lymph node biopsy.

METHODS: Women with age > 45 and post-menopausal status, localized, unifocal, invasive breast carcinoma were included in the study. Patients were diagnosed by needle biopsy, and suitable for wide local excision of invasive ductal carcinoma without nodal involvement on conventional examination (cT1 and small cT2 ≤ 3.5 cm, cN0, M0). Overall, 489 patients who received adjuvant IORT after breast-conserving surgery were identified between March 2016 to June 2023. The median age was 68 years (range 49-93). The median tumor size was 8 mm (0-40 mm). Adjuvant whole breast adiation therapy (WBRT), chemotherapy and endocrine were additionally offered in 36 patients (7.4%), 12 (2.4%) and 384 patients (78.5%) respectively.

RESULTS: After a median follow-up of 36 months (range, 0-100), the 3-year LR was 1.4% (95% CI 0.6-3.1%). The 3-year LRFS, LRRFS, and PFS were each 97.1% (95% CI 94.6-98.5%), while the 3-year MRFS and OS were both 98.3% (95% CI 96.1-99.2%). The 3-year outcomes did not differ significantly between the IORT and IORT + WBRT cohorts. Patients who did not receive ET (n = 104) experienced a significantly higher rate of local recurrence compared with those who received ET (n = 384) (3-year LR 4.0% vs. 0.7%; p = 0.01). LRFS and LRRFS showed borderline significance (5-year LRFS 96.9% vs. 100%; p = 0.05). MRFS, PFS, and OS did not differ significantly between the two groups.

CONCLUSIONS: Preliminary 3-year results show that IORT with 50 kV achieves excellent local control in selected early-stage breast cancer patients. Endocrine therapy reduced local recurrence, while WBRT added no significant benefit, underscoring the need for longer follow-up.}, } @article {pmid41574911, year = {2026}, author = {Wei, X and Xin, K and Zheng, Z and Cui, X and Nie, L}, title = {Apocrine Intraductal Carcinoma With A Frankly Invasive Salivary Duct Carcinoma Component: A Case Report Showing Novel Genetic Alterations.}, journal = {International journal of surgical pathology}, volume = {}, number = {}, pages = {10668969251407309}, doi = {10.1177/10668969251407309}, pmid = {41574911}, issn = {1940-2465}, abstract = {Intraductal carcinoma (IDC) and salivary duct carcinoma (SDC) are both rare tumors of the salivary glands that most frequently occur in the parotid glands. We present an example of apocrine IDC with a frankly invasive SDC component in the parotid gland. The clinicopathologic and molecular features were analyzed in this study. A 76-year-old female patient was admitted to hospital with a parotid mass. The biopsy result showed SDC, and radical resection surgery was performed. The tumor was characterized by an intraductal proliferation forming solid and cribriform structures with abundant eosinophilic cytoplasm, accompanied by comedo necrosis and apocrine secretion, some of which showed infiltrative growth without myoepithelial cells surrounding. Identifiable intravascular tumor thrombi and extensive lymph node (12 of 30) metastases were observed. The tumor cells were positive for androgen receptor and HER2, while negative for S100 and SOX10. The final diagnosis was apocrine IDC with an invasive SDC component. Next-generation sequencing revealed MET gene fusions and other gene mutations in the tumor cells. The rare MET gene fusions have not been reported in either IDC or SDC, which may enhance our understanding of the genetic alterations in a subset of SDCs that derive from IDC.}, } @article {pmid41561668, year = {2026}, author = {Claus, J and Pearce, J and Bojko, A and Manrai, P and Quddus, MR and Marketkar, S}, title = {Invasive Acantholytic Extramammary Paget's Disease of the Vulva With Mammary Carcinoma-Like Differentiation and MMR Loss: Report of an Unusual Case and Its Clinical Mimics.}, journal = {Gynecologic oncology reports}, volume = {63}, number = {}, pages = {102007}, pmid = {41561668}, issn = {2352-5789}, abstract = {BACKGROUND: Paget's disease (EMPD) of the vulva primarily affects postmenopausal women and can present significant challenges in early clinical detection.Case Presentation: We report an exceedingly rare case of invasive acantholytic extramammary Paget's disease in a 78-year-old female patient. After biopsy-proven carcinoma, a radical hemivulvectomy of the left vulva was performed, which revealed an invasive adenocarcinoma, most consistent with primary extramammary Paget's carcinoma. Histologic examination demonstrated a unique morphology, featuring an in-situ component with suprabasal intraepidermal acantholysis and an invasive component with various morphologies, including basaloid, skin adnexal-like, focal squamoid, and mammary-like differentiation, resembling ductal carcinoma in situ (DCIS) with comedonecrosis and invasive ductal carcinoma. This varied morphology has not been described before. Interestingly, the tumor shows loss of MMR protein (MSH2, MSH6).

CONCLUSION: In the literature, acantholytic Paget's disease and acantholytic anaplastic Paget's disease have been used interchangeably. While anaplastic Paget's disease has been reported in the mammary and extramammary sites (scrotum, esophagus), involvement of the vulva has been reported only once in the literature. However, the current case is the first documented loss of MMR. Both cases presented with invasive disease ranging in depth from 3-5 mm, and positive lymph nodes emphasizing on the urgent need to further explore prognostic factors of this rare entity and to differentiate it from other acantholytic lesions, such as squamous cell carcinoma in situ and other acantholytic dermatoses.}, } @article {pmid41559778, year = {2026}, author = {Sivrikoz, ON and Eroğlu, A and Öztürk, B and Öztop, İ and Sanal, SM}, title = {Benign prostatic hyperplasia to HPIN to carcinoma; the impact of mast cells and VEGF.}, journal = {Diagnostic pathology}, volume = {21}, number = {1}, pages = {10}, pmid = {41559778}, issn = {1746-1596}, abstract = {BACKGROUND: The process of transformation from Benign Prostatic Hyperplasia (BPH) to Prostate Cancer (PCa) is highly debatable; however, there is convincing information that it takes place in the background of inflammation. Multifocal high-grade prostatic intraepithelial neoplasia (HPIN), intraductal carcinoma (IDC-P), atypical intraductal proliferation (AIP), atypical adenomatous hyperplasia (AAH)/ adenosis, and proliferative inflammatory atrophy (PIA) are considered as precursor lesions during such transformation by Working Group 1 at the ISUP Cancer Precursors Meeting in September 2024. We specifically emphasize the need for further investigation of the inflammatory process, where stromal epithelial activity, angiogenesis, and mast cells are involved. In this study, we investigated the role of vascular endothelial growth factor (VEGF), and MCs during its progression from BPH to PCa. Additionally, we investigated the relationship between MCs and Gleason Grade Group (GG), as well as other prognostic variables.

METHODS: Retrospectively, 100 PCa patients whose pathology included areas of BPH and multifocal HPIN close to cancerous tissue. All the specimens were stained with CD117 as an MC marker and VEGF to evaluate for angiogenesis.

RESULTS: While there was overall intense MC infiltration in all areas of BPH in general, it was relatively less intense in areas of carcinomatous tissue. Nevertheless, MC infiltration intensified with higher GG. Similarly, with increasing MC infiltration in cancerous and HPIN tissues, VEGF staining also intensified, specifically in glandular areas. In HPIN areas, the relationship between MCs and VEGF was intermediate between BPH and cancerous areas, representing a progression.

CONCLUSION: Stromal changes, stromal-epithelial interactions, and coexisting inflammatory changes are important elements in the development of BPH and PCa. We specifically investigated the intratumoral MC population and glandular VEGF staining intensity with increasing GG; thus, assessing the role of MCs and VEGF in tumor progression towards cancer development. MCs and VEGF staining characteristics in HPIN areas emphasize the efficient role these elements play in the transition of tissues from BPH to HPIN and eventually to PCa.}, } @article {pmid41549218, year = {2026}, author = {Gallagher, K and Feldman, S and Barone, J and Mammen, J and Barone, R and Ochoa, D and McGinness, M and Frazer, T and Viscusi, R and Lang, JE and Lee, J and Adkins, LL and Johnson, S and Henry-Tillman, R and Korourian, S and Klimberg, VS}, title = {Prospective Phase II Multicenter Trial of Ablation after Breast Lumpectomy Added To Extend (ABLATE) Intraoperative Margins for the Sole Local Treatment of Breast Cancer.}, journal = {Annals of surgical oncology}, volume = {}, number = {}, pages = {}, pmid = {41549218}, issn = {1534-4681}, support = {CTSA Grant Award #UL1TR000039//University of Arkansas for Translational Research Institute/Arkansas Breast Cancer Research Program/ ; }, abstract = {BACKGROUND: Excision followed by radiofrequency ablation (eRFA) is an intraoperative method that utilizes intracavitary hyperthermia to create an additional tumor-free zone around the lumpectomy cavity in patients with breast cancer, similar to partial breast irradiation. We hypothesized that intraoperative eRFA extends the "final" tumor-free margin, decreases local recurrence, and maintains cosmesis without the need for radiation (XRT).

PATIENTS AND METHODS: Patients with unifocal ER+PR+HER2- or DCIS tumors less than or equal to 3 cm with clinically negative nodes were included. After standard lumpectomy, the RFA probe was deployed 1 cm circumferentially into the walls of the lumpectomy cavity. RFA was performed at 100°C for 15 min, followed by validated intraoperative Doppler sonography. Pain and cosmesis were assessed with the Radiation Therapy Oncology Group (RTOG) scales.

RESULTS: A total of 242 subjects were accrued to the study, with a median follow-up of 44 months (range 12-96 months); 60% were invasive ductal cancer (IDC), and 33% were ductal carcinoma in situ (DCIS). The average size was 1.1 ± 0.6 cm (0.2-3 cm). Reexcision for positive margins was < 5%. In-breast recurrence rate was 2.9%. Breast pain at 6 months was 19% with RFA combined with XRT versus 1.7% with RFA alone (p < 0.05). Cosmesis was good or excellent in 89% of subjects.

CONCLUSIONS: A majority of the subjects avoided whole breast XRT and mastectomy. Results indicate that eRFA, in lieu of XRT, is safe and effective, resulting in ~fivefold lower pain. By completing therapy in the operating room, eRFA can potentially enhance patient access and compliance, alleviate financial stress, and deliver superior cosmetic and quality-of-life outcomes.}, } @article {pmid41546339, year = {2025}, author = {Nishimura, A and Yatsuyanagi, M}, title = {[pT1c Breast Cancer Presenting with Skin Rupture without Skin Invasion-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {52}, number = {13}, pages = {1332-1334}, pmid = {41546339}, issn = {0385-0684}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/therapy/complications ; Aged ; Neoplasm Invasiveness ; *Carcinoma, Ductal, Breast/complications/pathology/therapy ; *Skin/pathology ; Rupture, Spontaneous/etiology ; Neoplasm Staging ; Sentinel Lymph Node Biopsy ; Mastectomy, Segmental ; }, abstract = {We report a case of breast bleeding caused by breast cancer without skin invasion. A woman in her 70s was aware of a mass in her right breast but left it untreated. About 6 months after noticing the mass, she visited our hospital due to bleeding from the right breast. Although needle biopsy did not reveal a diagnosis of breast cancer, we diagnosed her as having breast cancer based on clinical findings and recommended her to have surgery. Her consent was not obtained. Approximately 1 year later, she experienced bleeding from her right breast and visited our hospital. A tumor was identified, a biopsy was performed, and a diagnosis of breast cancer was made. A right lumpectomy and sentinel lymph node biopsy was carried out. Pathological diagnosis was invasive ductal carcinoma. No skin invasion was observed. The final diagnosis was pT1c, pN0 (sn), M0, pStageⅠ. After surgery, the patient was treated with tamoxifen and radiation therapy, and is currently free of recurrence.}, } @article {pmid41546327, year = {2025}, author = {Yoshioka, S and Hashizume, S and Sakai, S and Sawamura, N and Yasumoto, T and Ueda, R and Hayashi, S and Hara, A and Taniguchi, Y and Takeyama, H and Tanaka, N and Urano, N and Nishikawa, K and Okamura, S and Yokouchi, H}, title = {[Experience of Performing Liver Biopsy in Combination with TAE for Recurrence of HR-Positive HER2-Negative Breast Cancer with Rapid Appearance of Organ Metastases].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {52}, number = {13}, pages = {1297-1299}, pmid = {41546327}, issn = {0385-0684}, mesh = {Humans ; Middle Aged ; Female ; *Breast Neoplasms/pathology/therapy/chemistry/drug therapy/surgery ; *Liver Neoplasms/secondary/therapy ; Erb-b2 Receptor Tyrosine Kinases/analysis ; Biopsy ; Recurrence ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Liver/pathology ; }, abstract = {The patient was a 54-year-old woman diagnosed with right breast cancer at the age of 49 with cT4bN1M0, cStage ⅢB, and underwent radical surgery after preoperative chemotherapy. The histopathologic diagnosis was invasive ductal carcinoma, histological treatment effect Grade 1a, HR positive HER2 negative, chest wall irradiation and hormone therapy as postoperative treatment. At 5 years after surgery, there were no signs of recurrence on the imaging, but at a routine checkup 4 months later, left back pain and hip joint pain were observed, and bone metastases were diagnosed by MRI. PET- CT revealed multiple liver, lung, bone and lymph node metastases, and the course of recurrence was rapid in a short period of time. To re-evaluate the subtype, a liver biopsy was performed in combination with TAE to prevent bleeding for liver tumors with abundant blood flow. As a result, PgR turned negative, but there was no change in subtype. After irradiation to the pain area, paclitaxel and bevacizumab therapy was administered, and a marked reduction of pulmonary and liver metastases, and the disappearance of pain were observed. Local hepatic therapy with TAE followed by chemotherapy was thought to have helped the patient overcome the rapid tumor growth.}, } @article {pmid41546306, year = {2025}, author = {Sakurai, K and Suzuki, S and Adachi, K and Hirano, T and Kubota, H and Nagae, J and Sakamoto, A and Fujisaki, S and Ono, T and Tsuji, T}, title = {[Pleomorphic Invasive Lobular Carcinoma Developed after Surgery for Simultaneous Ipsilateral Multiple Cancers].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {52}, number = {13}, pages = {1234-1236}, pmid = {41546306}, issn = {0385-0684}, mesh = {Humans ; Female ; Middle Aged ; *Carcinoma, Lobular/surgery/pathology ; *Breast Neoplasms/surgery/pathology ; Neoplasm Invasiveness ; Mastectomy ; *Neoplasms, Multiple Primary/surgery/pathology ; }, abstract = {We report a case of pleomorphic invasive lobular carcinoma that developed after surgery for multiple ipsilateral cancers. The patient was a 54-year-old woman who visited our hospital after a tumor-like lesion was noted in her right breast. A needle biopsy revealed that the patient had invasive ductal carcinoma. No obvious distant metastasis was found;therefore, circular mastectomy and axillary lymph node dissection were performed. Histopathological examination revealed the following tumors;Tumor 1:Invasive ductal carcinoma(solid type), tumor diameter 33 mm, ER negative, PgR negative, HER2 negative, Ki-67 20.4%;and Tumor 2:Invasive lobular carcinoma, tumor diameter 6 mm, ER negative, PgR negative, HER2 negative, Ki-67 30.2%. The resection margin was negative, and lymph node metastasis was diagnosed as 3/12. Postoperative chemotherapy, radiation therapy, and endocrine therapy were performed. One year and 6 months after surgery, a hard lump was found in the remaining breast, and a needle biopsy confirmed it as pleomorphic lobular carcinoma. A pectoral muscle- sparing mastectomy was performed. Pathological examination of the excised specimen revealed new breast cancer:a pleomorphic lobular carcinoma, with tumor diameter 22 mm, and multiple daughter nodules. The resection margins were negative. The results were ER negative, PgR positive, HER2 negative, and Ki-67 25%. As the prognosis and treatment of invasive lobular carcinoma was unclear, caution was required.}, } @article {pmid41546284, year = {2025}, author = {Oshima, K and Hasegawa, M and Ogino, Y and Yamaura, M and Anno, K and Yanagisawa, K and Shinke, G and Katsuyama, S and Kinoshita, M and Hiraki, M and Iwagami, Y and Sugimura, K and Yasui, M and Takeda, Y and Murata, K}, title = {[A Case of Ipsilateral Breast Tumor Recurrence in Which a Sentinel Lymph Node Was Identified in the Contralateral Axilla].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {52}, number = {13}, pages = {1168-1170}, pmid = {41546284}, issn = {0385-0684}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/surgery ; Axilla/pathology ; Lymphatic Metastasis ; *Sentinel Lymph Node/pathology/surgery ; Aged, 80 and over ; Recurrence ; Sentinel Lymph Node Biopsy ; }, abstract = {The patient was a female in her 80s. She had undergone Bp+SN for left breast cancer 18 years ago. This time, she was referred to our department because of suspicion of ipsilateral breast tumor recurrence. Breast ultrasound revealed a 15 mm mass in the CA area of left breast, and biopsy revealed IDC, ER+, PgR+, HER2-. The diagnosis was cT1cN0M0, Stage Ⅰ, and the treatment plan was Bt+SN. Preoperative lymphoscintigraphy revealed a single accumulation in the contralateral axillary lymph node. Surgery was performed using the dye method, and the ipsilateral axilla was searched, but no sentinel lymph node was found. However, 1 sentinel lymph node in the contralateral axilla that only had RI uptake was found. Rapid diagnosis was negative for metastasis, so axillary dissection was omitted. Contralateral axillary lymph node metastasis is classified as distant lymph node metastasis according to the breast cancer treatment guidelines. However, contralateral axillary lymph node metastasis observed at the same time as ipsilateral breast tumor recurrence may be treated as regional lymph node metastasis if it is considered to be the result of changes in lymphatic flow caused by the initial surgery.}, } @article {pmid41546264, year = {2025}, author = {Kasagawa, T and Fujimori, T and Ishii, N and Ozaki, D and Yonemori, Y and Yasuda, S}, title = {[Three Cases of Esophageal Metastasis from Breast Cancer with Different Clinical Courses Based on Treatment Strategies].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {52}, number = {13}, pages = {1110-1112}, pmid = {41546264}, issn = {0385-0684}, mesh = {Humans ; Female ; *Esophageal Neoplasms/secondary/therapy ; Aged, 80 and over ; *Breast Neoplasms/pathology/therapy ; Aged ; Middle Aged ; Fatal Outcome ; }, abstract = {Esophageal metastasis from breast cancer is rare and seldom diagnosed before death, with no established standard treatment. We report 3 cases managed at our institution. Case 1:A 78-year-old woman previously underwent surgery for invasive ductal carcinoma(ER+, PgR+, HER2-)at the age of 65. Eight years postoperatively, the first recurrence occurred, followed by progressive dysphagia 5 years later, leading to the diagnosis of esophageal metastasis. Case 2:A 63-year-old woman had surgery at age 48 for invasive ductal carcinoma(ER+, PgR+, HER2-). Fourteen years postoperatively, she experienced a recurrence, and 1 month later, rapidly progressive dysphagia developed, resulting in the diagnosis of esophageal metastasis. Case 3:An 81-year-old woman was diagnosed with stage Ⅳ(bone)invasive ductal carcinoma(ER+, PgR+, HER2-)at age 73. After 8 years of systemic treatment, esophageal metastasis was diagnosed. In Cases 1 and 3, radiation therapy was selected, leading to symptomatic improvement and maintenance of oral intake until death. In contrast, Case 2, complicated by interstitial pneumonia, was treated with chemotherapy, but symptoms did not improve, and the patient remained unable to take food orally until death.}, } @article {pmid41546245, year = {2025}, author = {Sakurai, K and Suzuki, S and Adachi, K and Hirano, T and Kubota, H and Nagae, J and Sakamoto, A and Fujisaki, S and Ono, T and Tsuji, T}, title = {[A Case of T4b Breast Cancer That Developed 17 Years after Radiofrequency Ablation].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {52}, number = {13}, pages = {1055-1057}, pmid = {41546245}, issn = {0385-0684}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/pathology/therapy/surgery ; *Radiofrequency Ablation ; Time Factors ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Mastectomy ; *Carcinoma, Ductal, Breast/surgery/therapy ; Neoplasm Staging ; }, abstract = {We report a case of T4b breast cancer that developed 17 years after radiofrequency ablation(RFA). The patient was a 64- year-old woman. She had been diagnosed with left breast cancer 17 years ago and had undergone RFA. After radiation therapy, she had been administered AI drugs for 5 years. She was diagnosed with a mass in her left breast and visited our department. At the time of admission, a mass measuring 7 cm in diameter was palpable in her left breast. A needle biopsy revealed the diagnosis of invasive ductal carcinoma. A systemic examination revealed no obvious distant metastasis. A pectoral muscle-sparing mastectomy+partial pectoralis major muscle resection+axillary lymph node dissection+reconstruction using a rhomboid flap was performed. Histopathological findings of the resected specimen showed invasive ductal carcinoma, tumor diameter 53 mm, negative resection margin, and no lymph node metastasis. ER positive, PgR positive, HER2 positive, Ki-67 30%, and the diagnosis was T4bN0M0, Stage ⅢB. After postoperative chemotherapy, radiation therapy was performed. After that, trastuzumab+pertuzumab was administered 17 times. Currently, the patient is being followed up with fulvestrant. Two years after surgery, there has been no obvious metastasis or recurrence.}, } @article {pmid41546236, year = {2025}, author = {Adachi, K and Nagae, J and Kubota, H and Suzuki, S and Hirano, T and Ishibashi, N and Sakurai, K}, title = {[Bone Only Metastasis Breast Cancer with Effective Disease Control by Primary Tumor Resection-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {52}, number = {13}, pages = {1029-1031}, pmid = {41546236}, issn = {0385-0684}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/surgery/drug therapy ; Middle Aged ; *Bone Neoplasms/secondary/surgery/drug therapy ; Mastectomy ; *Carcinoma, Ductal, Breast/surgery/drug therapy/secondary ; }, abstract = {We report a case of metastatic breast cancer in the bones effectively treated with locoregional surgery. The patient was a 52-year-old woman who presented with an increasing right breast lump. A mass accompanied by skin redness 5 cm in diameter was palpable in the AC area of the right breast. Ultrasonography revealed multiple other masses in the bilateral breasts that were suspected to be malignant. Core needle biopsy led to the diagnosis of invasive ductal carcinoma in both breasts. Tumor marker 1-CTP was elevated, and bone scintigraphy showed multiple abnormal accumulations in the thoracic and lumbar spine, indicating multiple bone metastases. Bilateral mastectomy was first performed for local control. Histopathological diagnosis was invasive ductal carcinoma(scirrhous type)in both breasts, with multiple lesions, hormone receptor positive, and HER2 negative. After surgery, chemotherapy followed by endocrine therapy was administered, and tumor markers decreased, and bone metastases remained stable disease(SD). Two years and 2 months after surgery, no local recurrence or appearance of new lesions have been observed.}, } @article {pmid41546229, year = {2025}, author = {Sugimoto, Y and Terada, I and Nakamura, S and Aoki, T and Okamoto, J and Yamazaki, H and Zaimoku, R and Tsukioka, Y}, title = {[A Case of Sarcoid-Like Reaction That Was Difficult to Distinguish from Breast Cancer Relapse].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {52}, number = {13}, pages = {1008-1010}, pmid = {41546229}, issn = {0385-0684}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/drug therapy/diagnosis ; Recurrence ; Aged, 80 and over ; Diagnosis, Differential ; *Carcinoma, Ductal, Breast/drug therapy/secondary ; *Sarcoidosis/diagnosis ; Lymphatic Metastasis ; Positron Emission Tomography Computed Tomography ; }, abstract = {An elderly woman in her 80s with a medical history of rheumatoid arthritis and chronic hepatitis B was diagnosed with Stage Ⅳ, ER-negative, HER2-positive invasive ductal carcinoma of the left breast, with mediastinal lymph node metastases. She received chemotherapy combined with anti-HER2 therapy and achieved a complete remission after 12 months. Three years and 7 months later, FDG-PET/CT revealed enlargement of the left axillary lymph nodes, and they were suggested as recurrences. Radiotherapy was administered, resulting in temporary reduction in lymph node size. However, 10 months later, the lymph nodes re-enlarged and were subsequently surgically resected. Histopathological examination revealed that they were non-caseating granulomas without any evidence of malignancy, consistent with a diagnosis of sarcoid-like reaction. The patient has been followed up postoperatively without recurrence for 12 months.}, } @article {pmid41542527, year = {2026}, author = {Rima, XY and Majumder, S and Hu, C and Patel, DS and Li, H and Huang, X and Nguyen, KT and Doon-Ralls, J and Nagaraj, CK and Hade, MD and Magaña, SM and Shankar, E and Zhang, X and Stover, DG and Ramaswamy, B and Reátegui, E}, title = {Multidimensional Cellular Micro-Compartments to Model Invasive Lobular Carcinoma Dormancy.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.09.698501}, pmid = {41542527}, issn = {2692-8205}, abstract = {Invasive lobular carcinoma (ILC) accounts for 10-15% of breast cancers. Despite favorable responses to anti-estrogen therapy, the dissemination of cancer cells and resistance to therapies are significant risks for patients with ILC. Late recurrences are prevalent in ILC, suggesting that disseminated tumor cell dormancy may be a mechanism preceding their late overt growth into metastatic lesions. Herein, we investigated the relationship between anti-estrogen resistance and dormancy through multidimensional in vitro models. The bioengineered platforms recapitulated the morphological characteristics of ILC and highlighted its distinction from invasive ductal carcinoma. Inducing a dormant phenotype revealed epigenetic changes and enhanced chemical and mechanical sensing of anti-estrogen-resistant ILC cells to the substrate surface, with p27Kip1 signaling playing a central role. We propose this platform as a high-throughput method to investigate the propensity of dormancy and its manifestation via a simplified and expedited approach.}, } @article {pmid41540462, year = {2026}, author = {Thabet, DM and Abu Bakr, ASWK}, title = {Immunohistochemical expression of CANT1 and B3GNT3 in invasive ductal carcinoma of the breast: diagnostic and prognostic significance in lymph node metastasis.}, journal = {Diagnostic pathology}, volume = {21}, number = {1}, pages = {12}, pmid = {41540462}, issn = {1746-1596}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/mortality/diagnosis ; *Lymphatic Metastasis/pathology ; Middle Aged ; *Biomarkers, Tumor/analysis ; Adult ; *N-Acetylglucosaminyltransferases/analysis/metabolism ; Immunohistochemistry ; Aged ; *Carcinoma, Ductal, Breast/pathology/mortality/diagnosis/secondary ; Prognosis ; Kaplan-Meier Estimate ; Progression-Free Survival ; Lymph Nodes/pathology ; NM23 Nucleoside Diphosphate Kinases ; }, abstract = {BACKGROUND: Breast cancer is a leading global health concern, with lymph node metastasis (LNM) being a key prognostic factor affecting patient outcomes. Glycosylation-related enzymes such as calcium-activated nucleotidase 1 (CANT1) and Beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3) have been implicated in tumour progression, yet their roles in breast cancer, particularly invasive ductal carcinoma (IDC), are not well defined. This study investigates the immunohistochemical expression and correlation of CANT1 and B3GNT3 in IDC and their potential role in predicting LNM and clinical outcomes.

MATERIALS AND METHODS: Slides from paraffin blocks of 140 IDC cases and 108 corresponding metastatic axillary lymph nodes were stained with CANT1 and B3GNT3 antibodies. Associations between markers' immunoreactivity and clinicopathological variables were evaluated. Progression-free survival (PFS) was analysed using the Kaplan-Meier method. The prognostic significance of each variable was evaluated using both univariate and multivariate Cox proportional hazards regression analyses.

RESULTS: High CANT1 and B3GNT3 expression was observed in 47.1% and 45.7% of cases, respectively. Both markers were significantly associated with tumour grade, tumour stage, Nottingham prognostic index, lymph node status, lymph node ratio, Her2 status, Ki-67 proliferative index and distant metastasis. A significant positive correlation was found between CANT1 and B3GNT3 expression (p < 0.001). Co-expression of both markers was strongly associated with LNM, along with a significant difference in the expression levels of each marker between primary tumours and corresponding LNM. Univariate analysis showed that tumour grade, stage, ER status and high B3GNT3 expression were all significantly associated with worse PFS. Multivariate Cox regression identified B3GNT3 expression, tumour grade and tumour stage as independent predictors of poor prognosis in IDC. High expression levels of CANT1 and B3GNT3 were associated with reduced PFS across all IDC cases (p = 0.035 and p = 0.001, respectively).

CONCLUSIONS: High CANT1 and B3GNT3 expressions are associated with aggressive clinicopathological features in IDC and predict unfavourable outcomes. These markers may serve as potential prognostic indicators and independent predictors of LNM in IDC patients.}, } @article {pmid41540255, year = {2026}, author = {Morigny, P and Vondrackova, M and Ji, H and Brejchova, K and Krakovkova, M and Makris, K and Trubacova, R and Samanci, TF and Kaltenecker, D and Ng, SP and Karthikaisamy, V and Chrysostomou, SE and Bidovec, A and Ponce-de-Leon, M and Krauss, T and Seeliger, C and Prokopchuk, O and Martignoni, ME and Claussnitzer, M and Hauner, H and Schweiger, M and Bindels, LB and Berriel Diaz, M and Herzig, S and Lutter, D and Kuda, O and Rohm, M}, title = {Multi-omics profiling of cachexia-targeted tissues reveals a spatio-temporally coordinated response to cancer.}, journal = {Nature metabolism}, volume = {8}, number = {1}, pages = {237-259}, pmid = {41540255}, issn = {2522-5812}, support = {UM1 DK126185/DK/NIDDK NIH HHS/United States ; 949017//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; }, mesh = {*Cachexia/metabolism/etiology/genetics ; Animals ; *Neoplasms/metabolism/complications ; Mice ; Humans ; Male ; *Metabolomics/methods ; Disease Models, Animal ; Glucose/metabolism ; Muscle, Skeletal/metabolism ; Multiomics ; }, abstract = {Cachexia is a wasting disorder associated with high morbidity and mortality in patients with cancer. Tumour-host interaction and maladaptive metabolic reprogramming are substantial, yet poorly understood, contributors to cachexia. Here we present a comprehensive overview of the spatio-temporal metabolic reprogramming during cachexia, using integrated metabolomics, RNA sequencing and [13]C-glucose tracing data from multiple tissues and tumours of C26 tumour-bearing male mice at different disease stages. We identified one-carbon metabolism as a tissue-overarching pathway characteristic for metabolic wasting in mice and patients and linked to inflammation, glucose hypermetabolism and atrophy in muscle. The same metabolic rewiring also occurred in five additional mouse models, namely Panc02, 8025, Apc[Min], LLC and KPP, and a humanised cachexia mouse model. Together, our study provides a molecular framework for understanding metabolic reprogramming and the multi-tissue metabolite-coordinated response during cancer cachexia progression, with one-carbon metabolism as a tissue-overarching mechanism linked to wasting.}, } @article {pmid41539423, year = {2026}, author = {Cingir Koker, S and Mhamane, A and Geppert, J and Shakir, G and Guillamat-Prats, R and Chen, B and Katra, P and Geiger, M and Tsokanos, FF and Wolff, G and Szendrödi, J and Rohm, M and Daniel, C and Maegdefessel, L and Steffens, S and Herzig, S}, title = {Nuclear receptor co-factor TBL1X/TBL1XR1 T cell activity protects against atherosclerosis.}, journal = {Molecular metabolism}, volume = {104}, number = {}, pages = {102318}, pmid = {41539423}, issn = {2212-8778}, mesh = {Animals ; *Atherosclerosis/metabolism/immunology ; Humans ; Mice ; *Repressor Proteins/metabolism/genetics ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; Mice, Knockout ; Male ; *CD4-Positive T-Lymphocytes/metabolism/immunology ; Mice, Inbred C57BL ; *Nuclear Proteins/metabolism/genetics ; Female ; Plaque, Atherosclerotic/metabolism ; }, abstract = {Atherosclerosis is a long-term complication of obesity and diabetes and as such a key driver of vascular dysfunction and eventually mortality in affected patients. Both aberrant lipid metabolism and inflammatory reactions promote atherosclerotic plaque development in the vessel wall by triggering a cascade of cellular events involving multiple cell types, including smooth muscle cells, monocytic macrophages, and lymphocytes. Despite its eminent impact on human health, molecular drivers of cellular dysfunction in atherosclerosis remain poorly defined and therapeutic options are scarce. Here we show by single-cell RNA sequencing that the expression of the nuclear receptor co-factors, TBL1X and TBL1XR1, was particularly prominent in the CD4[+] T cell population of human carotid artery plaques. Indeed, genetic double deletion of TBL1X/TBL1XR1 in CD4[+] T cells led to a substantial shift from naïve CD44[low]CD62L[hi] cells to CD44[hi]CD62L[low] effector and Foxp3[+] Tregs. CD4[+] TBL1X/TBL1XR1 KO cells exhibited enhanced cytokine production capacity upon ionomycin/PMA stimulation, correlating with the induction of pro-inflammatory and cytokine-producing transcriptional pathways in these cells. Consistently, transplantation of bone marrow from CD4[+]-specific TBL1X/TBL1XR1 knock out mice into LDLR KO recipients doubled the development of atherosclerotic plaques in the aortic arch compared with wild-type bone marrow transplanted littermates. As TBL1X/TBL1XR1 expression levels were diminished in carotid arteries from patients with advanced unstable plaques compared to stable plaques or healthy controls, these data suggest that aberrant inhibition of TBL1X/TBL1XR1 in CD4[+] T cells may contribute to the development of atherosclerosis in humans. Restoration of TBL1X/TBL1XR1 functionality may thus serve as a novel, druggable strategy for preventing or limiting atherosclerosis progression.}, } @article {pmid41538117, year = {2026}, author = {Holmes, DR and Manoian, S and Rahman, RL and Ward, RC and Carp, NZ and Plaza, M and Kozlowski, K and Abe, S and Bailey, L and Kruper, L and Jones, V and Patterson, S and Tamayo, J and Littrup, P}, title = {Cryoablation: A Minimally Invasive Alternative for Early-Stage Breast Cancer: 6-Year Outcomes of the FROST Clinical Trial.}, journal = {Annals of surgical oncology}, volume = {}, number = {}, pages = {}, pmid = {41538117}, issn = {1534-4681}, abstract = {BACKGROUND: Cryoablation is emerging as a minimally invasive alternative to lumpectomy for select women with early-stage breast cancer. The FROST trial (NCT01992250) was a prospective, phase 2 multicenter study evaluating the outcome of cryoablation in the management of stage I, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-negative invasive ductal carcinoma.

METHODS: Women 50 years old or older with unifocal, ultrasound-visible tumors were stratified by age: stratum 1 (age ≥70 years, endocrine therapy only) and stratum 2 (age 50-69 years, endocrine therapy + radiotherapy + optional sentinel node biopsy). Cryoablation was performed using a single cryoprobe under ultrasound guidance. Core biopsy 6 months after ablation was performed to confirm complete ablation. Patients were followed with clinical exams and imaging.

RESULTS: The study included 83 completed cryoablations and follow-up evaluations. The median tumor size was 9 mm. More than 85% of the subjects in each group received endocrine therapy (stratum 1 [89%, 43/48], stratum 2 [85.7%, 30/35]) and 74.3% (26/35) of the subjects in stratum 2 received recommended whole-breast radiation. Of the 83 patients, 82 received a post-ablation core biopsy 6 months after cryoablation showing no residual cancer, and 1 patient declined a core biopsy. During a median follow-up period of 6.1 years, the 5-year ipsilateral breast tumor recurrence rate (IBTR) was 3.64% overall (stratum 1, 2.08%; stratum 2, 5.80%). The invasive IBTR-free survival rate was 97.59% overall (stratum 1, 97.92%; stratum 2, 97.14%). No serious adverse events occurred.

CONCLUSIONS: The FROST trial adds to the growing body of literature supporting the efficacy and safety of cryoablation and supports ongoing research on cryoablation as a strategy for de-escalating breast cancer therapy.}, } @article {pmid41536970, year = {2025}, author = {Kitagawa, Y and Miki, H and Yamamoto, T and Sakai, Y and Watanabe, J and Fukunaga, Y}, title = {Atypical Intestinal Metastases from Invasive Lobular Carcinoma of the Breast: Two Surgical Cases Mimicking Primary Gastrointestinal Tumors.}, journal = {Surgical case reports}, volume = {11}, number = {1}, pages = {}, pmid = {41536970}, issn = {2198-7793}, abstract = {INTRODUCTION: Gastrointestinal metastasis arising from invasive lobular carcinoma (ILC) of the breast is a rare but clinically significant manifestation. Unlike invasive ductal carcinoma, ILC has a higher propensity to metastasize into the gastrointestinal (GI) tract, often presenting with non-specific symptoms and mimicking primary GI tumors. Its accurate diagnosis requires a high index of suspicion and immunohistochemical (IHC) confirmation. Herein, we report 2 cases of intestinal metastases from ILC presenting with bowel stenosis.

CASE PRESENTATION: Case 1 involved a 45-year-old woman with no known primary malignancy, who presented with duodenal and small bowel strictures. CT revealed narrowing of the small intestine, along with multiple sclerotic bone lesions. Surgical resection was performed, following which histopathological examination revealed ILC with a characteristic IHC profile (CK7[+], CK20[-], GATA3[+], CDX2[-], E-cadherin[-]). Retrospective breast imaging and biopsy confirmed a diagnosis of primary ILC. Case 2 involved a 57-year-old woman with a known history of luminal-type ILC. At 56 months postoperatively, bone metastasis was detected and PET-CT revealed uptake in the sigmoid colon. Furthermore, colonoscopy demonstrated stricture with no visible mucosal lesions. Surgical resection was subsequently performed, following which IHC confirmed metastatic ILC with a receptor status (ER[+], PgR[+], HER2[-]) matching that of the primary tumor.

CONCLUSIONS: These cases demonstrate the diagnostic challenges posed by GI metastases arising from ILC, particularly due to submucosal infiltration and lack of endoscopic findings. IHC plays a critical role in differentiating these lesions from primary GI tumors. Although surgical resection may not prolong survival, it is valuable for symptomatic relief and for establishing a definitive diagnosis. Surgeons should be aware of the risk of ILC metastasizing into the GI tract. In patients presenting with atypical intestinal stenosis-particularly those with a history of ILC-metastasis should be considered. In such cases, IHC-guided diagnosis is essential.}, } @article {pmid41536875, year = {2026}, author = {Nakai, G and Yamada, T and Tanaka, T and Yamamoto, K and Osuga, K}, title = {Two cases of uterine metastasis from breast cancer: Radiologic-pathologic correlation and literature review.}, journal = {Radiology case reports}, volume = {21}, number = {3}, pages = {1191-1200}, pmid = {41536875}, issn = {1930-0433}, abstract = {Uterine metastasis from breast cancer is extremely rare and often misdiagnosed as primary uterine neoplasm due to nonspecific imaging features. We present 2 cases illustrating the radiologic-pathologic correlation of uterine metastases. Patient 1 was an 81-year-old woman with a history of invasive ductal carcinoma. Pelvic Magnetic resonance imaging (MRI) revealed a well-circumscribed uterine mass with intermediate signal intensity (SI) on T2-weighted images (T2WI), high SI on diffusion-weighted images (DWI), and minimal contrast enhancement. Patient 2 was a 67-year-old woman with prior invasive lobular carcinoma, presenting with abnormal uterine bleeding 18 years after initial treatment. Magnetic resonance imaging (MRI) revealed a lobulated mass in the posterior uterine wall showing heterogeneous T2 SI and high SI on DWI, resembling a degenerative leiomyoma. In both cases, the myometrium was diffusely thickened, with low to mildly high SI on T2-weighted images (T2WI) and mildly high SI on DWI. No discrete lesions were observed in the cervix on imaging. Radiologic-pathologic correlation confirmed metastatic involvement of the uterus, including the cervix, either diffusely or focally. MR findings may be influenced by the stromal composition of metastatic lesions and by the morphologic diversity of metastases-features that parallel those seen in primary breast cancer. Because metastatic lesions may mimic leiomyomas or remain occult, diagnosis should not rely on T2 SI alone. Rather, the combination of multiplicity, DWI hyperintensity, and clinical history should be considered. Clinicians should maintain a low threshold for endometrial biopsy in conjunction with serum tumor marker assessment during the diagnostic evaluation of uterine lesions.}, } @article {pmid41533600, year = {2026}, author = {Sato, S and Urabe, F and Iwamoto, Y and Iwatani, K and Imai, Y and Tashiro, K and Umemori, M and Miki, J and Shimoda, M and Kimura, T and Takahashi, H}, title = {Prognostic impact of intraductal carcinoma of the prostate and PTEN loss in metastatic castration-sensitive prostate cancer treated with androgen receptor pathway inhibitors.}, journal = {Japanese journal of clinical oncology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jjco/hyaf214}, pmid = {41533600}, issn = {1465-3621}, abstract = {BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) and phosphatase and tensin homolog (PTEN) alteration are established adverse features in prostate cancer. However, their coexistence and prognostic relevance in the era of androgen receptor pathway inhibitor (ARPI) therapy for metastatic castration-sensitive prostate cancer (mCSPC) remain unclear, particularly in Japanese populations. We evaluated the prevalence, concordance, and prognostic significance of IDC-P and PTEN loss in patients with mCSPC treated with ARPI plus androgen deprivation therapy (ADT).

METHODS: We retrospectively analyzed consecutive patients with mCSPC who received ARPI plus ADT between February 2018 and June 2024 across three Japanese institutions. IDC-P was assessed on hematoxylin-eosin-stained biopsy specimens. PTEN loss was defined as ≥90% absence of cytoplasmic staining, consistent with the CAPItello-281 trial criteria. The primary endpoint was castration-resistant prostate cancer-free survival (CRPC-FS). Overall survival was evaluated as a secondary endpoint. Survival outcomes were assessed using Kaplan-Meier analysis and multivariable Cox regression modeling.

RESULTS: In total, 121 patients were included. IDC-P was identified in 68.6% of biopsy specimens, and PTEN loss in 15.7%. Patients with IDC-P more frequently presented with CHAARTED high-volume and LATITUDE high-risk disease. During a median follow-up of 36 months, 44 patients (36.4%) developed CRPC. IDC-P was independently associated with shorter CRPC-FS [hazard ratio [HR] 2.4, 95% confidence interval (CI) 1.14-5.04; P = .02], whereas PTEN loss was not significantly associated with CRPC-FS or overall survival. Combined assessment of IDC-P and PTEN loss did not demonstrate additive prognostic value.

CONCLUSION: In this multicenter Japanese cohort, IDC-P, but not PTEN loss, independently predicted earlier progression to CRPC in patients with mCSPC treated with ARPI plus ADT. The limited overlap between IDC-P and PTEN loss suggests distinct biological mechanisms in Japanese populations. IDC-P remains a strong morphologic indicator of aggressive disease, whereas PTEN loss may serve as a therapeutic biomarker for phosphoinositide 3-kinase/AKT-targeted strategies.}, } @article {pmid41532824, year = {2026}, author = {Lawal, IO and Seidel, R and Li, X and Nayar, J and Mankoff, DA and Schuster, DM}, title = {[18F]Fluoroestradiol Uptake in Benign Nodular Sclerosing Adenosis of the Breast.}, journal = {Clinical nuclear medicine}, volume = {}, number = {}, pages = {}, doi = {10.1097/RLU.0000000000006332}, pmid = {41532824}, issn = {1536-0229}, abstract = {A 70-year-old woman with estrogen receptor-positive (ER+) invasive ductal carcinoma (IDC) of the right breast underwent 18F-fluoroestradiol (18F-FES) PET/CT demonstrating uptake in the IDC (SUVmax 2.5) and also extensive 18F-FES uptake in bilateral breasts corresponding to marked bilateral background enhancement on MRI. MRI-guided biopsy of a representative enhancing 18F-FES-avid region in the left breast (SUVmax 3.5) revealed nodular sclerosing adenosis without cellular atypia or malignancy, but with 30% ER positivity on immunohistochemistry. False-positive uptake of 18F-FES is reported in irradiated lung and interstitial lung disease. This case highlights another mechanism of false-positive 18F-FES uptake due to ER overexpression in benign breast tissue.}, } @article {pmid41531577, year = {2025}, author = {Nishimura, H and Mine, Y and Takahashi, Y and Deshpande, GA and Watanabe, J and Kutomi, G and Naito, T}, title = {Estrogen Receptor-Low Breast Cancer With Sternal Metastasis Presenting as "Stiff Neck" in a Young Female.}, journal = {Cureus}, volume = {17}, number = {12}, pages = {e99072}, pmid = {41531577}, issn = {2168-8184}, abstract = {A previously healthy 20-year-old Japanese woman was referred to the outpatient clinic for evaluation of right neck stiffness, which had persisted for two months, along with weight loss, malaise, and elevated inflammatory markers. On physical examination, spontaneous pain was noted in the right upper trapezius, along with incident pain around both clavicles and shoulders. Swelling was found around the sternal manubrium, and two palpable masses were present in the right breast. A computed tomography scan of the thorax revealed a low-density, lobulated area in the right breast, a soft-tissue mass in the sternal manubrium, multiple lymphadenopathies, and small nodules in the lungs and liver. Core needle biopsy of the breast mass confirmed estrogen receptor (ER)-low invasive ductal carcinoma, and testing for breast cancer susceptibility gene mutations was negative. Systemic chemotherapy was initiated for the treatment of metastatic triple-negative breast cancer. Breast cancer causing neck or shoulder pain is rare. The right neck stiffness likely resulted from brachial plexus compression due to bulky right axillary lymphadenopathy, leading to thoracic outlet syndrome. Lung metastasis could also cause referred pain through the vagus nerve. This case presented an atypical manifestation of "stiff neck" associated with thoracic tumors. Notably, the patient initially hesitated to share key symptoms, which may have contributed to a delayed diagnosis. We believe that the rapid progression of her lesions may have heightened her anxiety, which in turn further impaired her communication with the medical staff.}, } @article {pmid41530729, year = {2026}, author = {McKenzie, E and Borschmann, R and Saling, L and Hedrick, K}, title = {Hunger strikes among asylum seekers in Australian immigration detention: prevalence, precipitants, characteristics, and management.}, journal = {BMC public health}, volume = {26}, number = {1}, pages = {547}, pmid = {41530729}, issn = {1471-2458}, abstract = {BACKGROUND: Hunger strikes are commonly reported in places of detention, and Australia has some of the most restrictive immigration detention policies globally. Despite this, little is known about hunger strikes among immigration detainees in Australia. We aimed to examine the prevalence, precipitants, characteristics, and management of hunger strikes among asylum seekers in Australian onshore immigration detention.

METHODS: Via Freedom of Information, we obtained incident reports for all hunger strikes recorded in Australian onshore immigration detention between 3 October 2009 and 26 May 2011. Our primary methodological approach was content analysis. Data relating to hunger strike prevalence, detention type, location, gender, precipitating factors, and management of hunger strikes were extracted from each report. Hunger strike episode rates per 1000 asylum seekers were calculated using average adult population figures for 1) the entire onshore immigration detention network; 2) each held detention type (i.e., Immigration Detention Centres [IDCs], Immigration Transit Accommodation [ITA], Immigration Residential Housing [IRH], and Alternative Places of Detention [APODs]); and 3) each facility.

RESULTS: Three hundred twenty eight hunger strikes were included in the analyses. The hunger strike episode rate was 76/1000 asylum seekers (95% CI 59 – 94). On average, hunger strike episode rates were highest in IDCs (86/1000, 95% CI 68 – 104), followed by APODs (36/1000, 95% CI 24 – 48). Individual facility rates of hunger strikes ranged from 21/1000 asylum seekers (95% CI 12 – 31) in Christmas Island APODs to 317/1000 asylum seekers (95% CI 282 – 352) in Maribyrnong IDC. Compared with the average across all other facilities, hunger strike episodes were most commonly reported in Curtin IDC (126) (p < 0.001). The most reported precipitant was protest (75%). Details regarding the management of hunger strikes were noted in 7% of reports.

CONCLUSIONS: Our findings highlight concerningly high rates of hunger strikes among detained asylum seekers in Australia compared to other detained populations, with protest the most common trigger. Hunger strike management was inconsistent with international best practice. These findings highlight the deleterious impact of immigration detention on the physical and mental health of those detained. Further investigation, and policy and practice development consistent with ethical and human rights frameworks are warranted.}, } @article {pmid41529373, year = {2026}, author = {Erkan, S and Ghadage, K and Meister, P}, title = {Chromosome organization by Structural Maintenance of Chromosomes complexes in C. elegans.}, journal = {Current opinion in genetics & development}, volume = {96}, number = {}, pages = {102430}, doi = {10.1016/j.gde.2025.102430}, pmid = {41529373}, issn = {1879-0380}, mesh = {Animals ; *Caenorhabditis elegans/genetics ; Chromosomal Proteins, Non-Histone/genetics ; Chromatin/genetics ; *Multiprotein Complexes/genetics ; *Adenosine Triphosphatases/genetics ; *Chromosomes/genetics ; *DNA-Binding Proteins/genetics ; Cohesins ; Dosage Compensation, Genetic/genetics ; Cell Cycle Proteins/genetics ; Caenorhabditis elegans Proteins/genetics ; X Chromosome/genetics ; Chromosome Segregation/genetics ; }, abstract = {Genome folding is a key regulator of transcription, chromosome segregation, and genome stability. In Caenorhabditis elegans, chromatin folding strategies have diverged from those observed in mammals or flies, resulting in the absence of visible topologically associating domains (TADs) on autosomes. Here, condensin I, rather than cohesin, serves as the primary long-range loop extruder, while distinct cohesin isoforms specialize in mitotic cohesion and loop extrusion, forming enhancer-associated 'fountains' that modulate neuronal gene expression. On the X chromosome, dosage compensation depends on the dosage compensation complex, which incorporates a specialized condensin I[DC] to establish TADs, regulate chromatin states, and repress transcription. These multilayered mechanisms illustrate the evolutionary versatility of 3D genome organization and its intimate links to development, physiology, and lifespan, positioning C. elegans as a powerful model for dissecting structural maintenance of chromosomes-mediated genome regulation.}, } @article {pmid41526590, year = {2026}, author = {Del Riego, J and Estandía, C and Aynes, C and Campmany, A and Pallarés, F and Triginer, S and Papaleo, N and López, A and Aparicio, O and Dalmau, E and Tortajada, L}, title = {Upgrade to malignancy after excision of MRI-only B3 breast lesions: should the size and histological type of the lesion be considered for therapeutic management?.}, journal = {Insights into imaging}, volume = {17}, number = {1}, pages = {12}, pmid = {41526590}, issn = {1869-4101}, abstract = {OBJECTIVES: To determine the rate of malignancy upgrade in MRI-only B3 lesions and to identify clinical, imaging, and histological features that can predict upgrade.

MATERIALS AND METHODS: This retrospective single-center study included MRI-only lesions diagnosed as B3 after MRI-guided vacuum-assisted biopsy and excised between January 2007 and March 2023. We calculated upgrade rates for the entire series and for subgroups based on possible risk factors. To analyze variables considered risk factors for upgrade, we used logistic regression, calculating odds ratios (OR) and their 95% confidence intervals (CI).

RESULTS: Of 592 lesions biopsied, 89 (15.03%) were classified as B3. After excluding 30 lesions because excisional specimen results were unavailable, we analyzed 59 lesions in 51 patients. Biopsy classified 15 (25.4%) lesions as pure atypical ductal hyperplasia (ADH), 27 (45.8%) as pure flat epithelial atypia (FEA), 12 (20.3%) as mixed lesions, and 5 (8.5%) as lobular neoplasia. A total of 7 (11.9%) lesions were upgraded to malignancy (71.4% to ductal carcinoma in situ, 14.3% to invasive ductal carcinoma, and 4.3% to invasive lobular carcinoma). Although histological type was not associated with upgrade to malignancy (p = 0.47), 20% of pure ADH and only 3.7% of pure FEA lesions were upgraded. Larger lesion size on MRI was associated with upgrade [6.25% of lesions ≤ 20 mm vs. 36.4% of those > 20 mm, p = 0.02; OR 8.57 (95% CI: 1.57‒46.71) p = 0.01].

CONCLUSION: Lesion size may predict upgrade in MRI-only B3 lesions independent of histological type; imaging follow-up may suffice for FEA lesions measuring < 20 mm.

CRITICAL RELEVANCE STATEMENT: Considering lesion size and histological type could help define the management of MRI-only lesions classified as B3 after MRI-guided vacuum-assisted biopsy.

KEY POINTS: The management of MRI-only B3 lesions has yet to be established. Lesion size is a relevant factor to consider when deciding clinical management in MRI-only B3 lesions. Conservative management appears to be safe in selected flat epithelial atypia lesions (< 20 mm).}, } @article {pmid41526224, year = {2026}, author = {Wu, ZS and Huang, SM and Huang, YH}, title = {Tramadol induced hypoxia signaling and paraptosis-like cell death in breast cancer cells via HIF-1α and ATF4 dependent pathways.}, journal = {Redox report : communications in free radical research}, volume = {31}, number = {1}, pages = {2588866}, pmid = {41526224}, issn = {1743-2928}, mesh = {Humans ; *Tramadol/pharmacology ; *Activating Transcription Factor 4/metabolism/genetics ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; *Breast Neoplasms/metabolism/drug therapy/pathology ; Female ; Signal Transduction/drug effects ; Endoplasmic Reticulum Stress/drug effects ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism ; Cell Death/drug effects ; MCF-7 Cells ; Cell Survival/drug effects ; Cell Hypoxia/drug effects ; Paraptosis ; }, abstract = {OBJECTIVES: Tramadol, a clinically approved analgesic widely used for managing postoperative pain, has recently been shown to possess anticancer properties in several tumor models, especially in breast cancer. In this study, we explored the intricate molecular mechanisms by which tramadol induces cytotoxicity in breast cancer cell lines.

METHODS: Two invasive ductal carcinoma lines MCF-7 and MDA-MB-231 were used to verify the molecular cytotoxicity of tramadol using cell viability analysis, flow cytometry analysis, real-time polymerase chain reaction, western blotting, Seahorse biogenetic, and transmission electron microscopy analyses.

RESULTS: Our findings demonstrate that tramadol induces the normoxic stabilization and nuclear translocation of hypoxia-inducible factor- 1 alpha (HIF-1α) to activate hypoxia responsive genes. Concurrently, tramadol triggers endoplasmic reticulum (ER) stress and activates the p-eIF2α/ATF4/CHOP signaling axis, leading to the generation of reactive oxygen species, impaired autophagy, mitochondrial dysfunction, including mitochondrial membrane depolarization and the decline of ATP production, cytoplasmic vacuolization, and lipid droplet accumulation which is characteristics of paraptosis-like cell death. Notably, the knockout of HIF-1α or ATF4 significantly reduced tramadol-induced cytotoxicity, highlighting their crucial roles in mediating these cellular responses.

CONCLUSION: Tramadol induced breast cancer cell death via paraptosis which highlights its therapeutic potential in targeting resistant cancer subtypes such as triple-negative breast cancer.}, } @article {pmid41524503, year = {2026}, author = {Divband, G and Chehrara, M and Khodakarim, N and Nafissi, N and Hassanzadeh, L and Amini, H}, title = {Heterogeneous Response After [ 177 Lu]Lu-FAPI-2286 Combination Therapy in Metastatic Breast Cancer.}, journal = {Clinical nuclear medicine}, volume = {}, number = {}, pages = {}, doi = {10.1097/RLU.0000000000006242}, pmid = {41524503}, issn = {1536-0229}, abstract = {A 37-year-old woman with metastatic invasive ductal carcinoma, resistant to anti-HER 2 therapy, underwent [ 177 Lu]Lu-FAPI-2286 radionuclide therapy combined with antibody-drug conjugate chemotherapy. Baseline [ 68 Ga]Ga-FAPI-2286 PET/CT confirmed extensive fibroblast activation protein expression in metastatic sites. After 5 cycles, follow-up imaging showed a significant reduction in FAPI uptake in skin lesions, resolution of bone lesions, and decreased pleural thickening. Clinically, the patient reported pain relief and resolution of lymphedema. However, new metastases emerged in cervical, mediastinal, and abdominopelvic lymph nodes, indicating a heterogeneous response, and biopsy of these newly emerged lymph nodes confirmed disease recurrence.}, } @article {pmid41523374, year = {2025}, author = {Yoshida, M and Oura, S}, title = {Ultrasound Findings of Breast Cancer in Dialysis Patients Require Careful Evaluation: A Case Report.}, journal = {Cureus}, volume = {17}, number = {12}, pages = {e98937}, pmid = {41523374}, issn = {2168-8184}, abstract = {Literature on the effects of renal failure on breast imaging in breast cancer patients on dialysis is scarce. A 73-year-old woman on dialysis noticed a mass in her left breast. In the left breast, which consisted entirely of fat tissue, mammography revealed two spiculated masses. Ultrasound also showed two irregular masses with internal low echoes, slightly attenuated posterior echoes, obscured margins, high depth-to-width ratios, no halos, and widespread peritumoral high echoes. In addition to axillary lymphadenopathy, MRI of the masses showed low signals on T1-weighted images and weakly high signals on fat-suppressed T2-weighted images. Core needle biopsy of the mass pathologically revealed atypical cells growing in trabecular and tubular patterns, with interstitial connective tissue proliferation and fat invasion, leading to a diagnosis of invasive ductal carcinoma. Due to impaired renal function, the patient underwent primary surgery, including a partial mastectomy and axillary lymph node dissection. Postoperative pathological examination showed scirrhous-type invasive ductal carcinomas infiltrating the surrounding fat tissue, nine metastatic lymph nodes, and abundant fat tissue with very scant mammary gland around the tumors. The patient had higher-than-usual postoperative drainage volumes, which varied from day to day, presumably due to the effects of dialysis. Despite a large 100 mL drainage volume on the fifth postoperative day, the patient was discharged on day six per her preference. Diagnostic physicians should note that breast cancer patients on dialysis can present with atypical breast imaging compared with patients without renal failure and should be treated with optimal surgical procedures based on thorough image evaluation.}, } @article {pmid41521709, year = {2026}, author = {Bujassoum Al-Bader, S and Al-Mulla, H and Al-Habish, H and Kusasi, S and Abduo, N and Bakheet, N and Ghazouani, H and Sidenna, M and Abbaszadeh, F and Alsulaiman, R}, title = {Identifying a Recurrent BRCA1 Variant in the Qatari Population With Unique Genotype-Phenotype Correlations.}, journal = {Molecular genetics & genomic medicine}, volume = {14}, number = {1}, pages = {e70144}, pmid = {41521709}, issn = {2324-9269}, support = {//Hamad Medical Corporation/ ; }, mesh = {Humans ; Female ; Qatar/epidemiology ; *BRCA1 Protein/genetics ; Adult ; Middle Aged ; *Hereditary Breast and Ovarian Cancer Syndrome/genetics/epidemiology/pathology ; Genetic Association Studies ; Male ; Aged ; Retrospective Studies ; Ovarian Neoplasms/genetics ; }, abstract = {BACKGROUND: Hereditary breast and ovarian cancer syndrome (HBOC) is the most common cause of hereditary breast and ovarian cancers in Qatar and worldwide, which is caused by pathogenic variants in the BRCA1 and BRCA2 genes. The aim of this retrospective study is to describe a common recurrent pathogenic variant in the BRCA1 gene that was observed in the native Qatari population with unique genotype-phenotype correlations.

METHODS: Medical records of Qatari patients (affected and unaffected) with personal and/or family history of breast and ovarian cancers who carry pathogenic/likely pathogenic variants in the BRCA1 gene were reviewed between 2013 and 2020. Epidemiological information and clinical data were reviewed, including age, gender, ethnic background, personal history of cancer, tumour characteristics, and family history. We used frequencies and proportions to describe the data and used Kaplan-Meier curves and log-rank analysis to compare survival rates. For the analysis, we used Stata Corp. 2015. Stata Statistical Software: Release 14, College Station, TX: Stata Corp. LP.

ETHICAL COMPLIANCE: Ethical committee approval was obtained from Hamad Medical Corporation IRB committee (MRC-01-20-1086).

RESULT: Sixty-three Qatari affected patients and unaffected individuals who carry the BRCA1 variant were included in the study. Our result confirms the presence of a common recurrent pathogenic variant c.4787C>A p.(Ser1596Ter) among Qatari patients who belong to 8 consanguineous large families, followed by c.4065_4068del p.Asn1355fs, both in BRCA1. The BRCA1 c.4787C>A variant is highly associated with early onset breast cancer, specifically invasive ductal carcinoma (IDC) triple negative breast cancer (stage I, grade III), rather than ovarian cancer. Additionally, the c.4787C>A variant was found to exhibit high penetrance in families with early-onset breast cancer.

CONCLUSION: We showed that BRCA1 c.4787C>A pathogenic variant is a highly recurrent variant among Qatari consanguineous families and contributes to the early onset breast cancer in Qatar. Early identification of this variant can aid in improving patients' survival and guide early personalized treatment and prevention.}, } @article {pmid41519706, year = {2026}, author = {Adamson, B and van Boemmel-Wegmann, S and Horne, E and Soares, S and Zhang, Q and Kovacevic, L and Boualam, N and Somavanshi, R and Dorst, I and Sujenthiran, A and Buhl, C}, title = {Real-world evidence from Germany: representativeness analysis and mortality endpoint validation in electronic health record-derived oncology cohorts.}, journal = {BMC cancer}, volume = {26}, number = {1}, pages = {202}, pmid = {41519706}, issn = {1471-2407}, mesh = {Humans ; *Electronic Health Records/statistics & numerical data ; Germany/epidemiology ; Female ; Middle Aged ; Aged ; Male ; *Lung Neoplasms/mortality/pathology ; *Carcinoma, Non-Small-Cell Lung/mortality/pathology ; *Colorectal Neoplasms/mortality/pathology ; Cohort Studies ; *Breast Neoplasms/mortality/pathology ; Adult ; Aged, 80 and over ; Registries ; }, abstract = {BACKGROUND: High-quality real-world data (RWD) for oncology research remains limited in Germany despite significant clinical need. Electronic health record (EHR)-derived datasets offer potential to capture longitudinal clinical information, but their value depends on representativeness and data quality. We characterized EHR-derived oncology cohorts from Germany, evaluating alignment with national benchmarks and validating mortality endpoints for real-world evidence generation.

METHODS: We analyzed deidentified EHR data from the Germany Flatiron Health Research Database comprising adult patients diagnosed with breast cancer, non-small cell lung cancer (NSCLC), or colorectal cancer (CRC) between 2016 and 2024. Demographic and clinical characteristics were compared to national benchmarks. Overall survival was estimated using Kaplan-Meier methods. We validated our composite mortality variable against German Cancer Registry data.

RESULTS: The breast cancer cohort (n = 1,305, median age 58 years) included 75% early-stage disease, 80% invasive ductal carcinoma, 67% HR+/HER2-, and 19% triple-negative cases. The NSCLC cohort (n = 866, median age 69 years) comprised 49% stage IV disease, 73% non-squamous histology, and 16% EGFR-positive tumors among tested patients. The CRC cohort (n = 774, median age 67 years) included 31% stage IV disease with 90% receiving primary surgery. Cohort characteristics closely aligned with national benchmarks. Median overall survival from first-line therapy was 26.0 months (breast), 13.4 months (NSCLC), and 21.5 months (CRC). Mortality validation demonstrated 87.7% sensitivity and 91.7% specificity for vital status classification, with 98.8% temporal accuracy within 30 days.

CONCLUSIONS: German EHR-derived cancer cohorts are representative of national populations with validated mortality endpoints, supporting their use for robust real-world evidence generation in oncology research.}, } @article {pmid41517325, year = {2025}, author = {McMahon, JE and Craig, A and Cameron, ID}, title = {The Clinical Significance of the Manchester Colour Wheel in a Sample of People Treated for Insured Injuries.}, journal = {Journal of clinical medicine}, volume = {15}, number = {1}, pages = {}, pmid = {41517325}, issn = {2077-0383}, abstract = {Background/Objectives: The Manchester Colour Wheel (MCW) was developed as an alternative way of assessing health status, mood and treatment outcomes. There has been a dearth of research on this alternative assessment approach. The present study examines the sensitivity of the MCW to pain, psychological factors and recovery status in 1098 people with insured injuries treated in an interdisciplinary clinic. Methods: A deidentified data set of clients treated in a multidisciplinary clinic was conveyed to the researchers, containing results of MCW and injury-specific psychometric tests at intake, as well as recovery status at discharge. Systematic machine modelling was applied. Results: There were no significant differences between the four injury types studied: motor crash-related Whiplash Associated Disorder (WAD) and workplace-related Shoulder Injury (SI), Back Injury (BI) and Neck Injury (NI) on the MCW. Augmenting the MCW with Machine Learning (ML) models showed overall classification rates for Classification and Regression Tree (CRT) of 75.6% for Anxiety, 70.3% classified for Depression and 68.5% for Stress, and Quick Unbiased Efficient Statistical Trees could identify 68.5% of Pain Catastrophisation and 62.7% of Kinesiophobia. Combining MCW with psychometric measurements markedly increased the predictive power, with a CRT model predicting WAD recovery status with 80.7% accuracy, SI recovery status 81.7% accuracy and BI recovery status with 78% accuracy. A Naïve Bayes Classifier predicted recovery status in NI with 96.4% accuracy. However, this likely represents overfitting. Conclusions: Overall, MCW augmented with ML offers a promising alternative to questionnaires, and the MCW appears to measure some unique psychological features that contribute to recovery from injury.}, } @article {pmid41516506, year = {2025}, author = {Zeng, K and Yu, W and Qin, X and Long, S}, title = {Small-Target Detection Algorithm Based on Improved YOLOv11n.}, journal = {Sensors (Basel, Switzerland)}, volume = {26}, number = {1}, pages = {}, pmid = {41516506}, issn = {1424-8220}, support = {2025JC-YBMS-255//Research on Semantic Change Detection in PolSAR Images with Limited Samples by Knowledge Guidance and Data Drive/ ; }, abstract = {Target detection in UAV aerial photography scenarios faces challenges of small targets and complex backgrounds. Thus, we proposed an improved YOLOv11n small-target detection algorithm. First, a detection head is added to the 160 × 160 resolution feature layer, and non-adjacent layer feature is fused via Asymptotic Feature Pyramid Network (AFPN) to alleviate feature loss caused by downsampling and reduce cross-level feature conflicts. Second, the Spatial Channel Attention SPPF (SCASPPF) module replaces the original Spatial Pyramid Pooling-Fast (SPPF) module to highlight key features and suppress irrelevant ones. Moreover, the loss function is enhanced by fusing MPDIoU and InnerIoU to boost detection accuracy. Finally, Inception Deep Convolution (IDC) is adopted to improve the C3k2 module, expanding the model's receptive field and enhancing small-target detection performance. Experiments on the Visdrone2019 dataset show that the algorithm achieves 39.256% mAP@0.5, 6.689% higher than 32.567% mAP@0.5 of the benchmark model (YOLOv11n).}, } @article {pmid41514391, year = {2026}, author = {Imadoglu, O and Demirci, EE and Sural, S}, title = {Chemotherapy-associated coronary thrombosis presenting as acute coronary syndrome in breast cancer: a case report.}, journal = {BMC cardiovascular disorders}, volume = {26}, number = {1}, pages = {124}, pmid = {41514391}, issn = {1471-2261}, abstract = {BACKGROUND: Cancer patients face a high risk of thromboembolic complications due to disease-, treatment-, and patient-related factors. Chemotherapy regimens such as anthracyclines and alkylating agents can increase both venous and arterial thrombosis, leading to significant morbidity.

CASE SUMMARY: A 44-year-old woman with invasive ductal carcinoma of the right breast underwent right mastectomy and received adjuvant chemotherapy with doxorubicin (60 mg/m²) and cyclophosphamide (600 mg/m²). Five days after her second treatment cycle, she presented with chest pain. Electrocardiography showed inferolateral ST-segment elevation, and echocardiography revealed a left ventricular ejection fraction (LVEF) of 38%. Coronary angiography demonstrated total occlusion of the distal left anterior descending and circumflex arteries. She was treated with dual antiplatelet therapy, low-molecular-weight heparin, and a glycoprotein IIb/IIIa inhibitor. Follow-up angiography on day five showed complete thrombus resolution and restoration of TIMI III flow. During long-term follow-up, her left ventricular function recovered (LVEF 50%) and her cancer remained in complete remission.

CONCLUSION: This case illustrates a rare but clinically important complication of adjuvant doxorubicin–cyclophosphamide therapy, presenting as subacute inferolateral myocardial infarction secondary to coronary thrombosis. Awareness of this potential adverse effect and early management are crucial for improved outcomes.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-026-05512-6.}, } @article {pmid41510820, year = {2026}, author = {Yoon, EJ and Jeong, J and Choi, Y and Kim, DH and Kim, TM and Choi, EK and Kim, YB and Park, D}, title = {Therapeutic effect of amniotic membrane mesenchymal stem cell-derived exosome-rich conditioned medium in cerebral palsy model.}, journal = {Stem cells translational medicine}, volume = {15}, number = {1}, pages = {}, pmid = {41510820}, issn = {2157-6580}, support = {NRF-2022R1A2C1003624//Ministry of Education/ ; }, mesh = {*Exosomes/metabolism ; *Mesenchymal Stem Cells/metabolism/cytology ; Culture Media, Conditioned/pharmacology ; Animals ; *Cerebral Palsy/therapy/pathology ; Humans ; *Amnion/cytology ; Disease Models, Animal ; Rats ; Cell Differentiation/drug effects ; Female ; Apoptosis/drug effects ; Oligodendroglia/metabolism ; Male ; }, abstract = {BACKGROUND: Cerebral palsy (CP), primarily caused by perinatal cerebral hypoxia and ischemia, is a devastating neurological disease in children characterized by motor, behavioral, and cognitive disorders. This study aimed to evaluate the therapeutic effects of amniotic membrane mesenchymal stem cell-derived exosome-rich conditioned medium (ERCM) in a CP model.

METHODS: ERCM components were analyzed using enzyme-linked immunosorbent assay. Biodistribution was examined via fluorescence-labeled ERCM in both normal and CP induced animals. In vitro, the neuroprotective effects of ERCM against lipopolysaccharide and potassium cyanide-induced cytotoxicity were assessed in human neural stem cells and oligodendrocyte progenitor cells, focusing on apoptosis, inflammation, and oligodendrocyte differentiation. In vivo, ERCM was injected into CP-induced animals, followed by evaluation of antiapoptotic and anti-inflammatory signaling, motor and cognitive function, and white matter integrity.

RESULTS: ERCM contained a broad array of growth factors and demonstrated enhanced retention in CP-affected brain regions. In vitro, ERCM significantly reduced apoptos is and inflammation, and promoted oligodendrocyte maturation via upregulation of Nkx2.2, CN Pase, and MBP. In vivo, ERCM treatment improved motor and cognitive performance, in hibited cell death and inflammatory responses, and increased expression of oligodendrocyte markers, including Nkx2.2, Olig2, CNPase, and MBP via increasing growth factor expression. Furthermore, ERCM attenuated demyelination in the corpus callosum, a region particularly vulnerable in CP.

CONCLUSION: ERCM confers therapeutic benefits in CP by preserving neural stem and oligodendrocyte progenitor cells, modulating apoptosis and inflammation, and enhancing oligodendrocyte differentiation. Accordingly, ERCM may present a good candidate as a CP therapeutic agent.}, } @article {pmid41510595, year = {2026}, author = {Mooghal, M and Ali, ZM and Saleem, L and Yaqoob, A and Ahmad, F and Jamal, A}, title = {Evaluating Gentian Violet as a Low-Cost Alternative for Sentinel Lymph Node Biopsy in Breast Cancer: A Single-Center Retrospective Study.}, journal = {Asia-Pacific journal of clinical oncology}, volume = {}, number = {}, pages = {}, doi = {10.1111/ajco.70062}, pmid = {41510595}, issn = {1743-7563}, abstract = {BACKGROUND: Sentinel lymph node biopsy (SLNB) reduces morbidity in breast cancer (BC) surgery compared to axillary lymph node dissection. Standard tracers such as vital blue dye (VBD), methylene blue (MB), and radioisotopes (RIs) are effective but costly and logistically challenging. Gentian violet (GV), a low-cost alternative, offers a potential solution for resource-constrained settings.

METHODS: We conducted a single-center retrospective study at Cancer Foundation Hospital, analyzing 40 BC patients who underwent SLNB using GV and RI (January-December 2024). Sentinel lymph node (SLN) detection rates, concordance between GV and RI, and safety profiles were assessed. Detection was compared across tumor grade, histopathology, receptors, and chemotherapy status.

RESULTS: The median patient age was 52 years, with most patients having a BMI between 21 and 30 (72.5%). T2 tumors were the most common (60%), followed by T3 (17.5%). Stage II disease predominated (75%), and invasive ductal carcinoma (IDC) was the most frequent histological subtype (70%). Among the cohort, 60% were estrogen/progesterone receptor-positive, 22.5% were triple-positive, and 10% were triple-negative. GV dye successfully identified SLNs in 97.5% of cases, with GV detecting more nodes than RI in 32.5% of patients, while both methods identified the same number in 50% of cases. The false-negative rate for GV was 2.5%. Detection rates were consistent across tumor subtypes, grades, and receptor statuses, with no statistically significant differences (p > 0.05). Neoadjuvant chemotherapy (NACT) did not impact SLN detection (p = 0.803). GV dye exhibited a favorable safety profile, with no intraoperative or postoperative complications reported at Days 0, 3-7, and 30. No cases of staining-related reactions, dermatitis, tattooing, or skin necrosis were observed.

CONCLUSIONS: Gentian violet is a safe, effective, and affordable alternative to MB for SLNB in BC. It demonstrates high detection rates and excellent safety, particularly suitable for resource-limited settings. Larger studies are warranted to validate these findings and support broader clinical adoption.}, } @article {pmid41501628, year = {2026}, author = {Brown, AS and Llinás, M and Mahony, S}, title = {Chromatin state dynamics during the Plasmodium falciparum intraerythrocytic development cycle.}, journal = {BMC genomics}, volume = {27}, number = {1}, pages = {142}, pmid = {41501628}, issn = {1471-2164}, support = {R35 GM144135/GM/NIGMS NIH HHS/United States ; T32 GM152354/GM/NIGMS NIH HHS/United States ; R35 GM144135/NH/NIH HHS/United States ; }, abstract = {UNLABELLED: The interdependence of chromatin states and transcription factor (TF) binding in eukaryotic genomes is critical for the proper regulation of gene expression. In this study, we explore the connection between TFs and chromatin states in the human malaria parasite, Plasmodium falciparum, throughout its 48-hour asexual intraerythrocytic developmental cycle (IDC). Most P. falciparum genes are expressed in a periodic manner during the IDC, accompanied by dynamic shifts in histone modifications and chromatin accessibility. Leveraging genome-wide profiles of chromatin accessibility, histone modifications, and Heterochromatin Protein 1 (HP1) occupancy, we characterize chromatin state dynamics during the IDC. Our results indicate that several chromatin states remain stable throughout the lifecycle, while others are dynamic and are linked to gene activation or repression. We further characterize chromatin state dynamics at the genome-wide DNA binding sites for a selection of Plasmodium TFs, allowing us to group TFs according to their chromatin preferences. By correlating changes in chromatin accessibility, histone modifications, and TF binding, we provide a global overview of the chromatin state dynamics that coordinate P. falciparum asexual blood stage development.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-025-12455-3.}, } @article {pmid41497941, year = {2025}, author = {Bendadi, S and Afani, L and Zouiten, O and El Fadli, M and Belbaraka, R}, title = {Paraneoplastic Cerebellar Syndrome Revealing Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer: A Case Report.}, journal = {Cureus}, volume = {17}, number = {12}, pages = {e98519}, pmid = {41497941}, issn = {2168-8184}, abstract = {Paraneoplastic cerebellar degeneration (PCD) is a rare neurological disorder that can precede the diagnosis of an underlying malignancy by several months or even years. We report the case of a 46-year-old woman who presented with progressive gait instability, dysarthria, and nystagmus. Brain magnetic resonance imaging (MRI) revealed cerebellar atrophy without any mass lesion, and serologic testing showed strong anti-Yo antibody positivity. Two years later, she was diagnosed with a human epidermal growth factor receptor 2 (HER2)-positive, hormone receptor-negative invasive ductal carcinoma of the breast. The patient underwent a modified radical mastectomy followed by adjuvant chemotherapy and trastuzumab. Despite appropriate oncologic treatment, her neurological symptoms persisted and gradually worsened. This case highlights the diagnostic challenge of PCD, particularly when neurological manifestations precede tumor detection, and suggests that HER2-positive breast cancer may also be associated with anti-Yo antibodies. Early recognition of this syndrome and systematic malignancy screening are essential to improve patient outcomes.}, } @article {pmid41494265, year = {2026}, author = {Chen, Y and Wang, P and Zeng, J and Tan, M and Shan, K and Nie, L and Xue, Y and Wang, T}, title = {MGScreener: A multi-view mammography-based model optimized with active learning for breast cancer diagnosis.}, journal = {Talanta}, volume = {301}, number = {}, pages = {129345}, doi = {10.1016/j.talanta.2025.129345}, pmid = {41494265}, issn = {1873-3573}, mesh = {Humans ; *Breast Neoplasms/diagnostic imaging/diagnosis ; *Mammography/methods ; Female ; Middle Aged ; Machine Learning ; }, abstract = {Breast cancer remains the leading cause of cancer-related mortality among women worldwide. Early screening and accurate subtype classification are critical for guiding clinical decision-making. In this study, we present MGScreener, an interpretable multi-view framework that integrates dual-view mammography images, including cranial-caudal (CC) and mediolateral oblique (MLO) views, with patient-level clinical data. The model incorporates an active learning strategy to address two key classification tasks: distinguishing benign from malignant breast lesions and identifying invasive ductal carcinoma (IDC) among malignant subtypes. An entropy-based uncertainty sampling method is employed to select highly informative cases from 210 unlabeled samples for prioritized annotation, substantially reducing manual labeling costs. Across two independent test sets, MGScreener-1 achieved an accuracy of 89.7 % and an ROC-AUC of 0.941 for benign-versus-malignant classification (Task 1), while MGScreener-2 achieved an accuracy of 88.2 % and an ROC-AUC of 0.884 for IDC identification (Task 2). With MGScreener assistance, radiologists improved their diagnostic accuracy by more than 10 % compared with independent reading. Overall, MGScreener offers a scalable and effective solution for precise breast cancer screening and molecular subtype classification.}, } @article {pmid41494160, year = {2026}, author = {Eldesouky, O and Seebauer, L and Rukwied, R and Carr, R and Roshan, M and Gottlieb, H and Tsilingiris, D and Kopf, S and Herzig, S and Fleming, T and Kessler, J and Szendroedi, J and Schmelz, M and Kender, Z}, title = {Mismatch between intact electrical excitability and lost heat pain in diabetic neuropathy.}, journal = {Pain}, volume = {}, number = {}, pages = {}, doi = {10.1097/j.pain.0000000000003898}, pmid = {41494160}, issn = {1872-6623}, support = {SFB1158//Deutsche Forschungsgemeinschaft/ ; SFB1158//Deutsche Forschungsgemeinschaft/ ; 397846571//Deutsche Forschungsgemeinschaft/ ; Project Grant//Deutsche Diabetes Gesellschaft/ ; }, abstract = {Patterns of sensory involvement in diabetic neuropathy vary between studies and diagnostic approaches. Although some report early thermal deficits, others find predominant large-fiber changes, and hypersensitivity in early disease is inconsistently observed. Elevated heat pain thresholds (HPTs) may indicate either selective loss of heat transduction or advanced peripheral denervation of polymodal nociceptors. We examined whether thermal and mechanical pain functions align with psychophysical axonal excitability by combining German Research Network on Neuropathic Pain-quantitative sensory testing with slow depolarizing transdermal electrical stimulation of polymodal C-fibers in 66 adults with diabetes mellitus. Neuropathy was assessed by Toronto Consensus Criteria, quantitative sensory testing (QST), questionnaires, and serum neurofilament light chain (NfL) as a marker of axonal damage. Mechanical pain sensitivity correlated with electrically evoked pain (r ≈ 0.60-0.62, both P < 0.0001), consistent with parallel changes in mechanical transduction and axonal excitability, whereas HPT did not correlate with electrical pain. Many individuals with elevated HPT still exhibited strong electrically evoked pain responses, suggesting impaired heat transduction despite preserved superficial axonal excitability. Participants with sensory loss in QST showed reduced sensitivity to electrical stimuli and higher detection and pain thresholds, consistent with more advanced afferent dysfunction. NfL levels generally correlated with sensory impairment, although at low electrical intensities, higher NfL values were associated with stronger pain ratings, indicating intensity-dependent links between axonal pathology and nociceptor hyperexcitability. Combining QST with C-fiber-targeted electrical testing refines phenotyping of small-fiber dysfunction in diabetic neuropathy by revealing dissociation between thermal and electrical pain modalities and capturing the heterogeneous course from preserved function to selective thermal hypoalgesia and eventual sensory loss.}, } @article {pmid41490083, year = {2026}, author = {Li, J and Zhao, B and Chen, Y and Wang, G and Tian, X and Zhou, S}, title = {Research on the establishment of a four-classification model for breast mass ultrasound images based on transfer learning.}, journal = {PloS one}, volume = {21}, number = {1}, pages = {e0340111}, pmid = {41490083}, issn = {1932-6203}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/classification/pathology ; Retrospective Studies ; *Ultrasonography, Mammary/methods ; Neural Networks, Computer ; Middle Aged ; Adult ; Fibroadenoma/diagnostic imaging ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; *Breast/diagnostic imaging/pathology ; Adenocarcinoma, Mucinous/diagnostic imaging ; Deep Learning ; Aged ; }, abstract = {Breast mass classification via ultrasound is critical for early diagnosis but remains challenging due to overlapping morphological features. This study evaluates the efficacy of optimized transfer learning (TL) based on deep convolutional neural networks (DCNNs) in distinguishing four breast mass categories: invasive ductal carcinoma (IDC), fibroadenoma (FA), mucinous carcinoma (MC), and inflammatory mass (IM). Our approach comprises four key steps: (1) applying extensive data augmentation to a retrospective dataset of 346 ultrasound images from 294 patients (November 2021-March 2023) classified by pathological confirmation; (2) implementing transfer learning with five pretrained DCNN models (ResNet18, ResNet50, DenseNet121, MobileNetV2, GoogLeNet); (3) optimizing model hyperparameters for four-class classification; (4) comparing performance metrics (accuracy, precision, recall, F1-score, AUC-ROC) against two senior radiologists (8- and 10-years' experience) on a held-out test set. Results: The DenseNet121 and GoogLeNet models demonstrated superior overall accuracy (0.912 and 0.926, respectively), significantly outperforming the radiologists' consensus (0.691) (p < 0.01). In class-specific analysis, the optimized models achieved notably higher accuracy for IDC, MC, and IM. Statistical testing confirmed the significant performance improvement of the top models over human experts. Optimized TL with DCNNs, particularly DenseNet121 and GoogLeNet, enables highly accurate four-class breast mass classification in ultrasound images, surpassing expert radiologist performance with statistical significance. This approach holds promise for clinical decision support. Code is publicly available at https://github.com/jinlao777/BCC.}, } @article {pmid41486537, year = {2025}, author = {Elmansorry, E and Saja, A and Mawada, A and Mawada, F}, title = {CLINICAL RELEVANCE OF HORMONAL RECEPTOR EXPRESSION IN BREAST CANCER: AN IMMUNOHISTOCHEMICAL STUDY FROM TRIPOLI, LIBYA.}, journal = {Experimental oncology}, volume = {47}, number = {3}, pages = {338-346}, doi = {10.15407/exp-oncology.2025.03.338}, pmid = {41486537}, issn = {2312-8852}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/metabolism ; Middle Aged ; Adult ; *Receptors, Progesterone/metabolism ; Libya ; *Receptors, Estrogen/metabolism ; *Erb-b2 Receptor Tyrosine Kinases/metabolism ; Immunohistochemistry ; *Biomarkers, Tumor/metabolism ; Young Adult ; Ki-67 Antigen/metabolism ; Clinical Relevance ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most frequently diagnosed malignancy among women in Libya; however, limited data are available on the immunohistochemical (IHC) profiles of BC in the region. This study aimed to characterize BC cases in Western Libya based on clinical, pathological, and IHC features.

MATERIALS AND METHODS: Thirty formalin-fixed paraffin-embedded BC tissue samples were collected from the patients at the National Cancer Institute in Sabratha, Libya, between January and April 2024. IHC staining for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 was performed.

RESULTS: Patients' age ranged from 24 to 63 years (mean 44.60 ± 10.23), with the 44-53-year group being the most frequent (33%). Invasive ductal carcinoma was the most common subtype (74%), especially grade 3 (47%). Most tumors were ER-positive (78.6%), PR-positive (67.9%), and HER2-negative (67.9%), with low Ki-67 expression in 53.6% of cases. HER2 score 0 was most prevalent (40%). Mean PR expression was the highest in grade 2 tumors (53.0 ± 32.2), whereas Ki-67 in grade 3 tumors (51.1 ± 29.7). Significant associations were found between ER status and mean corpuscular hemoglobin (p = 0.039) and mastectomy status and mean cell hemoglobin concentration (p = 0.031).

CONCLUSION: The findings highlight the predominance of hormone receptor-positive and HER2-negative tumors in this Libyan cohort.}, } @article {pmid41485765, year = {2025}, author = {Park, B and Choi, S and Han, J and Jung, SY and Lee, S and Kang, HS and Kim, S and Kwon, Y and Lee, EG}, title = {Reoperation Versus Dose-Escalated Radiotherapy for Ductal Carcinoma In Situ at the Surgical Margin After Breast-Conserving Surgery for Invasive Ductal Carcinoma.}, journal = {Journal of breast cancer}, volume = {28}, number = {6}, pages = {381-392}, pmid = {41485765}, issn = {1738-6756}, abstract = {PURPOSE: The aim of this study was to compare local recurrence (LR) rates in patients with ductal carcinoma in situ (DCIS) at the surgical margins after breast-conserving surgery (BCS).

METHODS: This single-center, retrospective study included patients diagnosed with invasive ductal carcinoma (IDC) who underwent BCS at National Cancer Center between 2014 and 2020. Patients with DCIS at the surgical margin were eligible for inclusion. Those who did not undergo re-excision received whole-breast radiotherapy with an escalated tumor bed boost of 15 Gy in five fractions. The 5-year breast cancer recurrence rates were estimated using the Kaplan-Meier method, and prognostic factors were evaluated using univariate and multivariate Cox proportional hazards regression models.

RESULTS: Among the 235 eligible patients, 115 underwent re-excision (Re-excision + group), and 120 did not (Re-excision - group). With a median follow-up of 5.0 years (range, 3.1-6.6 years), the 5-year LR rate was 6.1% in the Re-excision + group and 5.8% in the Re-excision - group (log-rank p = 0.9). Re-excision was not significantly associated with differences in LR rates in multivariate analysis.

CONCLUSION: In cases where DCIS was present at the surgical margin after BCS, re-excision was not associated with a lower LR rate compared with dose-escalated radiotherapy. This study did not assess late radiation-related toxicities, such as breast fibrosis, which are important considerations for treatment decision-making. These findings should be interpreted with caution because of the retrospective design and limited event rate. Further prospective studies are warranted to determine optimal management strategies.}, } @article {pmid41478291, year = {2026}, author = {Gilman, L and Davis, A}, title = {Donor profiles, spreadsheets and video calls: un/known donor conception in the digital age.}, journal = {Human fertility (Cambridge, England)}, volume = {29}, number = {1}, pages = {2604885}, doi = {10.1080/14647273.2025.2604885}, pmid = {41478291}, issn = {1742-8149}, mesh = {Humans ; Male ; Female ; *Donor Conception/psychology ; Adult ; *Tissue Donors ; *Insemination, Artificial, Heterologous ; United Kingdom ; Reproductive Techniques, Assisted ; }, abstract = {This article explores how connections brought about through practices of donor conception are changing in the context of mediatisation and, in particular, how digital technologies shape possibilities for donors and recipient families to know one another. We focus on the growing practice of 'informal' donor conception (IDC) in the UK - donor conceptions which are arranged outside of medical institutions and often facilitated via online platforms. Drawing on interviews with 30 (intended) parents via IDC and 19 informal sperm donors, we show how donors and recipients carefully manage, or attempt to manage, the ways in which they are known and knowable to one another, and to a potential donor-conceived person. We identify four ways of knowing, and being known, within participants' accounts: 1) selective sharing of identifying information; 2) (dis)embedding donation connections within wider communities; 3) communicative forms of knowing; and 4) via the creation and management of digital artefacts. Donors and recipients sought to use and limit these different modes of knowing in varied combinations, shaped by their knowledge of (clinical) assisted reproduction practices, changing digital cultures and the legal marginalisation of IDC practices.}, } @article {pmid41476663, year = {2025}, author = {Elsharawi, I and Bethune, G}, title = {Extensive Intraductal Component (EIC) as the Most Predictive Factor for Residual Disease Post-Breast-Conserving Surgery With Close DCIS Margins: A Single Institutional Experience.}, journal = {International journal of breast cancer}, volume = {2025}, number = {}, pages = {8785445}, pmid = {41476663}, issn = {2090-3170}, abstract = {PURPOSE: We set out to assess whether the extensive intraductal component (EIC) status in invasive breast cancers serves as an independent predictor of residual disease (RD) in re-excisions performed at our institution. This laboratory-based study provides insights into the thresholds for additional surgical intervention in cases with close ductal carcinoma in situ (DCIS) margins following initial breast-conserving surgery (BCS). We also examined the unique characteristics specific to EIC-positive cases.

METHODS: BCS cases with invasive breast cancer and DCIS with close margins that had re-excisions following initial surgery (Dec 2019-Dec 2024) were selected and classified into EIC positive or EIC negative. Data collected on the initial excision included the EIC status and other clinicopathological information such as margin status, DCIS extent, cancer type and focality, TNM stage, biomarker status, and OncotypeDX Recurrence Score (RS). The RD status was collected on re-excision specimens.

RESULTS: Ninety-one cases were included (57 EIC positive and 34 EIC negative), with most being invasive ductal carcinoma. The rate of RD on re-excision was 70.2% and 32.4% in EIC-positive and EIC-negative cases, respectively (p < 0.001). EIC-positive cases showed a higher tendency to involve multiple margins, had a lower T stage and greater DCIS extent, and they were more commonly associated with multifocal cancer. Finally, when assessing predictors of RD, EIC status emerged as the most significant factor among other variables (adjusted odds ratio = 3.39). Secondary findings included a relatively increased proportion of EIC-positive cases (19%) exhibiting mucinous morphology (p = 0.0063) and HER2-positive tumor status (p = 0.035).

CONCLUSION: Findings show that EIC status is the most significant predictor of RD following BCSs with close DCIS margins. This emphasizes the importance of identifying EIC-positive cases in pathology reports and prioritizing them for additional re-excision when DCIS margins are close.}, } @article {pmid41476587, year = {2025}, author = {Huang, B and Han, Y and Zhang, Y and Liu, H}, title = {Breast cancer occult in renal cell carcinoma: a case report of a rare tumor-to-tumor metastasis and literature review.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1710242}, pmid = {41476587}, issn = {2234-943X}, abstract = {Metastasis from breast cancer (BC) to renal cell carcinoma (RCC) is rare. We retrospectively analyzed the clinical data, i.e., medical history, imaging, and laboratory examinations, as well as pathological features of a 62-year-old female with invasive ductal carcinoma of the breast metastasizing to clear cell renal cell carcinoma (CCRCC). A comprehensive literature review was also conducted. Her right breast mass was pathologically diagnosed as invasive ductal carcinoma eight months ago. A large mass in the left kidney was incidentally discovered during a computed tomography (CT) scan, which was consistent with RCC. She underwent neoadjuvant chemotherapy, radical mastectomy, and endocrine therapy, as well as laparoscopic left nephrectomy four months postoperatively. Her pathological examination revealed two heterogeneous tumor components in the kidney: typical CCRCC [CD10+, Vimentin+, carbonic anhydrase IX (CAIX)+, paired box gene 8 (PAX-8)+, 3% Ki-67 proliferation index) as well as multifocal metastatic invasive ductal carcinoma of the breast (estrogen receptor (ER) 50%+++, GATA binding protein 3 (GATA3) +, Human epidermal growth factor receptor-2 (HER-2) 1+, and 20% Ki-67 proliferation index). These findings met the diagnostic criteria for TTM. She also continued BC endocrine therapy postoperatively. However, no recurrence or metastasis was observed during the 11 follow-up months.}, } @article {pmid41471604, year = {2025}, author = {Luo, S}, title = {Sensing User Intent: An LLM-Powered Agent for On-the-Fly Personalized Virtual Space Construction from UAV Sensor Data.}, journal = {Sensors (Basel, Switzerland)}, volume = {25}, number = {24}, pages = {}, pmid = {41471604}, issn = {1424-8220}, support = {LSKJ202459//Central Government's Guide to Local Science and Technology Development Funds, Lhasa City Science and Technology Program/ ; }, abstract = {The proliferation of Unmanned Aerial Vehicles (UAVs) enables the large-scale collection of ecological data, yet translating this dynamic sensor data into engaging, personalized public experiences remains a significant challenge. Existing solutions fall short: static exhibitions lack adaptability, while general-purpose LLM agents struggle with real-time responsiveness and reliability. To address this, we introduce CurationAgent, a novel intelligent agent built upon the State-Gated Agent Architecture (SGAA). Its core innovation is an advanced hybrid curation pipeline that synergizes Retrieval-Augmented Generation (RAG) for broad semantic recall with an Intent-Driven Curation (IDC) Funnel for precise intent formalization and narrative synthesis. This hybrid model robustly translates user intent into a curated, multi-modal narrative. We validate this framework in a proof-of-concept virtual exhibition of the Lalu Wetland's biodiversity. Our comprehensive evaluation demonstrates that CurationAgent is significantly more responsive (1512 ms vs. 4301 ms), reliable (95% vs. 57% task success), and precise (85.5% vs. 52.7% query precision) than standard agent architectures. Furthermore, a user study with 27 participants confirmed our system leads to measurably higher user engagement. This work contributes a robust and responsive agent architecture that validates a new paradigm for interactive systems, shifting from passive information retrieval to active, partnered experience curation.}, } @article {pmid41465291, year = {2025}, author = {Chaudhuri, RK and Meyer, TA}, title = {Isosorbide Diesters: Mechanistic Insights and Therapeutic Applications in Skin and Neuroinflammatory Disorders.}, journal = {International journal of molecular sciences}, volume = {26}, number = {24}, pages = {}, pmid = {41465291}, issn = {1422-0067}, support = {None//Hallstar Beauty (United States)/ ; }, mesh = {Humans ; *Isosorbide/therapeutic use/pharmacology/chemistry/analogs & derivatives ; Animals ; *Neuroinflammatory Diseases/drug therapy ; *Esters/therapeutic use/chemistry ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; Skin/drug effects ; *Skin Diseases/drug therapy ; }, abstract = {Isosorbide fatty acid diesters constitute a novel class of bioactive compounds with emerging therapeutic applications in inflammatory and barrier-compromised disorders. Among them, isosorbide dicaprylate (IDC) and isosorbide di-linoleate/oleate (IDL) synergistically strengthen epidermal barrier integrity, enhance stratum corneum hydration, regulate keratinocyte differentiation, suppress proinflammatory signaling, and beneficially modulate the skin microbiome. Randomized, double-blind clinical trials in both pediatric and adult populations with atopic dermatitis (AD) demonstrate that topical IDC + IDL formulations significantly reduce pruritus, corticosteroid dependence, and Staphylococcus aureus colonization while improving sleep quality, disease severity scores, and overall quality of life. Extending applications within and even beyond dermatology, isosorbide dimethyl fumarate (IDMF)-a next-generation fumarate derivative designed to mitigate sensitization risk-exhibits potent anti-inflammatory and antioxidant activities through NRF2 activation and NF-κB/IRF1 suppression. Preclinical studies in psoriasis and neuroinflammatory models, including multiple sclerosis, reveal robust modulation of oxidative stress and immune pathways with improved safety and mechanistic precision compared to conventional fumarates, although its systemic use remains exploratory and requires clinical validation. Collectively, isosorbide diesters emerge as multifunctional therapeutic agents offering barrier repair, immune modulation, and inflammation control, representing promising alternatives to corticosteroids and systemic immunosuppressants across dermatologic and systemic inflammatory disorders.}, } @article {pmid41459862, year = {2025}, author = {Thipsanthiah, K and Champangoen, K and Dasaeng, R and Kamsa-Ard, S and Jena, PK}, title = {Incidence of Colorectal Cancer in Loei Province, Thailand: Report from a Population-Based Cancer Registry.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {26}, number = {12}, pages = {4477-4482}, doi = {10.31557/APJCP.2025.26.12.4477}, pmid = {41459862}, issn = {2476-762X}, mesh = {Humans ; *Colorectal Neoplasms/epidemiology ; Male ; Female ; Thailand/epidemiology ; *Registries/statistics & numerical data ; Incidence ; Retrospective Studies ; Middle Aged ; Aged ; Follow-Up Studies ; Adult ; Prognosis ; Aged, 80 and over ; Young Adult ; Adolescent ; }, abstract = {BACKGROUND: Data regarding trends in Colorectal Cancer (CRC) incidence within Loei province are currently unavailable. Additionally, there is a scarcity of information from previous studies examining CRC time trends across Thailand.

OBJECTIVE: The purpose of this study was to study the estimate the trend and incidence of CRC in Loei Province.

METHODS: An analytical retrospective cohort study was conducted using data from the Loei population-based cancer registry, collected through the Thai cancer-based program of National Cancer Institute of Thailand. A total of 754 patients were diagnosed with CRC (IDC-O-3, C18.0, C18.1, C18.2, C18.3, C18.4, C18.5, C18.6, C18.7, C18.8, C18.9, C1.9, C2.0) in Loei during 2017 - 2022. Age-standardized rates (ASR) were estimated, and their 95% confidence interval were reported. Annual percent change (APC) was calculated to quantify the incidence rate trends using Join-point regression. Both APC and 95% confidence interval were reported.

RESULT: We found that the overall ASR from 2017 to 2022 for all ages was 13.7 per 100 000 person-years for both sexes. (95% CI; 12.88, 14.56). Male ASR =15.54 per 100,000 person-years (95% CI; 14.70, 16.38). Female ASR = 12.07 per 100,000 person-years (95% CI; 11.23, 12.91). Additionally, the preliminary trends of overall CRC incidence increased between 2017 to 2022 by an APC of 3.72% (APC= 3.72; 95% CI; -6.62, 15.85). The percentage change for males increased by 5.49 % (APC= 5.49; 95% CI; -2.13, 14.26) per year. For females, the annual percentage change increased by 1.91 percent (APC= 1.91; 95% CI; -14.20, 22.53).

CONCLUSION: Our preliminary findings show an increasing trend in CRC incidence among both men and women in Loei Province. To gain a more comprehensive understanding and identify clearer patterns, future studies should analyze these trends over extended periods, such as 10 years or more. Evaluating the coverage and completeness of the cancer registry data will also be crucial. This knowledge will provide a foundation for planning effective CRC prevention and control strategies in the region.}, } @article {pmid41459855, year = {2025}, author = {Cabıoğlu, N and Türkyılmaz, Z and Özkurt, E and İğci, A and Müslümanoğlu, M and Kapkaç, M and Yeniay, L and Taşdelen, İ and Aksaz, E and Haydaroğlu, A and Alanyalı, S and Çelik, V and Gazioğlu, E and Gökgöz, Ş and Şenol, K and Önal, B and Özbaş, S and Ok, E and Akcan, A and Canturk, NZ and Koçak, S and Güllüoğlu, B and Demirer, S and Koyuncu, A and Tükenmez, M and Girgin, S and Çolak, T and Velidedeoglu, M and Karadeniz, E and Akçay, MN and Oltulu, M and Kebudi, A and Emiroğlu, S and Uras, C and Özmen, V}, title = {Poor Prognostic Clinicopathological Features of Young Women with Breast Cancer in the MF18-04 Turkish National Breast Cancer Registry Study.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {26}, number = {12}, pages = {4407-4417}, doi = {10.31557/APJCP.2025.26.12.4407}, pmid = {41459855}, issn = {2476-762X}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/surgery/metabolism/epidemiology ; Adult ; Turkey/epidemiology ; Middle Aged ; Prognosis ; Young Adult ; Adolescent ; Registries ; Aged ; Aged, 80 and over ; Follow-Up Studies ; Age Factors ; *Carcinoma, Ductal, Breast/pathology/surgery/metabolism ; Mastectomy ; Receptors, Estrogen/metabolism ; Neoplasm Staging ; Lymphatic Metastasis ; *Carcinoma, Lobular/pathology/surgery/metabolism ; Receptors, Progesterone/metabolism ; Lymph Node Excision ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Survival Rate ; }, abstract = {OBJECTIVE: The role of younger age as a prognostic factor in breast cancer remains debated. Despite its association with an aggressive clinical course, there is insufficient research on its etiology. This study aimed to analyze age-related differences in breast cancer diagnosis among Turkish women.

MATERIALS AND METHODS: Data from 23,594 patients in the National Breast Cancer Database (NBCD) were analyzed. The demographic, clinical, and pathological characteristics of patients aged ≤40 years were compared with those >40 years.

RESULTS: The median age was 50 years (range 18-97). Among them, 4,535 patients (19%) were 40 years old or younger, with 84% of this subgroup being over 30 years old. Conversely, 19,059 patients (81%) were older than 40. Patients in the younger age group were less likely to have pathologic T1 disease (41% vs. 47%), N0 disease (49% vs. 55%), and Stage I disease (25% vs. 31%) compared to those over 40 (p<0.001). The rates of mastectomy (41% vs. 39%; p = 0.024) and axillary dissection (71% vs. 65%; p = 0.001) were higher among patients diagnosed at 40 years of age or younger. Multivariate analysis identified significant associations in younger patients, including invasive ductal carcinoma (95% CI, 1.06-1.43), estrogen receptor (ER) negativity (95% CI, 1.26-1.87), PR negativity (95% CI, 1.21-1.75), high histologic grade (95% CI, 1.43-1.87), multifocality/multicentricity (95% CI, 1.26-1.72), T3-T4 tumors (95% CI, 1.06-1.66), and axillary positivity (95% CI, 1.025-1.321).

CONCLUSIONS: Breast cancer diagnosed at ≤40 years is more likely to exhibit aggressive biology, multifocality, or multicentricity presentation, and present at advanced stages. Consequently, younger patients experience higher rates of mastectomy and axillary dissection. These findings suggest a poorer prognosis, highlighting the need for more intensive therapeutic strategies in this population.}, } @article {pmid41457395, year = {2026}, author = {Dudipala, H and Nazari, SS and Werneck da Cunha, I and Coligado, N and Baca, Y and Wei, S and Elliott, A and Smith, ND and Geynisman, DM and Brown, JT and Zarrabi, KK and Agarwal, N and Antonarakis, ES and Herchenhorn, D and McKay, RR}, title = {Molecular alteration profiles characterize intraductal carcinoma of the prostate.}, journal = {Cancer}, volume = {132}, number = {1}, pages = {e70238}, doi = {10.1002/cncr.70238}, pmid = {41457395}, issn = {1097-0142}, mesh = {Humans ; Male ; *Prostatic Neoplasms/genetics/pathology/surgery ; Aged ; Middle Aged ; Prostatectomy ; Mutation ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/surgery ; *Biomarkers, Tumor/genetics ; *Carcinoma, Ductal/genetics/pathology ; Tumor Microenvironment ; High-Throughput Nucleotide Sequencing ; }, abstract = {BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is an intra-acinar and/or intraductal neoplastic epithelial proliferation that is a distinct histological entity according to the 2016 World Health Organization (WHO) classification system. Clinically, it is associated with higher grade tumors and a more aggressive disease course. However, the molecular underpinnings of IDC-P are not well elucidated.

METHODS: This study identified radical prostatectomy (RP) cases from the Caris Life Sciences database, classified as prostatic adenocarcinoma with grade group 4/5 or with the words "cribriform," "necrosis," or "intraductal" in the pathology report. Digitized hematoxylin-eosin slides underwent central pathology review by a board-certified genitourinary pathologist to identify the presence of IDC-P according to the 2022 WHO classification. IDC-P cases (n = 175) were compared to non-IDC-P cases (n = 5334). Prostatic tumor specimens were sequenced via next-generation DNA/RNA sequencing.

RESULTS: Compared to non-IDC-P cases, the IDC-P cohort had significantly more mutations in MUTYH (4.5% vs. 1.4%; p < .01), FANCA (2.7% vs. 0.5%; p < .01), NBN (2.5% vs. 0.6%; p < .05), and MTOR (0.6% vs. 0.1%; p < .05). IDC-P tumors were enriched for DLL3 and CEACAM5 expression, with lower expression of STEAP1, TROP2, ERBB2, PSCA, and B7-H3, compared to non-IDC-P tumors. IDC-P had significantly higher neuroendocrine prostate cancer signature scores and IFN-γ signature scores, and similar androgen receptor signature scores, compared to non-IDC-P. The tumor microenvironment of IDC-P had significantly higher cell fractions of M2 macrophages and fewer dendritic cells.

CONCLUSIONS: IDC-P possesses a distinct molecular and immunological profile. Understanding these molecular underpinnings is crucial for the development of personalized treatment strategies for histologically distinct prostate cancer subsets.}, } @article {pmid41455364, year = {2026}, author = {Hao, S and Zhou, J and Siriwardena, T and Javor, S and Gan, B and He, R and Song, Y and Wang, Z and Xiao, W}, title = {A novel polypeptide molecule attenuates atopic dermatitis by targeting CCR8-CCL1 axis.}, journal = {International immunopharmacology}, volume = {170}, number = {}, pages = {116051}, doi = {10.1016/j.intimp.2025.116051}, pmid = {41455364}, issn = {1878-1705}, mesh = {*Dermatitis, Atopic/drug therapy/immunology ; Animals ; Humans ; *Receptors, CCR8/metabolism/antagonists & inhibitors ; *Peptides/therapeutic use/pharmacology ; *Chemokine CCL1/metabolism ; Mice ; Skin/pathology/drug effects/immunology ; Disease Models, Animal ; Dendritic Cells/drug effects/immunology ; Cell Movement/drug effects ; Mice, Inbred BALB C ; Mast Cells/drug effects/immunology ; Cytokines/metabolism ; Female ; }, abstract = {Atopic dermatitis (AD) is a common chronic inflammatory skin disease with diverse clinical phenotypes. Although a variety of drugs are available, the current clinical treatment still cannot meet the needs of patients with AD. In this study, we designed a series of polypeptides through a new drug discovery technology combined with big data and artificial intelligence in our polypeptide library and successfully screened 2 candidates by in vitro and in vivo study. As results showed that the 2 candidates have a high affinity for human CC chemokine receptor 8 (CCR8) and significantly inhibited interstitial dendritic cell (iDC) migration induced by CC chemokine ligand 1 (CCL1) via interfering with the CCL1-CCR8 axis. The efficacy of CCR8 polypeptide candidates on AD were further evaluated in two dermatitis mouse models. We found that applying SP-TG02 to the skin ameliorated MC903 and OXA-induced skin AD-like symptoms and histological damage, reduced mast cell infiltration and down-regulated the expression of pro-inflammatory cytokines in skin tissue. Collectively, SP-TG02 may be a promising novel CCR8 polypeptide inhibitor for the treatment of atopic dermatitis.}, } @article {pmid41454442, year = {2025}, author = {Brix, N and Samaga, D and Gehr, K and Dankó, B and Schumann, M and Drexler, G and Alnatsha, A and Beyer, G and Mahajan, U and Selmansberger, M and Mayerle, J and Belka, C and Zitzelsberger, H and Lauber, K}, title = {LDAcoop: Integrating non-linear population dynamics into the analysis of clonogenic growth in vitro.}, journal = {Molecular oncology}, volume = {}, number = {}, pages = {}, doi = {10.1002/1878-0261.70185}, pmid = {41454442}, issn = {1878-0261}, support = {551613698//Deutsche Forschungsgemeinschaft/ ; 02NUK047A//Bundesministerium für Bildung und Forschung/ ; 02NUK047C//Bundesministerium für Bildung und Forschung/ ; 02NUK061A//Bundesministerium für Bildung und Forschung/ ; 02NUK061C//Bundesministerium für Bildung und Forschung/ ; 02NUK086A//Bundesministerium für Bildung und Forschung/ ; 02NUK086B//Bundesministerium für Bildung und Forschung/ ; 02NUK087//Bundesministerium für Bildung und Forschung/ ; }, abstract = {The limiting dilution assay (LDA) is a key method to quantify clonogenic cells with self-renewing capacity in vitro, crucial for preclinical cancer research and therapy response assessment. It estimates the frequency of individual clonogenic, stem-like cells within a population based on their ability to form colonies with ≥50 cells at limiting cell numbers. Standard LDA analysis relies on linear, single-hit Poisson models, yet clonogenic growth under single-cell conditions often involves cooperative or competitive dynamics, violating this linearity assumption. Here, we present a modeling framework incorporating non-linear population dynamics into LDA analysis and introduce LDAcoop, an R-based tool for universal quantification of clonogenic cells in LDA formats. Across multiple cancer cell types, we benchmarked LDA against the colony formation assay (CFA) and show that LDA outperforms CFA, especially for patient-derived organoids, suspension cultures, and higher throughput applications. This renders the LDA format particularly suitable for larger-scale pharmacogenomic screening and drug sensitivity testing in complex models. Our results establish LDA and LDAcoop as versatile, scalable tools for robust quantification of clonogenic growth, supporting preclinical drug development and molecular precision oncology research.}, } @article {pmid41454324, year = {2025}, author = {Dahms, PA and Hinckley, B and Prekeris, R and Behbod, F and Lyons, TR}, title = {Semaphorin-7A promotes macrophage-mediated mammary epithelial and ductal carcinoma in situ invasion.}, journal = {Breast cancer research : BCR}, volume = {28}, number = {1}, pages = {25}, pmid = {41454324}, issn = {1465-542X}, support = {R01 CA211696/CA/NCI NIH HHS/United States ; R01GM122768/GM/NIGMS NIH HHS/United States ; P30 CA046934/CA/NCI NIH HHS/United States ; R01CA211696-01A1/CA/NCI NIH HHS/United States ; R01 GM122768/GM/NIGMS NIH HHS/United States ; RSG-16-171-010CSM//American Cancer Society/ ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) accounts for 20–30% of all breast cancer diagnoses. Considered stage 0, DCIS is contained in the ducts by the myoepithelium that surround the luminal cells in the mammary gland. DCIS can progress to invasive ductal carcinoma (IDC) if the tumor cells break through the myoepithelium and invade the surrounding breast tissue. While 30–50% of DCIS tumors will progress to IDC, a majority will remain in a DCIS-like state. The mechanisms that drive this progression are not completely understood. There is currently no clinically recognized biomarker for predicting risk of DCIS progression. Therefore, all DCIS tumors are treated with standard of care, resulting in overtreatment. We have previously identified independent roles for semaphorin-7A(SEMA7A) and collagen in promoting DCIS progression to IDC.

METHODS: To investigate the relationship between SEMA7A and collagen remodeling in the mammary gland, we utilized patient tissues and mouse models of normal development and DCIS progression as well as a novel SEMA7A-blocking antibody.

RESULTS: We show that SEMA7A increases in patient samples of DCIS compared to matched normal tissues and in IDC compared to matched DCIS and normal tissues. This increase was correlated with the presence of CD68 + macrophages. Using puberty in the mammary gland as a model for normal epithelial invasion facilitated by macrophages, we show SEMA7A knockout mice exhibit delayed ductal elongation as well as decreased macrophages. Additionally, our SEMA7A-blocking antibody in a mouse model of DCIS decreased invasive tumor phenotypes and decreased organized collagen around the tumor. The invasive tumors had increased collagen and macrophage influx in the tumor. Finally, we show that SEMA7A activates an AKT/GSK3β/β-catenin signaling pathway within macrophages to promote expression of pro-inflammatory cytokines and the matrix remodeling enzyme MMP9 to facilitate invasion.

CONCLUSIONS: Our results demonstrate that SEMA7A regulates normal and transformed epithelial cell invasion through regulation of pro-invasive matrix remodeling via macrophages. Our studies also suggest that SEMA7A expression, macrophage phenotype, and collagen structure may be a predictor of risk for DCIS invasion. Thus, blocking SEMA7A may be a novel therapeutic strategy for high-risk DCIS patients to slow or prevent progression of disease.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-025-02180-w.}, } @article {pmid41445797, year = {2025}, author = {Cheng, C and Wang, T}, title = {Case Report: Solitary scalp metastasis after surgery for invasive ductal carcinoma of the breast.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1709244}, pmid = {41445797}, issn = {2234-943X}, abstract = {BACKGROUND: Breast cancer is one of the most common malignancies among women, and more than 90% of breast cancer-related deaths attributed to metastasis. Cutaneous metastases are relatively uncommon, and scalp involvement is exceedingly rare. Because of its atypical clinical presentation, scalp metastasis is often recognized and diagnosed only after a delay.

CASE PRESENTATION: We report the case of a 45-year-old woman diagnosed with invasive ductal carcinoma (IDC) of the right breast with ipsilateral axillary lymph node involvement (clinical stage cT4bN3M0). The patient received six cycles of neoadjuvant chemotherapy and achieved a partial response (PR) according to RECIST 1.1 criteria. Subsequently, she underwent a right simple mastectomy with axillary lymph node dissection. Pathology demonstrated a Miller-Payne grade 3 response, with metastases identified in all 13 dissected axillary lymph nodes (13/13). Immunohistochemistry (IHC) revealed estrogen receptors (ER) and progesterone receptors (PR) positivity, human epidermal growth factor receptor-2 (HER2) expression of 0, and Ki-67 expression of 20%. She subsequently received adjuvant radiotherapy and endocrine therapy. Surveillance imaging during follow-up showed no evidence of recurrence or distant metastasis. In December 2023, the patient developed a painless, round, skin-colored nodule on the left frontal scalp, accompanied by diffuse right periorbital edema and headache. Over the following year, she was evaluated in dermatology, neurosurgery, and oncology clinics. However, breast cancer metastasis was not initially suspected, resulting in misdiagnosis and delayed treatment. In April 2025, fine-needle aspiration of the scalp nodule confirmed metastatic carcinoma. IHC showed ER and PR positivity, HER2 expression of 1+, and Ki-67 expression of 35%. No additional metastatic lesions were identified. The patient was started on systemic therapy with fulvestrant plus dalpiciclib, and after four cycles, she achieved marked regression of the scalp lesion along with resolution of periorbital edema. The most recent examination, however, detected meningeal and calvarial metastases. Consequently, the patient received localized radiotherapy to these sites while continuing the original treatment protocol.

CONCLUSION: This case highlights the diagnostic challenges of atypical scalp metastases in breast cancer and underscores the importance of early detection and prompt initiation of comprehensive treatment.}, } @article {pmid41443500, year = {2025}, author = {Sekiya, N and Okamoto, K and Fukushima, K and Hosoda, T and Takahashi, K and Gu, Y}, title = {Prognostic stratification in cancer candidemia under routine infectious disease consultation: Palliative Prognostic Index identifies patients with favorable short-term outcomes.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {164}, number = {}, pages = {108338}, doi = {10.1016/j.ijid.2025.108338}, pmid = {41443500}, issn = {1878-3511}, abstract = {OBJECTIVES: Although consultations with infectious disease physicians (IDC) improve adherence to guidelines and reduce mortality in candidemia, data on mortality risk during routine IDC are scarce, especially in cancer patients.

METHODS: This retrospective cohort study included cancer patients with candidemia between January 2013 and December 2023 at a Japanese cancer center and assessed the European Confederation of Medical Mycology Quality of Clinical Candidaemia Management (EQUAL) score and factors associated with 30-day mortality during routine IDC using Firth's penalized likelihood logistic regression.

RESULTS: Of 227 patients with candidemia, 197 were included in the final analysis. Most cases were hospital-acquired (91%), and the 30-day mortality was 28%. Solid tumors (78%) and central venous catheter placement (82%) were common. The most frequent species were Candida albicans (37%), C. parapsilosis (23%), and C. glabrata (20%). The median EQUAL score with and without CVC placement was 22 (interquartile range [IQR]: 20-22) and 19 (IQR: 17-19), respectively. Factors associated with 30-day mortality were the Palliative Prognostic Index (PPI) score (adjusted odds ratio [aOR]: 14.64; 95% confidence interval [CI]: 6.21-38.51; P < .001) and the EQUAL score (aOR: 0.019; 95%CI: 0.003-0.073; P < .001). These findings were consistent in patients with solid tumors. Patients with a low PPI score (< 4) had a 30-day mortality of 10.9%.

CONCLUSIONS: The PPI score before candidemia onset independently predicted mortality during routine IDC in cancer patients. These results highlight IDC mortality benefits stratified by PPI and may stimulate discussion about ID's role in end-of-life cancer care practice.}, } @article {pmid41441520, year = {2025}, author = {Suzuki, S and Horiuchi, H and Kabasawa, T and Oizumi, T and Kobayashi, Y}, title = {Paclitaxel-Induced Collagenous Colitis: A Case Report in Male Breast Cancer.}, journal = {Reports (MDPI)}, volume = {8}, number = {4}, pages = {}, pmid = {41441520}, issn = {2571-841X}, abstract = {Background and Clinical Significance: Collagenous colitis is an uncommon form of microscopic colitis characterized by chronic watery diarrhea and thickening of the subepithelial collagen layer. While various medications have been implicated in its pathogenesis, paclitaxel-associated collagenous colitis remains exceptionally rare in the literature. Recognition of this adverse event is crucial for appropriate management, particularly in patients receiving dose-modified chemotherapy regimens. This case highlights the importance of considering drug-induced collagenous colitis in cancer patients presenting with severe diarrhea during chemotherapy. Case Presentation: We report a 71-year-old Japanese male with metastatic breast cancer who developed acute-onset collagenous colitis during paclitaxel treatment. His primary tumor was invasive ductal carcinoma with hormone receptor-positive, HER2-negative disease (ER+, PgR+, HER2-, Ki-67 46%) and progressive metastatic disease. Given pre-existing renal dysfunction, paclitaxel was initiated at 60% dose reduction. Sixteen days after treatment initiation, the patient experienced abrupt onset of profuse watery diarrhea with approximately 10 bowel movements daily, necessitating hospital admission. Colonoscopic evaluation demonstrated increased vascular permeability and superficial mucosal erosions. Histopathological analysis revealed diagnostic features of collagenous colitis with a markedly thickened subepithelial collagen band measuring 23 μm. Following immediate cessation of paclitaxel, the patient experienced complete resolution of diarrheal symptoms without subsequent relapse. Conclusions: This case represents a rare manifestation of paclitaxel-induced collagenous colitis. Clinicians should maintain heightened awareness of this potential complication in patients receiving taxane-based chemotherapy who develop significant diarrhea. Prompt recognition and immediate drug discontinuation are essential for favorable outcomes and symptom resolution.}, } @article {pmid41437877, year = {2025}, author = {Gosein, M and Yong-Hing, CJ and Johal, P and Mar, C and Martin, T}, title = {Contrast-Enhanced Mammography for Detection and Characterization of Invasive Lobular Carcinoma.}, journal = {Canadian Association of Radiologists journal = Journal l'Association canadienne des radiologistes}, volume = {}, number = {}, pages = {8465371251398520}, doi = {10.1177/08465371251398520}, pmid = {41437877}, issn = {1488-2361}, abstract = {Invasive lobular carcinoma (ILC) poses distinct diagnostic challenges due to its infiltrative single-file growth pattern, which often renders it mammographically occult, particularly in dense breast tissue. Contrast-enhanced mammography (CEM) combines the anatomical detail of conventional mammography with functional information from contrast uptake, likely improving the detection, staging, and assessment of ILC compared to conventional imaging techniques. CEM shows value in evaluating ILC tumor size and disease extent, especially in multifocal and multicentric disease, although MRI remains the gold standard. This review outlines the spectrum of ILC imaging features on CEM, including findings on both low-energy and recombined images. While CEM can provide ILC size and extent estimates comparable to MRI, its accuracy may be reduced in cases of non-mass enhancement or tumors larger than 3 cm. Additionally, ILC may demonstrate lower conspicuity enhancement than invasive ductal carcinoma (IDC), necessitating careful image interpretation. As clinical adoption of CEM increases, radiologists must become familiar with the variable imaging characteristics of ILC, to facilitate more accurate interpretation. Improved recognition of these features has the potential to support more precise treatment planning and better patient outcomes.}, } @article {pmid41437607, year = {2025}, author = {Ishikawa, Y and Ando, J and Takemae, M and Toyota, T}, title = {[Safe Use of Anti-HER2 Antibodies to a Patient with HER2-Positive Breast Cancer and Markedly Reduced Cardiac Function-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {52}, number = {12}, pages = {889-892}, pmid = {41437607}, issn = {0385-0684}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/physiopathology/pathology/surgery ; Middle Aged ; *Erb-b2 Receptor Tyrosine Kinases/immunology/analysis ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; Trastuzumab/administration & dosage ; Neoadjuvant Therapy ; Antibodies, Monoclonal, Humanized/administration & dosage ; }, abstract = {The patient was a 53-year-old female diagnosed with right breast cancer cT2N2bM0, cStage ⅢA, and the histopathological findings revelaed invasive ductal carcinoma, NG2, HG2, ER 90%, PgR 30%, HER2 3+, and Ki-67 50%. Cardiac function tests to assess suitability for neoadjuvant chemotherapy revealed a left ventricular ejection fraction of 39.7% and left ventricular hypokinesis. Trastuzumab was the preferred treatment for the breast cancer, and after consultation with the cardiologist, trastuzumab+pertuzumab+paclitaxel was initiated as neoadjuvant chemotherapy, in combination with an angiotensin Ⅱ receptor blocker and a beta-blocker. Post-surgery, histopathological examination revealed a non-pathological complete response, and treatment was continued with a T-DM1+aromatase inhibitor. The patient's cardiac function remained stable during anti-HER2 antibodies. We encountered a case in which anti-HER2 antibodies were administered to a patient with a HER2-positive breast cancer and markedly reduced cardiac function. With regular monitoring, appropriate cardiac care, and cardioprotective medications, anti-HER2 antibodies can be safely administered to patients with impaired cardiac function.}, } @article {pmid41436320, year = {2026}, author = {Tekcan Sanli, DE and Sanli, AN}, title = {Deep Learning-Based Differentiation of DCIS and IDC from Mammographic Microcalcifications.}, journal = {Academic radiology}, volume = {33}, number = {3}, pages = {919-920}, doi = {10.1016/j.acra.2025.12.002}, pmid = {41436320}, issn = {1878-4046}, } @article {pmid41436217, year = {2025}, author = {Khan, NU and Ali, SM and Pandit, DG and Chhetri, SK}, title = {Anti-AMPA receptor limbic encephalitis as the initial manifestation of metastatic breast cancer.}, journal = {BMJ case reports}, volume = {18}, number = {12}, pages = {}, doi = {10.1136/bcr-2025-268324}, pmid = {41436217}, issn = {1757-790X}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/complications ; *Limbic Encephalitis/immunology/diagnosis/etiology/therapy ; *Receptors, AMPA/immunology ; *Carcinoma, Ductal, Breast/secondary/complications ; *Autoantibodies/cerebrospinal fluid ; Magnetic Resonance Imaging ; Middle Aged ; Plasma Exchange ; Diagnosis, Differential ; }, abstract = {Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor limbic encephalitis is a rare neurological disorder often associated with malignancies. We present the case of a patient in her forties who initially presented with symptoms misattributed to migraine, later progressing to fever, confusion, declining consciousness and focal seizures. MRI findings were consistent with encephalitis, and cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis with negative infectious workup. Despite initial empiric treatment for infectious encephalitis, her condition deteriorated. CT of the chest, abdomen and pelvis showed suspicious nodules in the left breast; biopsy confirmed the presence of metastatic invasive ductal carcinoma. She made a marked improvement following plasma exchange. Subsequently, the CSF autoimmune encephalitis panel returned positive for AMPA receptor antibodies, confirming the diagnosis of paraneoplastic encephalitis. This case underscores the need for early consideration of autoimmune and paraneoplastic causes in atypical or refractory encephalitis presentations, even prior to the availability of confirmatory antibody testing.}, } @article {pmid41433251, year = {2025}, author = {Joshua, D and Rahimi, H and Seni, J and Ally, M and Omar, M and Joshi, J and Ali, F and Mohammed, S and Poulsen, A and Lund, S and , }, title = {Serial C-Reactive Protein Point-of-Care testing to optimize antibiotic treatment in hospitalized children with signs of infection in Zanzibar: A feasibility study.}, journal = {PLOS global public health}, volume = {5}, number = {12}, pages = {e0004777}, pmid = {41433251}, issn = {2767-3375}, abstract = {Bacterial infections are among the leading causes of morbidity and mortality in children, especially in low- and middle- income countries. As a result, antibiotics are frequently prescribed to children with signs of infection, even when cause may not be bacterial. This contributes to antimicrobial resistance (AMR), a global health concern. Integrating serial CRP point-of-care testing with culture and susceptibility testing may improve decision-making by facilitating earlier differentiation between bacterial and non-bacterial infections, promoting more appropriate antibiotic use.The study examined the feasibility of serial CRP POCT to guide discontinuation of antibiotic treatment in children in selected hospitals in Zanzibar, and to determine barriers to methods and procedures for the upcoming randomised controlled trial (RCT) (ISRCTN25937092).This prospective, individually randomized feasibility study was conducted between February 5 and March 3 2024 in two hospitals in Zanzibar. Research assistants and healthcare workers (HCWs) were trained on the use and interpretation of CRP POCT. Eligible neonates and children were randomized to CRP-guided or standard care antibiotic management. Feasibility was assessed using Bowen's framework; clinical outcomes were interpreted as exploratory.Eighty-two children participated, with a 96.0% follow-up rate. The CRP POCT intervention was rated "very important" by 89.7% of 58 HCWs. Adherence to CRP-based antibiotic guidance was high, though early discharges due to caregiver pressure were noted. The intervention integrated successfully into existing workflows and HCWs adapted the flowcharts in practice. Exploratory analysis showed CRP guidance reduced antibiotic treatment days in neonates with signs of infection (5.1 vs 6.6 days), and children aged 6 months to 12 years with febrile illness or diarrhoea (4.8 vs 6.7 days) compared to standard care, but the study was not powered for statistical inferences. This study suggests that the RCT of serial CRP POCT in guiding antibiotic treatment decision is feasible, and operationally implementable in this setting.}, } @article {pmid41432796, year = {2025}, author = {Donica, WRF and Shartzer, DS and Ramakrishnan, VG and Kuhl, E and Mais, DD and McMasters, KM and Ajkay, N}, title = {External Validation of a Pragmatic Scoring System for Predicting Upgrade of Atypical Ductal Hyperplasia at the Time of Surgery.}, journal = {Annals of surgical oncology}, volume = {}, number = {}, pages = {}, pmid = {41432796}, issn = {1534-4681}, abstract = {BACKGROUND: Atypical ductal hyperplasia (ADH) carries a variable risk of upgrade at the time of surgery to ductal carcinoma in situ (DCIS) or invasive malignancy. We sought to externally validate a pragmatic upgrade risk scoring system previously demonstrated to have an upgrade rate of 0-2% in patients with a risk score of 0 out of 5.

METHODS: A multicenter, retrospective review of all percutaneous biopsies containing ADH was performed from 2017 to 2023. Women aged ≥ 18 years who underwent diagnostic mammography and surgical excision for pathologic correlation were included.

RESULTS: Among the 183 cases included, the mean age was 58 years ± standard deviation 11, and 91 patients (50%) reported a family history of breast cancer. Most biopsies were stereotactic (75%), vacuum-assisted (84%), and used 9-gauge needles (73%). Three of 14 (21%) patients with a risk score of 0 were upgraded to DCIS following surgical excision. Seven (19%) patients had a risk score of 1 upgraded - six to DCIS and one to an estrogen receptor-positive/progesterone receptor-positive/human epidermal growth factor receptor 2-negative invasive ductal carcinoma measuring 5.45 mm in largest diameter. On multivariate analysis, age, mammographic lesion size, and suspicion of DCIS on biopsy were predictive of upgrade.

CONCLUSIONS: The risk model evaluated generally predicts the risk of upgrade of ADH at excisional biopsy but may underestimate the upgrade rate in the lowest-risk cohort. Because of the small sample size, further work is needed to determine whether the rate of upgrade is truly low enough in this lowest-risk cohort to recommend against excisional biopsy.}, } @article {pmid41432120, year = {2025}, author = {Xu, W and Fan, L}, title = {Antitumor Effects of Tumor-Derived Exosomes in Murine Hepatocellular Carcinoma Models.}, journal = {Iranian journal of immunology : IJI}, volume = {22}, number = {4}, pages = {310-321}, doi = {10.22034/iji.2025.106436.3025}, pmid = {41432120}, issn = {1735-367X}, mesh = {Animals ; *Exosomes/metabolism/immunology ; *Carcinoma, Hepatocellular/immunology/therapy/pathology ; *Dendritic Cells/immunology ; Mice ; *Liver Neoplasms/immunology/therapy/pathology ; Disease Models, Animal ; Cell Line, Tumor ; Humans ; Antigens, Neoplasm/immunology/metabolism ; Cytokines/metabolism ; }, abstract = {BACKGROUND: Exosomes (EXOs) are small vesicles derived from endosomes and secreted by most living cells including tumor cells. In recent years, these vesicles have been recognized as key mediators of intercellular communication, playing essential roles in the regulation and orchestration of diverse physiological and pathological processes within the organism.

OBJECTIVE: To further investigate hepatocellular carcinoma (HCC)-derived exosomes containing tumor-associated antigens and to evaluate their immunostimulatory capacity and antitumor effects using in vitro and in vivo approaches.

METHODS: Following isolation from tumor cells, exosomes were characterized and subsequently co-cultured with dendritic cells (DCs). The expression of surface molecules associated with DC maturation was then assessed using flow cytometry. A mouse liver cancer model was established and animals were randomly assigned to three groups: a negative control group (treated with PBS), an iDC group, and a DC-TEXs (tumor-derived exosomes) group. Tumor volume was monitored in all groups, with a focus on changes in immune cell populations and cytokine levels.

RESULTS: Our in vitro studies showed that Hepa1-6 cell-derived EXOs dose-dependently enhanced dendritic cell (DC) maturation, as evidenced by increased expression of surface MHC-II molecules, co-stimulatory markers (CD40, CD80, CD86), and the maturation marker CD83. In vivo studies using subcutaneous HCC mouse models demonstrated that TEX administration significantly alters the tumor immune microenvironment, mainly through increased T lymphocyte infiltration and proliferation.

CONCLUSION: Our results suggest that TEXs can serve as endogenous immunotherapeutic agents by eliciting tumor-specific T lymphocyte responses through DC activation cascades. These findings provide novel insights into the therapeutic exploitation of tumor-derived vesicles for the treatment of hepatocellular carcinoma.}, } @article {pmid41430004, year = {2025}, author = {Roy, S and Shanmugam, G and Rakshit, S and Pradeep, R and George, M and Sarkar, K}, title = {Retraction Note: Exploring the immunomodulatory potential of brahmi (Bacopa monnieri) in the treatment of invasive ductal carcinoma.}, journal = {Medical oncology (Northwood, London, England)}, volume = {43}, number = {2}, pages = {58}, pmid = {41430004}, issn = {1559-131X}, } @article {pmid41429548, year = {2025}, author = {Mao, J and Wang, JQ and He, H and Li, YH and Peng, JQ and Peng, HZ and Xu, YQ and Xie, XB}, title = {[Analyzing the impact of chemotherapy on cellular heterogeneity and identifying potential therapeutic targets in breast cancer patients via single-cell RNA sequencing].}, journal = {Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]}, volume = {59}, number = {12}, pages = {2147-2156}, doi = {10.3760/cma.j.cn112150-20250425-00356}, pmid = {41429548}, issn = {0253-9624}, support = {22JBZ037//Hunan University of Chinese Medicine "Unveiling and Commanding" Program for Discipline Development/ ; kq2502082//Changsha Municipal Natural Science Foundation/ ; 2024CX123//Graduate Innovation Research Project of Hunan University of Chinese Medicine/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; *Single-Cell Analysis ; *Sequence Analysis, RNA ; Tumor Microenvironment ; Case-Control Studies ; Transcriptome ; }, abstract = {Objective: Profiling tumor cell heterogeneity before and after chemotherapy in breast cancer patients to delineate the cellular evolutionary trajectory at single-cell resolution, thereby identifying potential targets for intervention. Methods: Using a case-control study design, a female patient with breast cancer admitted to the Department of Breast Surgery, The First Affiliated Hospital of Hunan University of Chinese Medicine in September 2020 was enrolled as the subject. Fresh tumor tissue samples, collected both before and after chemotherapy, were subjected to single-cell RNA sequencing to assess transcriptomic profiles and observe the impact of chemotherapy on the intratumoral microenvironment. Specifically, a pre-chemotherapy biopsy sample was obtained in June 2020, and a post-chemotherapy surgical resection sample was obtained in September 2020. Pathological diagnosis confirmed Grade Ⅲ invasive ductal carcinoma for both samples, with a molecular subtype of Luminal B. Results: A significance threshold of |log2FC|>2 and a P-value <0.05 were set to define statistically significant differences for subsequent bioinformatic analysis. Sequencing data revealed that a total of 8 599 cells were profiled in this study, with 4 180 (48.6%) and 4 419 (51.4%) cells derived from pre- and post-chemotherapy tumor tissues, respectively. It characterized the cellular composition of the tumor microenvironment and identified 13 distinct cell clusters. These included basal cells, pericytes, plasma cells, T cells, B cells, fibroblasts, endothelial cells, NK cells, mast cells, epithelial cells, macrophages, cycling cells, and plasmacytoid dendritic cells. Signaling pathways and transcription factors associated with these cell clusters were subsequently analyzed and subjected to enrichment analysis. Furthermore, this study delineated the precise cellular architecture and developmental trajectories of breast cancer before and after chemotherapy. It also predicted that the APOD, ELN, and F2R genes may play pivotal roles in disease progression. Conclusion: This study utilized single-cell RNA sequencing to analyze intra-tumoral cellular heterogeneity in a breast cancer patient before and after chemotherapy. The findings may provide a clinically informative direction for identifying novel potential therapeutic targets during chemotherapy, prior to primary tumor resection.}, } @article {pmid41425867, year = {2025}, author = {Kumari, B and Lahariya, R}, title = {Somatic mutation counts as a surrogate marker for tumor mutation burden to predict progesterone receptor-positive (PR+) status in PIK3CA-mutated breast cancer.}, journal = {German medical science : GMS e-journal}, volume = {23}, number = {}, pages = {Doc16}, pmid = {41425867}, issn = {1612-3174}, mesh = {Humans ; Female ; *Class I Phosphatidylinositol 3-Kinases/genetics ; *Breast Neoplasms/genetics/pathology ; *Receptors, Progesterone/metabolism/genetics ; Retrospective Studies ; Middle Aged ; *Biomarkers, Tumor/genetics ; Mutation ; Adult ; *Carcinoma, Ductal, Breast/genetics/pathology ; Aged ; }, abstract = {OBJECTIVES: Invasive ductal carcinoma (IDC), the most prevalent subtype of breast cancer, is characterized by significant genomic heterogeneity. Tumor mutation burden (TMB) has emerged as a predictive biomarker for immunotherapy response, yet its estimation via whole-exome sequencing remains complex and costly. This study aimed to evaluate whether total somatic mutation count can serve as a practical surrogate for TMB and assess its association with progesterone receptor (PR) status in PIK3CA-mutated IDC patients.

METHODS: This retrospective observational study utilized publicly available data from a previously published breast cancer sequencing study. A total of 164 female IDC patients with confirmed PIK3CA mutations and documented PR status were included. Relevant genomic and demographic parameters - TMB, mutation count, and age - were extracted and analyzed. Statistical analyses included correlation, intergroup comparisons by PR status, and binary logistic regression. Predictive performance was assessed using area under the receiver operating characteristic (AUROC) curves.

RESULTS: Patients with PR-negative status exhibited significantly higher TMB and mutation count than PR-positive patients (p-value<0.001 for both). TMB and mutation count were positively correlated (r=0.61, p-value<0.001), indicating overlapping representation of genomic instability. Logistic regression showed that mutation count was a significant predictor of PR status (p-value=0.01). Mutation count demonstrated a slightly superior predictive performance (AUROC=0.738) compared to TMB (AUROC=0.737).

CONCLUSION: Total mutation count shows strong potential as a surrogate biomarker for TMB and a predictive marker for PR status in PIK3CA-mutated IDC, offering a cost-effective genomic tool in personalized breast cancer stratification.}, } @article {pmid41421880, year = {2026}, author = {Xu, W and An, Y}, title = {Author Response to "Letter to Editor: Deep Learning-Based Differentiation of DCIS and IDC from Mammographic Microcalcifications".}, journal = {Academic radiology}, volume = {33}, number = {3}, pages = {921}, doi = {10.1016/j.acra.2025.12.001}, pmid = {41421880}, issn = {1878-4046}, } @article {pmid41416307, year = {2025}, author = {Abdelgelil, M and Alshangiti, A and Taha, W and Soliman, O and Aldandan, R and Alabbas, A and Abbas, H and Azam, F}, title = {Understanding the Rare Breast Cancer Subtypes With Variations in Histopathology, Molecular Profiling, Clinical Outcomes and Therapeutic Approaches.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e96952}, pmid = {41416307}, issn = {2168-8184}, abstract = {Background Breast cancer is a heterogeneous disease with significant variation in clinical behaviour, pathological morphology and molecular patterns. While most of the breast cancer cases follow common histological and clinical patterns, but a few rare subtypes behave differently with a difference in prognosis and response to therapy. Recognizing these subtypes of breast cancer is important for accurate diagnosis and treatment planning. Aims and objectives This study aimed to evaluate the clinical features, pathological criteria, and outcomes of patients with these rare breast cancer subtypes treated at King Fahad Specialist Hospital (KFSH-D), a biggest regional tertiary care center. Patients and methods This is a retrospective, observational, descriptive study analyzing 30 patients diagnosed with rare breast cancer subtypes and treated at KFSH-D between January 2019 and December 2024. Results We included 30 patients with rare pathological breast cancer subtypes. Among them, eight patients (27%) had apocrine carcinoma. The mean age at diagnosis for this group was between 55 and 60 years and a mean tumor size was greater than 2 cm. Additionally, 14 (46%) patients had metaplastic carcinoma, with a mean age at diagnosis of 45-60 years and tumor sizes ranging between 3 and 5 cm. Five (17%) patients were diagnosed with mucinous adenocarcinoma. Their mean age at diagnosis was 70 years, with tumors larger than 2 cm. All of these patients had stage N0-N1 disease and were positive for estrogen receptor (ER), progesterone receptor (PR), and negative for Her-2/neu on immunohistochemistry (IHC). One (3%) patient had lymphoepithelioma-like carcinoma. She was diagnosed at 51 years of age, with a tumor size of 2.2x3.2 cm. She underwent simple mastectomy and sentinel lymph node biopsy (SLNB). The tumor was histologic grade III with no lymphovascular invasion or intraductal component. We also identified two (7%) patients with invasive ductal carcinoma (IDC) showing neuroendocrine differentiation. Both were positive for chromogranin A and synaptophysin on IHC. Their ages at diagnosis were 55-65 years, and tumor sizes ranged from 4 to 6 cm. These tumors were histologic grade III, hormone receptor-positive, and Her-2/neu negative. Survival outcomes varied across groups, with mucinous carcinoma showing the most favorable prognosis. Conclusion Rare subtypes of invasive breast cancers have distinct clinical and pathological behaviours with different outcomes. Recognition of these tumors will help in patient-tailored treatment strategies and will contribute to better patient management.}, } @article {pmid41415796, year = {2025}, author = {Sivacoumarane, S and Krishnamoorthy, A and Augustine, P and Dinesh, D}, title = {Neoplasm within Neoplasm-A Rare Case of Breast Carcinoma with Isolated Metastasis to a Uterine Leiomyoma.}, journal = {Indian journal of surgical oncology}, volume = {16}, number = {6}, pages = {1766-1768}, pmid = {41415796}, issn = {0975-7651}, abstract = {The most common sites of metastasis from breast cancer are the bone, lungs, and liver. Metastasis to uterine leiomyomas from breast cancer is extremely rare, and here we present such a case. A 46-year-old premenopausal lady presented with a left breast lump, diagnosed as cT4bN2M0 invasive ductal carcinoma. Imaging revealed a large asymptomatic subserosal uterine fibroid with no signs of metastasis elsewhere. She received neoadjuvant chemotherapy and underwent modified radical mastectomy with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histopathology showed metastatic breast carcinoma within the leiomyoma, confirmed by GATA3 positivity and morphological similarity to the breast tumor. The ovaries, fallopian tubes, and cervix were free of disease. This case underscores the importance of thorough histopathological evaluation of surgical specimens, even without preoperative suspicion of metastasis.}, } @article {pmid41415782, year = {2025}, author = {Delshad, B and Abdolahad, M and Aghasi, M and Hosseinpour, P and Kohan, FZ and Akbari, ME}, title = {Evaluation of the Concordance of Cancer Diagnostic Probe Findings During Surgery and Suspected Distortion in Pre-surgical Mammography Based on Pathology.}, journal = {Indian journal of surgical oncology}, volume = {16}, number = {6}, pages = {1748-1754}, pmid = {41415782}, issn = {0975-7651}, abstract = {Cancer diagnostic probe stations (CDP) are expensive, and they are better used in patients with suspicious findings in initial mammography. For the first time, this study investigated the compatibility of suspicious findings observed in mammograms of patients before surgery with CDP findings based on pathology findings as the gold standard. This prospective study was conducted on 26 patients with breast cancer candidates for conservative surgery with suspicious findings in the initial mammography, who were referred to our institute between April 2024 and September 2024. Ultrasound and mammography findings before surgery, frozen findings, CDP during surgery, and pathology results of patients were collected using a checklist. A breast fellowship and a radiologist, with the guidance of the positions and hourly codes of the Quadrants of Breasts, classified the position of suspicious findings in CDP and mammography. The concordance rate between the two methods was evaluated with the Kappa coefficient. Based on mammography findings, 9 (36.4%) suspicious findings were observed in the lateral, 8 (30.8%) in the medial, and 5 (19.2%) in the interior of the breast. These results were confirmed in the CDP findings. Based on the pathology findings, 7 cases of lesions were of invasive type (4 IDC and 3 ILC), while the frozen results were free in all cases. The degree of concordance and correlation between mammography and CDP findings was 96.2%. Mammography findings were almost completely consistent with intraoperative CDP findings. Suppose there are suspicious findings in the mammography of patients who are candidates for conservative breast surgery. In that case, CDP can be used intraoperatively for these slight distortions of the surrounding tumor tissue to reduce recurrence and cost and increase patient survival.}, } @article {pmid41415763, year = {2025}, author = {Grewal, P and Kadayaprath, G and Sobti, P}, title = {A Rare Case Report-an Early-Stage Invasive Lobular Carcinoma with Her 2 Neu Positivity.}, journal = {Indian journal of surgical oncology}, volume = {16}, number = {6}, pages = {1362-1363}, pmid = {41415763}, issn = {0975-7651}, abstract = {Invasive lobular breast cancer is a rare and special subtype of breast cancer which has a different clinical behaviour and is morphologically different from other subtypes. However, it is not any different in terms of outcome as compared to invasive ductal carcinoma. It accounts for 5-15% of the invasive breast cancers (Li et al. in Br J Cancer 93:1046-1052, 2005). Her 2 Neu positivity in invasive lobular cancers (ILCs) is even rarer and has been linked to adverse outcomes, although limited literature is available. Management of ILCs with Her 2 Neu positivity is according to standard multimodality breast cancer management guidelines. Here, we report a case report of an early-stage invasive lobular breast cancer with hormone receptor and Her 2 Neu positivity.}, } @article {pmid41415758, year = {2025}, author = {Roy-Chowdhury, A and Swain, SS and Biswas, G and Kar, D and Mohanty, SK and Banerjee, B}, title = {Landscape and Immuno-Molecular Phenotyping of 301 Eastern Indian Breast Carcinoma Cases- A Comparative Assessment of TNBC Incidence.}, journal = {Indian journal of surgical oncology}, volume = {16}, number = {6}, pages = {1780-1787}, pmid = {41415758}, issn = {0975-7651}, abstract = {UNLABELLED: In the 2022-2024 Globocan data, India alone contributed 15.5% (1.4 million) of the staggering 23.8% of breast carcinoma (BC) cases globally and in the lot 0.85 million people succumbed to the disease. BC remains a complex and multifaceted disease that poses a significant threat and is a public health concern. Region-specific molecular subtyping is required with the updating trends of the disease. The study was conducted retrospectively at the Central Reference Laboratory, inDNA Life Sciences, Bhubaneswar, Odisha, from January 2021 to December 2023. A total of 301 BC patients were recruited in the study from multiple institutions in a consecutive manner across West-Bengal and Odisha. Statistical analysis was performed using GraphPad Prism (version 8.3.0) software. The study included 294 (97.6%) women and 7 (2.3%) men. Invasive ductal carcinoma (IDC) was the most common histopathologic type observed in 90.2% (n = 267) of patients. Majority of them were diagnosed in the 4th to 6th decade of their life (n = 173; 58.45%) with a mean age of 50.8 years. ER + expression was detected in 104 (35.1%) and PR + in 87 (29.4%) cases. HER-2/neu overexpression was observed in 89 (30.1%) cases. A striking 39.8% (n = 118) triple-negative or basal-like status was noted in the cohort. Immunohistochemistry-based classification remains the gold-standard method for sub-typing of BC. The study highlights alarming numbers of TNBC cases and is the most prevalent sub-group in the 40-60 years age-group of eastern-Indian BC cases in comparison with region-specific incidence. Additionally, concurrent use of HER2/neu FISH on equivocal cases revealed a HER2/neu positivity conversion rate of 28%. Apart from studying the routine histo-molecular attributes, BRCA-based genetic screening needs to be brought into the mainstream testing for all clinically diagnosed BC cases.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13193-025-02282-z.}, } @article {pmid41415643, year = {2025}, author = {Park, SH and Yun, KW and Yoon, GY and Cho, Y and Kim, S}, title = {Effectiveness of Transcatheter Arterial Embolization in Locally Advanced Triple-Negative Breast Cancer Resistant to Neoadjuvant Chemotherapy: A Case Report.}, journal = {Journal of the Korean Society of Radiology}, volume = {86}, number = {6}, pages = {1072-1078}, pmid = {41415643}, issn = {2951-0805}, abstract = {A 74-year-old woman was diagnosed with locally advanced invasive ductal carcinoma of the right breast, which was confirmed as triple-negative breast cancer (TNBC) by immunohisto-chemical analysis. Multiple ipsilateral axillary lymph node metastases were identified, but no distant metastases were detected. The patient underwent neoadjuvant chemotherapy, which was ineffective, and subsequently developed tumor-related wound bleeding. To control the bleeding and reduce tumor vascularity, transcatheter arterial embolization (TAE) was performed. Permanent embolization using Embosphere microspheres and glue induced in complete ischemia, leading to a significant reduction in tumor and lymph node size, thereby enabling surgical resection. A follow-up examination one year later revealed no evidence of recurrence or metastasis. This case report highlights the potential therapeutic efficacy of TAE in the management of locally advanced TNBC resistant to neoadjuvant chemotherapy.}, } @article {pmid41412445, year = {2025}, author = {Collins, K and Gupta, S and Cheng, L}, title = {Updates in bladder and prostate pathology: Diagnostic consensus and clinical relevance.}, journal = {Human pathology}, volume = {}, number = {}, pages = {106018}, doi = {10.1016/j.humpath.2025.106018}, pmid = {41412445}, issn = {1532-8392}, abstract = {Accurate grading, staging, and classification are essential components of bladder and prostate cancer pathology, directly influencing clinical management and patient outcomes. Recent initiatives by the International Society of Urological Pathology (ISUP) and the Genitourinary Pathology Society (GUPS) have produced key consensus updates aimed at refining diagnostic criteria and resolving long-standing controversies. This review highlights high-impact developments in bladder and prostate pathology, including updated grading systems and T1 substaging in bladder tumors, the proposed hybrid grading approach, and the classification of urachal carcinoma. Evolving perspectives in prostate pathology are also discussed, encompassing intraductal carcinoma of the prostate (IDC-P), neuroendocrine and aggressive variant tumors, and the clinical relevance of Grade Group 1 (GG1) disease in the context of active surveillance. Recent literature and consensus statements are summarized with attention to diagnostic challenges and practical implementation. These focused updates highlight the dynamic nature of urologic pathology and reflect a broader movement toward greater diagnostic precision, reproducibility, and clinical relevance, with adoption of ISUP and GUPS frameworks essential for improving patient outcomes.}, } @article {pmid41409392, year = {2025}, author = {Ramezanpour, S and Vulasala, SSR and Sharma, S and Sharma, S}, title = {An unusual case of breast cancer masked by hidradenitis suppurativa.}, journal = {Journal of clinical imaging science}, volume = {15}, number = {}, pages = {44}, pmid = {41409392}, issn = {2156-7514}, abstract = {We report a rare case of a 28-year-old African-American woman with chronic hidradenitis suppurativa (HS), in whom breast masses were initially misattributed to HS-related inflammation, delaying diagnosis of breast cancer. She presented with back pain and diagnostic work-up revealed thoracic vertebral metastasis. Dedicated breast imaging showed suspicious breast masses and biopsy confirmed invasive ductal carcinoma. This case highlights the importance of breast imaging when inflammatory skin conditions of the breast fail to respond to standard treatment.}, } @article {pmid41403731, year = {2025}, author = {Abou-El-Naga, AM and El Saied, AM and Akl, MM and Abd El-Aziz, SA}, title = {Pathological and Molecular Significance of HER2/neu Overexpression in Familial Breast Cancer Among Egyptian Women: A Comprehensive Study on Diagnostic and Prognostic Implications.}, journal = {Advanced pharmaceutical bulletin}, volume = {15}, number = {3}, pages = {637-645}, pmid = {41403731}, issn = {2228-5881}, abstract = {PURPOSE: Breast cancer remains the most prevalent malignancy among women worldwide, with a strikingly high incidence in Egypt, particularly in familial cases. This study aims to comprehensively elucidate the pathological and molecular significance of ERBB2 (HER2/neu) overexpression in Egyptian familial breast cancer, highlighting its role in tumor aggressiveness, immune evasion, and precision oncology.

METHODS: We enrolled 44 Egyptian breast cancer patients along with 35 daughters and 24 sisters (2013-2015, Mansoura University Hospital). Comprehensive analyses included serum biochemical assays, histopathological evaluation, immunohistochemical staining for ERBB2, and molecular detection of ERBB2 amplification using first-round and nested PCR. Associations with clinical, hormonal, and metabolic variables were also explored.

RESULTS: Serum biochemical profiling revealed significantly elevated ALT (6.6±0.55 U/mL), LDH (16.8±1.4 U/mL), and CA15 3 (160±13.33 U/mL), with reduced AST (2.6±0.22 U/mL) compared to controls (P≤0.05). Histopathology confirmed invasive ductal carcinoma with dense stromal desmoplasia. Immunohistochemistry demonstrated ERBB2 overexpression in>10% of tumor cells. Nested PCR detected ERBB2 amplification in 72% of patients, and in daughters (17%) and sisters (20%). Notably, higher ERBB2 expression was observed in unmarried patients (100%), pre-menopausal women (73-72%), and those with diabetes or hypertension, suggesting hormonal and metabolic modulation via PI3K/AKT/mTOR and MAPK/ERK pathways. ERBB2 mutations were identified in 14% of patients, 2.1% of daughters, and 1.2% of sisters. Furthermore, ERBB2 may upregulate PD-L1, contributing to immune evasion.

CONCLUSION: Our findings highlight ERBB2 as a pivotal diagnostic and prognostic biomarker in Egyptian familial breast cancer and support integrating HER2-targeted therapies with immune checkpoint inhibitors and metabolic interventions. This approach could transform outcomes in high-risk familial cohorts. The study emphasizes the importance of genetic screening and precision medicine strategies that consider molecular, hormonal, and metabolic contexts in breast cancer care.}, } @article {pmid41398591, year = {2025}, author = {Roy, P and Aggarwal, Y and Kochar, SK and Kochar, DK and Das, A}, title = {Integrative transcriptomic and machine learning approaches to decipher mitochondrial gene regulation in severe Plasmodium vivax malaria.}, journal = {Malaria journal}, volume = {25}, number = {1}, pages = {47}, pmid = {41398591}, issn = {1475-2875}, support = {PID: 2019-1121//Indian Council of Medical Research (ICMR)/ ; }, mesh = {*Machine Learning ; *Plasmodium vivax/genetics ; *Malaria, Vivax/parasitology ; Humans ; *Transcriptome ; Gene Expression Profiling ; *Gene Expression Regulation ; *Mitochondria/genetics ; *Genes, Mitochondrial ; }, abstract = {Mitochondria in Plasmodium vivax are functionally vital despite possessing a highly reduced genome and differing substantially from the human organelle. Beyond their classical role in energy production, they dynamically coordinate processes like pyrimidine biosynthesis and heme metabolism, adapting their functions across the intra-erythrocytic development cycle (IDC). Their unique architecture and stage-specific roles enable the parasite to fine-tune mitochondrial gene expression, involving both protein-coding sense transcripts and long non-coding natural antisense transcripts (NATs). This study unveils an unprecedented regulatory complexity by integrating transcriptomic profiling with advanced machine learning to decode the role of mitochondrial sense and natural antisense transcripts (NATs) in severe P. vivax malaria. We reveal distinct, clinically relevant expression signatures, where NATs emerge not as transcriptional by-products but as potent regulators tightly linked to mitochondrial pathways and translational machinery. This dual-layered transcriptomic landscape reflects an intricate molecular strategy by which the parasite fine-tunes mitochondrial function to survive under severe disease conditions. Importantly, while these findings illuminate novel regulatory mechanisms and position mitochondrial NATs as promising targets for antimalarial drug development, they represent preliminary insights derived from a limited clinical cohort and should not be interpreted as definitive clinical indicators. Validation in larger and diverse patient populations is essential to confirm their broader biological and clinical relevance. However, these results serve as indicators for potential innovative therapeutic interventions aimed at disrupting parasite bioenergetics and regulatory networks.}, } @article {pmid41391258, year = {2026}, author = {Li, Y and Leberzammer, J and Blanchet, X and Duan, R and Lacy, M and Triantafyllidou, V and Eckardt, V and Briem, E and Jung, AS and Su, R and Guerra, J and Jansen, Y and Hristov, M and Enard, W and Bernhagen, J and Weber, C and Atzler, D and Bartelt, A and Döring, Y and Santovito, D and Kaltner, H and Ludwig, AK and von Hundelshausen, P}, title = {Galectin-1 induces macrophage immunometabolic reprogramming, modulates T cell immunity and attenuates atherosclerotic plaque formation.}, journal = {Atherosclerosis}, volume = {413}, number = {}, pages = {120608}, doi = {10.1016/j.atherosclerosis.2025.120608}, pmid = {41391258}, issn = {1879-1484}, mesh = {*Galectin 1/pharmacology/metabolism ; *Plaque, Atherosclerotic ; Animals ; Humans ; *Atherosclerosis/immunology/metabolism/pathology/prevention & control/genetics ; *T-Lymphocytes/immunology/metabolism/drug effects ; *Macrophages/metabolism/immunology/drug effects ; Disease Models, Animal ; Mice, Knockout, ApoE ; Mice, Inbred C57BL ; Mice ; Foam Cells/metabolism/immunology/drug effects ; Interleukin-10/metabolism ; Male ; Cells, Cultured ; Energy Metabolism/drug effects ; Cell Differentiation ; Phenotype ; }, abstract = {BACKGROUND AND AIMS: Atherosclerosis is a chronic immunometabolic disease driven by lipid accumulation and immune cell infiltration. Macrophages and T cells play key roles throughout plaque development. Galectin-1 (Gal-1), a glycan-binding protein, modulates immune functions in these cells and has been reported to attenuate atherosclerosis, though its mechanisms remain incompletely understood. Here, we investigated the effects of Gal-1 on macrophages and T cells during plaque formation.

METHODS: Effects of Gal-1 on atherosclerosis, macrophages and T cells during lesion formation were studied in Apoe[-/-] mice treated with recombinant Gal-1. Complementary mouse peritoneal foam cell and in vitro macrophage and T cell culture experiments were performed to study T cell differentiation, macrophage function, polarization and energy metabolism. The impact of Gal-1 on human macrophages was further evaluated in endarterectomy specimens.

RESULTS: Gal-1 treatment reduced lesion size and increased circulating IL-10 levels, inversely correlating with plaque burden. Unexpectedly, IL-10 neutralization also mitigated atherosclerosis, indicating that its action is at least partially IL-10-independent. In plaques, Gal-1 promoted anti-inflammatory macrophage phenotypes, mirrored by a quiescent metabolic and anti-inflammatory profile in foamy macrophages ex vivo. The use of the Gal-1[E71Q] variant revealed that these effects were only partly dependent on glycan binding. Beyond IL-10, Gal-1 reshaped cytokine profiles by increasing IL-17, IL-22, and IL-23, consistent with a macrophage-driven regulatory Th17 response, alongside higher frequencies of IL-10-producing and regulatory T cells.

CONCLUSION: Gal-1 protects against atherosclerosis associated with reprogramming macrophages and tuning T cell immunity through glycan-dependent and -independent pathways.}, } @article {pmid41385917, year = {2026}, author = {Smyth, NM and Zaborowski, AM and Bolarinwa, BV and Hembrecht, S and Culhane, RJ and Narsiman, A and Canavan, CT and Sørensen, J and Downey, E and Allen, M and Butt, A and Power, C and McArdle, O and Morris, PG and Healy, N and McKenna, L and Hill, ADK}, title = {Do Not Rush to Omit Sentinel Lymph Node Biopsy for Early Breast Cancer Patients.}, journal = {Clinical breast cancer}, volume = {26}, number = {1}, pages = {58-63}, doi = {10.1016/j.clbc.2025.11.006}, pmid = {41385917}, issn = {1938-0666}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/therapy/surgery ; *Sentinel Lymph Node Biopsy/statistics & numerical data ; Middle Aged ; Aged ; Retrospective Studies ; Adult ; Aged, 80 and over ; Axilla ; Mastectomy, Segmental/statistics & numerical data ; Lymphatic Metastasis ; Neoplasm Staging ; *Carcinoma, Ductal, Breast/pathology/therapy ; Ireland ; }, abstract = {INTRODUCTION: Recent data suggest that sentinel lymph node biopsy (SLNB) can be omitted in select patients with early breast cancer. The aim of this study was to determine the utility of SLNB for patients with early breast cancer.

METHODS: A retrospective analysis of patients diagnosed with breast cancer in a Level IV hospital in Dublin, Ireland, between December 2013 and March 2024 was conducted. Inclusion criteria included: female patients ≥ 18 years, with cT1 disease and a negative preoperative axillary ultrasound, who underwent breast conserving surgery and a SLNB.

RESULTS: In total, 334 patients were included. The median age was 59 years (26-91 years). The majority had invasive ductal carcinoma (261 patients, 78.1%) and were hormone receptor-postive and human epidermal growth factor receptor 2-negative (274 patients, 82%). Final N stage was N0 in 282 (84%) of patients. Fifty-two patients (16%) had a positive-SLNB, despite a negative preoperative axilla. Twenty-four patients underwent an axillary clearance, of which 7 (14%) were positive, with only 3 patients (12.5%) upstaged following axillary clearance. Eighty-four patients (25%) received chemotherapy due to positive-SLNB. In line with contemporary data, 9 patients (2.7%) were eligible for CDK4/6 inhibitors, 48 patients (14%) for escalation to nodal radiation, or 275 patients (82%) for de-escalation to partial breast radiation.

CONCLUSION: While SLNB may be safely omitted in specific contexts, its omission carries the risk of under- and over-treatment. Our findings demonstrate that SLNB continues to guide adjuvant therapy for breast cancer patients, and thus, support the ongoing use of SLNB.}, } @article {pmid41383507, year = {2025}, author = {Vuppumalla, B and Ravichandran, A and Manickavasagam, M and Javvaji, CK and Vagha, K}, title = {Dual malignancies: a case report of the sequential occurrence of a trichilemmal tumor and breast carcinoma in a 56-year-old female.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1590725}, pmid = {41383507}, issn = {2234-943X}, abstract = {The authors present a rare case of the sequential occurrence of a malignant trichilemmal tumor (MPTT) and invasive ductal carcinoma of the breast in a 56-year-old woman. The patient initially presented with a palpable breast lump and a longstanding asymptomatic scalp swelling that had been present since childhood. Histopathological evaluation confirmed the breast lump as invasive ductal carcinoma, while the scalp swelling, initially suspected to be a benign cyst, was diagnosed as an MPTT. The patient underwent combination chemotherapy, which resulted in a favorable response of the breast carcinoma; however, the MPTT exhibited a discordant therapeutic outcome. Trichilemmal carcinoma is an uncommon cutaneous neoplasm, and its coexistence with breast carcinoma represents an exceedingly rare clinical scenario. Furthermore, the differential response of these malignancies to chemotherapy presents a significant therapeutic challenge. This case underscores the importance of accurate diagnosis, individualized treatment strategies, and a multidisciplinary approach for optimally managing such complex oncological presentations.}, } @article {pmid41381594, year = {2025}, author = {Makris, K and Fonda, V and Ramadhani, FF and Fadel, L and Davezac, M and Payet, B and Deligiannis, IK and Zhang, L and Horn, T and Heimerl, L and Jouffe, C and Heddes, M and Martinez-Jimenez, CP and Quagliarini, F and Uhlenhaut, NH}, title = {Hepatic metabolic reprogramming in male mice during short-term caloric restriction involves enhanced glucocorticoid rhythms.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {11106}, pmid = {41381594}, issn = {2041-1723}, support = {490946138//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 314061271//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 213249687//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; ERCCoG GRACE 101086997//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; }, mesh = {Animals ; *Caloric Restriction ; Male ; Receptors, Glucocorticoid/metabolism/genetics ; *Liver/metabolism ; *Glucocorticoids/metabolism ; Mice ; *Circadian Rhythm/physiology ; Mice, Inbred C57BL ; Signal Transduction ; Hepatocytes/metabolism ; Forkhead Box Protein O1/metabolism ; Mice, Knockout ; Metabolic Reprogramming ; }, abstract = {Caloric restriction prolongs lifespan and preserves health across species, with feeding times synchronized to day-night cycles further maximizing benefits. However, the mechanisms linking diet, diurnal rhythms, and lifespan remain unclear. In mice, the time point most strongly tied to dietary effects on lifespan coincides with the peak of glucocorticoid secretion (ZT12, lights-off). Caloric restriction raises circulating glucocorticoid hormone levels, implicating these signals as candidate mediators for its benefits. Here we show that in the liver, the glucocorticoid receptor (GR) is required for the metabolic response to caloric restriction. Hepatocyte-specific GR mutant males fail to mount this response, indicating that increased glucocorticoid amplitude is necessary for the adaptation. Using multiomics, we find that nutrient deprivation elicits a nuclear switch from active STAT signaling to increased FOXO1 activity, enabling GR to activate diet-specific gene expression programs. Our results suggest that glucocorticoid rhythms are crucial for caloric restriction-induced metabolic reprogramming.}, } @article {pmid41380603, year = {2026}, author = {Fabro, E and Silva, R and Cefarelli, AO and Mattera Coy, B and Montoya, N and Paparazzo, FE and Giberto, D and Almandoz, GO}, title = {Composition, distribution and toxicity of spring phytoplankton community in the San Jorge Gulf - Argentine Patagonia.}, journal = {Marine environmental research}, volume = {214}, number = {}, pages = {107721}, doi = {10.1016/j.marenvres.2025.107721}, pmid = {41380603}, issn = {1879-0291}, mesh = {*Phytoplankton/physiology/classification/growth & development ; *Environmental Monitoring ; Seasons ; Atlantic Ocean ; *Marine Toxins/analysis ; Argentina ; Biomass ; Seawater/chemistry ; }, abstract = {San Jorge Gulf (SJG) is one of the most productive regions in the southwestern Atlantic Ocean, supporting a diverse community and key commercial species for fisheries. However, phytoplankton composition and dynamics in the area remain poorly studied, and most previous works have focused only on toxigenic phytoplankton. This study provides the first comprehensive assessment of the entire phytoplankton community (0.2-200 μm) in the SJG, northern waters (NW), and adjacent shelf waters (AW), as well as its relation to hydrographic conditions during two spring seasons. Furthermore, the occurrence of toxigenic species and the accumulation of toxins in benthic organisms are addressed. High biomass concentrations were observed in the SJG during both springs, with peaks of 706 μgC L[-1] in 2016 and 487 μgC L[-1] in 2017, associated with the North thermal Front System (NFS). Distinct hydrographic conditions were recorded in the two years, mainly reflecting differences in sampling time and in the penetration of the Patagonian Current (PC) into the gulf, which indicated different stages of the spring bloom. Microplanktonic diatoms such as Corethron pennatum, Leptocylindrus danicus, and Thalassiosira spp., dominated most sampling stations during both springs, particularly in the SJG, whereas nanoplanktonic chain-forming diatoms and dinoflagellates contributed substantially to total biomass in the NW and AW. The dinoflagellate Alexandrium catenella was the most abundant toxigenic species, associated with the detection of paralytic shellfish toxins (PSTs) in plankton samples as well as in several benthic organisms.}, } @article {pmid41377877, year = {2025}, author = {Gu, C and He, Y and Lin, J and Wang, Z and Guo, S and Yang, H and Wang, W and Sun, J and Gan, H and Li, H}, title = {Preoperative prediction of axillary lymph node metastasis in breast invasive ductal carcinoma patients using a deep learning model based on dynamic contrast-enhanced magnetic resonance imaging: a multicenter study.}, journal = {Gland surgery}, volume = {14}, number = {11}, pages = {2288-2301}, pmid = {41377877}, issn = {2227-684X}, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is the most common histological subtype of breast cancer, and axillary lymph node metastasis (ALNM) is a pivotal factor in clinical staging, prognostic assessment, and treatment planning. This study aims to develop and validate a deep learning (DL) model based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the prediction of ALNM in IDC patients.

METHODS: This multicenter study conducted a retrospective analysis of DCE-MRI images from 520 patients diagnosed with IDC of the breast. The training and internal validation sets consisted of 411 patients from The First Hospital of Qinhuangdao, while the external testing set included 109 patients from the Maternal and Child Health Hospital of Qinhuangdao. Radiomics and DL features were extracted separately from the DCE-MRI images. We evaluated five models (Clinical, Radiomics, Radiomics-Clinical, DL, DL-Clinical) using radiomics features, DL features, and clinical features. Finally, the predictive performance of the models was evaluated using the receiver operating characteristic (ROC) curve and the area under the curve (AUC).

RESULTS: The AUCs for the Clinical model and Radiomics model, which are machine learning models, and the DL-model, were 0.807, 0.840, and 0.865, respectively. The combined models incorporating clinical features, namely the Radiomics-Clinical and DL-Clinical models, achieved AUCs of 0.824 and 0.935, respectively. Among the five models, the DL-Clinical model demonstrated a significant advantage in predicting ALNM. Additionally, this model exhibited robust performance in both internal validation and external testing sets, with AUCs of 0.946 and 0.951, respectively.

CONCLUSIONS: The DCE-MRI-based DL-Clinical model provides a non-invasive adjunct tool for preoperative identification of ALNM in patients with breast IDC, thereby enhancing the efficacy of personalized treatment strategies and improving patient quality of life.}, } @article {pmid41377359, year = {2025}, author = {Jehangir, AM and Mehmood, N and Khan, MS and Abrar, Z and Riaz, AA and Antar, M and Khan, A}, title = {Concurrent malignant phyllodes tumor and invasive ductal carcinoma in a young female: a rare case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {87}, number = {12}, pages = {8903-8908}, pmid = {41377359}, issn = {2049-0801}, abstract = {INTRODUCTION: Phyllodes tumors are rare fibroepithelial breast neoplasms, typically affecting middle-aged women. Malignant phyllodes tumors (MPTs) account for a minority of these cases and are extremely uncommon in adolescents. The synchronous presentation of MPT with contralateral invasive ductal carcinoma (IDC) is exceptionally rare and presents unique diagnostic and therapeutic challenges.

CASE PRESENTATION: We report the case of a 19-year-old female who presented with a rapidly enlarging mass in the left breast, initially misdiagnosed as an abscess. On physical examination, a distinct right breast mass and bilateral axillary lymphadenopathy were also noted. Imaging and biopsy revealed an MPT in the left breast. Histopathology confirmed IDC in the right breast and metastatic adenocarcinoma in both axillae. Immunohistochemistry revealed high proliferative activity in the IDC. The patient underwent left mastectomy and was started on systemic chemotherapy, with a favorable initial response.

CLINICAL DISCUSSION: This case underscores the importance of considering rare malignancies in adolescents with atypical breast presentations and highlights the diagnostic limitations of imaging alone. The concurrent diagnosis of two distinct breast cancers in a young patient raises concern for a possible underlying genetic predisposition and supports the need for a multidisciplinary approach to management.

CONCLUSION: The simultaneous occurrence of MPT and IDC in adolescents is extraordinarily rare. Early histopathological assessment, comprehensive bilateral evaluation, and coordinated oncologic care are essential for optimal management in such complex cases.}, } @article {pmid41374465, year = {2025}, author = {Aydin, H and Bozkurt, C and Hayme, S and Bilge, AC and Oztekin, PS and Avdan Aslan, A and Ozcan, I and Gultekin, S and Eren, A and Durur Subası, I}, title = {Segmental Non-Mass Enhancement Features in Breast Magnetic Resonance Imaging: A Multicenter Retrospective Study of Histopathologic Correlations.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {23}, pages = {}, pmid = {41374465}, issn = {2075-4418}, abstract = {Background/Objectives: Segmental non-mass enhancement (NME) is the breast MRI distribution pattern with the highest positive predictive value (PPV) for malignancy. Despite its diagnostic relevance, its imaging characteristics have rarely been examined in isolation, leaving uncertainty in clinical practice. This multicenter retrospective cohort study aimed to evaluate multiparametric MRI features-including internal enhancement pattern, dynamic contrast-enhanced (DCE) kinetics, and diffusion restriction-in segmental NME to identify malignancy predictors. Methods: This retrospective cohort review included 14,834 breast MRI reports from five institutions (September 2017-February 2024), identifying 103 women (mean age, 44.4 ± 9.9 years) with segmental NME (70 malignant, 33 benign). MRI was performed at 1.5 T or 3 T using standardized protocols. Two breast radiologists, blinded to pathology, assessed internal enhancement, DCE kinetics, diffusion restriction, and short tau inversion recovery (STIR) features according to BI-RADS. Statistical analyses included chi-square/Fisher's tests and logistic regression. Results: Clustered ring enhancement (CRE) was significantly associated with malignancy (p = 0.004). Fast initial-phase enhancement (p < 0.001) and delayed-phase washout (p = 0.011) also correlated with malignancy. On multivariate analysis, fast initial-phase enhancement remained an independent predictor (odds ratio [OR] = 5.133, p = 0.031), whereas slow enhancement predicted benignity (OR = 0.194, p = 0.020). Histologies included ductal carcinoma in situ, invasive ductal carcinoma, granulomatous mastitis, and benign hyperplastic lesions. Conclusions: This study, focusing exclusively on segmental NME, identifies CRE, fast initial-phase enhancement, and washout kinetics as reliable imaging biomarkers. Incorporating these features into breast MRI interpretation may improve diagnostic accuracy, risk stratification, and management decisions.}, } @article {pmid41374413, year = {2025}, author = {Giannakaki, AG and Giannakaki, MN and Baroutis, D and Koura, S and Papachatzopoulou, E and Marinopoulos, S and Daskalakis, G and Dimitrakakis, C}, title = {Preoperative Breast MRI and Histopathology in Breast Cancer: Concordance, Challenges and Emerging Role of CEM and mpMRI.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {23}, pages = {}, pmid = {41374413}, issn = {2075-4418}, abstract = {Background: Preoperative breast MRI is widely used in surgical planning because of its high sensitivity. However, discrepancies with histopathology remain common and can affect tumor size assessment and treatment decisions. In addition, recent comparative studies have highlighted the growing role of contrast-enhanced mammography (CEM) and multiparametric MRI (mpMRI), both of which may improve specificity and accessibility compared to conventional MRI. Methods: A structured literature review was conducted in PubMed (2000-2025) according to PRISMA guidelines. Studies included if they evaluated preoperative breast MRI with histopathological correlation and reported sensitivity, specificity, or concordance outcomes. Data extraction focused on study design, patient and tumor characteristics, imaging methods, and clinical impact. Results: MRI demonstrates high sensitivity, particularly in detecting IDC and ILC. However, overestimation of tumor size remains a concern, particularly in ILC and high-grade DCIS, while underestimation is frequently observed after neoadjuvant therapy, especially in Luminal A tumors. Tumor size and stage significantly affect concordance, with advanced-stage tumors (T2-T3) showing better MRI-histopathology concordance than early-stage lesions (T0-T1). Specificity remains limited, particularly in DCIS and multifocal disease. Emerging evidence suggests that contrast-enhanced mammography (CEM) achieves comparable sensitivity with higher specificity, while multiparametric MRI (mpMRI) incorporating diffusion-weighted imaging (DWI) improves lesion characterization and prediction of treatment response. Conclusions: While MRI remains a valuable diagnostic tool for breast cancer, histopathological validation is essential to guide treatment decisions. Future research should focus on AI-enhanced imaging techniques, CEM and multiparametric MRI to improve concordance rates, reduce overdiagnosis and translate imaging advances into meaningful clinical outcomes.}, } @article {pmid41367817, year = {2025}, author = {Zhao, Y and Liu, Y and Zheng, Y and Xu, X and Wang, Y and Zhang, X}, title = {Left ventricular sphericity indexes by gated single photon emission computed tomography myocardial perfusion imaging: potential opportunities and challenges for cardiac remodeling and clinical prognosis-a narrative review.}, journal = {Quantitative imaging in medicine and surgery}, volume = {15}, number = {12}, pages = {12857-12870}, pmid = {41367817}, issn = {2223-4292}, abstract = {BACKGROUND AND OBJECTIVE: Left ventricular (LV) remodeling is a crucial process in cardiac pathophysiology, significantly influencing the progression of heart failure (HF). LV sphericity indexes (LVSI), which include the shape index (SI) and eccentricity index (EI), are derived from gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (G-MPI) and are emerging as essential biomarkers for assessing LV remodeling (LVR). This review aims to summarize the imaging principles of LVSI and explore the pathophysiological insights and clinical applications associated with these indexes.

METHODS: A comprehensive literature search was conducted to identify relevant publications pertaining to LVSI. PubMed was searched for articles published using a combination of keywords, including "left ventricular sphericity index", "shape index", "eccentricity index", "left ventricular remodeling", and "prognosis". Both original studies and review articles were considered. Additionally, the references of retrieved articles were manually screened to identify further relevant publications. The final selection of studies included in this narrative review was based on their relevance to the topic, originality, and contribution to the understanding the clinical value of LVSI.

KEY CONTENT AND FINDINGS: LVSI assessed by routine G-MPI protocol enhances the predictive accuracy of major adverse cardiovascular events (MACEs) and improves the risk stratification for different kind of cardiovascular disease, including ischemia with non-obstructive coronary artery disease (INOCA), suspected or known coronary artery disease (CAD), HF, and idiopathic dilated cardiomyopathy (IDC). The review also highlights the potential role of LVSI in guiding the personalizing treatment strategies, ultimately optimizing the management of patients with cardiovascular disease.

CONCLUSIONS: The integration of LVSI into routine G-MPI enhances the prognostic value without additional radiation or imaging. These indexes provide clinically relevant insights and are recommended for inclusion in the standard reporting to improve the outcome predictions and guide therapeutic decisions in the management of cardiovascular disease. Further investigation is warranted to standardize and optimize their application.}, } @article {pmid41363921, year = {2025}, author = {Panev, SD and Bozinovska, B and Veljanovska, BP and Bunovic, NP and Dimitrovska, MJ}, title = {Radiology Approach to Invasive Breast Lobular Carcinoma - Initial Experience.}, journal = {Prilozi (Makedonska akademija na naukite i umetnostite. Oddelenie za medicinski nauki)}, volume = {46}, number = {3}, pages = {135-142}, doi = {10.2478/prilozi-2025-0031}, pmid = {41363921}, issn = {1857-8985}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology ; *Carcinoma, Lobular/diagnostic imaging/pathology ; Middle Aged ; *Mammography/methods ; *Ultrasonography, Mammary/methods ; Aged ; Neoplasm Invasiveness ; Predictive Value of Tests ; Biopsy, Large-Core Needle ; Retrospective Studies ; }, abstract = {It is well known that invasive lobular carcinoma (ILC) accounts for approximately 5-15 % of invasive breast cancers that remain one of the most common malignancies among women globally. ILC is distinguished from the more common invasive ductal carcinoma (IDC) by characteristics histopathology features. The aim of the study was to emphasize the need of more specified diagnostic imaging approach in order to detect breast ILC, based on our institution experience. We describe a number of 17 female cases (58±7 years) who presented: breast fullness/asymmetry - 11 patients (64.7 %), pain - 2 patients (11.7 %), and the rest 4 patients (23.5 %) were asymptomatic. Diagnostic modalities used in this study were: 2D Mammography, Ultrasound, Digital Breast Tomosynthesis (DBT), and core biopsy in guidance by Ultrasound. On 2D Mammography, visible mass was found in 8 patients (47 %), and architectural distortion was found in 4 patients (23.5 %). On DBT additional 5 patients were examined from the total number of patients, and additional lesions were found such as occult lesions and additional architectural distortion. Using DBT, occult lesion was found in 3 patients (17.6 %) and architectural distortion was found in 2 patients (11.7%). Due to these inconclusive findings, DBT was carried out to improve visualization especially in those with more glandular tissue. The occult lesions were seen in 3 patients, which showed as false negative on 2D, as well as an architectural distortion in 2 patients, additionally seen on DBT. This multimodality approach, including DBT, holds promise for more reliable detection of occult lesions and distortions especially in denser breast, and for better clinical outcomes in patients with ILC, respectively.}, } @article {pmid41360305, year = {2026}, author = {Torki, F and Bendena, WG and Chin-Sang, ID}, title = {IDENTIFICATION of NLP-5 and NLP-6 as potential ligands for the NPR-9 receptor in Caenorhabditis elegans.}, journal = {General and comparative endocrinology}, volume = {376}, number = {}, pages = {114869}, doi = {10.1016/j.ygcen.2025.114869}, pmid = {41360305}, issn = {1095-6840}, mesh = {Animals ; *Caenorhabditis elegans/metabolism/genetics ; *Caenorhabditis elegans Proteins/metabolism/genetics ; *Neuropeptides/metabolism/genetics ; Ligands ; *Receptors, Neuropeptide/metabolism/genetics ; }, abstract = {Neuropeptides in Caenorhabditis elegans regulate physiological and behavioural responses to environmental cues, influencing locomotion, feeding, and fat storage via interactions with G-protein coupled receptors (GPCRs). C. elegans expresses a diverse repertoire of neuropeptides, including FMRFamide-related peptides, neuropeptide-like peptides (NLPs), and insulin-like peptides (INSs). Among these, the galanin/allatostatin-like GPCR, NPR-9, localized in the AIB interneurons, regulates locomotory behaviours (roaming and dwelling) and fat accumulation by inhibiting AIB activity. Recent studies identified NLP-1 as a ligand for NPR-9, modulating behaviour through direct receptor interaction. However, our research explored whether other neuropeptides, specifically NLP-5 and NLP-6 (allatostatin A-type/galanin-like neuropeptides), could also function as NPR-9 ligands, despite evidence suggesting NLP-1 as the primary ligand. In this study, we characterized phenotypes associated with NPR-9 receptor function, including Omega turns, roaming, and fat accumulation. Loss-of-function mutations in nlp-5, nlp-6, and nlp-1 exhibited behavioural phenotypes similar to npr-9 mutants, suggesting that NLP-5 and NLP-6 may act as additional ligands for NPR-9 or affect NPR-9 signalling. Furthermore, double-mutant analyses with candidate ligand genes suppressed phenotypes associated with NPR-9 overexpression, reinforcing the hypothesis that these neuropeptides may regulate NPR-9-mediated signalling.}, } @article {pmid41357819, year = {2025}, author = {Bedeir, A and Rabinowits, G and Adeyelu, T and Oberley, MJ and Evans, MG}, title = {Novel SZT2::MAST2 Fusion Detected in Salivary Duct Carcinoma.}, journal = {Case reports in pathology}, volume = {2025}, number = {}, pages = {3728015}, pmid = {41357819}, issn = {2090-6781}, abstract = {Salivary duct carcinoma (SDC) is an uncommon neoplasm that often develops early regional and distant metastasis. Standard treatment for SDC is wide surgical resection along with lymph node dissection followed by adjuvant radiation therapy. The role of adjuvant chemotherapy is not clear with an overall low survival rate. SDC resembles high-grade invasive ductal carcinoma (IDC) of the breast both histologically and by immunohistochemistry (IHC). Fusions involving microtubule-associated serine/threonine (MAST) kinases have been suggested to play role in a subset of breast cancer, although the exact mechanism remains unclear. In this report, we present a case of SDC harboring a novel exon 1 of SZT2 joined to exon 4 of MAST2 leading to a likely pathogenic SZT2::MAST2 fusion. Given the reported fusions involving the MAST kinases in breast cancer, this finding demonstrates an additional similarity between these two tumor types.}, } @article {pmid41354159, year = {2026}, author = {Wang, Y and Miyamoto, H}, title = {Quantitative assessment of cribriform intraductal carcinoma of the prostate is useful for risk stratification after radical prostatectomy.}, journal = {Human pathology}, volume = {167}, number = {}, pages = {106008}, doi = {10.1016/j.humpath.2025.106008}, pmid = {41354159}, issn = {1532-8392}, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/surgery/mortality ; *Prostatectomy ; Retrospective Studies ; Aged ; Middle Aged ; Risk Assessment ; Neoplasm Grading ; Neoplasm Recurrence, Local ; Risk Factors ; *Carcinoma, Ductal/pathology/surgery ; Treatment Outcome ; Kaplan-Meier Estimate ; *Adenocarcinoma/pathology/surgery ; }, abstract = {It remains uncertain if the extent of intraductal carcinoma of the prostate (IDC) exhibiting cribriform (Crib) morphology impacts on patient outcomes. We retrospectively analyzed long-term oncologic outcomes in 182 consecutive radical prostatectomy patients exhibiting Grade Group 2-4 conventional/acinar prostatic adenocarcinoma, along with Crib-IDC but no Gleason grade 5 patterns. A single Crib-IDC focus in the entire prostatectomy specimen was identified in 46 (25.3 %) cases, while others showed 2 (n = 36; 19.8 %), 3 (n = 27; 14.8 %), 4 (n = 11; 6.0 %), or ≥5 (n = 62; 34.1 %) Crib-IDC foci. The maximum Crib-IDC diameter in each case was ≤1-mm (n = 66; 36.3 %), >1/≤2-mm (n = 90; 49.5 %), >2/≤3-mm (n = 21; 11.5 %), or >3-mm (n = 5; 2.7 %). The summed maximum Crib-IDC diameters were ≤1-mm (n = 38; 20.9 %), >1/≤2-mm (n = 39; 21.4 %), >2/≤3-mm (n = 30; 16.5 %), >3/≤4-mm (n = 17; 9.3 %), >4/≤5-mm (n = 9; 4.9 %), or >5-mm (n = 49; 26.9 %). On univariate analyses, the risks of postoperative biochemical recurrence were significantly higher in cases with 3 (P = 0.022) or ≥3 (P < 0.001) Crib-IDCs (vs. 1-2) or ≥4 Crib-IDCs [P < 0.001 (vs. 1-3); P = 0.032 (vs. 3)]. Similarly, the recurrence risk was significantly higher in Crib-IDC cases with the maximum diameter of >1-mm (vs. ≤1-mm; P = 0.002) or the summed diameter of >3-mm (vs. ≤3-mm; P < 0.001). On multivariable Cox regression analyses, 3 [hazard ratio (HR) 2.742, P = 0.016], ≥3 (HR 3.969, P < 0.001), or ≥4 (HR 4.520, P < 0.001) Crib-IDCs (vs. 1-2) and the summed diameter of >3-mm (HR 3.074, P < 0.001) remained significantly predictive of recurrence. Quantitative assessment of Crib-IDC, particularly its number and cumulative diameter on prostatectomy, may thus enhance the postoperative risk stratification of Grade Group 2-4 prostate cancer.}, } @article {pmid41353478, year = {2025}, author = {Ilomäki, J and Wood, SJ and Tan, GSQ and Kim, SJ and Leung, MTY and Sing, CW and Cheung, CL and Lai, EC and Hsieh, MH and Ma, TT and Lau, WCY and Wong, ICK and Cameron, ID and Bell, JS}, title = {The effectiveness of bisphosphonates vs denosumab in people with dementia or frailty post hip fracture: a multi-database cohort study.}, journal = {Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA}, volume = {}, number = {}, pages = {}, pmid = {41353478}, issn = {1433-2965}, abstract = {UNLABELLED: Brief rationale: The effectiveness of bisphosphonates versus denosumab after hip fracture, especially in people with dementia or frailty, remains unclear.

MAIN RESULT: Bisphosphonates were associated with a higher rate of subsequent fracture and a lower mortality rate in men. There are no differences by dementia or frailty status. Significance of the paper: Sex may influence antiresorptive treatment choice.

PURPOSE: The relative effectiveness of first-line antiresorptive medications post-hip fracture in people with dementia or frailty is not understood. We investigated the risk of a subsequent fracture and death in people prescribed bisphosphonates or denosumab following hip fracture, including in people with dementia and frailty.

METHODS: Parallel population-based cohort studies were conducted in Australia, Hong Kong, Taiwan, and the United Kingdom. People aged ≥ 50 prescribed or dispensed a bisphosphonate or denosumab within 60 days of discharge following their first hip fracture were included. Subgroup analyses were conducted for people with dementia, frailty, women, and men. Outcomes were second hip fracture, any subsequent fracture, and death. Inverse probability of treatment weighted Cox and competing risk models were used to estimate hazard ratios (HR) and subdistribution hazard ratios (sHRs) with 95% confidence intervals (CIs) for outcomes. Results across jurisdictions were combined using meta-analyses.

RESULTS: There were 18,292 bisphosphonate users and 8560 denosumab users. Bisphosphonates versus denosumab were associated with similar rates of second hip fracture (sHR 1.13; 95% CI 0.76-1.69) and mortality (HR 0.99; 95% CI 0.94-1.04), but higher rates of any subsequent fracture (sHR 1.16; 95% CI 1.11-1.21), including in men (sHR1.27; 95% CI 1.15-1.42) but not in women (sHR 1.23; 95% CI 1.00-1.52), or in people with dementia or frailty. Men who used bisphosphonates had lower rates of mortality (HR 0.90; 95% CI 0.81-0.99) than men who used denosumab.

CONCLUSION: Bisphosphonate users had higher rates of subsequent fracture than denosumab users. Mortality rates in men were lower with bisphosphonates than denosumab. There were no significant differences by dementia and frailty status.}, } @article {pmid41333038, year = {2025}, author = {Habbani, SF and Yang, Z and Mohammad, M and Hamid, MM and Alfadil, R and Lawis, DE and Mohammed, SI and Wu, H}, title = {Prevalence and Predictors of Triple-Negative Breast Cancer Among Sudanese Women: A Retrospective Analysis of Newly Diagnosed Cases.}, journal = {International journal of women's health}, volume = {17}, number = {}, pages = {4933-4947}, pmid = {41333038}, issn = {1179-1411}, abstract = {PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and a poor prognosis. Data on TNBC in Sudan are scarce. This study assessed the prevalence and predictors of TNBC and other molecular subtypes (Luminal A, Luminal B, and HER2-enriched) in relation to histopathological patterns, age at diagnosis, and sociodemographic risk factors.

METHODS: A retrospective, single-center study was conducted of 1480 women diagnosed with breast cancer between 2016 and 2021. Histological subtypes included carcinoma in situ (CIS), invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), or medullary carcinoma (MC). Estrogen receptor (ER), progesterone receptor (PR), and HER2 status were determined by immunohistochemistry. Multivariate logistic regression identified predictors of TNBC.

RESULTS: TNBC accounted for 21% (n=307; mean age, 49 years) of all cases. Luminal A tumors represented 49% (n=722; mean age, 55), Luminal B 16% (n=237; mean age, 51), and HER2-enriched 14% (n=214; mean age, 50). TNBC was particularly frequent in MC (77%) compared to IDC (21%), CIS (20%), and ILC (15%). In multivariate analysis, younger age was a significant predictor of TNBC; each additional year of age reduced the odds by approximately 3% (Adjusted Odds Ratio [AOR]=0.97; 95% CI: 0.96-0.99; p<0.001). Histological subtype was also a significant determinant, with MC showing the strongest association with TNBC compared to other diagnoses.

CONCLUSION: TNBC is highly prevalent among Sudanese women, especially those younger than 50 years and those with MC. These findings underscore the importance of early diagnosis and wider access to molecular profiling to guide treatment in low-resource settings.}, } @article {pmid41331937, year = {2025}, author = {Zhang, J and Wang, L and Chen, H and Yan, Y and Ge, G and Wang, K and He, J}, title = {A population-based analysis of a risk stratification system for predicting radiotherapy benefits in invasive breast carcinoma of no special type with medullary pattern.}, journal = {European journal of medical research}, volume = {31}, number = {1}, pages = {34}, pmid = {41331937}, issn = {2047-783X}, mesh = {Humans ; Female ; *Breast Neoplasms/radiotherapy/pathology/mortality ; Middle Aged ; Nomograms ; Risk Assessment/methods ; Aged ; Prognosis ; Adult ; SEER Program ; *Carcinoma, Ductal, Breast/radiotherapy/pathology ; }, abstract = {BACKGROUND: Invasive breast carcinoma of no special type (IBC-NST) with medullary pattern is a rare histological subtype, accounting for 3-5% of breast malignancies. Its distinct clinicopathological features and uncertain benefit from radiotherapy (RT) pose unique therapeutic challenges. Current guidelines extrapolate treatment protocols from invasive ductal carcinoma, yet prognostic heterogeneity and the absence of validated biomarkers underscore the need for precision stratification tools to guide RT decisions.

METHODS: Using data from the SEER database (2010-2018), we conducted univariate and multivariate Cox regression analyses to develop a prognostic stratification model and stratified the whole cohort into different risk groups to determine the optimal candidates to benefit from radiotherapy. The accuracy of the nomogram was evaluated by discrimination and calibration evaluation.

RESULTS: Among 667 eligible patients, 535 were allocated to the training set and 132 to the validation set (8:2 ratio). Five independent prognostic factors were identified: age, T stage, N stage, molecular subtype, and chemotherapy status. These were incorporated into a nomogram predicting 3- and 5-year overall survival (OS). Using an optimal cutoff, patients were stratified into low- and high-risk groups. Radiotherapy significantly improved OS in low-risk patients compared to those not receiving RT (P = 0.017), but not in high-risk patients (P = 0.47). The model demonstrated strong predictive performance, with 3- and 5-year AUC values of 0.777 and 0.775 in the training set, and 0.747 and 0.712 in the validation set. Calibration curves indicated close agreement between predicted and observed outcomes.

CONCLUSION: We developed and validated a prognostic nomogram for IBC-NST with medullary pattern that accurately stratifies patients by risk. Our findings indicate that radiotherapy is associated with a survival benefit primarily in low-risk patients, offering a practical tool to optimize RT personalization and avoid overtreatment in high-risk individuals.}, } @article {pmid41327766, year = {2025}, author = {Alharbi, MO and Eid, TM and Baig, MR and Naqvi, S and Al-Abassi, FA and Al-Bar, OA and Nweke, MC and Kumar, V and Anwar, F}, title = {Prospective Clinical and Biochemical Evaluation of Breast Cancer in Patient Cohorts.}, journal = {Current cancer drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115680096369835250610135029}, pmid = {41327766}, issn = {1873-5576}, abstract = {INTRODUCTION: Breast cancer is one of the most prevalent malignancies in women globally, characterized by diverse histological and molecular subtypes, each with varying clinical outcomes. Understanding these subtypes and their associated risk factors is critical for accurate diagnosis, prognosis, and treatment planning.

METHODOLOGY: The study scrutinized 187 breast cancer (BC) patients from Hail region of Saudi Arabia, focusing on ABO blood group distribution, histological type, cancer subtype, metastases size, age distribution, body mass index (BMI), gestational diabetes mellitus (GDM) status, and biochemical markers, including plasma calcium, magnesium, and HBA1C levels.

RESULTS: Blood group distribution showed O+ (50.27%) as the most common blood type, followed by A+ (14.97%) and B+ (11.2%). Histologically, Invasive Ductal Carcinoma (IDC) accounts for 64.1% (120) cases, while Triple Negative Breast Cancer (TNBC) con-stitutes 17.1% (32) cases. The most common metastatic sites are the lungs (25.1%) and ax-illary lymph nodes (17.6%). HER2-positive breast cancer, seen in 9.1% of cases, can lead to multi-organ metastases in some cases. Age distribution indicated most patients were 46-55 years old (50 cases), while BMI data exhibited the highest frequency in the obese cate-gory (~90 cases), with 12 having GDM and 177 not having GDM. Calcium levels across age groups slightly fell below the typical adult range (2.1-2.6 mmol/L) with an average of around 2.06 mmol/L. Magnesium levels were elevated in patients less than 35 years of age (7.02 mmol/L) and were low in other groups. HbA1C levels in all age groups ranged from 6.44 to 6.67 mg/dL, aligning with prediabetic or diabetic thresholds. Plasma calcium and magnesium levels were elevated in the weight category, showing slight deviations from the normal range. Underweight patients displayed the lowest HbA1C levels with all weight cat-egories exceeding 6.5 mg/dL, indicating diabetes.

CONCLUSION: The results highlight IDC as a predominant BC type, with O+ as the most common blood group among patients. TNBC remains a treatment challenge due to a lack of hormone receptors. Metastases mainly affect the lungs and lymph nodes. Elevated BMI, calcium, and magnesium levels correlate with increased HbA1C, suggesting a diabetic link. Emphasizing personalized treatment, obesity management, and electrolyte monitoring., the present research advocates a holistic approach for improved BC outcomes and suggests fu-ture exploration of metabolic influences.}, } @article {pmid41327199, year = {2025}, author = {Annamalai, K and Dilliker, S and Buchholz, E and Castro-Hernández, R and Panyam, N and Pommeranz, A and Wiederhake, P and Wery von Limont, N and Hempel, N and Ebner, V and Swarnkar, S and Mohamed, BA and Streckfuss-Bömeke, K and Steffens, S and Herzig, S and Ebert, A and Fischer, A and Toischer, K}, title = {Deregulation of m6A-RNA methylation impairs adaptive hypertrophic response and drives maladaptation via mTORC1-S6K1-hyperactivation and autophagy impairment.}, journal = {Cell communication and signaling : CCS}, volume = {23}, number = {1}, pages = {522}, pmid = {41327199}, issn = {1478-811X}, abstract = {BACKGROUND: Pressure overload first leads to compensated hypertrophy and secondary to heart failure. m6A-RNA methylation is a fast process for the adaptation of cell composition. m6A-RNA-methylation is regulated by the demethylase, fat mass and obesity-associated protein (FTO), and FTO protein levels are diminished in heart failure. Cardiomyocyte-specific FTO-transgenic/knockout-mice have shown the relevance of FTO in pressure overload remodeling. However, its functional downstream regulatory mechanisms are still unclear. In this study, we discover the harmful signaling pathways that are triggered by m6A imbalance and FTO loss, which eventually lead to adverse cardiac remodeling and heart failure.

METHODS: FTOcKO animals were generated by crossing FTO[fl/fl] mice with [Formula: see text]-MHC Cre mice using Cre-lox system. Control and the FTOcKO animals groups were subjected to TAC (transverse aortic constriction) surgery. Echocardiography was performed 1-week post-TAC surgery. MeRIP (m6A RNA immunoprecipitation) sequencing was performed from the heart tissues of mice after one week TAC surgery. Additionally, the mechanistical interrelation between the signaling pathways during FTO loss and adverse cardiac remodeling were investigated in human iPS-CMs (hiPS-CMs).

RESULTS: One week post-TAC surgery, FTOcKO mice showed impaired cardiac function (EF: CreC TAC (45%) vs. FTOcKO TAC (25%), p < 0.0001) and increased LVID (CreC TAC(3.9 mm) vs. FTOcKO TAC (4.8 mm), p < 0.0001), indicating a lack of adaption to pressure overload. Knockdown of FTO in hiPS-cardiomyocytes also reduced endothelin-induced hypertrophic response. MeRIP-seq data of FTOcKO mice showed that the differentially hypermethylated transcripts were associated with cardiac apoptosis inhibition (CDK1, CFLAR), mTORC1 signaling pathway (AKT1S1) and autophagy regulation (TFEB). mTORC1 was identified as a central player of dysregulation with hyperactivation of its canonical substrates phospho-S6K1 (Thr 389) and phospho-S6 (ser235/236) ex-vivo (FTOcKO) and in-vitro (FTO-KD-hiPS-CMs). Moreover, FTO-deficient cardiomyocytes cause autophagic flux impairment and defective autophagy. The effect of atrophy and induced apoptosis upon FTO-m6A imbalance could be rescued by pharmacological inhibiton of the mTORC1-S6K1 pathway.

CONCLUSIONS: Downregulation of FTO leads to mTORC1-S6K1 hyperactivation that shift the compensative hypertrophic response to atrophy and apoptosis leading to progressive heart failure. These findings might pave the way for the development of novel therapeutic targets for the early phases of heart failure treatments.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-025-02509-0.}, } @article {pmid41323054, year = {2025}, author = {Al-Bitar, A and Nasra, AB and Alsaoub, L and Aldakak, MA and Saifo, M}, title = {Synchronous Bilateral Breast Cancer with Heterogeneous Histology: Invasive Ductal and Lobular Carcinoma - A Case Report.}, journal = {Case reports in oncology}, volume = {18}, number = {1}, pages = {1457-1467}, pmid = {41323054}, issn = {1662-6575}, abstract = {INTRODUCTION: Synchronous bilateral breast cancer (SBBC) is rare, comprising 2-5% of all breast cancer cases. Even more uncommon is the presence of discordant histologies in each breast. This report discusses a case involving invasive ductal carcinoma (IDC) in the left breast and invasive lobular carcinoma (ILC) in the right breast.

CASE PRESENTATION: A 46-year-old Arab woman presented with a 6-month history of a growing lump in the left breast and a newly noticed nodule in the right breast. Imaging and biopsy confirmed IDC (Grade 2, ER+/PR+/HER2-) in the left breast and ILC with LCIS in the right breast. Bilateral axillary lymphadenopathy was observed. She underwent neoadjuvant chemotherapy (doxorubicin/cyclophosphamide followed by paclitaxel), followed by a left radical mastectomy with axillary dissection. Hormonal therapy (goserelin and exemestane) and adjuvant radiotherapy were initiated. Right-breast surgery is pending.

CONCLUSION: SBBC with discordant histology necessitates a multidisciplinary, individualized treatment approach. Hormone receptor status, tumor biology, and extent of disease all influence treatment decisions. This rare clinical scenario highlights the need for further research and specific management guidelines.}, } @article {pmid41321828, year = {2025}, author = {Koishybayeva, D and Balmagambetova, S and Zhakiev, B and Koishybayev, A and Mussin, NM and Sakhanova, S and Aitmagambetova, M and Tulyayeva, A and Tamadon, A}, title = {The oncogenic role of human papillomavirus in breast cancer: a comprehensive systematic review and meta-analysis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1712118}, pmid = {41321828}, issn = {1664-302X}, abstract = {INTRODUCTION: Human papillomavirus (HPV) has been increasingly implicated in the pathogenesis of breast cancer (BC), though its role remains controversial. Understanding HPV prevalence and genotype distribution across histological types and regions may clarify this potential association.

METHODS: A comprehensive systematic review and meta-analysis was conducted using PubMed, Scopus, and Web of Science databases for studies published between January 1990 and April 2025. Eligible studies reported HPV prevalence in BC tissues stratified by histological classification. Non-English studies, reviews, and those lacking histological stratification were excluded. Data from 49 studies encompassing 4,173 BC cases were extracted. Pooled HPV prevalence and odds ratios (ORs) were calculated using random-effects models. Subgroup analyses were performed by histology, geographic region, and HPV genotype (16/18). Risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist for cross-sectional studies and the Newcastle-Ottawa Scale for case-control designs.

RESULTS: The pooled prevalence of HPV in BC tissues was 23% (95% CI: 18-28%), highest in invasive ductal carcinoma (24%). HPV-positive individuals exhibited a 3.6-fold higher risk of developing BC (OR = 3.63, 95% CI: 2.33-5.64), with the strongest association in invasive lobular carcinoma (OR = 4.41). HPV-18 showed a more consistent correlation with BC than HPV-16. Regional variation was observed, with Asian populations showing higher HPV prevalence and stronger associations.

DISCUSSION: This meta-analysis suggests a significant association between HPV infection-particularly genotype 18-and breast cancer risk, especially in Asian regions and specific histological subtypes. These findings highlight the need for mechanistic studies and standardized molecular detection to elucidate the potential oncogenic role of HPV in breast tissue.

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=1051960 identifier CRD420251051960.}, } @article {pmid41321605, year = {2025}, author = {Ong, MM and Shimshon, HK and Lavin, L and Alshaikh, H and Moy, A and Rossi, A}, title = {Axillary Breast Cancer Masquerading as Extramammary Paget Disease after Bilateral Total Mastectomy: A Case Report.}, journal = {Case reports in dermatology}, volume = {17}, number = {1}, pages = {498-504}, pmid = {41321605}, issn = {1662-6567}, abstract = {INTRODUCTION: Mammary Paget disease (MPD) and extramammary Paget disease (EMPD) are distinct conditions typically differentiated by anatomical location: MPD occurs on the breast and is indicative of underlying breast carcinoma, while EMPD arises in apocrine gland-rich areas like the genitals or axilla. MPD is almost always associated with underlying breast cancer, whereas EMPD may occur with or without malignancy. Both present as erythematous, scaly lesions with histopathologic features of Paget cells, necessitating clinicopathologic correlation for diagnosis.

CASE PRESENTATION: We present a diagnostically challenging case of an erythematous, scaly plaque in the axilla of a 56-year-old female with a history of invasive ductal carcinoma and bilateral mastectomy. Initial findings, including positivity for CK7, CEA, and HER2, suggested EMPD. However, given the proximity to the previously afflicted breast, a wide local excision was performed and revealed tumor cells within mammary epithelium and glands, leading to a final diagnosis of MPD (in situ breast carcinoma involving the skin). The lesion's location in the axillary tail, overlapping with her prior breast cancer site, raised concerns for residual disease. Imaging showed no metastatic disease or pathologic mutations. Clear margins were achieved, and adjuvant radiation was deferred due to her history, limited disease extent, and potential toxicity.

CONCLUSION: This case highlights the diagnostic challenges of MPD in atypical locations and underscores the importance of clinicopathologic correlation, particularly in patients with a history of breast cancer. It also emphasizes the need for individualized treatment strategies and long-term surveillance, even after mastectomy, to detect and manage rare recurrences. Clinicians must maintain vigilance for atypical presentations of recurrent or residual disease, as breast cancer can manifest unexpectedly years after definitive treatment.}, } @article {pmid41318755, year = {2025}, author = {Effiong, ME and Chinedu, SN and Afolabi, IS and Ezike, KN and Oguntebi, EE and Abdul, OA and Achusi, IB and Benye, TA and Bella-Omunagbe, M and Ogbodo, PN}, title = {Age-specific patterns of breast cancer in Nigerian women unraveled through histological analysis.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {128}, pmid = {41318755}, issn = {2045-2322}, support = {For Women in Science, Sub-Saharan Africa (2024)//United Nations Educational, Scientific and Cultural Organization/ ; }, mesh = {Humans ; Female ; Nigeria/epidemiology ; Middle Aged ; Adult ; *Breast Neoplasms/epidemiology/pathology ; Young Adult ; Adolescent ; Aged ; Child ; Age Factors ; Retrospective Studies ; Child, Preschool ; Aged, 80 and over ; Infant ; Risk Factors ; Infant, Newborn ; Prevalence ; }, abstract = {Sub-Saharan African women face a high burden of breast cancer, influenced by genetic and lifestyle factors. However, the lack of comprehensive, age-stratified data hinders the identification of risk factors and the development of effective, population-specific interventions. This study aimed to assess age-related variations in breast cancer prevalence among Nigerian women, providing insight into associated risk factors and disease trends. A retrospective review of 3,263 breast histopathology records (9.46% of total from 2015 to 2023) was conducted. Lesions-benign and malignant-were analyzed across five age groups: children and adolescents (0-19), young adults (20-39), middle-aged (40-59), higher-aged (60-79), and elderly (≥ 80), using MS Excel and GraphPad Prism 8.0. Statistical comparisons were performed by age and lesion type. Most cases were in young adults (45.97%) and middle-aged women (33.83%). The left breast was more commonly affected (46.86%) and had higher malignancy rates than the right (44.41%) or bilateral lesions (7.20%). Benign lesions were predominant (56.76%), especially among young adults (57.34%). Malignancy incidence increased with age, peaking in middle-aged women (53.30%). Fibroadenoma was the most frequent benign lesion in children and adolescents and young adults, while fibrosis predominated in middle age. Invasive ductal carcinoma (IDC) was the leading malignant subtype, with a sharp rise by 2023-particularly among middle-aged (172 cases) and young adult women (71 cases). Among 339 immunohistochemically profiled cases, triple-negative breast cancer (TNBC; 42.77%) and ER+/PR+ tumors (36.87%) were most common. TNBC was the only subtype detected in children and adolescents. Middle-aged women bore the highest burden of all subtypes, with a marked increase in TNBC and ER+/PR+ cases in 2023. The rising incidence of aggressive subtypes, particularly TNBC, highlights the need for enhanced molecular diagnostics and personalized therapies. Age-specific trends reinforce the urgency for targeted screening, especially for young and middle-aged Nigerian women.}, } @article {pmid41315737, year = {2025}, author = {Pazicky, S and Tjia, S and Farias, GB and Piwon, N and Philip, N and Sobota, RM and Waters, AP and Gilberger, TW and Bozdech, Z}, title = {MAP-X reveals distinct protein complex dynamics across Plasmodium falciparum blood stages.}, journal = {Nature microbiology}, volume = {10}, number = {12}, pages = {3229-3244}, pmid = {41315737}, issn = {2058-5276}, support = {MOE2019-T3-1-007//Ministry of Education - Singapore (MOE)/ ; NRF-CRP24-2020-0005//National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore)/ ; MOH-001107//Ministry of Health -Singapore (MOH)/ ; GRK2771-No 453548970//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; ALTF 1115-2009//European Molecular Biology Organization (EMBO)/ ; 083811/Z/07/Z//Wellcome Trust (Wellcome)/ ; }, mesh = {*Plasmodium falciparum/growth & development/metabolism/genetics ; *Protozoan Proteins/metabolism/genetics ; *Erythrocytes/parasitology ; Proteome ; Humans ; Malaria, Falciparum/parasitology ; Protein Interaction Maps ; *Protein Interaction Mapping/methods ; Proteomics/methods ; Life Cycle Stages ; }, abstract = {The malaria parasite Plasmodium falciparum undergoes a complex intraerythrocytic developmental cycle (IDC) that relies on a dynamic network of protein-protein interactions. These are usually mapped ex vivo, limiting our understanding of their dynamics and composition in natural environments. Here we introduce the meltome-assisted profiling of protein complexes (MAP-X) that maps the complexome through thermal proteome profiling in intact cells. We applied MAP-X across seven timepoints in the P. falciparum IDC. MAP-X predicted more than 20,000 interactions, resolving conserved protein complexes, reproducing previously identified interactions and finding previously unreported associations. We found that malaria protein complexes undergo distinct dynamic alterations, and we predicted their moonlighting subunits that dissociate from their native complex to assume different biological functions. Altogether, our findings provide a resource for uncovering Plasmodium biology and show that MAP-X can characterize protein complexes in intact cells to reveal cellular physiology at a proteome-wide level.}, } @article {pmid41314093, year = {2026}, author = {Addie, M and Miron, AD and Iny, E and Wong, SM and Ross, VMS and Prakash, I and Meterissian, S}, title = {Patients with positive axillary nodes undergoing upfront surgery: Can axillary dissection be safely omitted?.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {52}, number = {1}, pages = {111304}, doi = {10.1016/j.ejso.2025.111304}, pmid = {41314093}, issn = {1532-2157}, mesh = {Humans ; Female ; Middle Aged ; *Lymph Node Excision/methods ; *Breast Neoplasms/pathology/surgery ; Axilla ; Retrospective Studies ; Aged ; Lymphatic Metastasis ; *Lymph Nodes/pathology/surgery/diagnostic imaging ; *Carcinoma, Ductal, Breast/surgery/pathology/secondary ; Mastectomy ; Mastectomy, Segmental ; Neoplasm Staging ; }, abstract = {PURPOSE: To determine the extent of axillary disease in patients with non-palpable but preoperatively biopsy-proven positive nodes, and to identify predictors of extensive lymph node (LN) involvement, defined as ≥3 positive LNs (LN+).

METHODS: A retrospective cohort study of cT1-3 breast cancer patients diagnosed between 2005 and 2022. All patients had nonpalpable biopsy-proven axillary disease and underwent upfront axillary lymph node dissection (ALND). Patients were divided into two groups: 1-2 LN + on ALND versus ≥3 LN+. Clinicopathologic factors were compared between groups. Multivariate regression was used to identify preoperative predictors of extensive (≥3) LN involvement.

RESULTS: Our cohort included 111 patients, with a median age of 63 years (IQR: 52-73 years) and tumour size of 20 mm (IQR: 13-29 mm). Most patients had invasive ductal carcinoma (90 %, n = 100). Most patients were HR+/HER2-disease (86 %, n = 96). Of the entire cohort, 46 % (n = 51) underwent breast-conserving surgery, and 54 %(n = 60) underwent mastectomy. On final pathology, 34 %(n = 38) of patients had 1-2 LN+, and 66 %(n = 73) had ≥3 LN+. Multivariate analysis preoperative predictors of ≥3 LN+: grade 3 disease (OR = 5.43, 95 % CI: 1.19-39.8, p = 0.049), two abnormal lymph nodes on US (OR = 9.11,95 % CI: 2.66-42.7, p = 0.001) and ≥3 abnormal nodes on ultrasound (OR 30.0, 95 % CI: 5.54-561, p = 0.001).

CONCLUSION: Most women with preoperatively nonpalpable, biopsy-proven axillary metastases had extensive nodal disease, but those with limited nodal positivity on ultrasound could be suitable for a more targeted axillary approach to avoid ALND.}, } @article {pmid41312922, year = {2025}, author = {Baloch, AH and Shuja, J and Bangulzai, N and Jan, M and Sattar, A and Brohi, SA and Habibullah, H and Baloch, DM and Ahmad, J}, title = {Predisposition of an Intronic Duplication in CHEK2 Gene in the Cases of Breast Cancer from Balochistan.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {26}, number = {11}, pages = {3975-3979}, pmid = {41312922}, issn = {2476-762X}, mesh = {Humans ; *Checkpoint Kinase 2/genetics ; Female ; *Breast Neoplasms/genetics/pathology/epidemiology ; *Genetic Predisposition to Disease ; *Introns/genetics ; Case-Control Studies ; Middle Aged ; Adult ; Prognosis ; Germ-Line Mutation ; *Biomarkers, Tumor/genetics ; *Carcinoma, Ductal, Breast/genetics/pathology/epidemiology ; Follow-Up Studies ; *Gene Duplication ; }, abstract = {OBJECTIVE: After BRCA 1&2, CHEK2 is the most frequently predisposing altered gene causing breast cancer in female. The prime objective of the current study was to analyze germline CHEK2 variants and their association with breast cancer in Balochistani population.

METHODS: Breast cancer is among the most prevalent cancers worldwide and most common diagnosed cancer in women. Mutations in many proto-oncogenes and tumor suppressor genes lead to the development of cancer. Along with the highly penetrance genes BRCA1 and BRCA2 increase the risk of breast cancer, mutations in other genes including CHEK2, a tumor suppressor gene have also been reported to be associated with breast cancer. In current study CHEK2 gene was analyzed for variation in breast cancer patients and controls of Balochistani population. Sequencing results of the DNA samples of the registered cases of breast cancer in CENAR were analyzed using Chromas software and bioinformatics tools including BLAT and  RNAfold web server.

RESULTS: An intronic variant c.319+38-43dupA falling 38 nucleotide away at splice donor site of the CHEK2 gene exon 2,  in 9%  breast cancer cases, was identified which has also been previously reported in non-Hodgkin Lymphoma cases. All the cases with identified variant, were affected with invasive ductal carcinoma. Higher tumor grade (III) was reported in >50% of the patients and > 70% of patients diagnosed with advanced stage of cancer. The RNA prediction results revealed the variant falling in the intronic region may code for miRNA that could play an important role in cancer progression.

CONCLUSION: Our results suggest that the intronic variant identified in breast cancer cases as well as reported previously may act as a cancer marker and causing a splice site disruption or altering the posttranscriptional modification of mRNA encoded by CHEK2 gene.}, } @article {pmid41312288, year = {2025}, author = {Wang, Y}, title = {Instructional design complexity and pop-up notification interference: effects on attention allocation and information retention in virtual classrooms.}, journal = {Frontiers in psychology}, volume = {16}, number = {}, pages = {1618121}, pmid = {41312288}, issn = {1664-1078}, abstract = {The growing prevalence of virtual multimedia learning environments raises questions about how instructional complexity and environmental interference jointly shape learning. This study examines the independent and interactive effects of instructional design complexity (IDC) and pop-up notification interference (PNI) on attention allocation and information retention. IDC was manipulated through instructional design, using streamlined layouts with concise text (low complexity) versus fragmented layouts with redundant on-screen text and background audio (high complexity). PNI (external-to-material) was manipulated through the presence or absence of periodic, task-irrelevant pop-up notifications. Drawing on Cognitive Load Theory (CLT), the Limited Capacity Model of Mediated Message Processing (LC4MP), and Media Multitasking Theory (MMT), a 2 × 2 between-subjects experiment was conducted with 240 Chinese undergraduates. Both IDC and PNI had significant adverse main effects, and their combination produced the lowest attention and retention scores. Structural equation modeling revealed that attention allocation partially mediated the relationship between the two factors and retention performance. Moderation analysis showed that learners with greater digital learning experience were less affected by PNI. This research advances CLT in ecologically valid digital contexts. It offers actionable design principles for creating distraction-resilient, cognitively sustainable virtual learning environments by integrating process-level attention metrics with clearly defined dual-factor manipulations.}, } @article {pmid41311760, year = {2025}, author = {Zablah, JA and Calderon, JJ and Burgos, AN and Gasca, JA and Montoya, KA and Orellana Banegas, L and Gracia, M}, title = {A Rare Case of Inflammatory Luminal B (HER2-Positive) Breast Cancer Misdiagnosed in a 30-Year-Old Woman: A Case Report.}, journal = {Cureus}, volume = {17}, number = {10}, pages = {e95528}, pmid = {41311760}, issn = {2168-8184}, abstract = {A 30-year-old woman presented with a six-month history of a rapidly enlarging, painful mass in the left breast, accompanied by erythema and intermittent fever. Initial imaging suggested a benign lesion, with differential diagnoses including granulomatous mastitis and phyllodes tumor. She was treated empirically with antibiotics and corticosteroids, but her symptoms worsened. Follow-up imaging revealed further mass enlargement and persistent inflammatory changes. A core needle biopsy confirmed human epidermal growth factor receptor 2 (HER2)-positive, lymphocyte-poor invasive ductal carcinoma, Nottingham Grade III, with a high Ki-67 index and extensive necrosis. Staging studies showed no distant metastases. The patient is recommended to undergo neoadjuvant chemotherapy with HER2 targeted therapy, with plans for radical mastectomy and axillary lymph node dissection. This case underscores the diagnostic challenge of distinguishing inflammatory breast conditions. Inflammatory breast symptoms unresponsive to conservative treatment should prompt early biopsy and multidisciplinary evaluation to avoid delays in diagnosis, especially in young women presenting with atypical features.}, } @article {pmid41311614, year = {2025}, author = {Glassman, H and Ismail, A and Kabbani, D and Smith, SW and Stewart, JJ and Lau, C and Chen, JZ}, title = {Appropriateness of intravenous vancomycin prescribing in a Canadian acute care hospital.}, journal = {Journal of the Association of Medical Microbiology and Infectious Disease Canada = Journal officiel de l'Association pour la microbiologie medicale et l'infectiologie Canada}, volume = {10}, number = {3}, pages = {252-256}, pmid = {41311614}, issn = {2371-0888}, abstract = {BACKGROUND: There are associated adverse effects with intravenous (IV) vancomycin, yet there is a paucity of published literature surveying the appropriateness of use. The objective of the study was to assess the appropriateness of IV vancomycin prescriptions at a Canadian acute care hospital.

METHODS: A pilot, pragmatic antimicrobial stewardship initiative using prospective audit and feedback (PAF) was conducted on incident IV vancomycin prescriptions for 4 weeks in 2022. The primary outcome was the percentage of IV vancomycin prescriptions assessed as appropriate against institutional prescribing guidelines. The secondary outcomes were to evaluate factors affecting appropriateness and to determine the number and types of ASP recommendations where IV vancomycin was assessed as suboptimal.

RESULTS: Out of 109 prescriptions audited, 43 (39%) were assessed to be suboptimal. Discontinuing or changing the agent was recommended in 39 cases (91%) and regimen optimization (duration or frequency change) was only recommended in only 4 (9%). ASP recommendations were fully or partially accepted in 88%. Infectious disease consultation (IDC) was associated with greater appropriateness (83% versus 53%; p = 0.004), as was Methicillin resistant Staphylococcus aureus (MRSA) colonization (75% versus 55%; p = 0.047), but not acute kidney injury (AKI) (62% versus 60%; p = 0.889). Adjusting for age, AKI and MRSA colonization, IDC remained a significant predictor of vancomycin appropriateness (adjusted odds ratio [aOR] = 4.27, [95% CI 1.44 to 12.70]; p = 0.009).

CONCLUSIONS: Prospective audit and feedback demonstrated inappropriate IV vancomycin use at our centre and an opportunity for quality improvement.}, } @article {pmid41309659, year = {2025}, author = {Chang, Y and Na, S and Ro, YG and Park, C and Jung, S and Park, YJ and Kwak, MS and Kim, J and Oh, H and Kim, J and Ko, H}, title = {Robust biodegradable synapse with sub-biological energy and extended memory for intelligent reflexive system.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {10610}, pmid = {41309659}, issn = {2041-1723}, support = {RS-2021-NR059784//National Research Foundation of Korea (NRF)/ ; }, mesh = {*Synapses/physiology ; Chitosan/chemistry ; Neuronal Plasticity/physiology ; *Memory, Long-Term/physiology ; Animals ; Humans ; Cellulose/analogs & derivatives/chemistry ; }, abstract = {Biodegradable artificial synapses hold great promise for sustainable neuromorphic electronics, yet combining long-term memory, ultralow energy consumption, and mechanical robustness remains challenging. Here, we report a fully biodegradable multilayer artificial synapse (M-AS) composed of crosslinked chitosan-guar gum (CS-GG) ion-active layers (IALs) and a cellulose acetate (CA) ion-binding layer (IBL). This trilayer architecture enhances ion trapping via ion-dipole coupling (IDC) at the IAL-IBL interface, while hydrogen-bonded crosslinking within the CS-GG matrix enhances mechanical and environmental stability. Sodium chloride, embedded in the IALs, serves as a mobile ionic species analogous to biological neurotransmitters, enabling low-voltage ion migration. Upon electrical stimulation, ion migration and dipole alignment induce IDC, leading to partial ion retention and cascade-like postsynaptic current responses that support memory formation. The M-AS supports key synaptic functionalities-including paired-pulse facilitation, short-term and long-term plasticity, multilevel memory encoding, and bidirectional modulation-under sub-millivolt operation. It achieves the longest long-term memory time (5944 s) reported among biodegradable artificial synapses and an energy consumption (0.85 fJ/event) lower than that of biological synapses. Integration with a thermistor and robotic actuator enables a bioinspired reflexive system capable of adaptive, stimulus-dependent learning and reflex-like behaviors. These results demonstrate the potential of M-AS for low-power, intelligent human-machine interfaces.}, } @article {pmid41306262, year = {2025}, author = {Gbadamosi, H and Nsaful, J and Mensah, YB and Dedey, F and Mensah, S and Essah, D and Clegg-Lamptey, JN}, title = {The Utilization of Wire-Guided Localization in the Management of Nonpalpable Breast Lumps at a Teaching Hospital in Ghana.}, journal = {Breast cancer : basic and clinical research}, volume = {19}, number = {}, pages = {11782234251392708}, pmid = {41306262}, issn = {1178-2234}, abstract = {INTRODUCTION: Breast cancer is the highest cause of female cancer deaths worldwide. Africa bears the brunt of this devastating disease mainly due to a lack of awareness and late presentation. Recently, a new cohort of patients in some jurisdictions in Africa have presented with small nonpalpable breast tumors due to early detection or following neoadjuvant chemotherapy.

AIM: This study documented the initial experience of wire-guided localization of nonpalpable breast tumors in a Ghanaian tertiary hospital, used to facilitate the achievement of negative surgical margins.

METHODS: This was a retrospective evaluation and analysis of clinical, radiological, and histopathological data of 45 patients who had image-guided wire localization of nonpalpable lumps immediately prior to surgical excision at the Korle Bu Teaching Hospital over more than a 4-year period. The study evaluated the preprocedural radiological diagnosis, tumor size, histology, and completeness of resection.

RESULTS: Median age at presentation was 50 years. Clinical indications of these nonpalpable lesions included 13.3% post neoadjuvant chemotherapy and 40.0% of chemotherapy naive histologically diagnosed breast cancers. The median size of the excised lesions was 13 mm. Excision was associated with clear margins in most cases. Up to 53.3% of the lesions were malignant, out of which invasive ductal carcinoma NST was the commonest histology.

CONCLUSION: Ultrasound-guided wire localization has proven to be a beneficial tool in breast-conserving surgery in an LMIC environment. More than half the pathologies localized were malignant, with 96% showing clear margins.}, } @article {pmid41303803, year = {2025}, author = {Agaoglu, AB and Erdogan, AP and Ekinci, F and Sahbazlar, M and Tekustun, GN and Tanriverdi, O and Tunbekici, S and Goker, E and Akarca, MS and Cangur, C and Guclu Kantar, T and Biter, S and Bayram, E and Colak, G and Demir, B and Basir, H and Ercolak, V}, title = {Neoadjuvant Regimens and Their Impact on Adjuvant T-DM1 Outcomes in HER2-Positive Early Breast Cancer.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {11}, pages = {}, pmid = {41303803}, issn = {1648-9144}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/drug therapy ; *Neoadjuvant Therapy/methods ; Adult ; Retrospective Studies ; *Ado-Trastuzumab Emtansine/therapeutic use ; Erb-b2 Receptor Tyrosine Kinases/analysis ; Trastuzumab/therapeutic use ; Chemotherapy, Adjuvant/methods ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cyclophosphamide/therapeutic use ; Doxorubicin/therapeutic use ; Paclitaxel/therapeutic use ; Docetaxel/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Treatment Outcome ; }, abstract = {Background and Objectives: In early-stage HER2-positive breast cancer, ado-trastuzumab emtansine (T-DM1) has been adopted as the preferred adjuvant approach for patients left with residual invasive disease despite neoadjuvant therapy. The influence of different neoadjuvant regimens on subsequent outcomes in real-world settings remains uncertain. Materials and Methods: From 2019 to 2025, 102 patients treated with adjuvant T-DM1 following surgery after neoadjuvant chemotherapy were retrospectively assessed. Neoadjuvant regimens included doxorubicin plus cyclophosphamide followed by trastuzumab-paclitaxel, doxorubicin plus cyclophosphamide with pertuzumab-trastuzumab-docetaxel, or docetaxel-carboplatin-trastuzumab-pertuzumab. Clinical features, treatment response, survival, and toxicity were evaluated. Results: The mean age of the cohort was 49.7 years, and the majority of patients (80.4%) were aged 40 years or older. Hormone receptor positivity was 82.0%, and invasive ductal carcinoma accounted for 97.1% of cases. Regional responses included 39.2% with axillary pCR despite residual breast lesions, and 5.9% with breast pCR accompanied by axillary disease. Kaplan-Meier analysis demonstrated disease-free survival rates of 100%, 95.2%, and 92.2% at 1, 3, and 5 years, respectively. Adverse events were predominantly grade 1-2, while grade 3-4 toxicities occurred in under 5% of the cohort. Baseline characteristics varied across regimens, reflecting real-world treatment preferences, but survival outcomes remained comparable. Conclusions: Adjuvant T-DM1 was associated with high survival rates and manageable toxicity across different neoadjuvant regimens, underscoring its consistent benefit in routine clinical practice.}, } @article {pmid41298676, year = {2025}, author = {Pu, F and Yang, X and Yang, J and Chen, L and Yang, F}, title = {Contrast-enhanced mammography for tumor size assessment and detection of multifocal and multicentric disease in breast cancer subtypes.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {45388}, pmid = {41298676}, issn = {2045-2322}, mesh = {Humans ; Female ; *Mammography/methods ; *Breast Neoplasms/pathology/diagnostic imaging ; Middle Aged ; *Contrast Media ; Retrospective Studies ; Aged ; Adult ; Tumor Burden ; Neoplasm Staging ; Carcinoma, Ductal, Breast/pathology/diagnostic imaging ; }, abstract = {The role of Contrast-Enhanced Mammography (CEM) in preoperative staging of breast cancer with different histological types and molecular subtypes is investigated by assessing the size of the primary tumor and distinguishing multifocal and/or multicentric breast cancer (MMBC). Data were continuously collected from patients who underwent CEM imaging due to suspected breast lesions from July 2019 to July 2024. The correlation between CEM measurements and histopathological size measurements was analyzed by using Pearson correlation coefficients. Bland-Altman plots were constructed to compare the agreement between tumor size measured by CEM and tissue pathology size measurements from surgical specimens. The presence of multifocal and/or multicentric disease is also evaluated. The correlation between CEM-measured maximum tumor size and pathological measurements is poorer for non-special type/invasive ductal carcinoma compared to other histological types, with HER2 and triple-negative molecular subtypes showing better correlation than luminal A and luminal B subtypes. The frequency of MMBC identified solely by CEM did not show statistically significant differences across histological types or molecular subtypes. This retrospective study indicates that histological type and molecular subtype may influence the assessment of tumor size in breast cancer using CEM.}, } @article {pmid41293883, year = {2026}, author = {Kroon, LJ and Remmers, S and de Vos, II and Kweldam, CF and Rijstenberg, LL and van den Bergh, RCN and Roobol, MJ and van Leenders, GJLH}, title = {Rethinking Gleason pattern quantification in predicting metastasis: results of 20 years of follow-up in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer.}, journal = {Histopathology}, volume = {88}, number = {4}, pages = {881-888}, pmid = {41293883}, issn = {1365-2559}, support = {//Jaap Schouten Foundation/ ; }, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/diagnosis/mortality ; *Neoplasm Grading/methods ; Middle Aged ; Aged ; Follow-Up Studies ; Neoplasm Metastasis ; Disease-Free Survival ; Early Detection of Cancer ; Prognosis ; Prostate-Specific Antigen/blood ; }, abstract = {INTRODUCTION: The Gleason grading system for prostate cancer (PCa) is based on the proportions of Gleason patterns (GP) 3-5. While pure GP3 has minimal metastatic potential, it is unclear whether GP3 quantity in the presence of GP4 and GP5 affects oncological outcomes.

OBJECTIVE: To assess the predictive value of PCa biopsy GP lengths on long-term metastasis-free survival (MFS).

METHODS: Prostate biopsies of 1,881 men with screen-detected PCa who participated in the Dutch part of the European Randomized Study of Screening for Prostate Cancer (ERSPC) between 1993 and 2007 were revised for GP 3-5 length. Multivariable Cox regression analyses were used to evaluate the relationship between GP lengths and MFS truncated at 20 years, adjusting for clinical-tumour stage (cT), prostate-specific antigen (PSA), percentage positive biopsies and the presence of invasive cribriform/intraductal carcinoma (CR/IDC).

RESULTS AND LIMITATIONS: On multivariable analysis, ≥cT2, PSA, percentage positive cores and absolute length of GP4 and GP5 were all significantly associated with MFS. The discriminative ability was improved by adding CR/IDC to the model. Total GP3 length was neither associated with MFS in the model with (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.97-1.00, P = 0.3) nor without CR/IDC (HR 0.98, 95% CI 0.96-1.01, P = 0.2). A limitation is the lack of targeted biopsies.

GP3 length does not have an impact on the prediction of MFS in biopsies, once GP4/GP5 lengths are known. Although GP3 percentage is essential in Gleason grading, MFS is related to absolute GP4 and GP5 quantity rather than their proportion to GP3.}, } @article {pmid41293157, year = {2025}, author = {Han, H and Semenov, M and Li, C and Zhang, Y and Lin, T and Zheng, P and Cai, J}, title = {Case Report: Possible association between dermatomyositis and Trastuzumab Deruxtecan therapy of triple-negative breast cancer patient.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1636581}, pmid = {41293157}, issn = {1664-3224}, mesh = {Humans ; Female ; *Dermatomyositis/chemically induced/diagnosis/drug therapy ; *Trastuzumab/adverse effects/therapeutic use ; Adult ; *Triple Negative Breast Neoplasms/drug therapy ; *Lung Diseases, Interstitial/chemically induced/diagnosis ; *Antineoplastic Agents, Immunological/adverse effects ; Camptothecin/analogs & derivatives ; Immunoconjugates ; }, abstract = {INTRODUCTION: we present the case of the first documented occurrence of concurrent dermatomyositis and interstitial pneumonia associated with Trastuzumab Deruxtecan (T-DXd) therapy. We hypothesize that T-DXd likely induced an autoimmune response through tumor antigen release, resulting in multi-system involvement of skin, muscle, and pulmonary tissues. The shared pathogenesis of dermatomyositis and interstitial pneumonia involves aberrant activation of the type I interferon pathway, NF-κB signaling, and TGF-β cascade, collectively driving inflammatory and fibrotic processes. Notably, progression of breast cancer temporally coincided with the onset of dermatomyositis. Although anti-TIF1-γ antibodies were not detected, the possibility of paraneoplastic dermatomyositis cannot be definitively excluded.

a 43-year-old woman initially diagnosed with Luminal B-type invasive ductal carcinoma of the left breast and experienced tumor recurrence after modified radical mastectomy. Lymph node biopsy confirmed triple-negative breast cancer (cT2N3cM0, stage IIIC) with HER2 ultra-low expression (1+). During palliative second-line treatment with Trastuzumab Deruxtecan, patient developed typical dermatomyositis symptoms and proximal muscle weakness 7 days after the first cycle of administration. Following glucocorticoid treatment, dermatomyositis symptoms showed partial relief. However, with continued administration of T-DXd in compliance with original protocol (cycles 2-6), the manifestation of dermatomyositis significantly worsened. The condition remained poorly controlled despite administration of Prednisone combined with Hydroxychloroquine, and showed no significant improvement after adding methotrexate. Concurrent tumor evaluation revealed disease progression, too. Following the third treatment cycle, chest CT revealed interstitial pneumonia.

CONCLUSION: reported here findings suggest that T-DXd may trigger multi-system involvement through immune-mediated mechanisms, resulting in drug-induced dermatomyositis and interstitial pneumonia. Our findings highlight the need for heightened vigilance regarding such immune-related adverse events during T-DXd therapy, where early recognition and intervention are critically important to avoid irreversible and possibly fatal complications.}, } @article {pmid41290771, year = {2025}, author = {Choudhary, DK and Pratap, K}, title = {Small scale lowpass and quad-band bandpass filter for 5G application.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {41922}, pmid = {41290771}, issn = {2045-2322}, abstract = {This work offers a new small-scaled lowpass and quad-band passband filter with low insertion loss and high selectivity. By integrating a shorted interdigital capacitor (IDC), closed ring resonator, meander line, and rectangular-shaped virtual ground plane, better impedance matching and transmission properties have been attained. Initially, the lowpass response structure comprises shorted IDC and closed ring resonators. Further utilizing pairs of meander lines and rectangular stubs on both sides of ring resonators, a quad bandpass along with a lowpass filter was constructed. Excluding the fifty-ohm feedline the proposed filter area measures only 0.04λg × 0.06λg (15.6 mm×24.6 mm) at the lowpass frequency of 3dB cutoff, 0.75 GHz. The fractional bandwidth at 3-dB of the proposed four passband zones are 63.76% (1.39-2.78 GHz), 22.55% (3.26-4.09 GHz), 17.15% (4.42-5.24 GHz), and 4.3% (5.64-5.89 GHz) at operating frequencies of 02.18, 3.68, 4.78 and 5.82 GHz, respectively. Moreover, the resonance frequencies of each band can be adjusted by altering the structural parameters of the intended filter, which results in modifications to their relative lumped parameters. By doing experimental measurements that correlate with simulated ones, the suggested filter is validated. The designed filter may be useful for 5G communication frequency range-1 (FR1), 0.45-6.0 GHz bands.}, } @article {pmid41287722, year = {2025}, author = {Saunders, LM and Fung, M and Middleton, D and McGalie, C and Scally, NP}, title = {A Rare Complication of Lichen Simplex Chronicus Following Deep Inferior Epigastric Perforator Flap Reconstruction.}, journal = {Cureus}, volume = {17}, number = {10}, pages = {e95331}, pmid = {41287722}, issn = {2168-8184}, abstract = {Autologous breast reconstruction using deep inferior epigastric perforator (DIEP) flaps is widely regarded as the gold standard technique, offering excellent aesthetic outcomes and reduced donor site morbidity. However, dermatological complications affecting either the reconstructed breast or donor site are infrequently reported and often under-recognized. This manuscript aims to raise awareness of a rare dermatological complication following DIEP flap reconstruction and to discuss its diagnostic and therapeutic considerations. We report a case of a 49-year-old woman who developed a persistent, pruritic rash of the neo breast and abdominal donor site following DIEP flap reconstruction. Surgery formed part of the treatment of a T1aN0M0 invasive ductal carcinoma of the right breast. The patient did not require post-surgical radiotherapy. A biopsy confirmed the diagnosis of lichen simplex chronicus (LSC), a chronic pruritic dermatosis characterized by thickened, scaly plaques resulting from repetitive scratching. To our knowledge, this is the first reported case of LSC occurring specifically within the skin of the transplanted DIEP flap and its donor site. We discuss diagnosis, potential contributing factors - including surgical trauma and possible allergic contact dermatitis - and outline the successful treatment approach using topical corticosteroids and emollients. This case highlights a rare dermatological complication following autologous breast reconstruction and the importance of considering LSC in the differential diagnosis of post-surgical rashes.}, } @article {pmid41287212, year = {2026}, author = {Davies, I and Turland, A and Tran, HD and Wong, C and Cahn, O and Dunsterville, C and Sun, Y and Xiao, Y and Murphy, KG and Bloom, SR and Jones, B and Tan, TMM}, title = {A metabolic comparison of GIPR agonism versus GIPR antagonism in male mice.}, journal = {Diabetes, obesity & metabolism}, volume = {28}, number = {2}, pages = {1160-1167}, pmid = {41287212}, issn = {1463-1326}, support = {BB/W001497/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/X017273/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; //Eli Lilly LRAP programme/ ; MR/N014103/1//MRC Doctoral Training Partnership/ ; /WT_/Wellcome Trust/United Kingdom ; MR/X021467/1/MRC_/Medical Research Council/United Kingdom ; 20/0006295/DUK_/Diabetes UK/United Kingdom ; MR/Y013980/1/MRC_/Medical Research Council/United Kingdom ; 310835/Z/24/Z/WT_/Wellcome Trust/United Kingdom ; //NIHR BRC/ ; MR/Y00132X/1/MRC_/Medical Research Council/United Kingdom ; 18/0005886/DUK_/Diabetes UK/United Kingdom ; //Metsera Inc/ ; 301619/Z/23/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Receptors, Gastrointestinal Hormone/agonists/antagonists & inhibitors ; Male ; Mice ; *Obesity/metabolism/drug therapy/etiology ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; Gastric Inhibitory Polypeptide/pharmacology ; Insulin Resistance ; Liver/metabolism/drug effects ; Energy Metabolism/drug effects ; Triglycerides/metabolism ; Adipose Tissue/metabolism/drug effects ; Eating/drug effects ; Blood Glucose/metabolism ; Body Weight/drug effects ; Weight Loss/drug effects ; }, abstract = {AIMS: Targeting the glucose dependent insulinotropic polypeptide receptor (GIPR) is of growing interest for treating type 2 diabetes and obesity, though the optimal approach remains unclear. Both GIPR agonism and antagonism, respectively, incorporated into drugs like tirzepatide and maridebart cafraglutide, have paradoxically both shown significant weight loss effects in humans.

MATERIALS AND METHODS: In this study, the metabolic impacts of a GIPR agonist (GIP108) and antagonist (NN-GIPR-Ant) were evaluated in lean and high-fat diet (HFD)-induced obese male mice. We assessed the impacts on food intake, body weight, glucose and insulin tolerance, liver triglyceride levels, bone markers and adipose tissue lipolytic gene expression.

RESULTS: In lean mice, neither peptide affected food intake or body weight, but GIP108 improved glucose tolerance. In obese mice, both agents reduced food intake and body weight, with NN-GIPR-Ant producing more sustained appetite suppression. Energy expenditure remained unchanged, as weight loss matched that of pair-fed controls. GIP108 improved glucose tolerance independently of weight loss, whereas NN-GIPR-Ant reduced insulin sensitivity compared to pair-fed controls. Both treatments slightly increased liver triglyceride content compared to their pair-fed controls, and no treatment significantly affected plasma bone marker levels. Finally, NN-GIPR-Ant reduced the expression of adipose tissue lipolytic genes.

CONCLUSIONS: Our data highlights the distinct metabolic effects of GIPR agonism and antagonism, offering insights for their future application in personalised metabolic disease treatments. Further human studies are needed to understand the long-term metabolic impacts of these therapies.}, } @article {pmid41287038, year = {2025}, author = {Bardakçı, MR and Yılmaz, HK and Yazici, AB and Kupana, MN and Yazici, E}, title = {Examining the relationship between preferred music types and temperament-character in individuals diagnosed with alcohol and substance use disorders.}, journal = {BMC psychology}, volume = {13}, number = {1}, pages = {1299}, pmid = {41287038}, issn = {2050-7283}, support = {2023/2 -1919B012331562//The Scientific and Technological Research Council of Türkiye (TÜBİTAK)/ ; }, mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; Adult ; *Substance-Related Disorders/psychology ; *Music/psychology ; *Temperament ; Middle Aged ; *Alcoholism/psychology ; *Character ; Cluster Analysis ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Individuals with Alcohol Use Disorder (AUD) and Substance Use Disorder (SUD) face significant challenges at personal, familial, and social levels. Temperament and character traits play a key role in addictive behaviors, yet their relationship with music preferences in these patients has rarely been examined. This study explores the relationship between temperament-character traits and music preferences in AUD or SUD patients.

METHODS: This cross-sectional study included 351 patients diagnosed with AUD or SUD, who were receiving treatment at the Inpatient Detoxification Centre (IDC). All participants completed the Sociodemographic Data Form, Music Preferences Questionnaire (MPQ), Temperament and Character Inventory (TCI), and Addiction Profile Index (API).

RESULTS: The participants were classified into three distinct clusters as determined by cluster analysis. Cluster 1 comprised individuals demonstrating a preference for high-energy and modern styles (n = 53), while most subjects (n = 246) were included in the cluster characterized by low interest and fantasy arabesque preferences (Cluster 2). Cluster 3 consisted of subjects with broad and balanced preferences (n = 52). There were no significant sociodemographic differences among the clusters, but significant variations in personality traits were found, particularly in novelty seeking, reward dependence, and cooperativeness. Alcohol users preferred Classical Turkish music (p <.005), while substance users favoured Hip-hop/Rap (p <.005) and Techno/Electronic music (p <.005). A weak but significant positive correlation was found between Hip-hop/Rap preference and educational status (ρ = 0.179, p = .001). Similarly, Classical Turkish Music preference showed a weak positive correlation with age (ρ = 0.263, p < .001).

CONCLUSIONS: In conclusion, AUD or SUD patients have low interest in music types and limited musical tastes. It has been observed that there is a relationship between these patients' novelty seeking and cooperativeness traits and their music preferences, and that individuals prefer certain music types more than others, depending on their diagnosis with weak additional associations with demographic factors, particularly age and educational level.

TRIAL REGISTRATION: Not applicable.}, } @article {pmid41285981, year = {2025}, author = {Fayh, APT and Soares, IFM and Ferreira, GMC and Miranda, AL and Bezerra, ADL and Medeiros, GOC and Costa-Pereira, JP and Prado, CM and Gonzalez, MC and Verde, SMML}, title = {CT-based body composition and its demographic and clinical associations in women aged 20 to 40 with non-metastatic breast cancer.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {45321}, pmid = {41285981}, issn = {2045-2322}, abstract = {This cross-sectional study investigated the relationship between CT-based body composition parameters and demographic and clinical factors in young women (< 40 years) with non-metastatic (I–III) breast cancer. Data on anthropometry, sociodemographic characteristics, and tumor profiles were extracted from medical records. Body composition was assessed using CT scans at the third lumbar vertebra (L3), measuring skeletal muscle cross-sectional area (SM), skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). A total of 173 patients were included (mean age: 33.8 ± 4.1 years). Most women had stage III tumors and hormone receptor-positive status. Higher VAT levels were associated with older age (P = 0.001). A higher education level was associated with higher SAT values. Women with invasive ductal carcinoma or positive estrogen receptor status were less likely to have high VAT. Patients with high VAT and SAT had higher BMI, SM, and SMI, and lower SMD (all P < 0.005). Our findings suggest that SAT and VAT are associated with educational level and tumor aggressiveness, respectively, highlighting the importance of monitoring body composition as part of clinical care in young women with breast cancer.}, } @article {pmid41285399, year = {2026}, author = {Hinrichs, A and Pafili, K and Sancar, G and Laane, L and Zettler, S and Torgeman, M and Kessler, B and Nono, JL and Kunz, S and Rathkolb, B and Barosa, C and Prehn, C and Cecil, A and Renner, S and Kemter, E and Kahl, S and Szendroedi, J and Bidlingmaier, M and Jones, JG and Hrabĕ de Angelis, M and Roden, M and Wolf, E}, title = {Corrigendum to "Transient juvenile hypoglycemia in GH insensitive Laron syndrome pigs is associated with insulin hypersensitivity" [Mol Metabol (2025) 102273].}, journal = {Molecular metabolism}, volume = {103}, number = {}, pages = {102286}, doi = {10.1016/j.molmet.2025.102286}, pmid = {41285399}, issn = {2212-8778}, } @article {pmid41284233, year = {2025}, author = {Li, Y and Ni, K and Gu, C and Zhang, Y}, title = {Clinical Characteristics and Prognosis of Breast Signet Ring Cell Carcinoma: A Propensity Score-Matched, Population-Based Study.}, journal = {British journal of hospital medicine (London, England : 2005)}, volume = {86}, number = {11}, pages = {1-18}, doi = {10.12968/hmed.2025.0245}, pmid = {41284233}, issn = {1750-8460}, mesh = {Humans ; Female ; Propensity Score ; *Breast Neoplasms/pathology/mortality/therapy ; Middle Aged ; *Carcinoma, Signet Ring Cell/mortality/pathology/therapy ; Prognosis ; SEER Program ; Aged ; *Carcinoma, Ductal, Breast/pathology/mortality/therapy ; Nomograms ; Neoplasm Staging ; Adult ; Kaplan-Meier Estimate ; United States/epidemiology ; }, abstract = {Aims/Background Breast signet ring cell carcinoma (SRCC) represents an uncommon tumour that has not been extensively studied. This investigation sought to assess the clinical characteristics and prognosis of breast SRCC and compare them with those of invasive ductal carcinoma (IDC). Methods We obtained clinicopathological data from the Surveillance, Epidemiology, and End Results (SEER) database, including 222 patients with breast SRCC and 492,559 patients with IDC. Clinical features, treatments, and survival outcomes were compared between the two groups. Propensity score matching (PSM) methodology was used to balance baseline characteristics when evaluating overall survival (OS) and cancer-specific survival (CSS). Sensitivity analyses employing E-values quantified the potential impact of unmeasured confounding, and multiple imputation by chained equations (MICE) was used to address missing data for molecular subtype and histological grade. Additionally, predictive models in the form of nomograms were developed to estimate OS and CSS for patients with breast SRCC. Results Compared with IDC, breast SRCC was significantly associated with older age and more advanced tumour, node, metastasis (TNM) stage (p < 0.05 for all). Kaplan-Meier analyses revealed that breast SRCC patients exhibited markedly poorer survival outcomes (OS and CSS, p < 0.05) compared to IDC patients before PSM. For breast SRCC, the median OS was 67.0 months and the median CSS was 90.0 months. The OS rates at 3, 5, and 8 years stood at 60.9%, 51.5%, and 39.6%, respectively, while the corresponding CSS rates were 67.7%, 59.7%, and 48.6%. Following PSM analysis, survival outcomes between breast SRCC and IDC patients became comparable (p > 0.05). Multivariable assessment identified age, histological grade, T stage, and surgical intervention as independent OS predictors (p < 0.05 for all) in breast SRCC, while histological grade, T stage, and surgical approach were independent CSS factors (p < 0.05 for all). The nomograms were subsequently validated using the concordance index (C-index), receiver operating characteristic (ROC), calibration curves, and decision curve analysis (DCA), demonstrating robust prognostic capability. Sensitivity analysis revealed E-values of 1.35 (OS) and 1.49 (CSS), which exceeded typical confounder effects. Multiple imputation demonstrated consistent results (OS: hazard ratio [HR] = 1.20, 95% confidence interval [CI] 0.94-1.54; CSS: HR = 1.30, 95% CI 0.86-1.97), supporting the robustness of the findings. Conclusion Breast SRCC is associated with poorer outcomes primarily due to more advanced stage at presentation rather than histological type alone. Nomograms were developed to estimate OS and CSS for patients with breast SRCC.}, } @article {pmid41283126, year = {2025}, author = {Ahuja, S and Singh, N and Yadav, AK and Ranga, S and Chintamani, C}, title = {Mathematical Pathological Approach as a Novel Tool for Prognosis in Breast Cancer.}, journal = {Indian journal of surgical oncology}, volume = {16}, number = {5}, pages = {1018-1025}, pmid = {41283126}, issn = {0975-7651}, abstract = {Breast cancer is the leading cause of cancer in women worldwide. The novel mathematical pathology approach was founded to identify important patient-specific predictors of tumor growth to improve the accuracy of intervention and prognosis. Diffusion penetration length, a model-derived mathematical function, measures how far chemotherapeutic agents diffuse through the tumor tissue. The present study evaluated the diffusion penetration length in patients of invasive ductal carcinoma and its correlation with histopathological type, grade, stage, and surrogate molecular classification. Routine histopathological processing followed by hematoxylin and eosin staining and immunohistochemistry for ER, PR, Her2neu, Ki67, and cleaved caspase-3. Each case was evaluated for histological type, grade, stage, and surrogate molecular classification. The proliferative and apoptotic index were calculated manually by hotspot counting. Mammographic measurements of tumor dimensions were performed by reviewing the images and the geometric mean was calculated. The above values were used to calculate diffusion penetration length in the mathematical working model. The diffusion penetration length was higher in Grade III than in Grade II. However, it was not statistically significant. The correlation of diffusion penetration length with pathological tumor size, nodal involvement, and the stage was found to be statistically insignificant. However, a significant correlation could be established between diffusion penetration length and surrogate molecular classification. Although diffusion penetration length could not be established as an independent prognostic parameter, its evaluation in infiltrating ductal carcinoma of breast may be of great utility.}, } @article {pmid41282559, year = {2025}, author = {Xu, H and Huang, H and Yan, A and Li, R and Xiao, E and Wang, H and Wang, Y and Ge, T and Huang, G}, title = {SEER-based hypothesis-generating research for minimum lymph node evaluation in early-stage pancreatic ductal adenocarcinoma patients.}, journal = {Frontiers in surgery}, volume = {12}, number = {}, pages = {1605726}, pmid = {41282559}, issn = {2296-875X}, abstract = {BACKGROUND: Invasive ductal carcinoma of the pancreas (IDCP) is one of the most lethal of all solid cancers, with regional lymph nodes contributing to recurrent IDCP. Given the dismal prognosis of IDCP, the number of ELNs plays a vital role in patient prognosis. However, the optimal number of examined lymph nodes (ELNs) for stage I and II IDCP patients has not been defined by the 7th and 8th editions of the American Joint Committee on Cancer.

METHODS: All patients diagnosed with invasive ductal carcinoma pancreatic cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database (http://seer.cancer.gov/) using SEER*Stat Software (version 8.3.9.2). The minimum number of ELNs or ELN/regional nodes positive (RNP) ratio threshold for optimal survival of IDCP patients was calculated using the R packages "survminer" and "survival" and propensity score matching. Subgroup survival analysis based on the best cut-off values for ELNs was assessed for the following groups: age >69 years, age ≤69 years, female, male, N0, N1, T3, and stage I or II. We used a machine learning model (XGboost) to demonstrate that ELNs are the most significant prognostic factor in patients with IDCP. We also demonstrated significant prognostic effects and predictive models for the truncated values of ELNs using multivariate Cox regression. Finally, we assessed the correlation between ELN/RNP ratio and IDCP mortality using restricted cubic spline.

RESULTS: The present study demonstrates the following points: (1) ELNs are some of the most important factors affecting the prognosis of stage I and II IDCP patients. (2) The minimum cut-off value for stage I and II IDCP patients to achieve the best survival is ELNs ≥10, which is more suitable for surgical treatment options for stage II IDCP patients. (3) The optimal threshold of survival benefit for T3N1M0 patients is ELNs >12, with ELNs >7 for T3N0M0 patients. (4) Taking into consideration the effect of the number of RNP on the value of ELNs, the ELN/RNP ratio of 9 is the minimum threshold for optimal survival benefit in stage I or II IDCP patients.

CONCLUSION: The minimum threshold for optimal survival of stage I or II IDCP patients in ELNs ≥10 and ELN/RNP ratio = 9, which is more appropriate for stage II IDCP patients. The optimal threshold of survival benefit for T3N1M0 patients is ELNs >12, with ELNs >7 for T3N0M0 patients.}, } @article {pmid41278106, year = {2025}, author = {Trabulsi, N and Alkhateeb, NA and Attiah, FO and Altaifi, R and Fakeeh, B and Shabkah, A and Farsi, A and Bawazeer, SS and Sait, S and Al-Hajeili, M}, title = {Short-term outcomes and mortality in older patients with breast cancer at a single tertiary center.}, journal = {Surgery in practice and science}, volume = {23}, number = {}, pages = {100313}, pmid = {41278106}, issn = {2666-2620}, abstract = {BACKGROUND: Breast cancer (BC) affect women worldwide, and with a rising global incidence, it represents a burden on health systems. In Saudi Arabia, the number of cases of BC and its age distribution have notably increased. Despite this increase, data on BC characteristics, management, and outcomes in this demographic are limited.

METHODS: We performed this retrospective descriptive study at King Abdulaziz University Hospital in Jeddah, Saudi Arabia, spanning 2008 to 2020. It included older women (60 years or older) diagnosed with primary BC. Data from hospital records included patient demographics, comorbidities, treatments, and short-term outcomes within 30 days of treatment. We aimed to determine the significant associations of patient, disease and treatment factors with length of stay, short-term outcomes, and mortality.

RESULTS: The study included 115 older female patients with BC, with a mean age of 67 years. Comorbidities such as diabetes (39.1 %) and hypertension (40.9 %) were prevalent. Most patients were diagnosed with stage T2 (49 %) and N1 (42 %) nonmetastatic invasive ductal carcinoma (88.7 %). The recurrence rate was 21 %, while the crude all-cause mortality rate was 20 %. Short-term outcomes showed a 4.35 % readmission rate and a 2.6 % reoperation rate, with an average hospital stay of 3.61 days. Positive surgical margins, type of surgery, and the presence of metastasis significantly predicted extended hospital stays. Smoking was significantly linked to overall morbidities within 30 days.

CONCLUSION: This study highlights the unique characteristics and treatment outcomes of older women with BC. Comorbidities, tumor stage, and receptor status are crucial for its management and outcomes. The findings emphasize the need for tailored treatment strategies, in consideration of older patients' distinct profiles. Future research should include comparative analyses with younger cohorts to establish age-specific recommendations and optimize treatment approaches for older women.}, } @article {pmid41275856, year = {2025}, author = {Ghiarone, T and Hansen, E and Holaska, JM}, title = {Emerin expression stratification across breast cancer subtypes.}, journal = {Cancer treatment and research communications}, volume = {45}, number = {}, pages = {101037}, pmid = {41275856}, issn = {2468-2942}, support = {R15 AR069935/AR/NIAMS NIH HHS/United States ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/metabolism/genetics/classification ; *Membrane Proteins/metabolism/genetics ; *Nuclear Proteins/metabolism/genetics ; Biomarkers, Tumor/metabolism ; Carcinoma, Ductal, Breast/pathology/metabolism/genetics ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Middle Aged ; }, abstract = {Nuclear dysmorphism is a critical indicator of tumor aggressiveness, influencing cancer cell invasion and metastasis. Emerin, an integral nuclear envelope protein involved in nuclear architecture, is important for maintaining nuclear integrity. Our previous work demonstrated an inverse correlation between nuclear envelope-localized emerin expression and breast cancer aggressiveness. However, it failed to have the power to assess whether emerin loss correlates with cancer stage, grade, proliferation, or molecular phenotype. Here we analyzed emerin expression at the nuclear envelope across 243 breast cancer patient samples encompassing various tumor grades, stages, and molecular phenotypes. We found significantly reduced emerin expression in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and ductal carcinoma in situ (DCIS), compared to normal breast tissue. Notably, emerin loss correlated with advanced tumor stage, higher Ki-67 proliferation rates, elevated human epidermal growth factor receptor 2 (HER2) levels, and decreased estrogen receptor (ER) and progesterone receptor (PR) expression-markers associated with more aggressive breast cancers. Emerin expression was consistently reduced in triple-negative breast cancer (TNBC) and other receptor-negative subtypes, underscoring its potential role in tumor dedifferentiation and progression.}, } @article {pmid41274530, year = {2026}, author = {Toro-Pedroza, A and Victoria, JS and Cardona-Sepúlveda, M and García-Robledo, JE and Rios-Serna, LJ and Loukanov, A and Ortiz-Guzman, J and Hoyos, V and Mainguez-Rodriguez, JE and Cañas, CA and Jaramillo, FJ and Franco, W and Wills, B and Restrepo, JG and Baena, JC}, title = {Advancing CAR-T cell manufacturing in Latin America: Current landscape, future directions, and challenges.}, journal = {Critical reviews in oncology/hematology}, volume = {217}, number = {}, pages = {105041}, doi = {10.1016/j.critrevonc.2025.105041}, pmid = {41274530}, issn = {1879-0461}, mesh = {Humans ; Latin America ; *Immunotherapy, Adoptive/methods/trends ; *Receptors, Chimeric Antigen/immunology/therapeutic use ; }, abstract = {Chimeric antigen receptor T cell therapy has transformed outcomes in hematologic malignancies, yet access in Latin America remains limited by high costs, fragmented regulation, constrained manufacturing capacity, and uneven clinical readiness. This review synthesizes the regional landscape and distills practical strategies to advance sustainable manufacturing and delivery. We map the full value chain from discovery to routine care, highlighting instructive examples. India's talicabtagene autoleucel program built domestic vector and cell production to lower cost and shorten timelines, Brazil coupled a mature regulatory pathway with accredited centers and an emerging national platform for vectors and plasmids, Mexico demonstrated feasibility of hospital based closed system production under national oversight; Colombia and Chile are developing academic pipelines and locally relevant targets. From these experiences we propose a staged roadmap for Latin America that prioritizes domestic capability in vectors and cell processing, regulatory alignment to trusted standards, and workforce development anchored in manufacturing standards and consensus. Network models that combine reference centers with point of care manufacture can reduce logistics burden. Enabling systems are essential, reliable cold chain, precleared customs lanes for critical inputs, pharmacovigilance, and shared minimum datasets for outcomes and safety. Emerging technologies, including non viral nanoparticle transfection and artificial intelligence for construct selection and process control, can reduce costs and improve consistency if advanced through careful, stepwise evaluation. Finally, coordinated alliances among hospitals, professional societies, patient groups, academia, and industry are needed to secure policy support and public investment. Together, these measures provide with a realistic path to safe, equitable, and affordable access to CAR T therapy in Latin America.}, } @article {pmid41271917, year = {2025}, author = {Guo, Y and Zhou, X and Xu, H and Wang, G}, title = {SEPT9 methylation as a diagnostic and predictive biomarker in the progression of ductal carcinoma in situ to invasive breast cancer.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {41321}, pmid = {41271917}, issn = {2045-2322}, mesh = {Humans ; Female ; *Septins/genetics/metabolism ; *Breast Neoplasms/genetics/pathology/diagnosis/metabolism ; *DNA Methylation ; *Biomarkers, Tumor/genetics/metabolism ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/diagnosis/metabolism ; *Carcinoma, Ductal, Breast/genetics/pathology/diagnosis/metabolism ; Disease Progression ; Middle Aged ; Cell Line, Tumor ; Adult ; Aged ; MCF-7 Cells ; Decitabine/pharmacology ; Neoplasm Invasiveness ; }, abstract = {SEPT9 methylation has been closely linked to breast cancer, yet its role in differentiating disease stages remains unclear. In particular, Few studies previously have examined differences in SEPT9 methylation between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), or among DCIS lesions of varying nuclear grades. This study investigated SEPT9 methylation across 105 breast cancer cases, classified into pure DCIS, DCIS with invasive components (DCIS-INV), IDC alone, and metastatic breast cancer (MBC). Methylation levels were measured using real-time PCR, and in vitro experiments were conducted using MCF-7 and T47D cell lines treated with decitabine to explore the relationship between methylation and microtubule stability. SEPT9 methylation was significantly elevated in cancer cells compared to normal breast epithelium, with positivity rates of 90.6% in DCIS-INV, 77.8% in IDC, and 79.2% in MBC, versus only 18.2% in pure DCIS. SEPT9 methylation was negtive in low-grade DCIS and positive in 28.6% of intermediate- to high-grade cases. Positive methylation was significantly associated with high Ki-67 expression and lymph node metastasis (P < 0.05), but showed no correlation with age, menopausal status, tumor size, or hormone receptor status. Additionally, decitabine treatment induced a reduction in SEPT9 methylation levels, which affects microtubule stability, suggesting a potential mechanistic link to tumor invasion. These findings indicate that SEPT9 methylation is a promising biomarker for distinguishing invasive breast cancer from DCIS and for identifying high-risk DCIS lesions with greater potential for progression.}, } @article {pmid41271881, year = {2025}, author = {Tan, E and Chen, T and Hao, H and Gao, W and Guo, S and Cui, H and Song, B}, title = {Dynamic conditional survival nomogram for non-early-stage infiltrating ductal carcinoma based on SEER database.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {41258}, pmid = {41271881}, issn = {2045-2322}, mesh = {Humans ; *Nomograms ; Female ; *Breast Neoplasms/mortality/pathology ; SEER Program ; Middle Aged ; *Carcinoma, Ductal, Breast/mortality/pathology ; Aged ; Neoplasm Staging ; Prognosis ; Kaplan-Meier Estimate ; Adult ; Proportional Hazards Models ; }, abstract = {The prognosis of breast cancer varies by histologic subtype, with infiltrating ductal carcinoma (IDC) being the most prevalent, comprising 70% of infiltrating breast cancers. Long-term survival outcomes for IDC remain unclear, and some non-early-stage IDC patients exhibit better survival than initially expected. Dynamic survival probability offers a more accurate approach to life expectancy estimation compared to traditional methods such as Kaplan-Meier analysis and the tumor-node-metastasis (TNM) staging system-based nomogram (TNM nomogram) .This study aims to develop a conditional survival prediction model for non-early-stage infiltrating ductal carcinoma patients, with a particular focus on long-term survival assessment of female IDC patients at stage IIB and beyond (according to the AJCC classification), to support personalized treatment planning. Female IDC patients from the SEER database (2000-2022) were analyzed. Overall survival probabilities for additional y years after surviving x years were calculated using the Kaplan-Meier method. Lasso, subset regression, and multivariate Cox proportional hazards analysis were applied to identify significant predictors for constructing a conditional survival (CS) nomogram, where CS is defined as the probability of surviving y additional years given that a patient has already survived x years. The CS nomogram was compared to the TNM-nomogram using the concordance index, ROC curves, calibration plots and decision curve analysis (DCA). The conditional survival nomogram, incorporating 12 variables, predicted 3-, 5-, and 10-year survival, as well as 10-year conditional survival. It demonstrated higher predictive accuracy compared to the TNM-nomogram, reflected by a superior concordance index and improved ROC curves. Calibration plots further confirmed its greater precision, and decision curve analysis (DCA) highlighted better net benefits across varying risk thresholds. Unlike the traditional nomogram, which only provides unconditional survival probabilities at diagnosis, the CS-nomogram dynamically updates survival estimates according to the time already survived (CS(y|x) = OS(x + y)/OS(x)). The conditional survival nomogram provides more accurate and personalized survival predictions for non-early-stage IDC patients, surpassing traditional nomogram. This tool offers valuable guidance for clinical decision-making and improves the precision of survival estimations.}, } @article {pmid41261306, year = {2025}, author = {Bhavnagari, HM and Raval, AP and Tarapara, BV and Joshi, JS and Shah, FD}, title = {Translating genomic insights into therapy: an NGS-based mutation profiling study in breast cancer.}, journal = {Medical oncology (Northwood, London, England)}, volume = {43}, number = {1}, pages = {9}, pmid = {41261306}, issn = {1559-131X}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology ; *High-Throughput Nucleotide Sequencing/methods ; *Mutation ; Middle Aged ; Class I Phosphatidylinositol 3-Kinases/genetics ; Adult ; Aged ; DNA Copy Number Variations ; *Carcinoma, Ductal, Breast/genetics/pathology ; Genomics/methods ; DNA Mutational Analysis/methods ; Biomarkers, Tumor/genetics ; }, abstract = {The high prevalence of breast cancer is fairly frequent among women worldwide. In the current era of personalized medicine, understanding the molecular etiology of Breast Cancer is essential for better treatment options. Our investigation of the molecular alterations in tumors using next-generation sequencing targeted panels, specifically the Oncomine Precision Assay, has revealed clinically substantial somatic mutations. A total of 32 pretherapeutic invasive ductal carcinoma patients were enrolled in this study. The DNA extraction and quantification were carried out from tumor tissues and proceeded for the run and analyzed with genexus software. The analysis revealed a highly prevalent PIK3CA mutation which plays a significant role in tumorigenesis. PIK3CA mutation incorporated different single nucleotide variations including H1047R (COSMIC ID -775), E545K (COSMIC ID-763), E542K (COSMIC ID-760), H1047L (COSMIC ID-776) and N345K (COSMIC ID-754). While the most frequent copy number variations (CNV) were found for the ERBB2 gene. Apart from these frequent mutations, TP53 SNVs, FGFR, EGFR, CDKN2A, CD274, and PTEN Copy Number Variations were also present in the study cohort. The noteworthy observation is out of 7 Triple Negative Breast Cancer patients three patients were negative for any mutation. Hence, the association of genetic variation with clinicopathological parameters will be helpful in the selection of targeted treatment.}, } @article {pmid41255621, year = {2025}, author = {Chen, C and Tie, Y and Zhang, X and Hou, N and Song, Y and Ren, D}, title = {Case Report: Sneaky DCIS-like invasive ductal carcinoma of the breast in the setting of extensive DCIS.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1673998}, pmid = {41255621}, issn = {2296-858X}, abstract = {In most cases, invasive ductal carcinoma (IDC) of the breast is identifiable when it presents with classic infiltrative growth patterns. However, a subset of IDC can present in a very sneaky way, significantly mimicking the appearance of ductal carcinoma in situ (DCIS). In this condition, it is much easier to miss the invasive component without pulling ancillary staining when morphologic findings are extremely compatible with DCIS, especially the diagnosis of DCIS was made on the previous biopsy. Here, we report the case of a 55-year-old female patient who was found to have microcalcifications at the 11:00 o'clock position in the right posterior breast during a routine mammographic examination. A biopsy of the calcification area performed at an outside hospital reported high-grade DCIS (ER+, PR-). Histologic examination of the subsequent mastectomy specimen at our institution showed two separate areas that closely resembled DCIS. Immunohistochemical (IHC) staining showed that all myoepithelial markers-smooth muscle myosin heavy chain (SMMHC), p63, CK5/6, and S100-were retained at the periphery of the expanded acini in one of the areas. Unexpectedly and surprisingly, myoepithelial markers were completely lost at the periphery of a subset of the DCIS-looking acini in another area, a finding that was immunohistochemically consistent with the diagnosis of invasive ductal carcinoma admixed with DCIS. Knowing that invasive ductal carcinoma of the breast can exhibit a DCIS-like morphology, especially in cases where a prior biopsy has already established a diagnosis of DCIS, will enhance the awareness of pathologists to recognize invasive ductal carcinoma that mimics DCIS. In turn, this will prevent misdiagnosis and undertreatment of patients with invasive ductal carcinoma of the breast.}, } @article {pmid41251094, year = {2026}, author = {Aung, TH and Seth, N and Khan, A and Das, K}, title = {Metastatic Vulvar Paget's Disease Presenting in a Supraclavicular Lymph Node: A Diagnostic Challenge on Fine Needle Aspiration Cytology.}, journal = {Diagnostic cytopathology}, volume = {54}, number = {2}, pages = {E40-E45}, doi = {10.1002/dc.70050}, pmid = {41251094}, issn = {1097-0339}, mesh = {Humans ; Female ; Aged ; *Vulvar Neoplasms/pathology/diagnosis ; *Paget Disease, Extramammary/pathology/diagnosis ; *Lymphatic Metastasis/pathology ; *Lymph Nodes/pathology ; Biopsy, Fine-Needle ; Biomarkers, Tumor/metabolism ; }, abstract = {BACKGROUND: Extramammary Paget's disease (EMPD) of the vulva is a rare intraepithelial adenocarcinoma with a typically indolent course. Distant metastasis, particularly to supradiaphragmatic lymph nodes, is exceedingly uncommon and poses a significant diagnostic challenge.

CASE PRESENTATION: We report a rare case of metastatic vulvar EMPD presenting as a left supraclavicular lymph node enlargement in a 72-year-old woman with a known history of EMPD since 2014. Cytologic smears from the lymph node revealed large, discohesive epithelial cells with pale vacuolated cytoplasm and prominent nucleoli. The concurrent core biopsy demonstrated effacement of nodal architecture by similar cells forming loose clusters and abortive glandular structures. Immunohistochemistry showed tumor cells positive for CK7, CK20, GATA3, and TRPS-1, with focal mammaglobin expression and negative staining for CDX2, PAX8, CK5/6, P40, and P63. Special stain with mucicarmine highlighted abundant intracytoplasmic mucin-a key morphologic clue favoring EMPD over a breast primary.

CONCLUSION: This case illustrates the diagnostic complexity of EMPD metastasizing to an unusual site and highlights the critical role of cytomorphology, special stains, and immunohistochemistry in excluding alternate primaries. Mucicarmine staining highlighted abundant intracytoplasmic mucin, serving as a useful adjunct in raising suspicion for EMPD. While not specific, in conjunction with cytomorphology and immunohistochemistry, this supported EMPD over invasive ductal carcinoma of the breast. Given the rarity of such distant nodal metastases, a high index of suspicion should be maintained for EMPD in patients with a known history, even when metastases appear in non-regional lymph nodes.}, } @article {pmid41248479, year = {2025}, author = {van Deursen, B and van Jaarsveld, CHM and van der Bruggen, T and Raven, S and Swillens, JEM and Timen, A}, title = {Data-Driven Infectious Disease Control: Qualitative Study of Professionals' Attitudes, Barriers, and Needs.}, journal = {Journal of medical Internet research}, volume = {27}, number = {}, pages = {e81036}, pmid = {41248479}, issn = {1438-8871}, mesh = {Humans ; *Attitude of Health Personnel ; Netherlands ; Focus Groups ; Qualitative Research ; Male ; Female ; *Communicable Disease Control/methods ; Adult ; Middle Aged ; *Health Knowledge, Attitudes, Practice ; *Health Personnel/psychology ; }, abstract = {BACKGROUND: Data-driven strategies are increasingly integrated into infectious disease control (IDC), enabling professionals to act in a timely and proactive manner; however, their implementation requires alignment with professionals' needs. Little is known about professionals' views on data-driven IDC.

OBJECTIVE: This study aims to assess IDC professionals' knowledge, attitudes, and perceptions toward working in a data-driven manner, as well as their needs, facilitators, and barriers.

METHODS: We conducted exploratory online focus group discussions (FGDs) with IDC professionals from the Public Health Services (PHSs) in the Netherlands. FGDs were organized by profession, followed by a final mixed-group session that included medical doctors, nurses, infection preventionists, epidemiologists, policy advisors, project leaders, and managers working in IDC. The topic guide was based on the Attitude-Social Influence-Efficacy model and the Consolidated Framework for Implementation Research, complemented with questions on current practices within the PHS related to data-driven work (DDW). Framework and thematic analyses were performed.

RESULTS: Between September 2024 and January 2025, nine FGDs were conducted with 36 IDC professionals. Five main themes emerged: (1) context of the work environment, (2) interpretation of DDW in the context of IDC, (3) added value of DDW, (4) views on team participation, and (5) perspectives on development and implementation. While participants mentioned that some data-driven strategies were already implemented within the PHS, they observed that data were not often translated into action. Attitudes toward DDW varied across participants, particularly regarding its definition, application in daily practice, the importance of data interpretation by professionals, results, implementation, and added value. Participation in DDW varied within teams and was influenced by role, interest, workload, time, knowledge, and willingness to change. Participants also identified various facilitators, barriers, and needs at the individual, process, and organizational levels, such as a national approach of data-driven IDC guided by a shared vision, defined role assignments, and clear protocols for data registration.

CONCLUSIONS: In this study, IDC professionals generally expressed a positive attitude toward DDW but also identified several barriers and needs for future implementation. The limited translation of data into action was viewed as untapped potential. To support effective data-driven IDC, we recommend investing in a supportive work environment that promotes a clear, shared definition of DDW, including defined roles and responsibilities. By doing so, IDC professionals can shift from reactive to strategic, data-informed action and be better equipped future public health threats.}, } @article {pmid41241870, year = {2026}, author = {Hickey, A and De la Cruz Ku, G and King, C and Franco, C and Namazian, S and Roberts, S and Torres, KA and Persing, S and Nardello, S and Chatterjee, A}, title = {Do Racial and Income Disparities Exist in the Application of 21-Gene Recurrence Score?.}, journal = {Journal of surgical oncology}, volume = {133}, number = {1}, pages = {16-30}, doi = {10.1002/jso.70128}, pmid = {41241870}, issn = {1096-9098}, support = {//The study is self-funded./ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/ethnology ; *Neoplasm Recurrence, Local/genetics/pathology/ethnology/epidemiology ; Aged ; Middle Aged ; Adult ; Aged, 80 and over ; *Income/statistics & numerical data ; United States/epidemiology ; *Biomarkers, Tumor/genetics ; SEER Program ; }, abstract = {BACKGROUND: The 21-gene recurrence score is a useful tool to predict the recurrence risk in patients with early hormone receptor positive (HR +) and human epidermal receptor-2 negative (HER2-) breast cancer, which helps to determine those patients who may benefit from chemotherapy. Our goal was to assess whether there was a disparity in the use of the 21-gene recurrence score, especially between races and income levels.

METHODS: Using the SEER Medicare database, we analyzed breast cancer patients diagnosed from 2012 to 2017. Inclusion criteria were HR + /HER2- phenotype, clinical stages I and II in post-menopausal women, and Stage 1 cancers in premenopausal women. Differences in the application of the 21-gene recurrence score with regard to race and income level were studied using chi-square analysis.

RESULTS: Overall, 124 761 patients were included. Of these, 99.1% were females, and 32.9% had 21-gene recurrence score testing. The median age was 70 years (range 27-100). Most patients had invasive ductal carcinoma (86.6%) followed by invasive lobular carcinoma (13.4%), of which 66.0% were stage I and 34.0% as stage II. When comparing subgroups based on testing, White race had a lower application rate (83.8% vs. 84.3%, p = 0.031), compared to African-Americans (8.7% vs. 8.3%, p = 0.031). Similarly, patients with ≥ 10% poverty index showed a lower frequency of testing (46.0% vs. 47.3%, p < 0.001). However, clinically meaningful disparities by race or income were not observed. Underuse of 21-gene recurrence score was more evident among older patients ( ≥ 65, 76.9% vs. 61%, p < 0.001), separated/divorced/widowed individuals (38.7% vs. 28.4%, p < 0.001), and those undergoing mastectomy (39% vs. 29.5%, p < 0.001) compared to breast-conserving surgery.

CONCLUSIONS: No clinically significant disparities were observed in race or income level in the application of the 21-gene recurrence score, which is reassuring, particularly as chemotherapy treatment regimens continue to trend appropriately trend toward de-escalation. However, underuse was more evident among older patients, separated/divorced/widowed individuals, and those undergoing mastectomy, highlighting opportunities to improve equity and adherence to guideline-based testing.}, } @article {pmid41240798, year = {2026}, author = {Loap, P and Cheptea, C and Kirova, Y}, title = {Feasibility of a third breast-conserving treatment in ipsilateral breast cancer recurrence: A retrospective population-based analysis.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {52}, number = {1}, pages = {111184}, doi = {10.1016/j.ejso.2025.111184}, pmid = {41240798}, issn = {1532-2157}, mesh = {Humans ; Female ; *Mastectomy, Segmental/methods ; Retrospective Studies ; *Neoplasm Recurrence, Local/surgery/pathology ; Feasibility Studies ; Aged ; Aged, 80 and over ; Survival Rate ; *Breast Neoplasms/surgery/pathology ; Reoperation ; Middle Aged ; SEER Program ; *Carcinoma, Ductal, Breast/surgery/pathology ; Neoplasm Staging ; }, abstract = {INTRODUCTION: Breast-conserving surgery (BCS), followed by radiotherapy, is the standard treatment for early-stage breast cancer. In the event of ipsilateral recurrence, total mastectomy is typically recommended. While a second BCS has been explored in selected cases, no data exist on the feasibility of a third breast-conserving treatment (BCT) after two prior recurrences.

MATERIALS AND METHODS: We conducted a retrospective population-based study using the SEER database (17 registries, 2000-2020; November 2022 submission). Eligible patients were women with non-metastatic breast cancer who underwent three ipsilateral BCS procedures, each separated by at least 12 months. Clinical, pathological, and treatment data were collected for all episodes. Overall survival (OS) and breast cancer-specific survival (CSS) were analyzed from the diagnosis of the third tumor.

RESULTS: Twelve patients were identified. Median age at the third diagnosis was 82 years. While most tumors were small and hormone receptor-positive, some presented with more advanced features, including one T4b tumor and two node-positive (N+) cases. Histology was predominantly invasive ductal carcinoma. No patients received chemotherapy; two underwent breast re-irradiation following the third BCS. Median follow-up was 43 months (range: 10-108). Two patients (16.7 %) died from breast cancer. Estimated 5-year OS and CSS were both 71.4 % (95 % CI: 44.7-100 %). No clinicopathologic factor was significantly associated with survival.

CONCLUSION: This is the first study to report the use of three successive breast-conserving surgeries for ipsilateral recurrences. Despite advanced age and occasional high-risk features, outcomes suggest that this approach may be considered in carefully selected patients and warrants further clinical evaluation.}, } @article {pmid41237374, year = {2025}, author = {Thabet, DM and Thabit, DM}, title = {Immunohistochemical expression of POC1A, NUF2, and Ki-67 in invasive ductal carcinoma of the breast.}, journal = {American journal of clinical pathology}, volume = {164}, number = {6}, pages = {890-907}, doi = {10.1093/ajcp/aqaf114}, pmid = {41237374}, issn = {1943-7722}, mesh = {Humans ; Female ; Middle Aged ; *Ki-67 Antigen/metabolism ; *Biomarkers, Tumor/analysis/metabolism ; *Breast Neoplasms/pathology/metabolism/mortality ; Retrospective Studies ; *Carcinoma, Ductal, Breast/pathology/metabolism/mortality ; Adult ; Immunohistochemistry ; Prognosis ; Aged ; *Cell Cycle Proteins/metabolism ; Kaplan-Meier Estimate ; }, abstract = {OBJECTIVE: Breast cancer is a leading malignancy among women worldwide. Mitotic regulation proteins such as POC1A and NUF2 have been linked to tumor aggressiveness.

METHODS: This retrospective study evaluated the immunohistochemical expression of POC1A and NUF2 in 136 cases of invasive ductal carcinoma (IDC), 96 matched metastatic lymph nodes, and 48 adjacent normal breast tissues using Ki-67 as a supporting proliferation marker. Associations with clinicopathologic features were assessed, and survival analyses were conducted using Kaplan-Meier and Cox regression models.

RESULTS: POC1A and NUF2 were significantly overexpressed in tumor tissues compared to normal tissues (P < .001). High expression levels were associated with larger tumor size, higher grade and stage, lymphovascular invasion, distant metastasis, hormone receptor negativity, triple-negative breast cancer (TNBC), and poor Nottingham Prognostic Index scores. Both markers were significantly associated with lymph node involvement. Ki-67 expression also correlated positively with POC1A and NUF2 coexpression (r = 0.574; 95% CI, 0.449-0.677; P < .001). Multivariate analysis identified POC1A as an independent predictor of poor overall survival (OS) (hazard ratio, 2.102; 95% CI, 1.41-3.13; P < .001). Coexpression of POC1A and NUF2 was linked to significantly worse prognosis.

CONCLUSIONS: High expression levels of POC1A and NUF2 were significantly associated with aggressive clinicopathologic features and poorer prognosis in IDC. Their correlation with Ki-67 and enrichment in TNBC highlight their potential as prognostic markers and predictors of nodal metastasis. Importantly, POC1A expression was independently associated with worse OS in IDC, including TNBC. While not yet directly actionable, our findings nominate POC1A as a promising independent prognostic biomarker that could potentially refine risk stratification in IDC, particularly for aggressive subtypes like TNBC. However, prospective validation in larger cohorts is mandatory before any clinical application.}, } @article {pmid41236901, year = {2025}, author = {Beauchamp, L and Matoso, A}, title = {Clinical Outcomes of Incidental Small Foci of High-Grade Prostate Cancer Identified in Transurethral Resections of Prostate (TURP) Specimens.}, journal = {International journal of surgical pathology}, volume = {}, number = {}, pages = {10668969251384329}, doi = {10.1177/10668969251384329}, pmid = {41236901}, issn = {1940-2465}, abstract = {High-grade acinar prostatic adenocarcinoma, characterized by a Gleason score exceeding 7 (Grade Groups 4 or 5), is associated with a poorer prognosis, including increased risks of recurrence and metastasis. While much research has focused on high-grade prostate cancer diagnosed via needle biopsy, little is known about the clinical implications of incidental high-grade prostate cancer found in transurethral resection of the prostate (TURP) specimens. This study reviews the clinical outcomes of 18 patients with high-grade prostate cancer involving ≤ 5% of TURP tissue, diagnosed between 2014 and 2024. Inclusion criteria included a first-time diagnosis of prostate cancer, acinar adenocarcinoma with a Gleason score of 8 or higher, and involvement of less than 5% of TURP tissue. Clinical data, including age, prostate-specific antigen levels, treatment type, and follow-up, were recorded. The cohort had a mean age of 75 years, and the follow-up period averaged 34 months. Histopathologic findings included Grade Groups 4 and 5 tumors, with intraductal prostatic carcinoma (IDC) found in 5 patients. Treatment varied, with 39% receiving hormonal therapy and radiotherapy, 33% opting for active surveillance, and 11% undergoing radical prostatectomy. Notably, 17% of patients experienced disease progression, with IDC present in all of these patients. Despite low-volume disease (≤ 5% of specimens), a notable proportion of patients developed metastasis or died from prostate cancer, challenging the traditional view that incidental findings in TURP are of limited consequence. Patients with IDC appear especially vulnerable to adverse outcomes.}, } @article {pmid41235321, year = {2025}, author = {Kobayashi, Y and Miyazawa, K and Shinseki, K and Kushima, A and Takahashi, M and Fujibayashi, M}, title = {Solid-Basaloid Adenoid Cystic Carcinoma of the Ipsilateral Breast Remnant in Postoperative Luminal HER2-Type Breast Cancer: A Case Report.}, journal = {Surgical case reports}, volume = {11}, number = {1}, pages = {}, pmid = {41235321}, issn = {2198-7793}, abstract = {INTRODUCTION: Solid-basaloid adenoid cystic carcinoma (SB-AdCC) is a rare and aggressive variant of AdCC of the breast. Moreover, it is an extremely rare subtype of triple-negative breast cancer, accounting for <1% of all breast cancers. We report a case of SB-AdCC.

CASE PRESENTATION: Ten years ago, an 82-year-old woman underwent a partial mastectomy for the luminal HER2 (human epidermal growth factor receptor type 2)-type invasive ductal carcinoma of the left breast cancer. Ten years later, she noticed another lump in her left breast. A needle biopsy was performed, and an unclassified carcinoma was detected. Histological examination revealed that the carcinoma was of the triple-negative type. A mastectomy of the left breast and sentinel lymph node biopsy were performed. The postoperative pathological diagnosis was an SB-AdCC of the breast. The Ki-67 index was 80%, corresponding to a high-grade malignancy. She received postoperative chemotherapy with tegafur-gimeracil-oteracil potassium. At 1 year postoperatively, she is recovering well without signs of metastasis.

CONCLUSIONS: We reported a case of SB-AdCC.}, } @article {pmid41233492, year = {2025}, author = {Gagnon, JR and Allen, CH and Diop, MK and Dallaire, F and Leblond, F and Trudel, D and Murugkar, S}, title = {Label-free histological identification of intraductal carcinoma of the prostate using texture analysis-based multimodal stimulated Raman scattering microscopy.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {39874}, pmid = {41233492}, issn = {2045-2322}, support = {PJT-169164/CAPMC/CIHR/Canada ; PJT-169164/CAPMC/CIHR/Canada ; PJT-169164/CAPMC/CIHR/Canada ; PJT-169164/CAPMC/CIHR/Canada ; PJT-169164/CAPMC/CIHR/Canada ; PJT-169164/CAPMC/CIHR/Canada ; PJT-169164/CAPMC/CIHR/Canada ; RGPIN-2022-04897//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN-2022-04897//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN-2022-04897//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN-2022-04897//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN-2022-04897//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN-2022-04897//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN-2022-04897//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/diagnostic imaging/diagnosis ; *Spectrum Analysis, Raman/methods ; Support Vector Machine ; Prostate/pathology/diagnostic imaging ; Machine Learning ; *Nonlinear Optical Microscopy/methods ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is a very aggressive histopathological subtype of prostate cancer (PCa) that is strongly associated with poor clinical outcomes but for which no accurate biomarkers exist. Here, we demonstrate a novel application of texture analysis-based machine learning alongside multimodal nonlinear optical imaging using second-harmonic generation (SHG) and stimulated Raman scattering (SRS) at 1450 cm[-1] and 1668 cm[-1] Raman shifts to distinguish IDC-P from regular PCa and benign prostate. Images from each tissue type were analyzed to extract the first-order statistics and texture-based second-order statistics derived from the gray-level co-occurrence matrix of the images. A machine learning model was constructed using support vector machine (SVM) to classify the prostate tissue based on these statistics. Our results demonstrate that SVM models trained on either SHG or SRS images accurately classify IDC-P as well as high-grade PCa, low-grade PCa, and benign tissue with a mean classification accuracy exceeding 89%. Moreover, a mean classification accuracy of 98% was achieved using an SVM model trained on combined SHG and SRS images. Our study demonstrates that multimodal nonlinear optical imaging using SHG and SRS can be combined with texture analysis-based SVM classification to provide pathologists with a reliable biomarker of IDC-P.}, } @article {pmid41233488, year = {2025}, author = {Nuzla, AN and Nabeel, AKM and Nirmal, WAS and Hewavithana, PB and Jayatilake, ML}, title = {Machine learning-based classification of histological subtypes of invasive breast cancer using MRI contralateral breast texture features.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {39815}, pmid = {41233488}, issn = {2045-2322}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology/classification ; *Machine Learning ; *Magnetic Resonance Imaging/methods ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology/classification ; *Breast/pathology/diagnostic imaging ; Algorithms ; *Carcinoma, Lobular/diagnostic imaging/pathology/classification ; Middle Aged ; Image Processing, Computer-Assisted/methods ; Adult ; }, abstract = {Invasive Breast Cancer (IBC), encompassing Invasive Ductal Carcinoma (IDC) and Invasive Lobular Carcinoma (ILC), is the most prevalent cancer in women. This study aimed to develop a machine learning (ML) model for distinguishing between its histological subtypes (IDC and ILC) by analyzing glandular texture features from the contralateral breast. T1-weighted pre-contrast MRI images were sourced from the Cancer Imaging Archive, with image segmentation performed in 3D Slicer software, yielding a dataset of 2444 slices (1890 IDC, 554 ILC). First-order and GLCM texture features were extracted using MATLAB, and feature selection via ANOVA F-test revealed correlation (0.1233) and mean (0.5335) as the least significant features. Despite this, the initial model with all features achieved an accuracy of 0.9038, suggesting the importance of all extracted features. To address dataset imbalance, the SMOTE technique was applied, creating balanced training (80%) and testing (20%) subsets. Various ML algorithms were tested, and the Random Forest Classifier achieved the highest cross-validation scores for both SMOTE (0.8723 ± 0.0209) and original (0.8989 ± 0.0224) datasets. The final model achieved an accuracy of 91% on the original and 87% on the SMOTE dataset, revealing a comprehensive classification. The findings support early diagnosis and make an innovative contribution to the literature.}, } @article {pmid41233220, year = {2025}, author = {Kandzi, JD and Englisch, A and Boeer, B and Hahn, M and Wallwiener, M and Volmer, L and Brucker, S and Hartkopf, A and Engler, T}, title = {Reconciling Sentinel Node Omission with CDK4/6 Inhibitor Eligibility in HR+/HER2- Early Breast Cancer: A Real-World Cohort Analysis.}, journal = {Clinical breast cancer}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.clbc.2025.10.003}, pmid = {41233220}, issn = {1938-0666}, abstract = {PURPOSE: Omission of sentinel lymph node biopsy (SLNB) in selected hormone receptor-positive (HR+), HER2-negative (HER2-) early breast cancer patients has demonstrated safety in prospective trials. However, accurate axillary staging remains important for identifying candidates for adjuvant CDK4/6 inhibitor therapy. We quantified the impact of SLNB omission on CDK4/6 eligibility and explored predictors of occult nodal disease in a real-world cohort.

METHODS: We retrospectively analyzed 948 patients treated 2014 to 2022 at Tübingen University Hospital who met criteria proposed for potential SLNB omission: age ≥ 50 years, cT1 cN0, HR+/HER2-, grade 1 to 2 tumors treated with breast-conserving surgery and whole-breast irradiation. We assessed the prevalence of occult nodal metastases and potential eligibility for adjuvant abemaciclib (monarchE-criteria) or ribociclib (NATALEE-criteria) based on final pathology and fitted multivariable logistic models.

RESULTS: Among 948 patients meeting SLNB omission criteria, 143 (15.1%) harbored occult nodal disease. Of these node-positive patients, 17 fulfilled the criteria for abemaciclib eligibility. For ribociclib, 105 node-positive patients were eligible. On multivariable analysis, multifocality (OR = 2.3; P ≤ .001) and cT1c tumor stage (OR = 1.76; P = .008) predicted axillary upstaging; invasive lobular carcinoma (ILC) showed higher crude upstaging than IDC/NST (22.6% vs. 14.0%) but did not retain independent significance after adjustment.

CONCLUSIONS: Omitting sentinel node biopsy in selected patients leads to under-detection of nodal metastasis in a relevant proportion of patients, particularly with cT1c tumors, multi-focal tumors and ILC. As these patients may benefit from more intensive adjuvant treatment, omission of sentinel-node biopsy should be part of decision-making. Future trials should investigate the impact of adjuvant treatment for patients with occult lymph node metastases.}, } @article {pmid41232681, year = {2026}, author = {Ben-David, BM and Arieli Zaks, E and Palgi, Y}, title = {Psychological whiplash: Resilience and peritraumatic distress predict psychiatric risk, days after repeated missile attacks - A 14-month cohort study.}, journal = {Journal of affective disorders}, volume = {394}, number = {Pt B}, pages = {120703}, doi = {10.1016/j.jad.2025.120703}, pmid = {41232681}, issn = {1573-2517}, } @article {pmid41232271, year = {2026}, author = {Zhang, P and Chen, J and Zhang, X and Chen, Z and Guo, D and Ouyang, Z and Yan, J and Zhu, Y and Liang, J and Luo, Y and Zhu, D and Chen, Z}, title = {Accurate identification and mechanism of breast invasive ductal carcinoma based on combining steady-state and time-resolved label-free fluorescence spectroscopy.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {348}, number = {Pt 2}, pages = {127113}, doi = {10.1016/j.saa.2025.127113}, pmid = {41232271}, issn = {1873-3557}, mesh = {Humans ; Spectrometry, Fluorescence/methods ; Female ; *Breast Neoplasms/pathology/diagnosis ; *Carcinoma, Ductal, Breast/diagnosis/pathology/metabolism ; Middle Aged ; Discriminant Analysis ; Aged ; Flavin-Adenine Dinucleotide ; Adult ; }, abstract = {Breast cancer (BC) remains the most prevalent malignant tumor and a major threat to women's health. Frozen section examination, a standard method for margin assessment during breast-conserving surgery (BCS), is time-consuming and highly dependent on pathologist expertise. This study investigates the feasibility of using laser-induced fluorescence (LIF) spectroscopy to classify ex vivo breast tissues. Tissues from 17 patients were examined using steady-state and time-resolved fluorescence spectroscopy. A new spectral fluorescence intensity ratio (FIR) was calculated and analyzed combining with the mean fluorescence lifetime (MFL). Linear discriminant analysis (LDA) was applied to assess classification accuracy. The results indicate that the intrinsic fluorescence of breast tissue can be attributed to NAD(P)H, FAD, collagen, and elastin. Carcinoma tissues showed statistically lower FIR and shorter MFL (P < 0.001) than normal tissues. Changes in steady-state spectra might reflect elevated NAD(P)H levels and variations in binding ratios. Meanwhile, the observed shortening of fluorescence lifetime could potentially result from a reduced fluorescence contribution of structural proteins and a decreased proportion of bound NAD(P)H. Combining the fluorescence intensity ratio and MFL within an LDA framework significantly improved diagnostic accuracy and enabled reliable classification of ex vivo breast carcinoma and normal tissues. This spectroscopic approach offers a label-free, quantitative tool with potential for real-time margin assessment during BCS, aiding precise intraoperative decision-making.}, } @article {pmid41232117, year = {2025}, author = {Erginöz, E and Çavuş, GH and Öztürk, T and İlvan, Ş and Kayadibi, Y and Özdil, A and Zenger, S and Velidedeoğlu, M}, title = {Prognostic Significance of Tumor Budding in Invasive Ductal Carcinoma of the Breast with Neuroendocrine Differentiation.}, journal = {International journal of surgical pathology}, volume = {}, number = {}, pages = {10668969251391355}, doi = {10.1177/10668969251391355}, pmid = {41232117}, issn = {1940-2465}, abstract = {IntroductionInvasive ductal carcinoma (IDC) with neuroendocrine differentiation (NED) is a rare subgroup of breast cancer that is treated the same way as invasive ductal carcinoma-no special type (IDC-NST). In this study, we aimed to study the effects of tumor budding on clinicopathological outcomes and survival.MethodsFifty-seven patients previously diagnosed with breast cancer were included in this analysis. Patients were grouped into IDC-NST and IDC with NED using the neuroendocrine markers chromogranin A and synaptophysin. Histological features were re-evaluated by two different pathologists in terms of tumor budding characteristics.ResultsPatients diagnosed with IDC with NED tended to be older (62.9 ± 15.4 vs 51.7 ± 9.9; P = 0.02). Compared to IDC-NST, IDC with NED group tended to display type A and B mammographic breast composition (P = 0.018), have higher tumor budding (2.7 vs 2, P = 0.009), larger in diameter (3.9 ± 2.3 cm vs 2.5 ± 1.5 cm; P = 0.015), and show higher lymphatic invasion (P = 0.017), vascular invasion (P = 0.042), and perineural invasion (P = 0.045). However, no differences were found in the 5-year overall survival and disease-free survival between the two groups.ConclusionCompared to IDC-NST, IDC with NED exhibited higher levels of tumor budding, were typically larger, and displayed higher lymphatic invasion, vascular invasion, and perineural invasion.}, } @article {pmid41224957, year = {2025}, author = {Ji, H and Rohm, M}, title = {Reawakening cAMP signalling in cancer cachexia.}, journal = {Nature metabolism}, volume = {7}, number = {12}, pages = {2388-2389}, pmid = {41224957}, issn = {2522-5812}, } @article {pmid41224411, year = {2025}, author = {Yang, E and Wen, HY}, title = {Special Subtypes of Triple Negative Breast Carcinoma.}, journal = {Surgical pathology clinics}, volume = {18}, number = {4}, pages = {665-673}, doi = {10.1016/j.path.2025.08.009}, pmid = {41224411}, issn = {1875-9157}, mesh = {Humans ; *Triple Negative Breast Neoplasms/pathology/diagnosis/therapy/classification ; Female ; Prognosis ; Biomarkers, Tumor ; }, abstract = {Triple-negative breast cancer (TNBC) encompasses a diverse group of tumors lacking expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2. While conventional TNBC of no special type (IDC-NST) is often aggressive, histologically special subtypes such as metaplastic carcinoma, apocrine carcinoma, adenoid cystic carcinoma, IDC-NST medullary pattern and secretory carcinoma display distinct morphologic, immunophenotypic, and molecular hallmarks that markedly influence prognosis and therapy. Several of these entities have favorable outcomes or actionable targets (eg, androgen-receptor antagonists or TRK inhibitors). This article summarizes current knowledge on their classification, diagnostics, and clinical management, emphasizing opportunities for precision medicine in TNBC.}, } @article {pmid41223787, year = {2025}, author = {Zweck, E and Piel, S and Schmidt, JW and Scheiber, D and Schön, M and Kahl, S and Burkart, V and Dewidar, B and Remus, R and Chadt, A and Al-Hasani, H and Mastrototaro, L and Aubin, H and Boeken, U and Lichtenberg, A and Distler, J and Polzin, A and Kelm, M and Westenfeld, R and Wagner, R and Schrauwen, P and Szendroedi, J and Roden, M and Granata, C}, title = {Impaired mitochondrial ketone body oxidation in insulin resistant states.}, journal = {EBioMedicine}, volume = {122}, number = {}, pages = {106007}, pmid = {41223787}, issn = {2352-3964}, mesh = {Humans ; *Insulin Resistance ; *Ketone Bodies/metabolism ; Animals ; Mice ; *Diabetes Mellitus, Type 2/metabolism/pathology ; Oxidative Phosphorylation ; *Mitochondria/metabolism ; Oxidation-Reduction ; Male ; Obesity/metabolism ; Muscle, Skeletal/metabolism ; Female ; Middle Aged ; Fatty Liver/metabolism ; Acetoacetates/metabolism ; Disease Models, Animal ; }, abstract = {BACKGROUND: Reduced mitochondrial respiratory function has been implicated in metabolic disorders like type 2 diabetes (T2D), obesity, and metabolic dysfunction-associated steatotic liver disease (MASLD), which are tightly linked to insulin resistance and impaired metabolic flexibility. However, the contribution of the ketone bodies (KBs) β-hydroxybutyrate (HBA) and acetoacetate (ACA) as substrates for mitochondrial oxidative phosphorylation (OXPHOS) in these insulin resistant states remains unclear.

METHODS: Targeted high-resolution respirometry protocols were applied to detect the differential contribution of HBA and ACA to OXPHOS capacity in heart, skeletal muscle, kidney, and liver of distinct human or murine cohorts with T2D, obesity, and MASLD.

FINDINGS: In humans with T2D, KB-driven mitochondrial OXPHOS capacity was ∼30% lower in the heart (p < 0.05) and skeletal muscle (p < 0.05) compared to non-diabetic controls. The relative contribution of KBs to maximal OXPHOS capacity in T2D was also lower in both the heart (∼25%, p < 0.05) and skeletal muscle (∼50%, p < 0.05). Similarly, in kidney cortex from high-fat diet-induced obese mice, both the absolute and relative contribution of KBs to OXPHOS capacity was ∼15% lower (p < 0.05). Finally, hepatic HBA-driven mitochondrial OXPHOS capacity was 29% lower (p < 0.05) in obese humans with hepatic steatosis compared to humans without.

INTERPRETATION: Mitochondrial KB-driven OXPHOS capacity is impaired in insulin resistant states in various organs in absolute and relative terms, likely reflecting impaired mitochondrial metabolic flexibility. Our data suggest that KB respirometry can provide a sensitive readout of impaired mitochondrial function in diabetes, obesity, and MASLD.

FUNDING: German Research Foundation, German Diabetes Center, German Federal Ministry of Health, Ministry of Culture and Science of the state of North Rhine-Westphalia, German Federal Ministry of Education and Research, German Center for Diabetes Research, German Heart Foundation, German Diabetes Society, Christiane-and-Claudia Hempel Foundation, European Community and Schmutzler Stiftung.}, } @article {pmid41220400, year = {2026}, author = {Fedai, NK and Koc, I and Kavgaci, G and Uner, M and Uner, A and Aksoy, S and Kertmen, N}, title = {Prognostic significance of ductal carcinoma in situ coexisting with invasive ductal carcinoma: Biological behavior, immune response and survival outcomes.}, journal = {Molecular and clinical oncology}, volume = {24}, number = {1}, pages = {1}, pmid = {41220400}, issn = {2049-9469}, abstract = {Biological differences exist between invasive ductal carcinoma (IDC) and IDC + ductal carcinoma in situ (DCIS) tumors including variations in tumor grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) expression, proliferative activity and molecular subtype. The present study evaluated the impact of the coexistence of IDC + DCIS on tumor microenvironment, tumor-infiltrating lymphocytes (TILs), clinical and pathological features, prognosis and survival. A total of 165 patients with IDC and 404 with IDC + DCIS were enrolled and treated in the outpatient clinic, Hacettepe University Department of Medical Oncology (Ankara, Turkey) between January 2014 and July 2021. Compared with IDC, patients with IDC + DCIS were more likely to be hormone receptor-positive and had a lower rate of mastectomy and Ki-67 index (both P<0.05). The co-existence of DCIS was associated with significantly improved overall survival (OS) and disease-free survival (DFS) (both P<0.05). Furthermore, patients with IDC had 2.14-fold higher odds of death and 2.44-fold higher odds of recurrence/distant metastasis/death than patients with IDC + DCIS. The present study supports the behavioral differences of IDC and IDC + DCIS and suggests these two groups of tumors may also behave differently in terms of antitumor immune response. As the DCIS component is positively associated with favorable prognostic features, the presence of the DCIS is associated with improved DFS and OS. DCIS accompaniment may have prognostic value for patients with breast cancer.}, } @article {pmid41216105, year = {2025}, author = {Tweed, EK and Berman, AJ and Josey, M}, title = {Invasive Breast Carcinoma With a Multi-cystic Papillary Growth Pattern: A Unique Morphology of Invasion Not Currently Well Classified by the World Health Organization.}, journal = {Cureus}, volume = {17}, number = {10}, pages = {e94223}, pmid = {41216105}, issn = {2168-8184}, abstract = {Papillary neoplasia of the breast is notoriously difficult to classify, even for seasoned pathologists and those subspecialized in breast pathology. Over the past few decades, the classification of these lesions has undergone multiple updates, and several newly recognized entities have been added. Multiple benign and malignant breast entities are characterized by the World Health Organization (WHO). Despite these categorizations, pathologists are sometimes presented with papillary morphologies and features that do not fit perfectly into any one of these classifications. We present a case of a 62-year-old female with an invasive breast carcinoma of a type that we believe is not currently well characterized by the WHO and that exhibits a papillary growth pattern, specifically invading as multi-cystic papillary structures.}, } @article {pmid41212525, year = {2026}, author = {Avidor, S and Shenkman, G and Shrira, A and Cohn-Schwartz, E and Palgi, Y and Greenblatt-Kimron, L}, title = {Views of aging and symptoms of posttraumatic stress disorder among older adult war veterans in the context of renewed war.}, journal = {The journals of gerontology. Series B, Psychological sciences and social sciences}, volume = {81}, number = {2}, pages = {}, doi = {10.1093/geronb/gbaf226}, pmid = {41212525}, issn = {1758-5368}, support = {RA2200000313//University of Ariel/ ; }, mesh = {Humans ; *Stress Disorders, Post-Traumatic/psychology/epidemiology ; *Veterans/psychology/statistics & numerical data ; Aged ; Male ; Aged, 80 and over ; *Aging/psychology ; Female ; Israel ; Longitudinal Studies ; *Warfare ; }, abstract = {OBJECTIVES: For aging combat veterans, experiencing renewed war in old age can exacerbate coping with age-related challenges. The present study sought to examine how past and current war-related stressors affect long-term trajectories of posttraumatic stress disorder (PTSD) symptoms and views of aging (VoA) among a sample of older adult war veterans during wartime.

METHODS: The participants were 239 combat veterans of the 1973 Yom Kippur War (YKW), randomly selected to complete a longitudinal web-based survey, aged between 69 and 88 years (M = 73.76, SD = 3.66 in T3). The present study relied on data collected before the Israel-Hamas War (T1) and several months into the war (T2 and T3).

RESULTS: Controlling for chronological age and self-rated health, we conducted three path analyses predicting one of three VoA measures (attitudes toward own aging [ATOA], subjective accelerated aging, and subjective age), PTSD symptoms from the YKW, as well as PTSD symptoms from the Israel-Hamas War at T3. Cross-lagged effects revealed that higher PTSD symptoms from the YKW at T2 predicted higher PTSD symptoms from the Israel-Hamas War at T3, but not vice versa. T1 VoA predicted T2 PTSD symptoms from the YKW, and T2 VoA predicted T3 PTSD symptoms from both the current and the past wars, while PTSD symptoms in previous assessments did not predict subsequent VoA.

DISCUSSION: Present findings suggest that exposure to current trauma of war among older adult war veterans might uniquely shape the long-term trajectories of their VoA and PTSD symptoms, while contradicting the previously found PTSD symptoms-VoA directionality.}, } @article {pmid41210442, year = {2025}, author = {Alarfaj, L and Almass, AA and Takrouni, A and Alajmi, S}, title = {Rectus sternalis-a rare anatomical variation found during mastectomy: report of two cases and literature review.}, journal = {AME case reports}, volume = {9}, number = {}, pages = {150}, pmid = {41210442}, issn = {2523-1995}, abstract = {BACKGROUND: Rectus sternalis (RS) is a rare normal variant of the anterior chest wall musculature; in humans, it is occasionally found while it is part of some animals' musculature. It was first reported in 1604, but it did not catch much attention and was only formally described in 1726. Many names have been used to refer to it, such as RS or musculus sternalis. It is mostly observed in Asians, and in Saudi Arabia, the prevalence was found to be 4%. It can be confused with tumors of the anterior chest wall during routine mammography. Also, it can affect the radiation field after surgery and can be utilized in reconstructive surgery. So, we believe that it is important for oncology surgeons, radiologists, radiation oncologists and reconstructive surgeons to have the knowledge of this rare anatomical variation.

CASE DESCRIPTION: We report two cases of RS muscle discovered in Saudi Arabian females during modified radical mastectomy for breast cancer, paying special attention to its correct identification, its clinical importance, and its impact on treatment of breast cancer. The first case is a 47-year-old female with bilateral RS who underwent mastectomy for inflammatory breast cancer, while the second is a 50-year-old female with a unilateral muscle who underwent mastectomy for invasive ductal carcinoma.

CONCLUSIONS: Surgeons should be knowledgeable of such variation as the muscle can be a differential diagnosis, may affect the management of breast cancer, and can be used in reconstructive surgery.}, } @article {pmid41210062, year = {2025}, author = {Matsushima, T and Oura, S}, title = {Subnipple Cyst Formation Is an Important Diagnostic Clue for Mixed-Type Squamous Cell Carcinomas of the Breast: A Case Report.}, journal = {Cureus}, volume = {17}, number = {10}, pages = {e93978}, pmid = {41210062}, issn = {2168-8184}, abstract = {It is well known that breast squamous cell carcinomas (SCCs) have highly cystic components. It, however, is not yet known whether the location of cystic areas contributes to the diagnosis of breast SCCs. A 62-year-old woman with a right breast mass was referred to our hospital. Mammography showed an oval mass just under the right nipple and distortion of the adjacent mammary gland with pleomorphic calcifications. Ultrasound showed a subnipple large oval cystic lesion with solid parts, microcalcifications, and an adjacent polygonal mass, both with a high depth/width ratio and internal punctuate high echoes. Magnetic resonance imaging (MRI) of the masses clarified the connection between the two masses at their deep borders and showed low signals on T1-weighted images and high and slightly high signals at the cyst and mass parts on T2-weighted images, respectively. Core needle biopsy of the solid mass pathologically showed atypical cells growing in tubular and cord-like fashions with connective tissue proliferation, leading to the diagnosis of scirrhous type invasive ductal carcinoma (IDC). The patient, therefore, underwent mastectomy and sentinel node biopsy, showing pathological node negativity on frozen section. Postoperative pathological study showed that the scirrhous type IDC cells were connected to pleomorphic spindle cells and further tied up to SCC cells with central cystic structures. In addition to estrogen and progesterone receptor negativity, immunostaining showed human epidermal growth factor receptor type 2 (HER2) negativity in the IDC components and equivocality in the SCC components. Thereafter, fluorescence in situ hybridization clarified no amplification of human epidermal growth factor receptor type 2 (HER2) genes in the SCC components. The patient recovered uneventfully, received dose-dense chemotherapy, and is scheduled for long-term follow-up on an outpatient basis. Diagnostic physicians should consider mixed-type breast SCCs when breast tumors have cystic structures just under the nipple and an adjacent solid mass.}, } @article {pmid41209903, year = {2025}, author = {Nagata, Y and Kinoshita, I and Saeki, T and Uchiyama, D and Fujikawa, T}, title = {Intertumoral Heterogeneity in Multifocal Breast Cancer Mimicking a Collision Tumor on Imaging: A Case Report.}, journal = {Cureus}, volume = {17}, number = {10}, pages = {e94235}, pmid = {41209903}, issn = {2168-8184}, abstract = {Breast cancer exhibits heterogeneity characterized by intertumor heterogeneity, where distinct lesions present different subtypes, and intratumor heterogeneity, where a single tumor evolves over time. We present a unique case of synchronous, adjacent multifocal breast cancers demonstrating histological findings of distinct molecular subtypes. A 72-year-old woman with a history of ovarian cancer and a family history of breast cancer presented with a right breast lump. Imaging showed two contiguous but distinct lesions. Core needle biopsy identified invasive ductal carcinoma. Immunohistochemistry revealed luminal B and luminal B/human epidermal growth factor receptor 2 (HER2)-positive subtypes. Total mastectomy and sentinel lymph node biopsy were performed, and pathology confirmed two partially fused tumors separated by fibrous stroma. The HER2-positive component demonstrated higher proliferative activity and nuclear grade. Postoperatively, the patient received chemotherapy, anti-HER2 therapy, and remains disease-free on endocrine therapy. This case highlights a rare breast cancer presentation with identical histology but different molecular subtypes mimicking a collision tumor on imaging. It underscores the clinical relevance of tumor heterogeneity and the importance of combining imaging, pathology, and molecular profiling for accurate diagnosis and tailored treatment.}, } @article {pmid41204507, year = {2025}, author = {Tian, C and Wu, J and Wang, Z}, title = {Diagnostic value of automated breast volume scanner for breast ductal carcinoma in situ.}, journal = {Medicine}, volume = {104}, number = {45}, pages = {e45499}, pmid = {41204507}, issn = {1536-5964}, support = {XZ2024ZR-ZY117(Z)//Xizang Autonomous Region Natural Science Foundation Group Medical Aid Project/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology/diagnosis ; Middle Aged ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology/diagnosis ; *Ultrasonography, Mammary/methods ; Adult ; Aged ; Diagnosis, Differential ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Retrospective Studies ; Breast/diagnostic imaging/pathology ; }, abstract = {This study explores the differential diagnostic value of conventional dimensional ultrasound (US) and automated breast volume scanner (ABVS) for breast ductal carcinoma in situ (DCIS) patients. A total of 986 female patients who underwent breast tumor surgery in our hospital from December 2019 to December 2022 were included. Clinical, US, ABVS, and pathological information were collected from all of the patients. Pathological results were used to separate patients into 3 groups: benign, DCIS, and invasive ductal carcinoma (IDC). Single-factor and multivariate analyses were conducted to evaluate the characteristics of DCIS. Of the 986 patients with breast tumors included in this study, 498, 193, and 295 were diagnosed with benign, DCIS, and IDC tumors, respectively. Compared with benign tumors, DCIS tumors were characterized by higher age at onset and breast imaging-reporting and data system (BI-RADS) grades, together with high rates of extension to the nipple, microcalcification, convergence sign, abundant blood supply, and nipple discharge proportion. Relative to IDC patients, DCIS tumors exhibited lower BI-RADS grades, aspect ratio values, and Ki-67 index values together with lower rates of irregular morphology, unclear boundaries, posterior echo attenuation, convergence sign, enhanced peripheral echo, nipple discharge, and palpable masses, and higher rates of extension to the nipple. Higher microcalcification rates in DCIS tumors were observed than the proportion of non-calcification in IDC cases. Conventional US and ABVS images of DCIS tumors exhibit certain distinctive characteristics that can aid in the differential diagnosis of DCIS.}, } @article {pmid41203847, year = {2025}, author = {Bernardino, RM and Lobo, J and Kaouk, J and van der Kwast, T and Prendeville, S and Zattoni, F and Bianchi, L and Martini, A and Rajwa, P and Kasivisvanathan, V and Marra, G and Fleshner, N and , }, title = {Atypical intraductal proliferation in prostate biopsy - a diagnostic grey zone with clinical implications.}, journal = {Nature reviews. Urology}, volume = {}, number = {}, pages = {}, pmid = {41203847}, issn = {1759-4820}, abstract = {Atypical intraductal proliferation (AIP) is considered a borderline lesion, characterized by architectural complexity and cytological atypia greater than that seen in high-grade prostatic intraepithelial neoplasia, but insufficient to fulfil the diagnostic criteria for intraductal carcinoma (IDC). Consequently, AIP remains diagnostically challenging, and the clinical significance of this lesion is still uncertain. Emerging evidence suggests that AIP in prostate biopsy specimens is a strong predictor of unsampled IDC and other adverse pathological features, warranting reconsideration of the AIP role in prostate cancer risk stratification. Results from prospective and molecular studies indicate that AIP frequently coexists with intermediate-risk prostate cancer and shares molecular alterations with IDC, such as PTEN loss and ERG overexpression, reinforcing AIP potential as a marker of occult aggressive disease. Considering the growing emphasis on precision diagnostics and active surveillance in prostate cancer management, understanding the implications of AIP is particularly relevant.}, } @article {pmid41202469, year = {2025}, author = {Esposito, A and Corsaro, L and Delle Cave, I and Nicolella, V and Palladino, R and Affinito, G and Selvaggi, F and Petracca, M and Carotenuto, A and Lanzillo, R and Portella, G and Castaldo, G and Brescia Morra, V and Moccia, M}, title = {Anti-EBV antibody reduction during ocrelizumab treatment is not associated with multiple sclerosis outcomes.}, journal = {Multiple sclerosis and related disorders}, volume = {104}, number = {}, pages = {106830}, doi = {10.1016/j.msard.2025.106830}, pmid = {41202469}, issn = {2211-0356}, mesh = {Humans ; Female ; Male ; Adult ; *Antibodies, Monoclonal, Humanized/therapeutic use/pharmacology ; *Multiple Sclerosis/drug therapy/blood/immunology/virology/diagnostic imaging ; *Immunoglobulin G/blood ; Middle Aged ; *Immunologic Factors/therapeutic use/pharmacology ; *Herpesvirus 4, Human/immunology ; *Antibodies, Viral/blood ; *Epstein-Barr Virus Infections/immunology/drug therapy/complications ; Disease Progression ; Follow-Up Studies ; }, abstract = {BACKGROUND: The pathogenesis of multiple sclerosis (MS) involves genetic, environmental and immunological aspects. Epstein-Barr virus (EBV) infection is recognized as a major risk factor for MS, potentially contributing through infection and transformation of CD20 B cells. Monoclonal antibodies targeting CD20, such as ocrelizumab, may exert therapeutic effects by depleting memory B cells harbouring latent EBV.

OBJECTIVE: We aim to evaluate changes in serum anti-EBV immunoglobulin G (IgG) titres and clinical correlates during ocrelizumab treatment.

METHODS: We analysed serum samples from 58 patients treated with ocrelizumab, with levels of total IgG, anti-CMV IgG, and anti-EBV IgG before treatment initiation and after mean follow-up of 4.8 ± 1.5 years. Statistical analyses included paired t-tests to evaluate longitudinal changes in antibody levels, and linear regression models to investigate associations between IgG changes and relapse occurrence, MRI activity, EDSS progression and their combination.

RESULTS: Over 4.8 ± 1.5 years, we observed significant reductions in anti-EBV IgG (percentage mean change -8.2%, p = 0.03), comparable to the decline in total IgG (-8.8%, p < 0.01) and anti-CMV IgG (-7.8%, p < 0.01). No significant associations were identified between changes in anti-EBV IgG and different outcomes.

CONCLUSIONS: Ocrelizumab treatment was associated with reductions in total, anti-EBV and anti-CMV IgGs. Antibody-mediated response to EBV was not associated with disease worsening.}, } @article {pmid41201012, year = {2025}, author = {Ozer, SP and Ozer, B and Aktas, G}, title = {Tumor budding in preoperative breast biopsies predicts sentinel lymph node metastasis.}, journal = {Biomolecules & biomedicine}, volume = {26}, number = {4}, pages = {662-667}, pmid = {41201012}, issn = {2831-090X}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/surgery ; Sentinel Lymph Node Biopsy ; Lymphatic Metastasis/pathology ; Middle Aged ; Aged ; Adult ; *Carcinoma, Ductal, Breast/pathology/surgery ; *Sentinel Lymph Node/pathology ; Preoperative Care ; Preoperative Period ; }, abstract = {Sentinel lymph node biopsy (SLNB) is a pivotal technique employed to assess the necessity for axillary lymph node dissection (ALND), evaluated during the preoperative phase through clinical and radiological findings. The preoperative identification of sentinel lymph node metastasis has gained paramount importance in the surgical management of breast cancer. Tumor budding (TB) has emerged as a significant prognostic marker across various cancers, including breast cancer, where it is instrumental in detecting lymph node metastasis. This study aims to investigate the role of tumor budding in predicting sentinel lymph node metastasis in preoperative breast biopsies. We included patients diagnosed with breast cancer, specifically those with invasive ductal carcinoma (IDC), who underwent preoperative needle biopsy and subsequent evaluation of postoperative surgical specimens, as well as SLNB at our medical center. The histological slides of these cases were reevaluated, and tumor cell clusters comprising up to four cells were classified as TB. Lymph nodes exhibiting tumor cell involvement, limited to macrometastasis, were classified as positive. A total of 65 patients were enrolled in the study. Among these, 36 patients exhibited TB in their preoperative biopsies, while 29 did not. The median tumor sizes were 20 mm (range: 6-50 mm) in the TB-positive group and 19 mm (range: 2-50 mm) in the TB-negative group (p=0.3). Sentinel lymph node metastasis was detected in 18 patients with TB, compared to only five patients without TB, a difference that was statistically significant (p=0.006). We conclude that evaluating tumor budding in breast tru-cut specimens, in conjunction with clinical and radiological findings, may enhance the preoperative assessment of breast cancer cases requiring SLNB.}, } @article {pmid41199830, year = {2025}, author = {Gao, X and Li, M and Hong, J and Wu, Y and Fu, T and Song, D}, title = {Case Report: A rare case of thyroid metastasis from breast cancer.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1692891}, pmid = {41199830}, issn = {2234-943X}, abstract = {INTRODUCTION: To analyze the clinicopathological features, diagnosis, and treatment strategies for metastatic breast carcinoma to the thyroid (MBCT) to enhance clinical awareness of this rare condition.

METHODS: Analysis of clinical data from one MBCT patient and literature review.

RESULTS: A 41-year-old female with left breast invasive ductal carcinoma (IDC) received neoadjuvant AC-T chemotherapy, breast-conserving surgery, radiotherapy, and endocrine therapy. At eight years post-diagnosis, thyroid lesions were detected. Total thyroidectomy with lymph node dissection confirmed MBCT pathologically. No progression was observed at 16 months post-thyroidectomy.

CONCLUSIONS: MBCT is a rare clinical entity characterized by nonspecific clinical and radiological findings. Immunohistochemical (IHC) analysis is essential for a definitive diagnosis. In patients with a breast cancer history, MBCT should always be considered in the differential diagnosis of thyroid abnormalities.}, } @article {pmid41199347, year = {2025}, author = {Wounounou, G and Tiono, AB and Ogutu, B and Manyando, C and Sagara, I and Schneitter, S and Bassat, Q and Gaaloul, ME and Marrast, AC and Demin, I and Winnips, C and Risterucci, C and Hugot, S and Hofstetter, G and Qian, Z and Su, G and Zhang, J and Renner, KC and Cousin, M and Venishetty, VK and Sayyed, S and Gandhi, P and Kabore, B and , }, title = {Pharmacokinetics, safety and efficacy of an optimized dose of artemether-lumefantrine in the treatment of acute uncomplicated Plasmodium falciparum malaria in neonates and infants of less than 5 kg body weight: a multicentre, open-label, single-arm phase 2/3 study (CALINA).}, journal = {Tropical medicine and health}, volume = {53}, number = {1}, pages = {151}, pmid = {41199347}, issn = {1348-8945}, support = {EDCTP2 Grant number RIA2018SD-2306//Novartis, Medicines for Malaria Venture, PAMAfrica consortium, European & Developing Countries Clinical Trials Partnership/ ; }, abstract = {BACKGROUND: Treatment recommendations for malaria in infants of < 5 kg body weight (BW) are not evidence-based. Due to pharmacokinetic characteristics of this population, weight-based dose adjustments for antimalarials may be suboptimal. The 20 mg artemether:120 mg lumefantrine dispersible tablet, even with dose adjustment, may lead to artemether over-exposure and reduced lumefantrine exposure in patients < 5 kg. PBPK modelling predicted that a 1:12 artemether:lumefantrine ratio dispersible tablet should match efficacious and safe drug exposures in patients 5- < 15 kg treated with the current artemether-lumefantrine dispersible tablet: the CALINA study used an exposure-matching approach to confirm that drug exposures were comparable.

METHODS: Sequential age cohorts (Cohort 1: > 28 days; Cohort 2: 1-28 days) of patients < 5 kg with Plasmodium falciparum malaria received the new artemether-lumefantrine dispersible tablet (each dose 5 mg artemether: 60 mg lumefantrine) twice daily for 3 days. Artemether Cmax, and lumefantrine C168h and Cmax were compared with historical data from patients 5- < 15 kg treated with the current artemether-lumefantrine dispersible tablet. The primary endpoint was met if the 90% CI for artemether Cmax contained the LS mean value from historical data (101 ng/mL). PCR-corrected and uncorrected ACPR at Days 15, 29 and 43 and parasite clearance time were evaluated. Adverse events, laboratory evaluations, and developmental assessments were performed.

RESULTS: In Cohort 1 (N = 22), geometric mean artemether Cmax was 68.0 ng/mL (90% CI 45.1,103 ng/mL); therefore, Cmax was comparable to that in historical data, meeting the primary endpoint. In Cohort 2 (N = 6), there were too few patients for formal analysis, but geometric mean artemether Cmax was comparable to that in Cohort 1 (62.2 ng/mL, 90% CI 33.6,115 ng/mL). In both cohorts, lumefantrine C168h and Cmax were comparable to historical data. PCR-corrected Day 29 ACPR was 95.5% and 100% in Cohorts 1 and 2, respectively. Treatment was well-tolerated. Developmental assessments at 12 months of age were within the normal range.

CONCLUSIONS: The optimized dose of artemether-lumefantrine (5 mg/60 mg) achieves the exposures required for optimal efficacy and safety in patients < 5 kg body weight with P. falciparum malaria, consistent with those in patients 5- < 15 kg treated with the current dispersible tablet (20 mg/120 mg).

TRIAL REGISTRY: Clinicaltrials.gov: NCT04300309.}, } @article {pmid41199300, year = {2025}, author = {Mustafa, A and Armaghan, M and Shabbir, M and Badshah, Y and Khan, K and Meraj, L and Trembley, JH and Afsar, T and Almajwal, A and Razak, S}, title = {Role of PRKCZ non-synonymous genetic variants in breast cancer development.}, journal = {Cancer cell international}, volume = {25}, number = {1}, pages = {390}, pmid = {41199300}, issn = {1475-2867}, abstract = {BACKGROUND: Non- synonymous single nucleotide polymorphisms (nsSNPs) impact disease onset and progression. Protein kinase C zeta (PRKCZ) is involved in oncological, neurological, and diabetes pathogenesis. The goal of the research presented here was to investigate the role of nsSNPs in PRKCZ in breast cancer (BC) pathogenesis.

METHODS: Genotyping analysis was performed to determine the association of PRKCZ genetic variants rs1236161858 (G/T), rs367917640 (G/A/C), rs202071893(A/G), and rs757469768(G/A) with BC risk and clinicopathological variables through Tetra-ARMS PCR.

RESULTS: rs1236161858(G/T) was linked to higher BC risk in codominant (OR = 5.227, RR = 2.225), allele model, (OR = 4.701, and RR = 2.186) and log additive (OR = 2.564). rs367917640 (G/A) was associated with increased BC risk in codominant model (OR = 6.419, RR = 2.350), recessive model (OR = 12.09 and, RR = 4.772) and log additive (OR = 3.340). rs367917640(G/C) was linked to higher BC risk in dominant (OR = 4.892, RR = 2.208), recessive (OR = 1.859, RR = 1.34), over dominant (OR = 3.675, RR = 2.028) and log additive (1.579) models respectively. For rs202071893(A/G) codominant model (OR = 2.295 RR = 1.547), dominant model (OR = 5.943, and RR = 1.781) and over dominant model (OR = 3.433, and RR = 1.974) showed significantly higher BC association. rs757469768(G/A) was linked to higher BC risk in both dominant (OR = 0.1479, and RR = 0.4688) and over dominant (OR = 2.005, and RR = 1.455) models. However, rs757469768(G/A) was associated with reduced BC risk in log additive model (OR = 0.4956).rs1236161858 correlated with DCIS and IDC. rs367917640(G/A/C) correlated with early cancer stage, LCIS, DCIS, IDC, luminal A and post-menopause. rs202071893 was associated with HER2[+]and IDC. rs757469768 was not associated with clinicopathological features and risk factors.

CONCLUSION: All five nsSNPs exhibited potential as predictive and prognostic biomarkers for BC. However, the current study findings should be validated by conducting research on large cohorts with representation from diverse population. Furthermore, biological mechanism by which these nsSNPs cause BC pathogenesis could be explored in future studies.}, } @article {pmid41190515, year = {2026}, author = {Dupuis, R and Fort, N and Mousset, C and Bruyère, F and Fromont, G}, title = {Spatial Characteristics of Intraductal Carcinoma of the Prostate.}, journal = {The Prostate}, volume = {86}, number = {3}, pages = {349-356}, doi = {10.1002/pros.70091}, pmid = {41190515}, issn = {1097-0045}, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/metabolism/surgery/genetics ; Aged ; Biomarkers, Tumor/metabolism ; Middle Aged ; *Carcinoma, Ductal/pathology/metabolism ; Receptors, Androgen/metabolism ; Tumor Suppressor Protein p53 ; *Prostate/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology/metabolism ; Ki-67 Antigen/metabolism ; Prostatectomy ; B7-H1 Antigen ; Glucose Transporter Type 1 ; PTEN Phosphohydrolase ; }, abstract = {BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is most often considered a retrograde spread of invasive prostate cancer (PCa) into prostatic ducts, and its presence is associated with a poor prognosis. The aim of our study was to evaluate the differential expression between IDC-P and the associated invasive component and the heterogeneity of expression within IDC-P foci.

METHODS: We studied 79 cases of PCa with an intraductal component treated by prostatectomy. TMA blocks were constructed with the intraductal and invasive components and used for immunohistochemical analysis of markers involved in the cell cycle, androgen signaling, hypoxia, DNA repair, and immune checkpoints.

RESULTS: We found a good concordance of expression between both components for ERG, PTEN, p53, and MMR genes, which nevertheless show in some cases a loss restricted to the intraductal component. The expression of Ki67, PD-L1, and GLUT1 was increased in IDP-C compared to the invasive component. Furthermore, spatial heterogeneity was observed in the intraductal component: Ki67, ERG, androgen receptor and p53 were more expressed in the periphery of the lesion, while the expression of PD-L1 and GLUT1 was restricted to the center.

CONCLUSIONS: Our results support a relatedness between invasive PCa and IDC-P, and show increased expression of markers related to PCa aggressiveness in the intraductal component. The spatial heterogeneity within IDC-P suggests a higher degree of hypoxia in the center of the lesion. Increased PD-L1 expression and loss of expression of some MMR genes in IDC-P could lead to increased sensitivity to immunomodulatory treatments.}, } @article {pmid41188210, year = {2026}, author = {Shi, H and Wang, Y and Miyamoto, H}, title = {Intraductal Carcinoma of the Prostate With a Solid Nest Pattern May Be More Aggressive Than Gleason Grade 5 Conventional Prostatic Adenocarcinoma.}, journal = {The American journal of surgical pathology}, volume = {50}, number = {2}, pages = {156-162}, doi = {10.1097/PAS.0000000000002480}, pmid = {41188210}, issn = {1532-0979}, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/mortality/surgery ; Neoplasm Grading ; Retrospective Studies ; Aged ; Middle Aged ; Prostatectomy ; *Adenocarcinoma/mortality/pathology/surgery ; Disease-Free Survival ; Kaplan-Meier Estimate ; Treatment Outcome ; Proportional Hazards Models ; Risk Factors ; }, abstract = {The grading of intraductal carcinoma of the prostate (IDC-P) associated with conventional prostatic adenocarcinoma (CPA) remains controversial, particularly regarding whether IDC-P exhibiting a solid nest pattern is prognostically equivalent to Gleason grade 5 CPA. We retrospectively analyzed consecutive radical prostatectomy patients with grade 5 CPA as a primary, secondary, or tertiary pattern, as well as cribriform IDC-P, while excluding cases exhibiting comedonecrosis within IDC-P. We then compared clinicopathologic features and long-term oncologic outcomes between those with (n=28 [24.3%]) and without (n=87 [75.7%]) solid-pattern IDC-P. Solid IDC-P cases were significantly associated with a higher incidence of lymph node metastasis, larger estimated tumor volume, and more frequent administration of adjuvant therapy immediately after prostatectomy. No significant differences were observed in preoperative prostate-specific antigen, Grade Group, pT stage, or surgical margin status between the 2 groups. Univariate analysis revealed significantly worse biochemical recurrence-free survival (P =0.010) and cancer-specific survival (P =0.003) in patients with solid IDC-P. In multivariable Cox regression analyses, solid IDC-P remained significantly predictive of postoperative recurrence when adjusting for prognostic factors, including Grade Group (hazard ratio 1.902, P =0.039) or the percentage of pattern 5 (hazard ratio 1.986, P =0.028). Solid-pattern IDC-P was thus found to represent an independent adverse prognostic indicator in men undergoing radical prostatectomy, further suggesting that the clinical impact of solid IDC-P versus Gleason grade 5 CPA (or cribriform IDC-P) was not comparable. It might therefore be inadequate to simply translate solid IDC-P as a grade 5 pattern.}, } @article {pmid41184956, year = {2025}, author = {Kang, E and Shin, IB and Jung, JJ and Byeon, J and Choi, Y and Cheun, JH and Lee, HB and Han, W and Kim, HK and Moon, HG}, title = {Differential prognostic significance of tumor size and node in invasive lobular carcinoma of breast.}, journal = {Breast cancer research : BCR}, volume = {27}, number = {1}, pages = {194}, pmid = {41184956}, issn = {1465-542X}, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common histological type of breast cancer. Despite its distinct clinical and pathological characteristics, ILC shares the same prognostic classification system and adjuvant treatment strategies as invasive ductal carcinoma (IDC).

METHODS: We reviewed the data of the 16,365 IDC and ILC patients who were treated between 2005 and 2022 at Seoul National University Hospital (SNUH). Also, we conducted a parallel analysis using the data of 247,290 IDC and ILC treated between 2010 and 2015 from the surveillance, epidemiology, and end results (SEER) database.

RESULTS: ILC patients were older at diagnosis, had larger tumors, and ILC tumors were predominantly HR-positive/HER2-negative. ILC exhibited unique prognostic implications of anatomic features. Unlike in IDC, the tumor size and nodal status showed differential prognostic impact on survival in ILC. While there was no significant survival difference for different T stages in ILC patients, the prognostic impact of nodal involvement was more pronounced for ILC in the SNUH dataset. Similar survival implication of tumor size and nodal involvement was observed for the ILC cases in the SEER dataset.

CONCLUSION: In ILC, tumor size may not be as strong a predictor of survival as in IDC, while advanced nodal involvement carries a particularly high risk for breast cancer-specific mortality.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-025-02141-3.}, } @article {pmid41183358, year = {2025}, author = {Jimenez Arranz, S and Pizarro, F and Fernandez Matamoros, MA and Torrens, J and Sotolongo, L and Fernandez, MT and Gonzalez, R and Delgado, M and Sanz, C and Ciruelos, E and Martinez, M and Martin Arriscado, C and Khan, AM and Nawaz, NE and Grobmyer, S and Albillos, JC}, title = {Vacuum-assisted Biopsy and Surgical Correlation in HER2-positive and Triple-Negative Breast Cancer Subtypes in MRI Responders After Neoadjuvant Systemic Therapy. BISUCO TRIAL.}, journal = {Journal of breast imaging}, volume = {7}, number = {6}, pages = {664-675}, doi = {10.1093/jbi/wbaf036}, pmid = {41183358}, issn = {2631-6129}, support = {i12-AY12-2018//Hospital Universitario 12 de Octubre, Madrid/ ; }, mesh = {Humans ; Female ; Neoadjuvant Therapy ; Middle Aged ; *Triple Negative Breast Neoplasms/pathology/diagnostic imaging/drug therapy/surgery ; Prospective Studies ; *Magnetic Resonance Imaging/methods ; *Image-Guided Biopsy/methods ; Vacuum ; Adult ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Aged ; *Breast Neoplasms/pathology/diagnostic imaging ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: To evaluate the diagnostic efficacy of 7G image-guided vacuum-assisted biopsy (VAB) in predicting pathological complete response (pCR) after neoadjuvant systemic therapy (NST) in HER2+ or triple-negative (TN) breast cancer (BC) showing complete response (CR) or almost-CR on MRI.

METHODS: A prospective study was conducted from June 2018 to October 2022 on 25 HER2+ or TN operable BC patients who achieved CR or almost-CR on post-NST MRI. Presurgery, stereotactic or US-guided 7G VAB of the tumor bed was performed, and the pathological findings were compared with surgical results to evaluate the negative predictive value (NPV), accuracy, sensitivity, positive predictive value (PPV), and specificity in predicting residual disease.

RESULTS: All tumors were invasive ductal carcinoma, with TN BC accounting for 52% (13/25) and HER2+ for 48% (12/25). MRI showed CR in 60% (15/25) of cases and almost-CR in 40% (10/25). Stereotactic VAB was performed in 84% (21/25) of cases and US-VAB in 16% (4/25), using 7G needles (average 10 samples) in all the cases. Posttreatment changes were demonstrated in all cases. Pathological CR was observed in 80% (20/25) of VAB cases and 84% (21/25) of surgical cases. Vacuum-assisted biopsy had a 100% NPV (95% CI, 83.2-100.0), 97.6% accuracy (95% CI, 92.9-100.0), 100% sensitivity (95% CI, 39.8-100.0), 80% PPV (95% CI, 28.4-99.5), and 95.2% specificity (95% CI, 76.2-99.9).

CONCLUSION: Image-guided VAB with 7G needles in HER2+ or TN BC with CR or almost-CR in post-NST MRI demonstrated a 100% NPV for detecting residual carcinoma when sample correlation and representativeness were ensured. Additional studies with larger patient cohorts are needed to confirm these promising results and to potentially omit surgery through image-guided VAB in selected TN BC and HER2+ BC cases.}, } @article {pmid41181894, year = {2025}, author = {Zainurin, NAA and Morphew, RM and Ganti, A and Ivanova, D and Gate, T and Tench, H and Phillips, H and Pennick, M and Mur, LAJ}, title = {The Urinary Proteome Differs with the Presence and Type of Breast Cancer.}, journal = {Journal of proteome research}, volume = {24}, number = {12}, pages = {5932-5947}, pmid = {41181894}, issn = {1535-3907}, mesh = {Humans ; Female ; *Breast Neoplasms/urine/diagnosis/pathology/classification ; *Proteome/analysis ; *Biomarkers, Tumor/urine ; Middle Aged ; Adult ; Proteomics/methods ; *Carcinoma, Ductal, Breast/urine/diagnosis/pathology ; *Carcinoma, Intraductal, Noninfiltrating/urine/diagnosis/pathology ; Aged ; ROC Curve ; }, abstract = {Despite advancements in screening and treatment, the incidence of breast cancer (BC) and associated mortality are projected to increase. Therefore, developing a companion diagnostic for BC remains important. Herein, we explore the urinary proteome for biomarkers of BC: 130 urine samples from (1) newly diagnosed breast cancer (BC), n = 46, (2) benign breast disease (BBD), n = 36, (3) symptom control (SC), n = 30, and (4) healthy control (HC), n = 18. The BC class included preinvasive: ductal carcinoma in situ (DCIS) (n = 3), invasive ductal carcinoma (IDC) (n = 23), and IDC accompanied by DCIS (n = 8) classes. Protein profiling was performed using ThermoScientific ProteomeDiscoverer and analyzed using MetaboAnalyst v6.0, DAVID, and STRING v12.0. Analyses identified 346 significantly (p < 0.05) differentially expressed proteins (DEP) across BC, BBD, SC, and HC. Multivariate Receiver Operating Characteristic curves (five proteins) suggested Area Under the Curve values of 0.985, 0.989, and 0.999 distinguishing BC from BBD, SC, and HC, respectively. DEP elevated in BC included beta-glucuronidase isoform 1, fibrinogen gamma chain, alpha-actinin-1, peptidase inhibitor 16, cysteine-rich C-terminal protein 1 isoform X1, guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, vascular cell adhesion protein 1, ATP-dependent translocase ABCB1, and tumor protein p63-regulated gene 1 isoform X1. BC types were differentiated based on calpain-2 and cystatin-C expression (p < 0.05). Thus, BC has distinct urinary-protein profiles based on clinical diagnosis, which could be used in real-time noninvasive BC monitoring.}, } @article {pmid41180847, year = {2026}, author = {Xing, X and Li, J and Wang, Y and Zhang, S and Li, J and Wang, Y and Zhang, D and Liao, D}, title = {Advanced dual primary male breast cancer and lung cancer: A case report and literature review.}, journal = {Oncology letters}, volume = {31}, number = {1}, pages = {2}, pmid = {41180847}, issn = {1792-1082}, abstract = {The current report presents a unique case of advanced male invasive breast cancer coexisting with synchronous primary lung adenocarcinoma, a rare clinical manifestation. The case contributes to the limited literature on male breast cancer and its association with multiple primary malignancies. The patient, a 59-year-old man, presented with a large ulcerative mass in the left breast (14×10 cm) and ground-glass opacities with calcified nodules in the right lower lung lobe (14×14 mm). Imaging and pathology confirmed stage IIIB invasive ductal carcinoma of the breast [human epidermal growth factor receptor-2-positive, estrogen receptor-positive (80%) and progesterone receptor-positive (5%)] and minimally invasive lung adenocarcinoma. Treatment consisted of neoadjuvant chemotherapy (epirubicin + carboplatin + trastuzumab + pertuzumab), a modified radical mastectomy with latissimus dorsi flap reconstruction and a thoracoscopic lung wedge resection. The therapeutic approach resulted in partial remission of the breast cancer prior to surgery and a stable disease status in the lung, with no recurrence at the 1-year follow-up. This case underscores the importance of comprehensive, integrative strategies and long-term follow-up for managing rare, complex cancer cases.}, } @article {pmid41179678, year = {2025}, author = {Baracioli, LS and Rezende, CP and Dos Santos E Silva, L and Alves, DL and da Nóbrega, DF and Chuffa, LGA and Zuccari, DAPC}, title = {Immunohistochemical analysis of Enolase-1 sublocalization in benign and malignant breast tumors: potential implications for tumor progression and prognosis.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1636394}, pmid = {41179678}, issn = {2234-943X}, abstract = {Breast cancer is the second most common neoplasm in women and one of the main causes of premature mortality, with a high incidence before the age of seventy. Among its histological subtypes, invasive ductal carcinoma accounts for approximately 65% to 70% of cases and is characterized by significant molecular and prognostic heterogeneity. Although some molecular subtypes benefit from targeted therapies, triple-negative carcinomas remain a considerable clinical challenge, predominantly affecting young women who often subjected to highly aggressive and not always effective conventional treatments. The identification of prognostic and predictive biomarkers is essential to optimize therapeutic choices and anticipate potential resistance mechanisms. Enolase-1 (ENO1), a glycolytic enzyme involved in cellular energy homeostasis, has been widely associated with tumor progression and metabolic adaptation in malignant neoplasms. In this study, we investigated ENO1 expression in benign and malignant breast tumors using immunohistochemistry, analyzing both the tissue distribution pattern and staining intensity. Our results suggest that ENO1 may play a predictive diagnostic role, aiding in more individualized therapeutic strategies and contributing to the advancement of precision medicine in breast cancer.}, } @article {pmid41176719, year = {2025}, author = {Katai, Y and Kamitori, T and Saida, S and Uchihara, Y and Akazawa, R and Isobe, K and Mikami, T and Kubota, H and Kato, I and Umeda, K and Ueno, H and Takita, J}, title = {Clinical Impact of Immunoglobulin Heavy Chain Clonality in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia.}, journal = {Cancer medicine}, volume = {14}, number = {21}, pages = {e71336}, pmid = {41176719}, issn = {2045-7634}, support = {JP19ck0106468//Japan Agency for Medical Research and Development/ ; 23ama221505//Foundation for Promotion of Cancer Research/ ; JP24ama221236//Foundation for Promotion of Cancer Research/ ; //Takeda Science Foundation/ ; //Princess Takamatsu Cancer Research Fund/ ; JP17H04224//Japan Society for the Promotion of Science/ ; JP18K19467//Japan Society for the Promotion of Science/ ; JP20H00528//Japan Society for the Promotion of Science/ ; JP21K19405//Japan Society for the Promotion of Science/ ; JP23K18264//Japan Society for the Promotion of Science/ ; JP24H00628//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Immunoglobulin Heavy Chains/genetics ; *Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics/mortality/immunology/pathology ; Child ; Male ; Female ; Child, Preschool ; Neoplasm, Residual/genetics ; Prognosis ; Adolescent ; Infant ; }, abstract = {INTRODUCTION: Recent advancements in risk stratification have greatly improved outcomes in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Despite favorable prognostic indicators, including the absence of cytogenetic abnormalities and minimal residual disease (MRD) negativity, relapse remains a major clinical concern.

METHODS AND RESULTS: We investigated the clinical significance of immunoglobulin heavy chain (IGH) clonality using RNA sequencing data in BCP-ALL. We analyzed IGH clonality from 136 patients. IGH abundance followed a power law distribution, which enabled us to identify disease clones as outliers based on read count. In total, 330 disease clones were detected, and patients were categorized into three clonotype groups: undetectable disease clone (UDC), incomplete disease clone (IDC), and complete disease clone (CDC). Clinical outcomes were compared across clonotypes, including in subgroups with high hyperdiploidy (HHD) and MRD negativity. Among patients with HHD, significant prognostic differences were observed across clonotypes (event-free survival [EFS], p = 0.01; overall survival [OS], p = 0.08), even among those who were MRD-negative (EFS, p = 0.01; OS, p = 0.03). Furthermore, comparisons of IGH sequences between diagnosis and relapse indicated that while initial disease clones often contributed to relapse, newly expanded clones frequently emerged, particularly in patients with HHD.

CONCLUSIONS: These findings highlight the importance of analyzing the IGH repertoire in refining risk stratification and underscore the need for advanced sequencing-based MRD monitoring.}, } @article {pmid41176437, year = {2026}, author = {Kaba, E and Tören, M and Asan, B and Çubukçu, Y and Öztürk, G and Okcu, O and Öztürk, Ç and Çubukçu, SS and Cinoğlu, RS and Özer, E and Çeliker, FB and Hürsoy, N}, title = {Comparative Evaluation of Advanced Deep Learning, Image-to-Text Models, and Radiomics for Predicting Tumor Budding and Tumor-Stroma Ratio from Breast Ultrasound in Invasive Ductal Carcinoma.}, journal = {Academic radiology}, volume = {33}, number = {1}, pages = {61-76}, doi = {10.1016/j.acra.2025.10.020}, pmid = {41176437}, issn = {1878-4046}, mesh = {Humans ; Female ; *Deep Learning ; *Breast Neoplasms/diagnostic imaging/pathology ; *Ultrasonography, Mammary/methods ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Middle Aged ; Adult ; *Image Interpretation, Computer-Assisted/methods ; Aged ; Neoplasm Invasiveness ; Radiomics ; }, abstract = {RATIONALE AND OBJECTIVES: This study aimed to predict tumor budding (TB) and tumor-stromal ratio (TSR), which are important parameters of the tumor microenvironment in invasive ductal carcinoma, from preoperative ultrasound images. To this end, image classification-based deep learning (DL), image-to-text-based DL, and radiomics-based machine learning (ML) approaches were compared.

MATERIALS AND METHODS: We included 153 patients diagnosed with histopathologically invasive ductal carcinoma. TB and TSR were classified into two groups, "low" and "high," and separate models were developed for each dataset. Three different methodological approaches were applied: (1) advanced image classification DL models (YOLOv11x-cls, DINOv2, Vision Transformer [ViT]), (2) the Bootstrapping Language-Image Pre-training (BLIP-2) model that converts images to text, and (3) ML algorithms with radiomic features (KNN, SVM, XGBoost). All models were trained on the training set, and their performance was then evaluated on the validation and test sets.

RESULTS: In TB prediction, the XGBoost model demonstrated the most superior performance (AUC: 0.87, accuracy: 0.87 on the validation set; AUC: 0.76, accuracy: 0.78 on the test set). In contrast, image classification-based DL models yielded lower AUC values ranging from 0.55 to 0.71 on the validation set, while the BLIP-2 model achieved an AUC value of 0.67. In the TSR prediction, XGBoost showed the highest discriminatory ability (AUC: 0.92, accuracy: 0.92 in the validation set; AUC: 0.84, accuracy: 0.85 in the test set). In contrast, image classification-based DL models exhibited AUC values ranging from 0.54 to 0.75 in the validation set, while the BLIP-2 model exhibited an AUC of 0.65.

CONCLUSION: The findings obtained indicate that radiomics-based ML models show promise in non-invasive TB and TSR prediction using ultrasound images in breast cancer. The clinical integration of these approaches could significantly contribute to the development of personalized treatment strategies for invasive ductal carcinoma and enhance patient management.}, } @article {pmid41174672, year = {2025}, author = {Dyer, SM and Kwok, WS and Dawson, R and Cameron, ID and Sherrington, C}, title = {Should whole body vibration be used for falls prevention in older people living in the community?.}, journal = {Systematic reviews}, volume = {14}, number = {1}, pages = {209}, pmid = {41174672}, issn = {2046-4053}, support = {1198371//NHMRC-funded Prevention of Falls Injuries Centre for Research Excellence/ ; }, mesh = {Aged ; Humans ; *Accidental Falls/prevention & control ; Independent Living ; *Vibration/therapeutic use ; Systematic Reviews as Topic ; Network Meta-Analysis as Topic ; }, abstract = {The Canadian Task Force on Preventive Health Care has recently published a systematic review and network meta-analysis that concludes that whole-body vibration (WBV) has moderate-certainty evidence for falls prevention for older people living in the community. However, as Cochrane Collaboration falls prevention review authors and clinicians, we suggest that when the range of possible effects captured with the 95% confidence intervals, the likelihood of adverse events and the lack of evidence for effectiveness in older people living in care facilities are taken into account, that this intervention should be implemented with caution in this population. Outside of the clinical trial setting, WBV in this population should only be implemented following an individually tailored assessment and with guidance from an appropriately trained health professional.}, } @article {pmid41169604, year = {2025}, author = {Zheng, M and Yao, L and Jing, N and Wang, Y and Wang, X and Yang, J}, title = {Personalized Treatment for Invasive Ductal Breast Carcinoma with Lung and Liver Metastases Based on Patient-Derived Organoids: A Case Report.}, journal = {OncoTargets and therapy}, volume = {18}, number = {}, pages = {1189-1194}, pmid = {41169604}, issn = {1178-6930}, abstract = {Patient-derived organoids (PDOs) are emerging as a potential preclinical tool in assessing cancer patients' responses to various therapies. Here, we first described a case of invasive ductal breast carcinoma with lung and liver metastases who obtained efficient response to the sensitive drugs identified by PDOs. A 54-year-old woman came to hospital with the chief complaint of an unpainful mass in the right breast. In combination with relevant examinations, she was diagnosed with cT3N1M0 breast cancer with HER2 amplification, but developed lung and liver metastases after use of multiple therapies. After treatment with erebulin, carboplatin and inetetamab sensitive revealed by the organoid drug sensitivity testing, partial response in lung metastasis and stable disease in liver metastasis were achieved. This typical case suggests that for the individual patients with advanced refractory breast cancer, especially those exhausting the standard treatment options, the PDOs may serve as an effective model for assessing individual drug sensitivity to optimize treatment decisions and improve treatment response.}, } @article {pmid41162834, year = {2025}, author = {Abdullah, HM and Boi-Dsane, NAA and Wepeba, G and Dakurah, T}, title = {Intradural Extramedullary Spinal Cord Metastasis of Breast Cancer in a Male: A Case Report.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {8}, number = {11}, pages = {e70382}, pmid = {41162834}, issn = {2573-8348}, mesh = {Humans ; Male ; *Breast Neoplasms, Male/pathology/surgery ; Aged ; *Spinal Cord Neoplasms/secondary/diagnosis ; *Carcinoma, Ductal, Breast/secondary/pathology/surgery ; Magnetic Resonance Imaging ; Fatal Outcome ; Mastectomy ; }, abstract = {INTRODUCTION: Breast cancer in males is rare, accounting for just 0.5% to 1% according to World Health Organization data. This is the first reported case of IESCM from breast cancer in an African male, which makes it noteworthy. Furthermore, unlike previously reported cases in females, this case involved L1-L2 metastasis with sphincter dysfunction and a subsequent relapse leading to mortality, thereby expanding the documented spectrum of IESCM presentations and outcomes.

CASE PRESENTATION: This is a case of a 77-year-old male with invasive ductal carcinoma of the left breast and intradural extramedullary spinal cord metastasis diagnosed via Magnetic Resonance Imaging after presenting with neurological symptoms 4 years post-mastectomy. He eventually passed away following a right Deep Venous Thrombosis, which led to bilateral pulmonary embolism after his second relapse.

CONCLUSION: Late presentation most likely contributed to the worsening of symptoms and poor prognosis. This report overstates the importance of prompt access to healthcare and the essence of thorough investigations, especially in breast cancer, where neurological symptoms may point to a metastatic diagnosis.}, } @article {pmid41155877, year = {2025}, author = {Kobayakawa, S and Matsunaga, T and Otake, H and Hino, S and Ogata, F and Misra, M and Kanai, K and Kawasaki, N and Nagai, N}, title = {Solid Tranilast Nanocrystal-Loaded Cationic Contact Lenses for Sustained Ocular Drug Delivery.}, journal = {Pharmaceutics}, volume = {17}, number = {10}, pages = {}, pmid = {41155877}, issn = {1999-4923}, abstract = {Background/Objectives Conventional eye drops are the primary therapeutic option for ocular diseases; however, their clinical utility is hindered by several drawbacks, including limited bioavailability and suboptimal patient compliance. To overcome these challenges, we designed a sustained-release contact lens (CL) device loaded with tranilast (TRA) and determined whether the TRA-laden CL could provide sustained drug delivery to the lacrimal fluid and aqueous humor. Methods TRA nanocrystals were prepared using the bead-milling approach. Using three types of CLs (nonionic, anionic, and cationic), we prepared TRA-laden CLs by employing a combination of solid TRA nanocrystals and soaking methods under high-temperature and high-pressure conditions in an autoclave (the hThP method). Male Japanese albino rabbits (2-3 kg) were used to evaluate the CLs. Results Bead milling reduced the size of the solid TRA nanoparticles (STNs) to approximately 35-180 nm. The TRA-laden cationic CLs prepared using STNs and the hThP method contained a higher amount of TRA than those prepared using the corresponding conventional soaking method. The CLs prepared using the hThP method remained transparent after drug loading. Compared with nonionic and anionic CLs, cationic CLs had the highest drug-loading capacity and allowed for sustained drug release. Moreover, STNs were observed in the released TRA, with no corneal damage or light scattering detected in the rabbits' eyes. TRA-laden cationic CLs prepared using the hThP method achieved sustained and higher drug delivery into the lacrimal fluid and aqueous humor than those prepared using the conventional soaking method. Conclusions Our findings suggest that TRA-laden cationic CLs prepared using STNs and the hThP method can overcome the challenges associated with the conventional soaking method, including low drug uptake and high burst release.}, } @article {pmid41151888, year = {2025}, author = {Yang, M and Han, J and Won, H and Chae, SW and Kim, HS and DO, SI}, title = {Automated Prediction of Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Carcinoma Using Deep Learning on Pretreatment Core Needle Biopsy Samples.}, journal = {Anticancer research}, volume = {45}, number = {11}, pages = {5167-5176}, doi = {10.21873/anticanres.17856}, pmid = {41151888}, issn = {1791-7530}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/drug therapy ; *Neoadjuvant Therapy/methods ; Middle Aged ; Biopsy, Large-Core Needle ; *Deep Learning ; Adult ; Aged ; *Carcinoma, Ductal, Breast/drug therapy/pathology ; Treatment Outcome ; }, abstract = {BACKGROUND/AIM: Early prediction of response to neoadjuvant chemotherapy (NAC) is essential for personalized treatment planning in breast carcinoma. Previous studies have relied on human-annotated regions of interest for digital pathology analysis rather than directly leveraging whole-slide images (WSIs). This study aimed to evaluate the predictive value of pretreatment core needle biopsy (CNB) WSIs for pathological complete response (pCR) to NAC using an artificial intelligence (AI)-based approach.

PATIENTS AND METHODS: We analyzed 130 patients with invasive ductal carcinoma who underwent anthracycline- or taxane-based NAC followed by surgery. From each pretreatment CNB WSI, five regions with the highest cellular density were selected to extract image patches. A fusion-based classification model was developed, integrating image data with clinical metadata, including age, hormone receptor status, and Ki-67 labeling index.

RESULTS: The model achieved an accuracy of 92.3%, comparable to those using expert annotations. Omitting either image or clinical data significantly reduced performance, underscoring their complementary roles. Optimal performance was achieved using five image patches of 1,000×1,000 pixels, balancing histological detail and computational efficiency.

CONCLUSION: Our AI-based model accurately predicted pCR to NAC in breast carcinoma using only a limited number of high-cellularity image patches and basic clinical metadata, without requiring expert annotation. This approach may facilitate earlier treatment decisions and improve preoperative outcome prediction.}, } @article {pmid41151718, year = {2026}, author = {Palatella, M and Kruse, F and Ji, H and Loriani Fard, AK and Becker, M and Daniel, C and Rohm, M and Huehn, J}, title = {Acsbg1 maintains intestinal immune homeostasis and controls inflammation by regulating ST2[+] Tregs.}, journal = {Mucosal immunology}, volume = {19}, number = {1}, pages = {1526-1537}, doi = {10.1016/j.mucimm.2025.10.009}, pmid = {41151718}, issn = {1935-3456}, mesh = {Animals ; *T-Lymphocytes, Regulatory/immunology/metabolism ; Mice ; Homeostasis ; Mice, Knockout ; *Citrobacter rodentium/immunology/physiology ; *Th17 Cells/immunology ; *Colitis/immunology ; *Inflammation/immunology ; *Intestinal Mucosa/immunology/metabolism ; *Enterobacteriaceae Infections/immunology ; Disease Models, Animal ; Mice, Inbred C57BL ; Immunity, Mucosal ; }, abstract = {The immune balance in mucosal tissues depends on a delicate interplay between inflammatory T helper 17 (Th17) cells and immunosuppressive regulatory T cells (Tregs). But what happens when this balance is disturbed? In this study, we uncovered a critical role for Acyl-CoA synthetase bubblegum family member 1 (Acsbg1) in shaping Th17 and Treg dynamics. Using Acsbg1-deficient mice, we show that while its absence does not disrupt homeostasis under steady-state conditions, it significantly alters Treg populations, particularly in gut-associated tissues. Under high-fat diet-induced metabolic stress, Acsbg1-deficient mice display mild metabolic changes but maintain systemic immune and metabolic function, indicating that Acsbg1 is dispensable for metabolic adaptation in vivo. However, upon infection with Citrobacter rodentium, these mice exhibit excessive Th1/Th17-driven inflammation and impaired resolution, accompanied by a strong reduction in IL-10-producing and ST2[+] Treg subsets. The impact is even more striking in an adoptive transfer colitis model, where Acsbg1-deficient Tregs fail to control inflammation, resulting in severe colitis and tissue damage. Our findings identify Acsbg1 as a key regulator of ST2[+] Treg function and a central player in mucosal immune homeostasis, highlighting its potential as a therapeutic target for inflammatory bowel disease and colorectal cancer.}, } @article {pmid41150812, year = {2025}, author = {Zhong, M and Zheng, S and Wen, Y and Zhang, J and Zhang, J and Wang, H and Mo, C and Xu, S and Chen, X}, title = {Integrating Multiple Methods to Validate Key Genes Driving the Progression of Breast Ductal Carcinoma In Situ.}, journal = {Current issues in molecular biology}, volume = {47}, number = {10}, pages = {}, pmid = {41150812}, issn = {1467-3045}, support = {2020B010//Fujian Provincial Finance Project/ ; 2021J01703//Natural Science Fundation of Fujian Province/ ; Joint Funds for the innovation of science and Technology, Fujian province//Joint Funds for the innovation of science and Technology, Fujian province/ ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) is a precursor to breast cancer. The mechanisms by which the stroma of DCIS affects disease progression remain elusive. Thus, the aim of this study is to identify key stroma genes that affect DCIS progression and to define high-risk DCIS cases.

METHOD: Gene expression matrix files from the Gene Expression Omnibus (GEO) database were selected to identify candidate genes associated with the stromal transition from DCIS to invasive ductal carcinoma (IDC). An integrative approach was employed to identify and functionally characterize driver genes of DCIS progression. In vitro experiments were performed to validate the role of these genes.

RESULTS: We identified 13 differentially expressed genes (DEGs), of which 5 were selected as candidate drivers. Gene set enrichment analysis (GSEA) revealed the biological functions of RAMP2 and ADM2, while in vitro functional assays demonstrated that ADM2 knockdown and RAMP2 overexpression in breast cancer cell lines significantly suppressed cellular proliferation and invasion.

CONCLUSION: This study identified and validated the roles and functions of ADM2 and RAMP2 and revealed their function as key driver genes in the progression of ductal carcinoma in situ (DCIS). Collectively, our findings elucidate critical genetic mechanisms underlying DCIS progression and provide novel insights for the development of personalized therapeutic strategies.}, } @article {pmid41147213, year = {2026}, author = {Kono, K and Shibayama, R and Murakami, H and Masumoto, T and Maehara, K and Imamura, T and Okubo, S and Hashimoto, M and Fujii, T and Takazawa, Y}, title = {Progressive Estrogen Receptor Acquisition During Malignant Transformation: Insights From MCN-Derived Anaplastic Pancreatic Carcinoma.}, journal = {Pathology international}, volume = {76}, number = {1}, pages = {e70061}, doi = {10.1111/pin.70061}, pmid = {41147213}, issn = {1440-1827}, mesh = {Humans ; Female ; Adult ; *Pancreatic Neoplasms/pathology/metabolism ; *Cell Transformation, Neoplastic/pathology/metabolism ; *Receptors, Estrogen/metabolism ; Biomarkers, Tumor/metabolism/analysis ; *Carcinoma/pathology/metabolism ; Disease Progression ; *Adenocarcinoma, Mucinous/pathology ; Pregnancy ; }, abstract = {Anaplastic pancreatic carcinoma (APC) arising from mucinous cystic neoplasm (MCN) is rare, with only 12 cases reported. The relationship between pregnancy-associaed hormonal changes and MCN progression remains poorly understood, particularly regarding hormone receptor expression patterns during malignant transformation. A 34-year-old woman presented with persistent abdominal pain 9 months post-delivery. Imaging revealed an 11 cm multilocular cystic mass in the pancreatic body and tail with mural nodules showing blood flow signals. Laboratory findings demonstrated normal. She underwent distal pancreatectomy and splenectomy and no recurrence at 6-month follow-up. Histopathological examination revealed MCN with ovarian-type stroma progressing from low-to-high grade dysplasia, invasive ductal carcinoma, and anaplastic carcinoma with osteoclast-like giant cells. Immunohistochemically, estrogen receptor (ER) expression showed stepwise pattern: negative in low-grade dysplasia, strongly positive in high-grade dysplasia and anaplastic components. Progesterone receptor positivity was observed in stromal and epithelial components, with elevated Ki-67 correlating with ER expression. This represents first documentation of progressive ER acquisition during MCN malignant transformation, suggesting autonomous hormone production by ovarian‑type stroma may help sustain tumor growth beyond pregnancy. Stepwise ER expression may serve as a biomarker for risk stratification and a potential target for therapy in hormone-sensitive pancreatic neoplasms.}, } @article {pmid41146811, year = {2025}, author = {Mohamed, EH and Anass, EA and Ayoub, K and Bouhout, T and Serji, B}, title = {A Scalp Tumor Revealing Metastatic Breast Cancer: A Case Report.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e93299}, pmid = {41146811}, issn = {2168-8184}, abstract = {Scalp metastases in invasive ductal carcinoma of the breast are extremely rare, occurring in less than 1% of patients. In large retrospective studies of cutaneous metastases, only a small proportion of patients with solid tumors develop skin involvement, with breast cancer being the most common source. We report a case of a patient who developed a single metastatic lesion involving the subcutaneous scalp tissue and the median frontal bone, with intracranial extension reaching the right temporo-occipital region, detected 11 years after the initial diagnosis and treatment of the primary breast tumor. This case highlights the importance of considering atypical metastatic sites during long-term follow-up of breast cancer survivors. It discusses the diagnostic and therapeutic challenges posed by such unusual presentations.}, } @article {pmid41142038, year = {2025}, author = {Bernardino, RM and Yin, LB and Lajkosz, K and Winquist, E and Cockburn, JG and Jenjitranant, P and Veloso, R and ÓConnell, C and Benitez, AM and Nguyen, DD and Matthiesen, R and Henrique, R and Joshua, AM and van der Kwast, T and Fleshner, NE}, title = {Intraductal Carcinoma Predicts Poor Response to Neoadjuvant Therapy in High-risk Prostate Cancer: A Retrospective Analysis of a Prospective Trial.}, journal = {European urology open science}, volume = {82}, number = {}, pages = {52-58}, pmid = {41142038}, issn = {2666-1683}, abstract = {BACKGROUND AND OBJECTIVE: High-risk localized prostate cancer (PCa) patients may require neoadjuvant treatment (androgen deprivation therapy [ADT] plus abiraterone with or without taxane-based chemotherapy) before radical prostatectomy (RP). Intraductal carcinoma of the prostate (IDC) is an aggressive histological variant of prostate adenocarcinoma. This study aims to evaluate the association of IDC on biopsy with pathological response in such PCa patients.

METHODS: A retrospective analysis was conducted using the prospective trial data from 75 patients with high-risk localized/locally advanced PCa treated with 24 wk of neoadjuvant therapy comprising ADT and abiraterone, with or without taxane-based chemotherapy, followed by RP. Pathological responses, including pathological complete response (pCR), minimal residual disease (MRD), and adverse pathology outcomes (ypN1 or ≥ypT3b), were analyzed. Multivariable logistic regression identified the predictors of poor pathological response.

KEY FINDINGS AND LIMITATIONS: Among 75 patients, 35 (47%) had IDC on biopsy. Patients with IDC had worse pathological outcomes: 32 of 35 (91%) failed to achieve a favorable response (pCR or MRD) compared with 26 of 40 (65%) in those without IDC. IDC was also associated with higher rates of adverse pathology at RP, occurring in 27 of 35 patients (77%) versus nine of 40 patients (22%) without IDC. IDC independently predicted poor response (odds ratio 6.18, 95% confidence interval 1.16-32.8; p = 0.032) after adjusting for tumor volume, Gleason grade, and prostate-specific antigen (PSA). In contrast, cribriform (Crib) pattern at biopsy did not impact response significantly. Metastatic progression and survival data were unavailable.

IDC, but not Crib, on biopsy predicts poor pathological response to neoadjuvant therapy (ADT plus abiraterone with or without taxane-based chemotherapy) in high-risk PCa after adjusting for tumor volume and PSA. An understanding of this treatment-resistant phenotype will improve PCa biology insights and guide novel therapeutic strategies.

PATIENT SUMMARY: Intraductal carcinoma (IDC) is a more aggressive form of prostate cancer that does not respond well to treatment. In our study, we found that 91% of patients who had IDC detected in their biopsy before surgery did not show a good response to presurgery therapy.}, } @article {pmid41140000, year = {2025}, author = {Shakuf, V and Ben-David, N and Abergil, H and Sa'adon, Y and Mezler, M and Ben-David, BM}, title = {Emotion through cognition: the role of cognitive limitations in shaping emotional speech identification among adults with intellectual and developmental disabilities.}, journal = {Cognition & emotion}, volume = {}, number = {}, pages = {1-18}, doi = {10.1080/02699931.2025.2568561}, pmid = {41140000}, issn = {1464-0600}, abstract = {Recognising emotions in speech is vital for social interactions. Adults with intellectual disabilities (AwID) often experience difficulties with emotion perception, affecting integration. However, less is known about spoken-emotion processing among AwID. The current research examines whether difficulties stem from a primary impairment in emotional processing associated with intellectual disability (ID) or a secondary impairment due to cognitive limitations associated with ID. Using an AwID-adapted version of the Test for Rating Emotions in Speech (T-RES), we assessed emotion identification in two studies. Study 1 examined spoken-emotion recognition across different levels of ID severity, focusing on lexical (semantic) and prosodic (tone of voice) cues separately. Results indicated that as ID severity increased, emotion recognition declined. Study 2 investigated the effects of task complexity on spoken-emotion perception among adults with mild ID. Findings revealed that while emotion identification was intact in simple (congruent, lexical and prosodic emotional cues match) conditions, performance deteriorated significantly in complex (incongruent, cues mismatch) conditions, suggesting a cognitive load effect. Additionally, unlike typically developed adults, AwID did not show prosodic bias. These findings support the secondary cognitive account, suggesting that spoken-emotion processing difficulties in AwID may stem from broader cognitive limitations, rather than specific impairments in emotional perception.}, } @article {pmid41139216, year = {2025}, author = {Ishii, K and Torii, M and Yoshibayashi, H and Matsumoto, Y and Matsutani, Y}, title = {Oral Tamoxifen and Abemaciclib in Postoperative Therapy for Male Breast Cancer: A Case Report.}, journal = {The American journal of case reports}, volume = {26}, number = {}, pages = {e949005}, pmid = {41139216}, issn = {1941-5923}, mesh = {Humans ; Male ; *Benzimidazoles/administration & dosage/therapeutic use ; *Breast Neoplasms, Male/therapy/drug therapy/pathology ; *Tamoxifen/administration & dosage/therapeutic use ; Adult ; *Aminopyridines/administration & dosage/therapeutic use ; *Carcinoma, Ductal, Breast/therapy/pathology/drug therapy ; Mastectomy ; Chemotherapy, Adjuvant ; Administration, Oral ; }, abstract = {BACKGROUND Abemaciclib is a selective cyclin-dependent kinase inhibitor that has been approved as an adjuvant treatment for advanced hormone-positive, human epidermal growth factor receptor-2 (HER2)-negative breast cancer and is usually used in combination with an aromatase inhibitor. This report describes the case of a 43-year-old man with a grade 2, stage IIIc, hormone receptor-positive, HER2-negative, invasive ductal carcinoma of the left breast successfully managed with left mastectomy, radiation therapy, and postoperative oral tamoxifen and abemaciclib. CASE REPORT A 43-year-old man presented to our Dermatology Department with a primary concern of non-healing erosion in the left areola that persisted despite 3 months of topical ointment application. Tissue diagnosis confirmed breast cancer, and the patient was referred to the Breast Surgery Department. Imaging studies and detailed tissue analysis revealed a grade 2, hormone receptor-positive, HER2-negative, invasive ductal carcinoma of the left breast. The preoperative stage was cT4bN1aM0 (tumor with skin involvement, limited axillary node metastases, no distant spread), corresponding to stage IIIB. The patient underwent surgery (left mastectomy with axillary lymph node dissection; levels I-III). The pathological stage was IIIC (pT4bN3aM0: skin involvement with extensive nodal metastases and no distant disease). We administered postoperative adjuvant chemotherapy with sequential administration of anthracycline and taxane, and postoperative radiation therapy, followed by postoperative adjuvant endocrine therapy with tamoxifen and abemaciclib. To date, no signs of recurrence have been observed. CONCLUSIONS This report describes a rare case of advanced male breast cancer and a successful outcome following postoperative treatment that included abemaciclib.}, } @article {pmid41127273, year = {2025}, author = {Celi, CV and Peshin, S and Dharia, A and Bashir, F and Erica, L}, title = {Exceptional Response to Pembrolizumab in Metastatic ER+/HER2- Breast Cancer With Liver Metastases: A Case Report and Literature Review.}, journal = {Case reports in oncological medicine}, volume = {2025}, number = {}, pages = {7970572}, pmid = {41127273}, issn = {2090-6706}, abstract = {BACKGROUND: Hormone receptor-positive (HR+) and HER2-negative breast cancer is the most common subtype in women, particularly in the postmenopausal setting. Unlike triple-negative breast cancer, the benefit of immune checkpoint inhibitors (ICIs) in HR+/HER2- disease remains uncertain because of low tumor immunogenicity and limited PD-L1 expression.

CASE PRESENTATION: We describe a case of a 70-year-old woman who presented with severe anemia and was incidentally found to have a bleeding left breast mass. Biopsy confirmed Grade 3 invasive ductal carcinoma (ER+/PR+ > 95%, HER2-) with nodal involvement but no distant metastases, consistent with Stage IIIc disease. She was treated with neoadjuvant anastrozole, modified radical mastectomy, adjuvant chemotherapy, radiation, and continued endocrine therapy. After 3 years, she developed extensive hepatic metastases. Biopsy revealed ER+/PR-/HER2- disease with striking PD-L1 expression (CPS 95%). The disease progressed on fulvestrant and palbociclib, but switching to carboplatin, gemcitabine, and pembrolizumab led to rapid improvement: liver function normalized and imaging showed near-complete response within 3 months. This remission lasted about 10 months before disease progression and transition to hospice care.

CONCLUSION: This case explains the potential role of ICIs in HR+/HER2- breast cancer with unusually high PD-L1 expression. It underscores the importance of biomarker-driven treatment and supports expanding PD-L1 testing to better identify patients who may benefit from immunotherapy in this traditionally resistant subtype.}, } @article {pmid41125144, year = {2026}, author = {Hinrichs, A and Pafili, K and Sancar, G and Laane, L and Zettler, S and Torgeman, M and Kessler, B and Nono, JL and Kunz, S and Rathkolb, B and Barosa, C and Prehn, C and Cecil, A and Renner, S and Kemter, E and Kahl, S and Szendroedi, J and Bidlingmaier, M and Jones, JG and Hrabĕ de Angelis, M and Roden, M and Wolf, E}, title = {Transient juvenile hypoglycemia in GH insensitive Laron syndrome pigs is associated with insulin hypersensitivity.}, journal = {Molecular metabolism}, volume = {103}, number = {}, pages = {102273}, pmid = {41125144}, issn = {2212-8778}, mesh = {Animals ; *Insulin Resistance/physiology ; *Hypoglycemia/metabolism ; Swine ; *Insulin/metabolism ; *Laron Syndrome/metabolism ; Male ; Female ; Liver/metabolism ; Glucose Clamp Technique ; Receptors, Somatotropin/metabolism/genetics/deficiency ; Adipose Tissue/metabolism ; Lipolysis ; Glucose/metabolism ; Disease Models, Animal ; Growth Hormone/metabolism ; Blood Glucose/metabolism ; }, abstract = {BACKGROUND AND AIMS: Fasting hypoglycemia has clinical implications for children with growth hormone (GH)-insensitivity syndrome. This study investigates the pathophysiology of juvenile hypoglycemia in a large animal model for GH receptor (GHR) deficiency (the GHR-KO pig) and elucidates mechanisms underlying the transition to normoglycemia in adulthood.

METHODS: Insulin sensitivity was assessed in juvenile and adult GHR-KO pigs and wild-type (WT) controls via hyperinsulinemic-euglycemic clamp (HEC) tests. Glucose turnover was measured using D-[6,6-[2]H2] glucose and [2]H2O. Clinical chemical and targeted metabolomics parameters in blood serum were correlated with qPCR and western blot analyses of liver and adipose tissue.

RESULTS: GHR-KO pigs showed increased insulin sensitivity (p = 0.0019), especially at young age (M-value +34% vs. WT), insignificantly reduced insulin levels, and reduced endogenous glucose production (p = 0.0007), leading to fasting hypoglycemia with depleted liver glycogen, elevated β-hydroxybutyrate, but no increase in NEFA levels. Low hormone-sensitive lipase phosphorylation in adipose tissue suggested impaired lipolysis in young GHR-KO pigs. Metabolomics indicated enhanced fatty acid beta-oxidation and use of glucogenic amino acids, likely serving as compensatory pathways to maintain energy homeostasis. In adulthood, insulin sensitivity remained elevated but less pronounced (M-value +20%), while insulin levels were significantly reduced, enabling normoglycemia and improved NEFA availability. Increased fat mass, but not sex hormones, appeared key to this metabolic transition, as early castration had no effect.

CONCLUSIONS: Juvenile hypoglycemia in GH insensitivity results from excessive insulin sensitivity, reduced glucose production, and impaired lipolysis. Normoglycemia in adulthood emerges through increased adiposity and moderated insulin sensitivity, independently of sex hormones. These findings elucidate the age-dependent metabolic adaptations in GH insensitivity.}, } @article {pmid41122452, year = {2025}, author = {Makino, M and Kusama, H and Hagiwara, M and Horimoto, Y and Sato, E and Ikeda, N and Ishikawa, T}, title = {A Case of Occult Breast Cancer Diagnosed during Immune Checkpoint Inhibitor Treatment for Recurrent Metastatic Lung Cancer.}, journal = {Surgical case reports}, volume = {11}, number = {1}, pages = {}, pmid = {41122452}, issn = {2198-7793}, abstract = {INTRODUCTION: Occult breast cancer (OBC) is a rare subtype of breast cancer, typically presenting as axillary lymph node metastasis without an identifiable primary tumor in the breast. Axillary lymphadenopathy requires differential diagnosis, including OBC. However, in patients undergoing treatment for another malignancy, distinguishing OBC from axillary metastasis of the known primary cancer can be challenging. Immune checkpoint inhibitors (ICIs) have extended survival in advanced non-small cell lung cancer (NSCLC), potentially allowing time for 2nd primary cancers to develop and be detected.

CASE PRESENTATION: A 71-year-old woman underwent right upper lobectomy for stage IIIA lung adenocarcinoma. Four months postoperatively, CT revealed a right chest wall mass and right axillary lymphadenopathy, which was interpreted as recurrence. Systemic therapy was administered, and third-line atezolizumab monotherapy led to complete remission of the chest wall mass; however, progressive enlargement of the axillary lymph nodes was subsequently observed. Imaging showed no detectable lesion in the breast, but core needle biopsy of the axillary node revealed metastatic invasive ductal carcinoma, negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) with a Ki-67 index of 80%. Immunohistochemistry was positive for GATA3 and negative for thyroid transcription factor-1 (TTF-1), consistent with OBC. The patient underwent axillary lymph node dissection, and postoperative observation without additional treatment was selected due to comorbidities. She has remained disease-free for 1 year.

CONCLUSIONS: This case illustrates that axillary lymphadenopathy during treatment for another malignancy may represent a 2nd primary cancer such as OBC. As ICI therapy prolongs survival, clinicians should pay attention for new malignancies, including breast cancer, even in the absence of breast lesions.}, } @article {pmid41114418, year = {2025}, author = {Tchabashvili, L and Leivaditis, V and Kitsou, KS and Mulita, F and Papadaki, H and Argentou, MI}, title = {The association between chemerin expression in breast cancer cells and aggressiveness.}, journal = {Przeglad menopauzalny = Menopause review}, volume = {24}, number = {3}, pages = {183-190}, pmid = {41114418}, issn = {1643-8876}, abstract = {INTRODUCTION: Breast cancer (BC), the most prevalent cancer amongst women globally, exhibits a complex relationship with obesity and its associated factors. Chemerin, an adipokine linked to both inflammatory and metabolic processes, has emerged as a potential player in tumor development and progression. This study delves into the potential role of chemerin in breast cancer by analyzing its expression patterns in tumor cells, fibroblasts, and adipocytes alongside corresponding clinico-pathological parameters.

MATERIAL AND METHODS: Encompassing 77 patients with invasive ductal carcinoma, the study revealed an interesting interplay between chemerin and disease characteristics.

RESULTS: While chemerin expression itself did not associate with established markers like BC stage, oestrogen receptor, or progesterone receptor status, its presence is elevated in patients with lymph node metastasis. Despite these insightful findings, the study acknowledges limitations inherent to its design. The absence of a healthy control group necessitates further controlled studies to solidify the observed associations. Additionally, external factors like diet and exercise, known to influence chemerin levels, were not accounted for, requiring more comprehensive patient history and examination data in future investigations.

CONCLUSIONS: While chemerin expression did not correlate with traditional BC markers, its apparent associations with lymph node metastasis, c-ERB2 expression, and involvement within the tumour microenvironment warrant further exploration. This study paves the way for future research to elucidate the precise role of chemerin in BC development and progression, potentially paving the path for the development of novel diagnostic and prognostic tools.}, } @article {pmid41111766, year = {2025}, author = {Khan, A and King, C and Patel, NB and Patel, A and Irani, Z and Thompson, J}, title = {A Case of Necrotic Metastases Imitating Hepatic Abscesses in a Patient With Multiple Primary Cancers.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e92466}, pmid = {41111766}, issn = {2168-8184}, abstract = {This case report highlights the diagnostic challenges in a 72-year-old female with a complex medical history, including metastatic stage IV squamous cell carcinoma of the right lung, invasive ductal carcinoma of the left breast, and recent acute illnesses. Initially, imaging studies suggested metastatic disease in the liver, but subsequent findings raised suspicion for a hepatic abscess. However, further investigations ultimately confirmed necrotic metastatic disease rather than infection. This case underscores the importance of multidisciplinary collaboration and advanced imaging in differentiating metastatic disease from an infectious process.}, } @article {pmid41107956, year = {2025}, author = {Ostaszkiewicz, J and Gilbert, AS and Tay, C and Watt, E and Barry, D and Taylor, W and Cecil, J and Cockerell, R and Crowe, H and Lau, L and Murray, M and Nakrem, S and Paterson, C and Peters, M and Sahay, A and Sweeney, A and Thompson, J and Westaway, J and Bower, W and Christina, J and Zana, A and Batchelor, F}, title = {IDC-IMPROVE: protocol for a cluster randomised feasibility trial of a care bundle to improve indwelling catheter care (IDC) in residential aged care homes in Australia.}, journal = {Pilot and feasibility studies}, volume = {11}, number = {1}, pages = {123}, pmid = {41107956}, issn = {2055-5784}, support = {MRFF2023825//Medical Research Future Fund (MRFF)/ ; }, abstract = {BACKGROUND: Indwelling urinary catheters (IDCs) are used by approximately 8% of Australian aged care residents. IDC use is often warranted but entails numerous risks, particularly if used longterm. Risks include catheter-associated urinary tract infections, catheter blockage, catheter leakage, bladder spasm, pain, urethral trauma and haematuria, and increased risk of hospitalisation. The Royal Commission into Aged Care Quality and Safety identified poor quality, unsafe practices related to IDCs in aged care homes. Enhancing the knowledge, confidence, and skills of aged care staff to deliver catheter care for residents with IDCs is fundamentally important. The IDC-IMPROVE project is supporting aged care providers to meet the care needs of people with IDCs in Australian aged care homes, by designing and validating a suite of resources titled the IDC-IMPROVE Catheter Care Bundle.

AIMS: This study aims to establish the feasibility of conducting a definitive randomised control trial to evaluate the effects of the IDC-IMPROVE Catheter Care Bundle in aged care homes in Australia.

METHOD: A multi-centre, facility-level clustered randomised control (cRCT) feasibility trial in 24 aged care homes across Victoria, Queensland, and South Australia. Twelve homes will receive the intervention and 12 will continue usual care. The IDC-IMPROVE Catheter Care Bundle intervention comprises principles for person-centred catheter care, online training for nurses and personal care workers, a practical skills workshop for nurses, a toolkit for managers, and an evidence-to-practice support model. The feasibility of the intervention will be assessed through a mix of qualitative and quantitative methods, including surveys, interviews, and audits. Feasibility outcomes are: (i) The acceptability of the Bundle, (ii) The fidelity of the implementation, (iii) The compatibility of the Bundle with standard aged care home IDC care.

DISCUSSION: By enhancing the knowledge, confidence and skills of the aged care workforce, IDCIMPROVE aims to reduce IDC-related complications. This study will provide insights into the acceptability and implementation of the intervention, informing future large-scale trials and potential policy changes.

ETHICS: The study has been approved by Austin Health Human Research Ethics Committee (reg: HREC/107165/Austin-2024) and is registered on the Australian New Zealand Clinical Trials Registry (reg: ACTRN12624001178538p).}, } @article {pmid41106127, year = {2025}, author = {Sabeti, S and Adl Parvar, T and Metanat, P and Larson, NB and Fazzio, RT and Fatemi, M and Alizad, A}, title = {Quantitative angiogenesis-based ultrasound biomarkers for differentiating radiologically challenging breast lesions: Radial scar vs invasive ductal carcinoma.}, journal = {Breast (Edinburgh, Scotland)}, volume = {84}, number = {}, pages = {104614}, pmid = {41106127}, issn = {1532-3080}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology/blood supply ; Middle Aged ; Diagnosis, Differential ; *Carcinoma, Ductal, Breast/diagnostic imaging/blood supply/pathology ; *Neovascularization, Pathologic/diagnostic imaging/pathology ; *Ultrasonography, Mammary/methods ; Adult ; Microvessels/diagnostic imaging/pathology ; *Cicatrix/diagnostic imaging/pathology ; Aged ; Biomarkers, Tumor ; ROC Curve ; Breast/blood supply/diagnostic imaging/pathology ; Angiogenesis ; }, abstract = {PURPOSE: To investigate the effectiveness of quantitative biomarkers derived from quantitative high-definition microvasculature imaging (qHDMI) for differentiation of radial scar (RS) and invasive ductal carcinoma (IDC).

METHODS: A total of 64 breast lesions from 62 participants were analyzed using breast pathology as the gold standard. Ultrasound data were processed with the qHDMI framework to visualize tumor microvessel networks and extract eight morphological biomarkers. Biomarker distributions were compared between groups using a two-sided Wilcoxon rank-sum test, and ROC AUC values with 95 % confidence intervals (CI) were calculated. P-values were adjusted for multiple testing using the Benjamini-Hochberg FDR method at a 5 % threshold.

RESULTS: Seventeen lesions were pathologically confirmed as RS and 47 as IDC. qHDMI biomarkers revealed distinct microvascular differences between the two groups. Overall, IDC lesions showed denser, thicker, and more complex microvessels. Five biomarkers demonstrated statistically significant distribution differences: vessel density (p-value: 0.016, adjusted p-value: 0.0288), number of vessel segments (p-value: 0.0055, adjusted p-value: 0.0288), number of branch points (p-value: 0.0098, adjusted p-value: 0.0288), maximum diameter (p-value: 0.014, adjusted p-value: 0.0288), and microvessel fractal dimension (p-value: 0.018, adjusted p-value: 0.0288). The AUC and CIs for these five biomarkers were 0.70, [0.56, 0.82] for vessel density, 0.73, [0.60, 0.86] for number of vessel segments, 0.71, [0.58, 0.83] for number of branch points, 0.70, [0.57, 0.82] for maximum diameter, and 0.70, [0.54, 0.82] for fractal dimension.

CONCLUSION: Distributions of qHDMI-derived biomarkers revealed distinct microvascular structural differences between RS and IDC, suggesting qHDMI may enhance diagnostic accuracy in distinguishing the two.}, } @article {pmid41105173, year = {2026}, author = {Chang, RC and Ehyaee, V and Wattar, R and Braun, A and Gattuso, P and Ahmed, A}, title = {Evaluation of PRAME Expression in Cases of Breast Carcinoma Metastatic to Skin.}, journal = {The American Journal of dermatopathology}, volume = {48}, number = {2}, pages = {107-113}, doi = {10.1097/DAD.0000000000003159}, pmid = {41105173}, issn = {1533-0311}, mesh = {Humans ; Female ; *Skin Neoplasms/secondary/mortality ; Middle Aged ; *Antigens, Neoplasm/analysis ; Retrospective Studies ; Aged ; *Biomarkers, Tumor/analysis ; Male ; *Breast Neoplasms/pathology/mortality ; *Triple Negative Breast Neoplasms/pathology/mortality ; Adult ; Immunohistochemistry ; Aged, 80 and over ; Prognosis ; *Carcinoma, Ductal, Breast/mortality/secondary ; }, abstract = {Cutaneous metastases of breast neoplasms indicate advanced disease with poor prognosis. The role of Preferentially Expressed Antigen in Melanoma (PRAME) expression in breast cancer skin metastases remains poorly understood. In this study, we investigate PRAME expression in breast carcinoma metastatic to the skin, particularly triple-negative breast cancers (TNBC). A retrospective review of breast cancer cases with skin metastasis was conducted from January 2005 to March 2023. PRAME immunostaining was performed on skin metastatic lesions and corresponding primary tumors. A comparison group of noncutaneous metastases (n = 11) was included. Thirty patients with cutaneous metastasis were identified (29 women, 1 man; mean age 63 years). The most common site of skin metastasis was chest (25 cases, 83%). Histologically, 25 cases (83%) were invasive ductal carcinoma. Eleven cases (37%) were TNBC. PRAME positivity was observed in 10 skin metastases (33%) with 70% being triple negative. Among 20 available primary samples, only 3 were PRAME positive with corresponding positive metastases. Comparison group showed minimal PRAME expression. In total, 40% of patients died, with TNBC associated with higher mortality (P = 0.04). All PRAME-positive TNBC patients with follow-up were deceased. In conclusion, PRAME expression occurred in approximately one-third of breast cancer skin metastases, with predominance in triple-negative breast cancer. These findings warrant further investigation of PRAME's role in cutaneous metastasis and its diagnostic implications.}, } @article {pmid41091344, year = {2026}, author = {Sturz-Ellis, JL and Vetter, CD and Day, CN and Boughey, JC}, title = {A Systematic Review of Occult Malignancy and Sentinel Lymph Node Metastasis at the Time of Contralateral Prophylactic Mastectomy.}, journal = {Annals of surgical oncology}, volume = {33}, number = {2}, pages = {1162-1170}, pmid = {41091344}, issn = {1534-4681}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery/pathology/prevention & control ; *Sentinel Lymph Node/pathology/surgery ; *Prophylactic Mastectomy ; Lymphatic Metastasis ; Sentinel Lymph Node Biopsy ; Prognosis ; Axilla ; Lymph Node Excision ; *Neoplasms, Unknown Primary/pathology/surgery ; }, abstract = {BACKGROUND: Occult malignancy (OM) identified in contralateral prophylactic mastectomy (CPM) presents a challenge for axillary management.

METHODS: This meta-analysis identified retrospective studies using PubMed, Embase, and Cochrane Reviews with the keywords OM and CPM. In this study, OM was defined as invasive disease only. To determine the proportion of OM and node positivity rates, MedCalc software was used.

RESULTS: The 27 studies in this meta-analysis included 5728 patients who underwent CPM, with OM identified in 87 patients. The pooled incidence of OM was 1.55%. Of the 73 patients with axillary staging details available, 41 patients with OM (56%) underwent surgical axillary staging. Of these 41 patients, 8 had a positive sentinel lymph node (SLN) (20%), and 4 of the 8 patients had subsequent axillary lymph node dissection (ALND) with no additional positive lymph nodes identified. For 64 of the 87 patients with OM, T category was available. Of these 64 patients, 62 (97%) had pT1 and 2 (3%) had pT2 carcinoma. Histologic subtype was available for 52 OMs. Of these, 39 (75%) were ductal, 8 (15%) were lobular, and 5 (10%) were other. Biomarkers were available for 33 OMs, of which 21 (64%) were luminal A, 3 (9%) were luminal B, 3 (9%) were luminal human epidermal growth factor receptor 2 (HER2), and 6 (18%) were triple-negative.

CONCLUSIONS: Occult malignancy in CPM is uncommon (1.55%), and when it occurs, it is predominantly pT1, luminal A, or invasive ductal carcinoma. Occult malignancy with SLN metastasis occurs in only 0.1% of CPMs, and when present, SLN metastasis is low volume (≤2 nodes). This supports the current guideline recommendations against routine SLN surgery at the time of CPM.}, } @article {pmid41089733, year = {2025}, author = {Gil, DG and Zaixso, HE}, title = {First Insights into the Vertical Patterns of Size Distribution, Abundance, and Spatial Aggregation of the Sea Urchin Pseudechinus magellanicus on a Wave-exposed Rocky Shore in San Jorge Gulf, Argentina.}, journal = {Zoological studies}, volume = {64}, number = {}, pages = {e8}, pmid = {41089733}, issn = {1810-522X}, abstract = {The sea urchin Pseudechinus magellanicus is a dominant species in coastal habitats of southern Argentina and Chile. This study investigates its size distribution, abundance, and spatial arrangement in relation to coastal environmental gradients and habitat complexity along a depth gradient in central Patagonia (Argentina) during the austral spring. P. magellanicus exhibited a unimodal response to depth, with lower densities observed at intertidal levels and depths greater than 12 m. Size distribution showed depth-related patterns, with larger individuals prevalent at subtidal levels, intermediate sizes more common in intertidal and shallow depths, and recruits and juveniles most abundant at the infralittoral fringe and subtidal zones. A positive relationship between structural complexity and sea urchin densities was found, especially for smaller size classes. Conversely, larger individuals tended to inhabit areas with lower structural complexity and higher food availability. Sedimentation impacted the vertical distribution, particularly affecting recruits, juveniles, and young adults. Spatial arrangement analysis showed that aggregation is the predominant pattern along the coastal depth gradient. However, at depths of 3-5 m, where the kelp forest (Macrocystis pyrifera) dominates, recruits, juveniles, and intermediate-sized sea urchins displayed a less aggregated, more random distribution. These findings reveal the critical role of habitat complexity and depth in shaping the population dynamics of P. magellanicus and highlight the adaptability of this species to varying habitat conditions and its potential as an indicator of coastal ecosystem health.}, } @article {pmid41089145, year = {2025}, author = {Ahmad, A and Mehmood Qadri, H and Rasool, N and Bashir, A}, title = {Patient Plan Customization in Hypofractionated CyberKnife Radiosurgery for Extensive Brain Metastases Within a Resource-Constrained Low-Middle-Income Country.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e92163}, pmid = {41089145}, issn = {2168-8184}, abstract = {Brain metastasis (BM) carries a dismal prognosis. In the setting of advanced breast cancer, BM has a formidable outcome, yet radiosurgery has played a pivotal role in palliating patients. Here, we present the case of a 62-year-old hypertensive female with biopsy-proven, triple-negative, invasive ductal carcinoma of the left breast (stage IV disease). Whole-brain radiotherapy (WBRT) failed to achieve radiological and clinical response for 60 intracranial metastatic space-occupying lesions. Her presenting complaint of intractable headache was accompanied by a normal neurological examination. A customized plan for stereotactic radiosurgery via CyberKnife S7 was utilized with a 2,200 cGy dose and 68% isocurve over five fractions on alternate days. Redo WBRT was not performed owing to the patient's comorbidities, age, and risk of cognitive deficits. Radiological remission of 81% and 88% with no neurological deficits was achieved at the fourth and eighth months of follow-up. To our knowledge, this is the first case of 60 secondaries in the human brain from a breast primary successfully managed with CyberKnife stereotactic radiosurgery, achieving remarkable radiological regression while preserving clinical function. A customized plan considering the patient's factors and risk versus benefit assessment is advisable in all cases of metastatic brain disease.}, } @article {pmid41089131, year = {2025}, author = {Kannappalli, K and Raju, K and Kamisetty, KP}, title = {Immunohistochemical Expression of Laminin 332 in Triple-Negative Breast Carcinoma: A Cross-Sectional Study.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e92206}, pmid = {41089131}, issn = {2168-8184}, abstract = {BACKGROUND: Breast carcinoma (BC) is the most common malignancy among women and is the leading cause of mortality among females. Triple-negative breast carcinoma (TNBC) is a diverse disease based on immunohistochemistry (IHC) and is estrogen receptor (ER) negative, progesterone receptor (PR) negative, and human epidermal growth factor (HER2) negative. TNBC has a distinct molecular profile, is more aggressive, lacks targeted therapies, and has a worse prognosis than other types of breast cancer. Laminin is a glycoprotein that plays several roles in cancer progression, including cell proliferation, invasion, metastasis, and epithelial-mesenchymal transition.

AIM AND OBJECTIVES: This study aimed to evaluate the immunohistochemical expression of laminin 332 in TNBCs and to study the association of laminin 332 expression with clinicopathological parameters of TNBCs.

MATERIALS AND METHODS: All the cases of TNBC received from the Department of Surgery at RL Jalappa Hospital and Research Institute to the Department of Pathology attached to Sri Devaraj Urs Medical College, Tamaka, Karnataka, from January 2019 to September 2024 were considered for the study. Both prospective and retrospective cases were considered. The data and paraffin blocks were retrieved from the archives of the Department of Pathology. Histopathological parameters of TNBC cases were studied, and laminin 332 IHC was performed. The association of IHC expression of laminin 332 and histopathological parameters was evaluated.

RESULTS: Among 50 TNBC cases, 26 (56%) were elderly patients above 50 years of age. A higher proportion of cases, i.e., 23 (46%), were grade 3 tumors; 46 (92%) cases had infiltrating ductal carcinomas (IDC); 39 (78%) had lymphovascular invasion (LVI); 46 (92%) were without perineural invasion (PNI); and 22 (44%) had high-grade tumor-infiltrating lymphocytes (TILS). All the TNBC cases exhibited positivity for either a laminin 332 IHC score of 5 (64%) or a laminin 332 IHC score of 6 (36%). Laminin 332 IHC score of 5 (71.8%) was associated with the presence of LVI, and laminin IHC scores of 6 (p-value 0.041) and 7 (63.6%) were associated with the absence of LVI, which has a statistically significant association with p-value 0.041.

CONCLUSIONS: All the TNBC patients were positive for laminin 322, but there was a statistically significant association only with lymphovascular invasion. TNBC, hence, exhibits aggressive behavior and is associated with unfavorable clinicopathological outcomes.}, } @article {pmid41088701, year = {2025}, author = {Wang, Y and Li, Q and Sun, D and Yang, N and Kong, Y and Shen, Y and Zhang, F}, title = {m6A RNA methylation regulator heterogeneous nuclear ribonucleoprotein C: A prognostic biomarker for invasive ductal carcinoma validated through Mendelian randomization and transcriptome analyses.}, journal = {Medicine}, volume = {104}, number = {41}, pages = {e44733}, pmid = {41088701}, issn = {1536-5964}, support = {2021A1515010040//Natural Science Foundation of Guangdong Province, China/ ; 2023A1515010829//Natural Science Foundation of Guangdong Province, China/ ; 20242BAB25448//Jiangxi Province natural science Foundation project/ ; }, mesh = {Humans ; Female ; *Heterogeneous-Nuclear Ribonucleoprotein Group C/genetics/metabolism ; *Breast Neoplasms/genetics/pathology/mortality/metabolism ; Prognosis ; Biomarkers, Tumor/genetics/metabolism ; *Adenosine/analogs & derivatives/metabolism ; *Carcinoma, Ductal, Breast/genetics/mortality/pathology/metabolism ; Gene Expression Profiling ; Methylation ; RNA-Binding Proteins/genetics/metabolism ; Middle Aged ; Gene Expression Regulation, Neoplastic ; RNA Splicing Factors/genetics ; RNA Methylation ; }, abstract = {Although aberrant N6-methyladenosine (m6A) RNA methylation has been linked to oncogenesis and tumor progression, the association between the deregulation of m6A regulators and invasive ductal carcinoma (IDC), the predominant subtype of breast cancer, remains unclear. In this study, we sought to determine the function of m6A RNA methylation regulators in IDC, with a particular focus on assessing their potential as prognostic biomarkers. To identify dysregulated m6A RNA methylation regulators, we systematically analyzed 656 samples from patients with IDC and 81 normal samples from The Cancer Genome Atlas (TCGA) database, and Cox univariate, LASSO-Cox regression, and stepwise regression analyses were conducted to construct a risk-prediction model for determining patient prognosis. Subsequently, we evaluated the prognostic value of the risk signature in IDC and assessed potential biological associations based on clinical survival analyses, examination of publicly available immunohistochemical staining data from the Human Protein Atlas, and two-sample Mendelian randomization. Among the IDC samples, we identified 12 m6A RNA methylation regulators characterized by significant dysregulation. Subsequently, a 4-gene signature comprising heterogeneous nuclear ribonucleoprotein C (HNRNPC), YTH domain-containing family proteins 2 and 3 (YTHDF2/3), and RNA-binding motif protein 15B (RBM15B) was constructed using machine learning algorithms. This signature was established to be an independent prognostic factor, particularly in patients with early stage IDC, and within the signature, HNRNPC was identified as a pivotal gene, the expression levels of which were demonstrated to be causally associated with the risk of IDC. On the basis of our findings in this study, we established a prognostic signature for IDC and identified a causal association between the expression of the signature gene HNRNPC and IDC risk. These findings indicate that m6A RNA methylation regulators could serve as molecular biomarkers for IDC and contribute to guiding therapeutic strategies.}, } @article {pmid41084011, year = {2025}, author = {Vignaroli, K and Perez, K and Lee, M and Raju, S and Nguyen, A and Malkoc, A and Martinetto, E and Burbank, R and Ibrahim, A and Ko, E and Ramiscal, JAB}, title = {Invasive ductal carcinoma of the breast with gallbladder metastasis: a rare case report.}, journal = {World journal of surgical oncology}, volume = {23}, number = {1}, pages = {367}, pmid = {41084011}, issn = {1477-7819}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/therapy/surgery ; *Carcinoma, Ductal, Breast/secondary/therapy/pathology ; Adult ; *Gallbladder Neoplasms/secondary/therapy ; Prognosis ; Fatal Outcome ; Mastectomy, Segmental ; }, abstract = {BACKGROUND: Invasive ductal carcinoma of the breast most commonly metastasizes to bone, lung, liver, and central nervous system. Breast cancer metastasis to the gallbladder is exceptionally rare, especially when it is secondary to breast cancer of ductal origin.

CASE PRESENTATION: We present the case of a pre-menopausal 43-year-old female with a history of major depressive disorder and no prior mammograms who was diagnosed with ER+/PR+/HER2+ invasive ductal carcinoma of the right breast. She developed late metastasis to the gallbladder, liver, lung and bone detected four years after breast conserving surgery with delayed neoadjuvant chemotherapy, adjuvant radiation, incomplete adjuvant biologic and hormone therapy, and lack of surveillance. The patient died three years and ten months after her lumpectomy.

CONCLUSIONS: Though rare, adequate suspicion should be maintained when evaluating patients with a history of breast cancer who present with symptoms of cholecystitis or biliary colic in order to promptly identify breast cancer metastasis to the gallbladder, as well as to more common metastatic sites.}, } @article {pmid41081190, year = {2025}, author = {Li, Y and Liu, H and Feng, H and Xu, Q and Grimm, R and Gao, L and Wang, M and Wang, Q and Wang, L}, title = {The value of breast ultrafast dynamic contrast-enhanced magnetic resonance imaging in diagnosing axillary lymph node metastasis in mass-type invasive ductal carcinoma of the breast.}, journal = {Quantitative imaging in medicine and surgery}, volume = {15}, number = {10}, pages = {9043-9054}, pmid = {41081190}, issn = {2223-4292}, abstract = {BACKGROUND: Breast cancer (BC) is the most prevalent malignant tumor among women worldwide, significantly impacting women's health and lives. The accurate assessment of axillary lymph node (ALN) status is critical for BC staging, treatment planning, and the evaluation of overall survival outcomes. This study aimed to explore the relationship between preoperative ultrafast dynamic contrast-enhanced magnetic resonance imaging (UF-DCE MRI) parameters and ALN metastasis in patients with mass-type invasive ductal carcinoma (IDC) of the breast, and to construct a nomogram model for predicting ALN metastasis.

METHODS: Preoperative UF-DCE MRI images and medical records of 96 breast IDC patients (38 with ALN metastasis, 58 without) confirmed by pathology were retrospectively analyzed. Conventional MRI features, UF-DCE MRI parameters, DCE parameters, and clinical features were evaluated. Receiver operating characteristic (ROC) curves and nomograms for univariate parameters and combined diagnostic efficiency were constructed.

RESULTS: Time-to-enhancement (TTE), time-to-peak (TTP) after enhancement, and time to center of maximum slope (TTMS) were significantly lower in the ALN metastasis group (10.05±4.91 vs. 15.59±15.04 s, 85.89±33.93 vs. 208.27±102.28 s, 19.05±22.25 vs. 19.81±9.29 s; all P<0.05), whereas tumor size was significantly smaller in the non-ALN metastasis group (2.2±1.1 vs. 3.0±1.5 cm, P<0.001). No other clinical or imaging parameters showed significant differences between groups. TTP had the best diagnostic efficacy for ALN metastasis, with an area under the curve (AUC) of 0.865 [95% confidence interval (CI): 0.794-0.937]. The combined parameter prediction model improved the diagnostic efficacy, with an AUC of 0.919 (95% CI: 0.864-0.974). The nomogram indicated that TTP had the greatest impact on lymph node metastasis, followed by tumor size and apparent diffusion coefficient (ADC). The nomogram indicated that metastasis probability = e[score]/1 + e[score], with score = 0.70 * tumor size - 2.49 * ADC - 0.03 * TTP + 3.78.

CONCLUSIONS: Multiple UF-DCE MRI parameters can predict ALN metastasis in patients with mass-like breast IDC before operation. The nomogram model combined with clinical and UF-DCE MRI parameters can better assist clinicians in making personalized treatment plans for patients.}, } @article {pmid41081182, year = {2025}, author = {Zhan, T and Tang, X and Dai, J and Deng, Y and Lu, C}, title = {Multiparametric MRI-based radiomics nomogram for noninvasive stratification of HER2 expression status in breast cancer.}, journal = {Quantitative imaging in medicine and surgery}, volume = {15}, number = {10}, pages = {10215-10237}, pmid = {41081182}, issn = {2223-4292}, abstract = {BACKGROUND: Accurate assessment of human epidermal growth factor receptor 2 (HER2) status, particularly HER2-low (formerly HER2-negative), is critical for guiding optimal HER2-targeted therapeutic decisions, as these patients may now be eligible for novel anti-HER2 antibody-drug conjugates. This study aimed to develop a radiomic nomogram based on multiparametric magnetic resonance imaging (MRI)-derived radiomic features combined with clinical characteristics for distinguishing HER2-positive and HER2-low breast cancer (BC) from HER2-negative BC (Task 1) and HER2-low from HER2-negative BC (Task 2).

METHODS: A total of 364 patients from two centers with invasive ductal carcinoma of BC were retrospectively enrolled from September 2022 to March 2024 and divided into two tasks. Patients from Center 1 (The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University) were randomly assigned to training cohort (Task 1: n=165; Task 2: n=112) and internal validation cohort (Task 1: n=71; Task 2: n=48). Patients from Center 2 (Ganzhou Cancer Hospital) were used as an external validation cohort (Task 1: n=78; Task 2: n=52). Radiomics signatures (RS) models were established using features from dynamic contrast-enhanced (DCE), T2-weighted image (T2WI), and combination (RS-Com). A clinical characteristic model was established through univariate and multivariate analyses, and a radiomics nomogram was developed by integrating radiomics score (Rad-score) with clinically significant characteristics. Its performance was evaluated through metrics such as the area under the curve (AUC), calibration assessment, and decision curve analysis (DCA).

RESULTS: For Task 1, RS-Com yielded a greater AUC for training, internal, and external validation of (0.861, 0.784, and 0.794, respectively) than did RS-DCE (AUC =0.743, 0.732, and 0.629, respectively) and RS-T2WI (AUC =0.741, 0.663, and 0.652 respectively). For Task 2, compared with RS-DCE (AUC =0.774/0.668/0.738) and RS-T2WI (AUC =0.771/0.677/0.637), RS-Com also exhibited greater AUCs for training, internal, and external validation (0.822/0.725/0.773). Univariate and multivariate analyses showed that the estrogen receptor (ER) and progesterone receptor (PR) statuses were independent predictors for distinguishing HER2 status. For both Tasks 1 and 2, the radiomic nomogram demonstrated the best performance with AUCs of 0.916/0.940/0.820 and 0.863/0.892/0.833, respectively.

CONCLUSIONS: The multiparametric MRI-based radiomic nomogram can more accurately categorize the levels of HER2 expression in invasive ductal carcinoma patients, especially for those with HER2-low expression, serving as an early-stage aid for clinicians to devise tailored and precise therapeutic strategies.}, } @article {pmid41079065, year = {2025}, author = {Yu, B and Yan, L and Wang, H and Yang, J and Yang, J}, title = {Invasive lobular carcinoma of the breast: metastatic patterns and treatment modalities-a review.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1631670}, pmid = {41079065}, issn = {2234-943X}, abstract = {Compared with invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC) exhibits distinct histologic, molecular, and clinical characteristics, including unique metastatic patterns. This review focuses on three major aspects: (1) an analysis of metastatic behavior across different ILC histologic subtypes, with a preliminary exploration of potential correlations with molecular features; (2) a synthesis of current treatment strategies, highlighting challenges such as endocrine resistance, limited tailored protocols, and emerging immunotherapeutic opportunities; and (3) a review of clinical trials from 2022 to 2024 to identify evolving strategies and future directions for individualized therapy. By integrating pathology, molecular profiling, and clinical data, this review emphasizes ILC's distinctive metastatic behavior and unmet clinical needs, providing a conceptual framework to guide future translational research and therapeutic development.}, } @article {pmid41074005, year = {2025}, author = {Fathima, ZS and Suresh, TNR and Kattepur, AK}, title = {Immunohistochemical expression of tumor-infiltrating lymphocytes CD8 and FOXP3 in invasive ductal carcinoma of breast.}, journal = {BMC cancer}, volume = {25}, number = {1}, pages = {1550}, pmid = {41074005}, issn = {1471-2407}, abstract = {BACKGROUND: Tumor-infiltrating lymphocytes (TILs) in breast cancer primarily comprise CD8+ T cells, which have anti-tumor properties, and FOXP3+ regulatory T cells (Tregs), which act as immune regulators. Both of these lymphocyte types play a significant role in breast cancer immunity. Understanding the relationship between TIL levels and the balance between CD8+ and FOXP3+ T cells is crucial for breast cancer management. Despite the growing recognition of their importance, the precise role and impact of these immune cells remain controversial and not fully understood. Evaluating the infiltration of CD8+ T cells and FOXP3+ Tregs in breast cancer tissues, as well as their correlation with tumor characteristics, can provide valuable insights into their prognostic value and their impact on cancer progression. Such a study has not yet been reported in India. Therefore, this study explores the connection between TILs, FOXP3/CD8, and various clinicopathological parameters, aiming to better understand these relationships and improve prognostic models and personalized immunotherapy for breast cancer patients.

AIM: To evaluate the immunohistochemical expression of TILs, CD8, and FOXP3 in invasive ductal carcinoma of the breast and analyze their association with clinicopathological parameters.

MATERIALS AND METHODS: Ninety-six histologically proven cases of Infiltrating ductal carcinoma (IDC) Breast were studied. Age, Laterality, tumor size, TNM stage, lymph node metastasis, histological grade, ER, PR, HER2neu, and Ki67 status were done. Both intensity and proportion of CD8 and FOXP3 expression were recorded.

STATISTICAL ANALYSIS: For qualitative data, the Chi-square test was used as a test of significance. The p-value (probability that the result is true) of < 0.05 was considered statistically significant after assuming all the rules of statistical tests.

RESULTS: There was an inverse correlation between CD8+ and FOXP3+ TILs (Pearson = − 0.508, p = 0.002), and a positive correlation between CD8+ TILs and overall TIL levels (Pearson = 0.419, p < 0.001). FOXP3+ TILs strongly correlated with a higher FOXP3/CD8 ratio (Pearson = 0.751, p < 0.001). These results suggest that higher CD8+ TILs are linked to robust anti-tumor immunity, while increased FOXP3+ TILs indicate an immunosuppressive environment. These insights highlight the importance of TIL balance in breast cancer prognosis and therapy.

CONCLUSION: This study investigated links between clinical and tumor immunity, spotlighting CD8 and FOXP3 and their ratio. The immunohistochemical analysis of tumor-infiltrating lymphocytes CD8 and FOXP3 in invasive ductal carcinoma of the breast reveals crucial insights into the tumor microenvironment. These findings highlights the potential of immune markers not only in refining prognostic models but also in guiding personalized immunotherapeutic approaches for breast cancer patients.}, } @article {pmid41072531, year = {2025}, author = {Hassan, M and Al-Askeri, M and Jawad, N}, title = {PROGNOSTIC IMPACT OF EGFR2 AND KI-67 OVEREXPRESSION WITH DOWNREGULATION OF MIR-17 AND MIR-1307 IN FEMALE BREAST CANCER PATIENTS.}, journal = {Georgian medical news}, volume = {}, number = {364-365}, pages = {303-313}, pmid = {41072531}, issn = {1512-0112}, mesh = {Humans ; Female ; *MicroRNAs/genetics/metabolism ; *Breast Neoplasms/genetics/pathology/diagnosis/metabolism ; *Ki-67 Antigen/genetics/metabolism ; Middle Aged ; Prognosis ; *Biomarkers, Tumor/genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Down-Regulation ; *Erb-b2 Receptor Tyrosine Kinases/genetics/metabolism ; Adult ; *Carcinoma, Ductal, Breast/genetics/pathology/diagnosis ; *Carcinoma, Lobular/genetics/pathology/diagnosis ; Aged ; Case-Control Studies ; }, abstract = {BACKGROUND: Breast cancer has distinct epidemiological patterns and heterogeneity. EGFR2 and Ki-67 are significant in determining the progression and therapeutic response in breast cancer. Additionally, miR-17 and miR-1307 are critical regulators of tumorigenesis. Our research investigates the function of these biomarkers across breast cancer progression, diagnostic and treatment response.

METHODS: Fifty-Three women with breast cancer and 25 healthy women were analyzed. ELISA was used to evaluate the concentrations of EGFR2 and Ki-67. For gene expression, qPCR was used to analyze the gene expression of miR-17 and miR-1307. The diagnostic value of the proteins and miRNAs, with significance set at a p-value <0.001 for all tests.

RESULTS: The study found a significant increase in EGFR2 and Ki-67 proteins in patients compared to controls. The concentration of EGFR2 in lobular carcinoma showed a significantly higher concentration compared to Invasive Ductal Carcinoma (IDC) and Mixed carcinoma, with a p-value of 0.001. Regarding Ki-67, Lobular carcinoma had significantly higher levels compared to IDC, with a p-value of 0.03. ROC curve analysis revealed excellent diagnostic accuracy for EGFR2 and Ki-67. Positive correlation was shown between EGFR2 and Ki-67 with each other, also miR-17 and miR-1307 showed a positive correlation with other. On the other hand, a negative correlation was seen between the protein level and gene expression.

CONCLUSION: This study found elevated EGFR2 and Ki-67 levels in breast cancer patients, indicating tumor aggressiveness, while the downregulation of miR-17 and miR-1307 suggests reduced tumor-suppressive activity. Their inverse correlation supports their use in diagnostic and treatment monitoring.}, } @article {pmid41072030, year = {2025}, author = {Vignaroli, KA and Malkoc, A and Perez, K and Daoud, A and Mamoun, L and Kim, SU and Guan, A and Ramiscal, JAB}, title = {Factors Associated with Positive Margin Requiring Re-Excision after Oncoplastic Breast-Conserving Surgery.}, journal = {Southern medical journal}, volume = {118}, number = {10}, pages = {663-666}, doi = {10.14423/SMJ.0000000000001887}, pmid = {41072030}, issn = {1541-8243}, mesh = {Humans ; Female ; Retrospective Studies ; *Mastectomy, Segmental/methods/statistics & numerical data ; Middle Aged ; *Margins of Excision ; *Breast Neoplasms/surgery/pathology ; *Reoperation/statistics & numerical data ; Aged ; Adult ; Carcinoma, Intraductal, Noninfiltrating/surgery/pathology ; Carcinoma, Ductal, Breast/surgery/pathology ; Risk Factors ; Carcinoma, Lobular/surgery/pathology ; }, abstract = {OBJECTIVE: Multiple factors are associated with re-excision after breast-conserving surgery (BCS), however there is minimal literature discussing factors associated with re-excision after oncoplastic BCS (OBCS). This retrospective study aimed to identify factors associated with positive margins requiring re-excision after OBCS.

METHODS: A retrospective review was performed on patients who underwent OBCS between October 2021 and May 2024. Subjects were divided into those who required re-excision and those who did not. Factors were evaluated including patient age, body mass index, smoking status, presence of hypertension and diabetes mellitus, tumor multifocality, microcalcifications, tumor size, human epidermal growth factor receptor 2[+] (HER2[+]) status, triple negative (estrogen receptor[-]/progesterone receptor[-]/HER2[-]) status, and tumor pathologies including ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and invasive lobular carcinoma.

RESULTS: The need for re-excision was significantly associated with a DCIS pathology (50% of patients, P = 0.021), and the lack of need for re-excision was associated with an IDC pathology (12.5% of patients, P = 0.005). There was no significant correlation in the need for margin re-excision based on age, body mass index, smoking status, the presence of hypertension or diabetes mellitus, tumor size, the presence of invasive lobular carcinoma, triple negative status, presence of HER2 or triple negative status, microcalcifications, or tumor multifocality.

CONCLUSIONS: Most factors associated with re-excision after BCS were not associated with re-excision after OBCS in our study. Similar to data published for BCS, however, our results show that DCIS pathology was significantly associated with re-excision in patients who undergo OBCS. In addition, the presence of IDC seemed to be negatively associated with re-excision after OBCS.}, } @article {pmid41069925, year = {2025}, author = {Sajid, J and Qureshi, R and Ahmad, H and Qureshi, AUR and Shafiq, A}, title = {Multi-modal Malignancies in Cowden Syndrome: Diagnostic Challenges in a Suspected Case From a Low-Resource Setting.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e91827}, pmid = {41069925}, issn = {2168-8184}, abstract = {Cowden syndrome (CS), a rare autosomal dominant disorder caused by mutations in the PTEN tumor suppressor gene, predisposes individuals to a wide range of malignancies, including breast, thyroid, endometrial, and renal cancers. This report presents a case of a 69-year-old woman with a history of papillary thyroid carcinoma, recently diagnosed invasive ductal carcinoma of the breast, and incidental clear cell renal cell carcinoma (RCC) - clinically pointing toward the diagnosis of CS. Genetic testing and endoscopic evaluations were not possible, as the case occurred in the setting of a developing country, with limited resources and financial constraints. This case underscores the importance of early recognition of hereditary cancer syndromes in patients with multiple malignancies, as well as the need for comprehensive genetic counseling, surveillance, and tailored treatment strategies. A multidisciplinary approach involving oncology, surgery, radiology, and genetics is crucial in managing the complex clinical presentation of patients with CS. The case also highlights the challenges faced when establishing a formal diagnosis in resource-constrained settings. These challenges are related not only to limited resources, but also to patient compliance, health literacy, and access to healthcare services.}, } @article {pmid41069807, year = {2025}, author = {Liu, H and Zhang, R and Gao, X and Jing, R and Zhang, Z and Miao, X}, title = {Exploring the impact of emergency risk information on construction workers' emergency information behavior: insights from confirmatory and exploratory PLS-SEM analyses.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1670767}, pmid = {41069807}, issn = {2296-2565}, mesh = {Humans ; *Construction Industry ; Surveys and Questionnaires ; Male ; Adult ; Self Efficacy ; Female ; China ; *Emergencies/psychology ; *Information Dissemination/methods ; Middle Aged ; Latent Class Analysis ; Least-Squares Analysis ; }, abstract = {Drawing on risk perception and information adoption theories, this study develops a structural equation model to examine the factors influencing emergency information behavior (EIB). The model includes risk information characteristics (RIC) and information dissemination channels (IDC) as independent variables, risk perception (RP) and information self-efficacy (ISE) as mediating variables, and EIB as the dependent variable. Data were collected from a questionnaire survey of 569 construction workers in Hangzhou and analyzed using Partial Least Squares SEM (PLS-SEM). The results indicate that RIC and IDC have a significant positive influence on RP, ISE, and EIB. Risk perception directly promotes EIB and indirectly influences it by enhancing information self-efficacy. Information self-efficacy, in turn, is also a significant driver of EIB, with the complete model explaining 55.5% of its variance (R [2] = 0.555). This study concludes that delivering high-quality risk information through multiple channels effectively enhances workers' ability to retrieve and use information during emergencies. This is achieved by improving their risk perception and information self-efficacy. The findings provide valuable empirical evidence and strategic recommendations for emergency management in the construction industry.}, } @article {pmid41068866, year = {2025}, author = {Nganou-Gnindjio, CN and Okobalemba, EA and Tasong, LA and Zende, AM and Elong, JT and Tumtchou, P and Mapoko, BE and Metogo, JA and Essiben, F and Hamadou, B}, title = {Evaluation of the cardiotoxicity risk based on the HFA-ICOS score in a group of sub-Saharan African women before breast cancer treatment by chemotherapy and/or radiotherapy: a cross-sectional study in a group of Cameroonian women.}, journal = {Cardio-oncology (London, England)}, volume = {11}, number = {1}, pages = {89}, pmid = {41068866}, issn = {2057-3804}, abstract = {BACKGROUND: Treatment of breast cancer by chemotherapy or radiotherapy exposes the patient to the risk of cardiotoxicity, which can be assessed pre-therapeutically using scores such as the Heart Failure Association and International Cardio-Oncology Society (HFA-ICOS) score. We aimed to evaluate the risk of cardiotoxicity using the HFA-ICOS score in a group of Cameroonian women before treatment of breast cancer by chemotherapy and/or radiotherapy.

METHODS: We conducted a cross-sectional analytic study using retrospective data collected from the Cardiology and Oncology departments at Yaounde Central Hospital and the Internal Medicine department at Yaounde General Hospital over an eight-year period, from 2017 to 2024, with a focus on the nine months from November 2023 to June 2024. Inclusion criteria consisted of patients with histologically confirmed breast cancer treated with chemotherapy and/or radiotherapy. We performed a multivariate analysis to determine the factors associated with moderate and high risk of cardiotoxicity, with a significance threshold of p ≤ 0.05.

RESULTS: Of the 130 patients recruited, the median age was 46.5 years (interquartile range, IQR, 36.75-58.00), with extremes of 21 and 76 years. Comorbidities mainly were overweight/obesity in 92 (70.7%) cases and arterial hypertension in 32 (24.6%) cases. Invasive ductal carcinoma was the main histological type, accounting for 126 (96.9%) cases, and triple-negative carcinoma was the most frequent molecular subtype, comprising 55 (42.3%) cases. Treatment consisted of exclusive chemotherapy in 96 (73.8%) cases and radiotherapy associated with chemotherapy in 27 (20.8%) cases. Based on the HFA-ICOS score, the cardiotoxicity risk was low in 93 (71.5%) patients. The independent factors associated with the risk of moderate to severe cardiotoxicity were age ≥ 60 years (adjusted OR: 5.97; 95% CI 1.73-20.60; adjusted p = 0.005), obesity (adjusted OR: 5.81; 95% CI 1.78-18.91; p = 0.003) and hypertension (adjusted OR: 27.10; 95% CI 7.51-97.76; p < 0.001). Exclusive chemotherapy was a protective factor (adjusted OR: 0.24; 95% CI 0.07-0.81; adjusted p = 0.021).

CONCLUSION: Women with breast cancer in Cameroon tend to be relatively young and present a low risk of cardiotoxicity before starting anti-cancer treatment.}, } @article {pmid41068218, year = {2025}, author = {Giorello, MB and Borzone, FR and Padin, MDR and Mora, MF and Wernicke, A and Labovsky, V and Chasseing, NA}, title = {Breast microcalcifications as indicators of bone metastasis risk in early-stage breast cancer.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {35311}, pmid = {41068218}, issn = {2045-2322}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/mortality ; *Calcinosis/pathology/diagnostic imaging ; Middle Aged ; *Bone Neoplasms/secondary ; Prognosis ; Adult ; Aged ; Neoplasm Staging ; Risk Factors ; }, abstract = {Bone metastasis is a leading cause of reduced survival in patients with advanced breast cancer. Therefore, identifying prognostic markers for bone metastasis at early disease stages is crucial. Microcalcifications are common findings in mammographic imaging and often serve as early diagnostic indicators. Certain types of microcalcifications have been linked to unfavorable genetic and molecular tumor profiles and are associated with poor prognosis. In particular, calcifications located within large ducts-such as casting-type, duct-centric patterns-have been described as independent markers of adverse outcome when compared to tumors with other calcification types or without calcifications. This study evaluated the prognostic significance of anarchic microcalcifications, defined as calcifications with irregular borders and/or disorganized patterns, in patients with early-stage breast cancer. Hematoxylin and eosin staining was used to assess the presence of these microcalcifications in invasive ductal carcinoma samples (n = 350). Their association with clinical and pathological characteristics was analyzed, including local relapse and bone metastasis occurrence. The presence of tumor microcalcifications was significantly associated with an increased risk of local relapse (p = 0.0360) and bone metastasis (p = 0.0020). Moreover, patients with microcalcifications exhibited shorter local relapse-free survival and bone metastasis-free survival (p = 0.0080 and p = 0.0020, respectively). Importantly, multivariate analysis confirmed that microcalcifications were an independent prognostic factor for both outcomes (p = 0.0150 and p = 0.0020, respectively). These findings suggest that the presence of tumor microcalcifications may serve as an independent prognostic marker for bone metastasis in early-stage breast cancer. Incorporating the evaluation of microcalcifications into routine pathological assessments could improve prognostic precision and support personalized treatment strategies. Further research is needed to elucidate the molecular mechanisms underlying the association between tumor microcalcifications and breast cancer progression.}, } @article {pmid41068186, year = {2025}, author = {Han, Z and Wang, B and Peng, S and Fu, Y and Yang, F and Ai, S and Wang, F and Zhuang, J and Guo, H and Qiu, X}, title = {The expression of prostate-specific membrane antigen in intraductal carcinoma of the prostate.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {35326}, pmid = {41068186}, issn = {2045-2322}, support = {BE2020622//Natural Science Foundation of Jiangsu Province/ ; 82172639, 81972388//National Natural Science Foundation of China/ ; ZDXKB2016014//The Project of Invigorating Health Care through Science, Technology and Education, Jiangsu Provincial Key Medical Discipline (Laboratory)/ ; QRX17128//Nanjing Medical Science and Technique Development Foundation/ ; }, mesh = {Humans ; Male ; *Prostatic Neoplasms/metabolism/diagnostic imaging/pathology/surgery ; Aged ; Positron Emission Tomography Computed Tomography ; *Glutamate Carboxypeptidase II/metabolism ; Middle Aged ; *Antigens, Surface/metabolism ; Retrospective Studies ; Gallium Radioisotopes ; Immunohistochemistry ; Prostatectomy ; Gallium Isotopes ; }, abstract = {To investigate the immunohistochemical expression of prostate-specific membrane antigen (PSMA) and radiological parameters of [[68]Ga]Ga-PSMA-11-PET/CT of intraductal carcinoma of the prostate (IDC-P). Seventy men with prostate cancer who had preoperative [[68]Ga]Ga-PSMA-11 PET/CT scan and following radical prostatectomy were retrospectively included. Radiological parameters including maximal tumor diameter, mean standard uptake value (SUVmean), and maximal standard uptake value (SUVmax) were derived from PET/CT images. Immunohistochemistry was used to determine the PSMA expression of IDC-P. The Mann-Whitney U test was performed for continuous variables and the chi-squared test for categorical variables. Logistic regression model was used for univariate analysis to compare the correlation between IDC-P and different preoperative variables. A total of 93 lesions were identified in 70 patients. Of these lesions, 21 (22.6%) in 20 patients (28.6%) were found to accompany IDC-P. The immune response score (IRS) of IDC-P lesions was significantly lower than that of prostate adenocarcinoma (P = 0.004).In multivariate analysis, SUVmean was found to be significantly lower in patients/lesions with IDC-P (P = 0.011, OR: 0.797 [95% CI 0.669-0.948] in the per-patient analysis and P = 0.028, OR: 0.829 [95% CI0.701-0.980] in the per-lesion analysis, respectively). SUVmean showed considerable AUC value of 0.71 (95% CI 0.589-0.839) in the per-patient analysis. Our results indicated lower histopathological PSMA expression and reduced [68Ga]Ga-PSMA-11 uptake in IDC-P compared to conventional prostate adenocarcinoma, suggesting that IDC-P may exhibit distinct biological features and could offer new insights for the radiological detection of intraductal carcinoma of the prostate in clinical practice.}, } @article {pmid41065768, year = {2025}, author = {Wante, M and Reddy, ASS and Nirhale, DS and Jeughale, K and Kavya, A}, title = {Study the Changing Trends of Age at Diagnosis of Breast Carcinoma in Correlation with Polycystic Ovarian Syndrome, Obesity, and Nutritional Status.}, journal = {Annals of African medicine}, volume = {}, number = {}, pages = {}, doi = {10.4103/aam.aam_203_25}, pmid = {41065768}, issn = {0975-5764}, abstract = {BACKGROUND: Hormonal factors, metabolic conditions such as polycystic ovary syndrome (PCOS), obesity, and nutritional deficiencies, influence the risk and prognosis of breast cancer risk. Understanding the interplay among these factors helps in identifying potential targets for prevention and treatment strategies.

AIM: The study aims to examine the shifting patterns in the age of breast cancer diagnosis and explore their associations with PCOS, obesity, and nutritional status.

METHODS: The prospective observational study included patients with histopathologically confirmed breast carcinoma. Detailed demographic and clinical data, including age at diagnosis, parity, menopausal status, and body mass index (used to classify obesity) were collected. Symptoms suggestive of PCOS and nutritional deficiencies (Vitamin D, iron, and iodine) were evaluated using laboratory and radiological findings. Histopathological findings and hormone receptor status were also noted.

RESULTS: Most women diagnosed with breast carcinoma were between 29 and 50 years (46.7%), postmenopausal (53.3%), overweight (58.7%), had PCOS (20.0%), and Vitamin D deficiency (68.0%). Invasive ductal carcinoma (90.7%) was the most common histopathological subtype, and most tumors were estrogen receptor (ER)-positive, especially ER + PR + Her2- (41.3%). None of the factors - PCOS, obesity, and nutritional status - were associated with histopathological subtypes (P > 0.05). However, PCOS was more common in ER-positive cases than ER-negative cases (P = 0.04), whereas obesity and nutritional status showed no association with hormone receptor status (P > 0.05).

CONCLUSION: High prevalence of breast carcinoma cases in women aged 31-50 years highlights shifting trend in its diagnosis. Nearly 80% of breast cancer patients had PCOS, suggesting its influence on tumor biology. Notable prevalence of nutritional deficiency (Vitamin D, serum iron, serum iodine, and folic acid deficiency) warrants further investigation into their role in breast cancer pathogenesis.}, } @article {pmid41064227, year = {2025}, author = {Singareddy, CTR and Nagaraj, C and Lakshmi, VVV and Vashishta, G and Malipatel, R}, title = {Unusual Gastric Metastasis from Invasive Ductal Carcinoma Breast Mimicking as Metachronous Primary on [18]F-FDG PET/CT.}, journal = {Indian journal of nuclear medicine : IJNM : the official journal of the Society of Nuclear Medicine, India}, volume = {40}, number = {4}, pages = {236-239}, pmid = {41064227}, issn = {0972-3919}, abstract = {The most common metastatic sites from carcinoma breast include the bones, lungs, liver, and brain. Breast cancer metastasizing to the gastrointestinal tract is very rare. This case report is about a compliant woman who was a known treated case of right breast cancer, in whom [18]F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography showed a focal FDG avid mural thickening in the body of stomach 4 years later, for which suspicion of a second primary of gastric origin was raised, considering the rarity of being metastatic. However, histopathology confirmed it as metastasis of breast origin. This case highlights the importance of considering gastric metastasis as a differential diagnosis in patients who present with a gastric lesion and a history of breast cancer.}, } @article {pmid41064097, year = {2025}, author = {Gao, C and Li, Y and Ma, X and Zhao, Z and Li, L and Liu, D and Li, B and Zhao, B}, title = {Clinical characteristics and prognosis of breast cancer patients with ovarian metastases.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1640067}, pmid = {41064097}, issn = {2234-943X}, abstract = {OBJECTIVE: This study aims to investigate the clinical characteristics, overall survival (OS), and prognostic factors associated with breast cancer patients who have ovarian metastasis (OM).

MATERIALS & METHODS: This retrospective single-center study analyzed 41 breast cancer patients with pathologically confirmed OM who underwent bilateral oophorectomy between 2011 and 2022. Data on clinical-pathological characteristics, molecular subtypes, detection methods, and survival were collected. The survival times were analyzed using Kaplan-Meier survival analysis. Prognostic factors were assessed through Cox regression models.

RESULTS: The cohort consisted of 33 (80.5%) invasive ductal carcinoma (IDC) and 8 (19.5%) invasive lobular carcinoma (ILC) cases. Most patients (87.8%) were hormone receptor-positive. Patients with ILC were significantly older at initial diagnosis than IDC patients (median 45 vs. 37 years, P = 0.014). OM was detected earlier in IDC, often incidentally during ablation surgery (54.5% vs. 12.5% for ILC, P = 0.032), whereas ILC patients typically presented with symptoms. For the entire cohort, the median OS was 85.0 months, while the median OS after OM was 28 months. Notably, patients with ILC exhibited a significantly shorter OS after OM (11.5 months) compared to those with IDC (30 months; P = 0.01). Furthermore, the interval from the initial diagnosis of breast cancer to the emergence of OM was significantly associated with the OS of these patients (P < 0.05), serving as an independent prognostic indicator.

CONCLUSIONS: OM, which may not exhibit overt clinical manifestations in the early stage, significantly affects the survival of BC patients. The ILC histological type is associated with a particularly unfavorable post-OM prognosis, and the interval from initial diagnosis to OM is a key prognostic indicator. These findings may guide clinical management in these patients.}, } @article {pmid41063895, year = {2025}, author = {Pavithran, S and Pavithran, K and Raj, M and Kumar, AA and Gopinath, S}, title = {Health-Related Quality of Life in Women With Invasive Ductal Carcinoma After Chemotherapy: Insight From the FACT-B+4 Questionnaire.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e91785}, pmid = {41063895}, issn = {2168-8184}, abstract = {Introduction Invasive ductal carcinoma (IDC) is the most common form of breast cancer in females, often treated with chemotherapy, either in the adjuvant or neoadjuvant setting. Malignancy as well as chemotherapy have a profound impact on the quality of life (QOL), with prognosis and survival largely dependent on early identification and treatment. Understanding the determinants of QOL is crucial to addressing its impact on physical, emotional, and social well-being. Aim This study aimed to determine the health-related quality of life (HRQOL) of patients with invasive ductal carcinoma after receiving chemotherapy and to explore factors contributing to a reduction in their HRQOL. Methods This was a prospective cohort study conducted among 294 women aged between 30 and 70 years who were histopathologically diagnosed with IDC and received chemotherapy from a Comprehensive Cancer Centre, Kerala. QOL was assessed using the Functional Assessment of Cancer Therapy-Breast+4 (FACT-B+4) questionnaire version 4.0, and sociodemographic and clinical data were collected through questionnaires, direct measurements, and from electronic medical records (EMR). The Mann-Whitney U test was used to compare the reduction (change) in QOL, and multiple logistic regression analysis was used to explore the factors contributing to the reduction in QOL after chemotherapy. Results The patients had a mean age of 51.56 ± 10.06 years, with the majority being 50 years and above (56.4%). Of 294 women who received chemotherapy, 228 (77.6%) developed chemotherapy-induced peripheral neuropathy (CIPN) of mild to moderate grades. Emotional well-being (EWB) had the lowest mean score before starting chemotherapy (those who developed CIPN: 14.46 ± 5.07 and those who did not develop CIPN: 13.72 ± 4.73). After chemotherapy, the maximum reduction in QOL occurred in physical well-being (PWB), with mean scores of 9.49 ± 5.57 and 3.49 ± 5.62, respectively, for those who developed and did not develop CIPN. Furthermore, in all domains, the reduction in QOL was greater in patients who developed CIPN than in those who did not. However, the difference in QOL change between the two groups was significant only for two domains: PWB (p < 0.001) and EWB (p = 0.013). The breast cancer subscale (BCS) (p < 0.001), arm (ARM) subscale (p = 0.033), and total scores (FACT-B TOI, FACT-G Total, and FACT-B Total) were also significantly lower in women who developed CIPN than in those who did not (p < 0.001). The factors contributing to the reduction in QOL were the presence of CIPN (OR = 3.623, 95% CI: 1.072-12.228, p = 0.038), age <50 years (OR = 4.016, CI: 1.236-12.987, p = 0.007), a higher number of chemotherapy cycles (eight cycles - OR = 38.488, 95% CI: 2.086-710.055, p = 0.053 and 12 cycles - OR = 70.655, 95% CI: 2.067-2415.638, p = 0.018), metastasis in the ipsilateral lymph nodes (OR = 3.623, CI: 1.204-10.902, p = 0.022), use of statins (OR = 7.608, CI: 1.269-45.617, p = 0.026), endocrine drugs (OR = 14.073, CI: 2.180-90.864, p = 0.005), and anaemia (OR = 30.606, CI: 1.867-15.001, p = 0.008). Conclusion The study highlights the significant impact of CIPN on the QOL of patients, along with factors such as age, number of chemotherapy cycles, presence of regional metastasis, histopathological subtypes, and anaemia. The study findings suggest the need for risk stratification and tailoring treatment strategies appropriately to minimise the risk of CIPN and optimise the QOL.}, } @article {pmid41063822, year = {2025}, author = {Ramos-Bartolomei, S and López-Fontanet, J and Muns-Aponte, S and Montes, JR and Noy, M}, title = {Metastasis of Neuroendocrine Carcinoma Masquerading as a Chalazion.}, journal = {Case reports in ophthalmology}, volume = {16}, number = {1}, pages = {628-632}, pmid = {41063822}, issn = {1663-2699}, abstract = {INTRODUCTION: Nonhealing or rapidly growing lesions should raise suspicion for malignancy, especially in a patient with a prior history of cancer. The purpose of this case was to highlight the importance of a thorough clinical history. A high index of suspicion and low threshold for biopsy are important, as is a fast diagnosis, as they can make a difference in adequate treatment and prognosis.

CASE PRESENTATION: We present a case of a 46-year-old female with a history of invasive ductal carcinoma of the breast presenting with a rapidly growing painless right lower eyelid lesion with biopsy remarkable for a high-grade neuroendocrine carcinoma suspected to be a result of metastasis with rare transformation of breast ductal carcinoma.

CONCLUSION: She had an eyelid lesion recurrence less than 2 months after biopsy and excision, demonstrating the importance of early detection and biopsy with immunohistochemistry to target malignant cells and improve life quality and expectancy.}, } @article {pmid41063546, year = {2025}, author = {Okubo, Y and Kasajima, R and Sato, S and Yamamoto, Y and Suzuki, A and Aigase, T and Yuguchi, S and Hasegawa, C and Yoshioka, E and Washimi, K and Matsuyama, R and Hiroshima, Y and Nakaigawa, N and Narimatsu, H and Kishida, T and Yokose, T and Miyagi, Y}, title = {Cribriform pattern and IDC-P in prostate biopsies: prognostic relevance and reporting in metastatic disease.}, journal = {The journal of pathology. Clinical research}, volume = {11}, number = {6}, pages = {e70052}, pmid = {41063546}, issn = {2056-4538}, support = {25K10294//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; Male ; Retrospective Studies ; Aged ; Middle Aged ; *Prostatic Neoplasms/pathology ; Prognosis ; Biopsy ; *Prostate/pathology ; Neoplasm Metastasis ; Aged, 80 and over ; Neoplasm Grading ; }, abstract = {Cribriform pattern and intraductal carcinoma of the prostate are recognized adverse histological features, yet their prognostic value in treatment-naïve metastatic disease remains uncertain. We conducted a single-center retrospective study of 183 biopsy-proven prostate carcinomas (105 with metastatic castration-sensitive prostate carcinoma and 78 non-metastatic high-grade cases) diagnosed between 2017 and 2024. Cribriform pattern, intraductal carcinoma of the prostate, and coagulative tumor necrosis were recorded per core and summarized as patient-level binary status and as semiquantitative proportions per cancer-positive core. Two multivariable logistic regression models (binary and semiquantitative) were fitted, and receiver operating characteristic (ROC) analysis evaluated the discriminatory performance of the cribriform proportion. Cribriform pattern and intraductal carcinoma of the prostate were more frequent in metastatic castration-sensitive prostate carcinoma. In the semiquantitative model, the cribriform proportion remained independently associated with metastatic status [odds ratio (OR) 1.29, 95% CI 1.07-1.55, p = 0.008; per 1.0 increase in the proportion, equivalent to OR 1.03 per 10%-point increase], whereas necrosis remained significant only in the binary model. The cancer-positive core rate and a lower total number of biopsy cores were predictive in both models, whereas prostate-specific antigen, intraductal carcinoma of the prostate, and Grade Group composition were not independent predictors. ROC analysis for the cribriform proportion yielded an area under the curve of 0.704, with a Youden Index cut-off of 0.445 (approximately half of cancer-positive cores), corresponding to a sensitivity of 57.1% and a specificity of 75.6%. These findings indicate that semiquantitative reporting of cribriform pattern - expressed as the proportion of cancer-positive cores - adds discriminatory information for metastatic status at presentation and could complement binary reporting in high-grade disease. From a clinical perspective, such evaluation may refine risk stratification at diagnosis and support treatment intensification strategies in very-high-risk patients.}, } @article {pmid41063232, year = {2025}, author = {Teng, L and Du, J and Dong, Y and Li, K and Tao, W}, title = {Survival analysis of metachronous bilateral ectopic breast cancer utilizing the SEER database and the pioneering construction of a nomogram model.}, journal = {European journal of medical research}, volume = {30}, number = {1}, pages = {934}, pmid = {41063232}, issn = {2047-783X}, support = {2021J17//First Affiliated Hospital of Harbin Medical University Fund for Distinguished Young Medical Scholars/ ; YXJL-2021-0302-0287//BEIJING MEDICAL AWARD FOUNDATION/ ; }, mesh = {Humans ; *Nomograms ; Female ; SEER Program ; *Breast Neoplasms/mortality/pathology/epidemiology ; Middle Aged ; *Neoplasms, Second Primary/mortality/pathology/epidemiology ; Prognosis ; Aged ; Adult ; Survival Analysis ; Risk Factors ; }, abstract = {INTRODUCTION: Metachronous bilateral ectopic breast cancer (MBEBC) is clinically rare, but the incidence has been increasing in recent years and no clear therapeutic guidance or prognostic assessment is available.

METHODS: Data on MBEBC patients from the Surveillance, Epidemiology, and End Results (SEER) database were gathered and randomly split into a training set and a validation set at a 7:3 ratio. Independent prognostic risk factors were identified through both univariate and multivariate analyses, and a nomogram was constructed based on these factors to predict survival outcomes.

RESULTS: From the SEER database, we collected data on a total of 8240 patients spanning the years 2005-2015. These patients were then randomly divided into a training set (5768) and a validation set (2472) for analysis. The clinicopathological features indicated that Grade 2 tumors were the most prevalent, with invasive ductal carcinoma comprising 71.2% of the cases. Additionally, the majority of MBEBC patients were classified as N0, and only a small fraction (4.2%) exhibited distant metastases. A multivariate COX regression model was developed to identify independent prognostic risk factors for patients whose first and second tumors were both invasive ductal carcinomas, as well as those with more extensive pathological types. Nomograms were also constructed for survival prediction of overall survival (OS) and breast cancer-special survival (BCSS) at 3, 5, and 10 years. Receiver operating characteristic (ROC) curves were plotted and area under the curve (AUC) values were calculated. The AUC was greater than 0.7 in all models, with a 10-year OS of 78.0 (76.0-80.0) and a BCSS of 77.6 (76.0-79.3) in all patients. The calibration curves and decision curve analysis (DCA) demonstrate that the nomogram possesses strong clinical predictive capability and high predictive accuracy.

CONCLUSION: This study detailed the clinicopathological characteristics of patients with the clinically rare MBEBC and identified independent prognostic risk factors across various pathology types. Additionally, a nomogram was developed for individualized prediction of patients' BCSS and OS, offering a new adjunctive tool for the clinical management of MBEBC patients.}, } @article {pmid41054366, year = {2025}, author = {Mohammed Mahmoud, M and Abdulla Kamil Abdulla, and Dler Omar Mohammed, }, title = {Molecular detection of Epstein-Barr virus in invasive ductal carcinoma of the breast: a case-control study.}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {71}, number = {9}, pages = {105-110}, doi = {10.14715/cmb/2025.71.9.13}, pmid = {41054366}, issn = {1165-158X}, mesh = {Humans ; Female ; Case-Control Studies ; *Breast Neoplasms/virology/pathology ; *Herpesvirus 4, Human/genetics/isolation & purification ; *Carcinoma, Ductal, Breast/virology/pathology ; Middle Aged ; Adult ; *Epstein-Barr Virus Infections/virology/complications ; Aged ; Viral Matrix Proteins/metabolism/genetics ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; }, abstract = {The uncertain contribution of Epstein-Barr virus (EBV) to the etiological processes underlying invasive ductal carcinoma (IDC) of the mammary gland, especially in relation to its molecular interactions within inflamed histological contexts, remains to be elucidated. This case-control research assessed the link between EBV infection and mammary IDC in a population of Iraqi females from Kirkuk. A total of 300 breast tissue specimens preserved in paraffin blocks were evaluated, including 150 samples diagnosed with IDC and 150 samples classified as fibroadenoma serving as controls. EBV latent membrane protein-1 expression was identified through the application of immunohistochemical staining and polymerase chain reaction methodologies. EBV positivity, defined as detection by both IHC and PCR, was observed in 7.3% of IDC cases and 4% of controls, with no statistically significant difference between groups (P=0.996). No significant association was found between EBV presence and estrogen or progesterone receptor status, while Her-2 expression differed significantly between EBV-positive and EBV-negative patients (P<0.001). EBV was more frequently detected in grade I tumors and stage II breast cancers, and older patients showed a higher prevalence of EBV infection. The results indicate that although Epstein-Barr virus (EBV) is identifiable in a fraction of invasive ductal carcinoma (IDC) breast specimens, a definitive causative relationship between EBV presence and IDC occurrence within this demographic is not established. Nonetheless, EBV detection appears to exhibit higher frequency in specific histopathological grades, clinical stages, and patient age categories.}, } @article {pmid41054106, year = {2025}, author = {Sun, Y and Chen, H and Wang, K and Liu, Y}, title = {Clinicopathological characteristics and survival outcomes in spindle cell carcinoma (SpCC) of the breast: A SEER population-based study.}, journal = {Medicine}, volume = {104}, number = {40}, pages = {e44851}, pmid = {41054106}, issn = {1536-5964}, support = {Grant No. 82204721//the National Natural Science Foundation of China/ ; }, mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; *Breast Neoplasms/pathology/mortality ; *Carcinoma/pathology/mortality ; *Carcinoma, Ductal, Breast/pathology/mortality ; Neoplasm Staging ; Prognosis ; Propensity Score ; Proportional Hazards Models ; Retrospective Studies ; SEER Program ; }, abstract = {Spindle cell carcinoma (SpCC) of the breast is a rare entity. The aim of this study was to provide more information for understanding this disease and to improve the management of it in the clinic. Patients with SpCC and invasive ductal carcinoma (IDC) of the breast were identified through the surveillance, epidemiology, and end results (SEER) database (2001-2018). 227 patients with SpCC and 565,388 patients with breast IDC were enrolled in the present cohort study. Comparative analyses were performed to investigate the heterogeneity in the clinicopathological characteristics and survival outcomes between these 2 groups. Propensity score matching (PSM) was used to balance the influences of baseline clinicopathological differences. The multivariate Cox proportional hazard model was carried out to identify potential prognostic factors of SpCC. Compared with IDC, patients with SpCC had a higher proportion of older patients and white individuals, a higher tumor grade, a lower tumor stage, a larger tumor size, a higher incidence of distant metastasis, a lower rate of lymph node involvement, a higher proportion of triple-negative breast cancer (TNBC) and less access to therapeutics. The prognosis of SpCC was profoundly poorer than that of IDC, whether before or after PSM. Subgroup analysis further showed that SpCC-TNBC had a worse clinical outcome than IDC-TNBC. Finally, we found that older age, advanced T stage, N stage and M stage were all risk factors for SpCC. SpCC of the breast presented with increasing aggressive behavior in comparison with IDC and inferior clinical outcome than IDC for both the whole group and the TNBC subgroup. Distinguishing SpCC from IDC is critical for improving treatment efficacy; therefore, further research must focus on this rare but aggressive disease.}, } @article {pmid41052010, year = {2025}, author = {Icht, M and Meirzada, A and Ben-David, BM}, title = {Little ears, literal emotions: the developmental pattern of emotional speech processing in elementary school-age children and the mediating role of expressive lexicon.}, journal = {Cognition & emotion}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/02699931.2025.2568550}, pmid = {41052010}, issn = {1464-0600}, abstract = {Processing spoken emotions, a critical skill for social interactions, develops from birth to adulthood. It relies on processing information in two auditory channels: semantics and prosody, and their integration. The current study examined the developmental pattern of emotional speech processing, comparing 8- and 12-year-old elementary school children (ES-Juniors and ES-Seniors, respectively). This age-range reflects developmental stages in emotional processing, social understanding, lexical development, and executive functions. Three basic abilities were tested: (1) Identifying semantic/prosodic emotions, (2) Selectively attending to a single channel, and (3) Integrating the two channels. Sixty participants rated how much they agreed that a spoken sentence expressed a specific emotion (happiness, sadness, or anger), in one or both channels. The ES-Senior group outperformed the ES-Junior group in semantic identification and selective attention. No significant differences were found for prosody. ES-Seniors showed better channel integration: While ES-Juniors performed with semantic dominance, ES-Seniors showed no significant dominance, approaching adult-like performance. Finally, expressive lexicon moderated group differences in semantic identification and prosody-semantics integration. The ES-Seniors' advantage over ES-Junior in these measures disappears for individuals with higher language scores. Findings may inform interventions for ES children experiencing emotional processing challenges.}, } @article {pmid41051950, year = {2026}, author = {Elverici, E and Gündoğdu, S and Gunbey Karabekmez, L and Kayaçetin, S and Altun Özdemir, B and Gökhan, MB and Özsoy, A}, title = {Diagnostic performance of contrast-enhanced spectral mammography in the evaluation of suspicious microcalcifications without associated mass.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {67}, number = {1}, pages = {34-42}, doi = {10.1177/02841851251380868}, pmid = {41051950}, issn = {1600-0455}, mesh = {Humans ; Female ; *Mammography/methods ; *Calcinosis/diagnostic imaging/pathology ; *Contrast Media ; Middle Aged ; Retrospective Studies ; *Breast Neoplasms/diagnostic imaging/pathology ; Aged ; Adult ; Breast/diagnostic imaging/pathology ; Aged, 80 and over ; }, abstract = {BackgroundContrast-enhancing magnetic resonance imaging is an expensive examination compared to contrast-enhanced spectral mammography (CESM) and cannot show microcalcifications.PurposeTo investigate the diagnostic performance of CESM for malignancy with microcalcifications alone and the relationship between tumor immunohistochemistry findings and tumor grade.Material and MethodsA total of 117 patients with suspected microcalcification at CESM were applied to our hospital between January 2022 and May 2024. Patients with accompanying mass and architectural distortion (n = 9) and the ones lacking pathology results (n = 11) were excluded. Patients with CESM and histopathological diagnosis (n = 97) were evaluated retrospectively. Mammography images were analyzed according to the American College of Radiology Breast Imaging-Reporting and Data System lexicon.ResultsIn our study, the diagnostic value of the presence of contrast enhancement in CESM was high in the evaluation of suspicious breast microcalcifications. Malignant pathology was detected in all of the microcalcifications with high-risk morphology. In addition, all of the microcalcifications that enhanced in solid and ground-glass form were invasive ductal carcinoma. However, no significant relationship was found between immunohistochemical parameters (ER, PR, CerB2, Ki-67 and grade) and enhancement in CESM. The highest enhancement rate among malignant subtypes was detected in the luminal B group.ConclusionCESM is useful to reduce the number of unnecessary benign biopsies with suspicious microcalcifications in the breast, and provides an important contribution to the radiologist's biopsy decision by simultaneously showing the morphological features of the microcalcification and the contrast enhancement information.}, } @article {pmid41050877, year = {2025}, author = {Stover, CS and Meshberg-Cohen, S and Portnoy, GA and Char, S and McCaskill, CW and Do, QA and Dziura, J and Martino, S}, title = {Efficacy of an integrated treatment for fathers with Co-occurring substance misuse and family violence.}, journal = {Contemporary clinical trials communications}, volume = {48}, number = {}, pages = {101555}, pmid = {41050877}, issn = {2451-8654}, support = {I50 HX003896/HX/HSRD VA/United States ; }, abstract = {Substance Use (SU) and Family Violence (FV) are both critical public health concerns and often occur together. However, most existing interventions target only one of these problems, without consideration of the other, and fail to address when individuals with these issues are parents. The current Stage II randomized clinical trial (RCT) aims to compare two individually delivered interventions, Fathers for Change (F4C) and Individual Drug Counseling (IDC) in 280 fathers who have used physical or psychological violence towards a partner, have a substance use disorder, and have a biological child between the ages of 3 months and 12 years. They will be recruited from two locations (Department of Veteran Affairs [VA] and community substance use treatment clinic). This efficacy study aims to demonstrate that F4C can achieve comparable SU reductions to IDC, while also reducing FV, with increases in emotion regulation meditating the relationship between the intervention group and reduced SU and FV. Findings from this study have large scale clinical and public health implications that can help target and address co-occurring SU and FV and mitigate negative outcomes for affected children and families.}, } @article {pmid41049938, year = {2025}, author = {Patel, RM and Korsunsky, S and El-Gazzaz, G and Abdulla, A}, title = {Robotic-Assisted Adrenalectomy for Presumed Metastasis in a Male Patient With Breast Cancer: A Case Report.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e91583}, pmid = {41049938}, issn = {2168-8184}, abstract = {We report the case of a 57-year-old male with T1N1M0, estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), and human epidermal growth factor receptor 2-negative (HER2-), corresponding to American Joint Committee on Cancer Stage IIA (AJCC Stage IIA) invasive ductal cell carcinoma of the left breast, who underwent a radical mastectomy with adjuvant chemotherapy. CT and MRI imaging demonstrated an adrenal nodule that persisted even after the patient's chemotherapy regimen was completed. Subsequent PET imaging detected a hypermetabolic left adrenal mass concerning for distant metastasis. Ultimately, the patient and care team decided that a robotic-assisted left adrenalectomy was likely the best course of action. Intraoperative frozen and final pathology both confirmed a benign adrenal fibroadenoma. This case highlights the diagnostic challenges faced when distinguishing adrenal metastasis from benign lesions in patients with a history of malignancy, especially when imaging findings are nonspecific. The case emphasized the sheer importance of multidisciplinary evaluation and potential surgical intervention in rare malignancies, such as male breast cancer, where existing guidelines are often extrapolated from female populations.}, } @article {pmid41048698, year = {2025}, author = {Dharia, A and Yan, K and Mammen, SV and Myers, M and Ahn, J and Jaiswal, G}, title = {Metastatic Invasive Ductal Carcinoma Presenting as Unilateral Adrenal Incidentaloma.}, journal = {AACE endocrinology and diabetes}, volume = {12}, number = {3}, pages = {169-173}, pmid = {41048698}, issn = {3050-9157}, abstract = {BACKGROUND/OBJECTIVE: The widespread use of cross-sectional imaging has led to increased detection of adrenal incidentalomas (AI), most of which are benign. However, a small fraction of AIs are malignant, with a significantly higher risk in patients with a history of cancer.

CASE REPORT: Sixty-nine-year-old woman with a remote history of invasive ductal breast carcinoma and thyroid carcinoma in remission presented with chronic abdominal pain. Imaging revealed 2 enlarging, right adrenal nodules with indeterminate features and no uptake on PET-CT. Hormonal tests indicated a nonfunctioning adrenal mass. Due to continued growth, she underwent laparoscopic adrenalectomy. Histopathology revealed metastatic breast carcinoma, and she subsequently initiated systemic chemotherapy.

DISCUSSION: This case highlights the diagnostic challenges posed by AIs in patients with known cancer and provides valuable insights into the detection and management of adrenal metastases.

CONCLUSION: Timely surgical intervention allowed for definitive diagnosis and appropriate oncologic management, highlighting the importance of individualized evaluation and multidisciplinary decision-making in cases of AIs.}, } @article {pmid41046212, year = {2025}, author = {Zhou, Z and Sun, Z and Zhao, F and Jin, Y and Chen, Y and Zhu, L and Guo, Y and Wang, W}, title = {Predictive Value of Nomogram-Based Clinicopathological Biomarkers Combined with Multiparametric MRI for Tumour-Infiltrating Lymphocyte Expression in Breast Cancer.}, journal = {Academic radiology}, volume = {32}, number = {12}, pages = {7134-7145}, doi = {10.1016/j.acra.2025.09.017}, pmid = {41046212}, issn = {1878-4046}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology/immunology ; *Lymphocytes, Tumor-Infiltrating/pathology ; *Nomograms ; Middle Aged ; *Multiparametric Magnetic Resonance Imaging/methods ; Adult ; Predictive Value of Tests ; Aged ; Sensitivity and Specificity ; Retrospective Studies ; Biomarkers, Tumor ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology/immunology ; *Magnetic Resonance Imaging/methods ; }, abstract = {RATIONALE AND OBJECTIVES: To investigate the value of clinicopathological features and multiparametric magnetic resonance imaging (MRI) in predicting tumour-infiltrating lymphocyte (TIL) levels in breast cancer.

MATERIALS AND METHODS: A total of 171 patients diagnosed with invasive ductal carcinoma who underwent preoperative MRI (2023-2025) were included. The analysis focused on the clinicopathological characteristics alongside conventional MRI features and a range of quantitative parameters. Multiple logistic regression analysis identified independent predictors of high and low TIL levels. A nomogram was constructed based on the multivariable logistic regression model results.

RESULTS: Logistic regression analysis identified histological grade, D, D*, Ktrans, and Kep as independent factors in the training cohort. The nomogram's C-index was 0.944 in the training cohort and 0.964 in the validation cohort. The area under the curve (AUC) of the nomogram model was 0.954 (85.1% sensitivity, 91.1% specificity, and 87.4% accuracy) in the training cohort and 0.974 (96.7% sensitivity, 92.1% specificity, and 92.6% accuracy) in the validation cohort, both significantly higher than those of the individual models in the corresponding cohorts (Z=3.018-6.653, all P<0.05 and Z=2.546-5.668, all P<0.05).

CONCLUSION: Combining clinicopathological characteristics with multiparametric MRI parameters significantly improves prediction accuracy for TIL levels in breast cancer. This integrated model holds considerable clinical potential, providing robust support for personalised treatment strategies.}, } @article {pmid41035082, year = {2025}, author = {Sarmadi, A and Javanmard, SH and Zeinalian, M and Hosseinzadeh, M and Tabatabaiefar, MA}, title = {Mono-allelic MUTYH mutation as the likely inherited etiology of hereditary breast cancer in a patient from a multi-cancer family- report of a family and literature review.}, journal = {BMC medical genomics}, volume = {18}, number = {1}, pages = {146}, pmid = {41035082}, issn = {1755-8794}, mesh = {Humans ; *DNA Glycosylases/genetics ; Female ; *Breast Neoplasms/genetics/pathology ; Pedigree ; *Alleles ; *Mutation ; Middle Aged ; *Genetic Predisposition to Disease ; Adult ; Exome Sequencing ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most prevalent cancer globally. Carriers of pathogenic variants in high- or moderate-penetrance genes, have an increased risk of developing hereditary BC (HBC). While, MUTYH is known to be associated with hereditary colonic polyposis and colorectal carcinoma, its role in BC is controversial. This study investigated the genetic cause of HBC in an Iranian family with a history of multiple cancer cases.

METHODS: Clinical examination and exome sequencing (ES) was performed in a patient suffering from invasive ductal carcinoma from a family with several cases of different types of cancer. The pathogenicity of detected variants was done based on American Collage of Medical Genetics (ACMG) and Sanger sequencing was carried out for its validation. Furthermore, we performed a comprehensive review of the literature.

RESULTS: Here, a pathogenic variant (p. A287Pfs*32) was identified in the MUTYH gene in mono-allelic status in four BC patients. However, this variant was previously reported as the cause of MutYH-associated polyposis (MAP) in homozygous status. The review of literature showed that the frequency of MUTYH mutation in BC patients population is in a range of 0.3-5.6%.

CONCLUSION: In this study, a heterozygous pathogenic variant in the MUTYH gene was identified as the possible cause of BC in a multi-cancer family using ES. While the potential association between mono-allelic MUTYH mutations and an elevated risk of BC remains controversial, these findings highlight the necessity for a careful interpretation when assessing the role of MUTYH mutations in BC risk.}, } @article {pmid41030644, year = {2025}, author = {Yee, G and Wu, R and Ishikawa, T and Takabe, K}, title = {Invasive Lobular Carcinoma Has Higher Immune Response Than Invasive Ductal Carcinoma in Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancers.}, journal = {World journal of oncology}, volume = {16}, number = {5}, pages = {446-456}, pmid = {41030644}, issn = {1920-454X}, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) are two major pathological diagnoses of breast cancer, but few studies have described their differences within luminal (estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative) subtypes at the molecular level.

METHODS: Using The Cancer Genome Atlas (TCGA) (n = 584) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n = 1,355) cohorts, we analyzed luminal ILC and IDC, excluding mixed type, in patients with stage I-III breast cancer.

RESULTS: ILC was associated with Nottingham histological grade 2, larger tumor size and more stage III disease than IDC (all P < 0.01) but no difference in lymph node nor distant metastasis in both cohorts. There was no survival difference between ILC and IDC. ILC had less aggressive genomic features compared to IDC, and the cell proliferation score and Ki67 gene expression were significantly lower in ILC in TCGA (P < 0.001); however, these findings were not validated in METABRIC. Hallmark cell proliferation-related gene sets (E2F targets, G2M checkpoint, MYC targets V1, and MTORC1 signaling) were significantly less enriched in ILC in both cohorts (all normalized enrichment score (NES) > 1.4, false discovery rate (FDR) < 0.12). While ILC appeared to have a lower trend of pathological complete response (pCR) in the GSE20194 and GSE1140494 cohorts, ILC was infiltrated with significantly more CD4[+] cells and dendritic cells and significantly less T helper type I (Th1) cells, regulatory T cells and M1 and M2 macrophages in both cohorts (all P < 0.05). Stromal cells, adipocytes and lymphatic endothelial cells were highly infiltrated in ILC, and cytolytic activity that represented the global anti-tumor immunity was significantly elevated in ILC in TCGA and subsequently validated in METABRIC.

CONCLUSIONS: ILC has higher immune response and immune cell infiltration than IDC in the luminal subtype.}, } @article {pmid41026283, year = {2025}, author = {Hawkins, KN and Dillard, J and Ye, Y and Wang, J and Hoffman, RM and Mcphail, K and Barsky, SH}, title = {Natural and induced epithelial-mesenchymal transition results in epigenetic silencing of HER2 overexpression.}, journal = {Journal of mammary gland biology and neoplasia}, volume = {30}, number = {1}, pages = {15}, pmid = {41026283}, issn = {1573-7039}, support = {U54 CA163069/CA/NCI NIH HHS/United States ; U54CA163069//Pathology Shared Resource Core, supported by NIH/ ; BC990959, BC024258, BC053405//Department of Defense Breast Cancer Research Program Grants/ ; }, mesh = {*Epithelial-Mesenchymal Transition/genetics ; Humans ; *Erb-b2 Receptor Tyrosine Kinases/genetics/metabolism ; Female ; *Epigenesis, Genetic ; *Gene Silencing ; Gene Expression Regulation, Neoplastic ; *Breast Neoplasms/genetics/pathology/metabolism ; Cell Line, Tumor ; Animals ; Transforming Growth Factor beta1 ; }, abstract = {Epithelial-mesenchymal transition (EMT) is a well-known phenomenon that has been implicated in diverse biological processes ranging from embryonal development to cancer invasion and metastasis. In epithelial-derived cancers which both invade and metastasize as epithelial clumps or clusters, EMT would have to be followed by MET (mesenchymal-epithelial transition) since both the initial cancer and the metastasis appear epithelial in nature. There is a rare subset of breast carcinomas, however, that exhibit biphasic epithelial and mesenchymal differentiation, so-called metaplastic carcinomas. Our initial studies were designed to examine whether EMT was indeed occurring in this unique subset of metaplastic breast carcinomas. Based on both RT-PCR and immunocytochemical studies, EMT was naturally occurring. Once this was confirmed, we wanted to investigate the effects of EMT beyond the immediate gene expression pattern that traditionally defined it. Although approximately 90% of metaplastic breast carcinomas are triple negative, 5-10% amplify and overexpress HER2. We then conducted both observational studies in these biphasic HER2 overexpressing metaplastic breast carcinomas and experimental studies with a HER2 overexpressing cell line, the HTB20, where TGFβ1 induced EMT. In the observational studies, HER2 gene amplification was equally present in both the epithelial and mesenchymal phases but both HER2 mRNA and protein levels were essentially silenced in the areas having undergone EMT. Similarly in the experimental studies where TGFβ1 induced EMT, HER2 gene amplification persisted but HER2 mRNA and protein levels were similarly silenced. These studies provide direct evidence that both naturally occurring and induced EMT results in epigenetically silencing of HER2 overexpression.}, } @article {pmid41025061, year = {2025}, author = {Singla, V and Bhatia, H and Garg, D and Bal, A and Sekar, A}, title = {A compendium of male breast imaging: The road less traveled.}, journal = {World journal of radiology}, volume = {17}, number = {9}, pages = {110906}, pmid = {41025061}, issn = {1949-8470}, abstract = {Male breast disorders, though less prevalent, present unique diagnostic challenges that differ significantly from their female counterparts. While benign entities such as gynecomastia are predominant, the risk of underlying malignancy, often diagnosed at an advanced stage, highlights the need for a systematic, image-guided assessment. Ultrasound and mammography are the first-line complementary tools, with magnetic resonance imaging reserved for problem-solving. This review outlines the anatomical, pathological, and radiological nuances of the male breast, describing crucial red flag signs, sonographic pitfalls, and mammographic mimics that aid in distinguishing benign entities from sinister pathologies such as invasive ductal carcinoma. Given the increasing visibility of transgender individuals, this review also addresses imaging considerations and screening recommendations tailored to this population. By integrating clinical insights with radiologic imaging, this review offers a comprehensive approach to both common and not-so-common male breast lesions, with an emphasis on an algorithmic stepwise diagnostic approach.}, } @article {pmid41024216, year = {2025}, author = {Kitagawa, Y and Nassiri, M and Mesa, H and Prakash, J and Popnikolov, N}, title = {Possible role of anastrozole-induced hormonal alterations in pathogenesis of mammary apocrine carcinoma and follicular lymphoma: a case report and review of the literature.}, journal = {Journal of medical case reports}, volume = {19}, number = {1}, pages = {465}, pmid = {41024216}, issn = {1752-1947}, mesh = {Aged, 80 and over ; Female ; Humans ; *Anastrozole/adverse effects ; Antineoplastic Agents, Hormonal/adverse effects ; *Aromatase Inhibitors/adverse effects ; *Breast Neoplasms/chemically induced/pathology/surgery ; *Carcinoma, Ductal, Breast/pathology/chemically induced/surgery ; *Lymphoma, Follicular/chemically induced/pathology ; Mammography ; Paget's Disease, Mammary/diagnosis/drug therapy ; }, abstract = {BACKGROUND: In postmenopausal women, aromatase inhibitors decrease estrogen levels and increase local dihydrotestosterone concentrations. In this case report, we describe interesting associations between aromatase-inhibitor-induced hormonal changes and the development of apocrine mammary carcinoma and follicular lymphoma.

CASE PRESENTATION: Here we report an 83-year-old Caucasian female patient who initially presented with Paget's disease of the right nipple and associated small focus of invasive ductal carcinoma (ERα + PR + HER2-). The patient did not pursue surgical resection and was treated only with anastrozole, and 5 years later, she was diagnosed with a 1.1 cm ipsilateral periareolar apocrine mammary carcinoma (ERα-ERβ + PR - AR + HER2-) that was detected during surveillance mammography. In addition to this tumor, the subsequent mastectomy specimen revealed an adjacent residual focus of the original invasive ductal carcinoma (ERα + ERβ + PR + AR + HER2-) within the nipple and a focus of follicular lymphoma (ERα-ERβ + AR[low]) in the retroareolar area. Sentinel lymph nodes and imaging studies were negative for malignancy. The patient was continued on observation. Anastrozole was stopped after 10 months, and 2 months later, during a routine screening, a 1.8 cm invasive apocrine carcinoma (ERα-ERβ + PR-AR + HER2-) was detected in the patient's contralateral breast and she underwent simple mastectomy with sentinel lymph node biopsy. The sentinel lymph node was negative. No chemotherapy or radiation therapy was recommended. All carcinomas exposed to anastrozole expressed androgen-responsive molecules (GCDFP-15, NKX3.1). Germline genetic testing for 19 genes associated with hereditary breast cancer syndromes was negative, and 3 years later, the patient is still alive with no recurrences.

CONCLUSION: Our case suggests that unopposed local androgen exposure and loss of ERβ-mediated suppressive effect of estrogens may be involved in development of apocrine mammary tumors and lymphomas, respectively. However, further studies are necessary to clarify the roles of steroid hormones in pathogenesis of apocrine carcinoma and follicular lymphoma. This case also illustrates the importance of patient follow-up during and after aromatase inhibitor therapy. Appropriate surveillance for lymphoma may also be considered for those patients. Finally, when lymphoid aggregates are encountered in specimens from patients with breast cancer, a clinical history of hormonal therapy should alert the pathologist for a possibility of lymphoma.}, } @article {pmid41023513, year = {2025}, author = {Aponte-Rueda, ME and Gómez-González, FM and Merck, B}, title = {Breast Cancer Heterogeneity in Latin America: A Scoping Review of Clinical-Pathological Characteristics, Molecular Subtypes, and Survival.}, journal = {World journal of surgery}, volume = {49}, number = {11}, pages = {3001-3025}, pmid = {41023513}, issn = {1432-2323}, mesh = {Humans ; Female ; Latin America/epidemiology ; *Breast Neoplasms/pathology/mortality/genetics/epidemiology ; Neoplasm Staging ; Middle Aged ; Neoplasm Grading ; }, abstract = {BACKGROUND: Breast cancer in Latin America (LATAM) exhibits distinct clinical-pathological and molecular features, shaped by genetic diversity and healthcare disparities. This scoping review evaluates these characteristics, focusing on histopathological, molecular subtype, and survival patterns and their implications for future research and public health initiatives.

METHODS: A systematic search across MEDLINE (via PubMed), LILACS (Latin American and Caribbean Health Sciences Literature), SciELO (Scientific Electronic Library Online), and Web of Science identified 54 studies across 19 Latin American countries. Data were extracted on histological grading, molecular subtypes, staging, and survival outcomes. Findings were analyzed in the context of regional and global trends.

RESULTS: Fifty-four studies involving 49,223 women from 19 countries were analyzed. The mean age at diagnosis was 54.3 years. Invasive ductal carcinoma was the most common (79.2%). Advanced-stage disease (Stages III/IV) was identified in 36.1% of cases. Luminal subtypes were most prevalent (Luminal A: 36.95% and Luminal B: 28.72%), whereas triple-negative (TNBC) and HER2-enriched subtypes accounted for 17.45% and 12.69%, respectively. Subtype prevalence varied by country, age, and tumor grade. Five-year survival rates ranged from 50.5% to 92.5%, with worse outcomes linked to advanced stage, high grade, and TNBC or HER2-enriched tumors.

CONCLUSION: Breast cancer in LATAM is characterized by significant heterogeneity in biological subtypes and clinical presentation, often diagnosed at advanced stages, with limited capacity for molecular testing. These findings highlight the urgent need for standardized diagnostic protocols, equitable access to treatment, and region-specific cancer control strategies to improve outcomes for Latin American women.}, } @article {pmid41021136, year = {2025}, author = {Larionesi, E and Pilet, ON and Sotiriou, C}, title = {Case report: metachronous male metastatic breast and colon cancer in a BRCA2 mutation carrier.}, journal = {Discover oncology}, volume = {16}, number = {1}, pages = {1751}, pmid = {41021136}, issn = {2730-6011}, abstract = {INTRODUCTION AND IMPORTANCE: Male breast cancer (MBC) is rare and typically diagnosed at later stages, often in older men. Pathogenic BRCA2 mutations are implicated in a significant proportion of MBC cases and may confer increased risk for other cancers.

CASE PRESENTATION: A 66-year-old male presented with right upper limb edema and back soreness. Imaging and biopsy confirmed stage IV invasive ductal carcinoma, Luminal B HER2-negative. Genetic testing revealed a germline BRCA2 mutation. During routine imaging, a second primary colon cancer was discovered and resected.

CLINICAL DISCUSSION: MBC represents less than 1% of all male cancers and is frequently associated with delayed diagnosis. BRCA2 mutations significantly increase the risk for male breast and gastrointestinal cancers. This patient underwent endocrine and CDK4/6 inhibitor therapy and followed by surgery and adjuvant chemotherapy for the colon carcinoma. Disease remained stable on follow-up.

CONCLUSION: This case highlights the importance of genetic testing, vigilance for second primary malignancies in BRCA2 carriers, and the value of multidisciplinary care for MBC patients. The co-occurrence of these malignancies in a male BRCA2 carrier is rare and underscores the need for broader surveillance in such patients.}, } @article {pmid41018463, year = {2025}, author = {Douligeris, CC and Boptsi, E and Theocharopoulos, C and Foteinou, D and Batis, A and Lampropoulos, P and Manolakos, O}, title = {A Rare Cause of Intestinal Obstruction: Invasive Lobular Breast Carcinoma Metastasizing to the Ileocecal Valve.}, journal = {Cureus}, volume = {17}, number = {8}, pages = {e90985}, pmid = {41018463}, issn = {2168-8184}, abstract = {Invasive lobular carcinoma (ILC) has a higher propensity for gastrointestinal metastases compared to invasive ductal carcinoma (IDC). We present the case of a 65-year-old woman with metastatic ILC who developed intestinal obstruction due to ileocecal metastases 30 months after undergoing total mastectomy and adjuvant therapy for left-sided breast cancer (BC). Abdominal computed tomography (CT) demonstrated a transition point at the ileocecal valve. Surgical resection was performed to relieve the small bowel obstruction, and histopathology confirmed metastatic ILC with receptor discordance compared to the primary tumor. This case highlights the diagnostic and therapeutic challenges of intestinal metastases from BC, including receptor conversion and resistance to therapy. Molecular profiling and tailored treatment are crucial for optimal management of complex metastatic disease.}, } @article {pmid41018083, year = {2025}, author = {Sołek, J and Zielińska, A and Kordek, R and Romańska, H and Braun, M}, title = {FGFR2 expression relates to subtype-specific tumour microenvironment (TIME) during luminal breast cancer evolution.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1655438}, pmid = {41018083}, issn = {2234-943X}, abstract = {BACKGROUND: Fibroblast growth factor receptor 2 (FGFR2) is an oncogenic driver in luminal breast cancer (BCa), with emerging evidence linking it to tumour immune microenvironment (TIME) modulation. While FGFR2's role in endocrine resistance is established, its potential involvement in shaping immune infiltration-particularly in the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC)-remains underexplored.

METHODS: This retrospective study analysed 99 BCa specimens collected between 2004-2019. Immunohistochemistry was used to assess FGFR2 expression and immune markers (CD8, CD68, CD163, FOXP3). Clinical and pathological variables were evaluated, and immune cell densities were compared across disease stages and BCa subtypes (luminal vs. non-luminal). Correlations between FGFR2 expression and immune markers were assessed using non-parametric statistical tests.

RESULTS: Progression from DCIS to IDC was associated with increased infiltration by CD8+ T cells and CD68+ macrophages. FGFR2 expression showed differences between DCIS and IDC with an extensive DCIS component and was positively correlated with CD8+, CD163+, and FOXP3+ cell densities. The latter associations were exclusive to luminal A tumours, with no such correlations observed in non-luminal subtypes.

CONCLUSIONS: FGFR2 expression in luminal A BCa correlates with markers of immunosuppressive TIME, particularly CD163+ macrophages and FOXP3+ T cells. These subtype-specific interactions suggest a synergistic role of FGFR2 and estrogen receptor signalling in immune evasion and tumour progression, warranting further mechanistic and therapeutic investigation. However, the small number of cases in certain subgroups, particularly DCIS and non-luminal tumours, limits the generalizability of these findings and warrants cautious interpretation.}, } @article {pmid41006264, year = {2025}, author = {De Crem, AS and Tummers, P and Depypere, H and Braems, G and Salihi, R and Vergauwen, G and Cisternino, G and Van de Vijver, K and De Visschere, P and De Man, K and Van den Broeck, B and Hendrickx, S and Veldeman, L and Monten, C and Debacker, JM and Denys, H and Göker, M}, title = {Breast cancer Intraoperative Margin Assessment using specimen PET-CT (BIMAP).}, journal = {NPJ breast cancer}, volume = {11}, number = {1}, pages = {101}, pmid = {41006264}, issn = {2374-4677}, support = {HPC.2017.0515//Agentschap voor Innovatie door Wetenschap en Technologie, Belgium (IM-IWT)/ ; }, abstract = {Positive surgical margins in breast-conserving surgery (BCS) for breast cancer occur in 20% of cases, making intraoperative margin assessment (IMA) crucial to avoid re-operations. This study evaluated specimen PET-CT imaging for IMA in 41 patients undergoing BCS. Specimen PET-CT imaging was performed with the ß-CUBE/X-CUBE (MOLECUBES) or the AURA 10 (XEOS). Seven physicians, with varying experience, assessed margin status postoperatively as positive, close (≤1 mm), or negative using PET-CT images at 10 min acquisition time and low reconstructed [[18]F]FDG dose (0.8MBq/kg). Close margins on PET-CT were analyzed once as positive and once as negative. Histopathology was the gold standard. The proposed technique showed 91% sensitivity and 86% specificity for invasive ductal carcinoma (IDC). Histopathology identified 9 positive margins in 31 IDC cases; 88% were detected by all physicians on specimen PET-CT whereas standard of care identified 44%. Therefore, specimen PET-CT will improve IMA in BCS and potentially reduce re-operation rates. The trial is registered since 20/01/2020 on ClinicalTrials.gov (ID: NCT04343079) with the title: "Intra-operative PET-CT: a Novel Approach to Determine Excision Margins in Lumpectomy Breast Cancer".}, } @article {pmid41005725, year = {2025}, author = {Sulaj, A and Nguyen, PBH and Poschet, G and Kliemank, E and Fleming, T and Henke, L and Neibig, W and Kopf, S and Hell, R and Longo, VD and Herzig, S and Nawroth, PP and Menden, MP and Szendroedi, J}, title = {Periodic fasting induced reconstitution of metabolic flexibility improves albuminuria in patients with type 2 diabetes.}, journal = {Molecular metabolism}, volume = {102}, number = {}, pages = {102257}, pmid = {41005725}, issn = {2212-8778}, mesh = {Humans ; *Diabetes Mellitus, Type 2/metabolism/diet therapy/complications ; *Albuminuria/metabolism/diet therapy ; *Fasting/metabolism ; Male ; Female ; Middle Aged ; Diabetic Nephropathies/metabolism/diet therapy ; Aged ; Lipid Metabolism ; Metabolomics/methods ; Diet, Mediterranean ; Metabolome ; }, abstract = {OBJECTIVE: Metabolic inflexibility has been shown to be associated with type 2 diabetes (T2D) and diabetic nephropathy (DN). However, data are lacking, proving that reconstitution of metabolic flexibility by using a 6-month periodic fasting (PF) regimen may improve albuminuria.

METHODS: In this post hoc analysis of a randomized-controlled trial, we investigated whether the PF regimen enhanced metabolic flexibility in individuals with T2D and DN showing improvement of albuminuria (responders) compared to non-responders. Participants followed every month either a 5-day fasting-mimicking diet or a Mediterranean diet for 6 months. LC-MS/MS-based comprehensive metabolic profiling was performed in plasma samples before, during, and after the intervention. Changes in metabolomic patterns and enriched signalling pathways were analysed between study groups.

RESULTS: PF induced a sustained shift toward enhanced fatty acid oxidation, lipid utilization, and amino acids turnover, particularly in responders. Responders exhibited persistent elevations in short-chain acylcarnitines and cholesteryl esters, indicating more efficient lipid oxidation and tighter integration of lipid metabolism with the tricarboxylic acid cycle. Increased glycine and serine levels suggested enhanced cellular maintenance, a protein-sparing effect, and a metabolic shift favouring lipid over carbohydrate. In contrast, non-responders demonstrated only transient and limited metabolic shifts. Unsupervised clustering identified distinct metabolic response patterns, reinforcing the potential of personalized dietary interventions.

CONCLUSIONS: These findings demonstrate that diet-induced restoration of metabolic flexibility is associated with improved albuminuria in T2D, suggesting broader implications for precise nutritional strategies in diabetes management.}, } @article {pmid40999310, year = {2025}, author = {Fedko, VA and Artamonova, EV and Stroganova, AM and Mileyko, VA and Lisitsa, TS and Novikov, AK and Kovalenko, EI}, title = {Clinical and Morphological Features of gPALB2-Associated Breast Cancer in the Russian Population.}, journal = {Bulletin of experimental biology and medicine}, volume = {179}, number = {3}, pages = {355-358}, pmid = {40999310}, issn = {1573-8221}, mesh = {Humans ; Female ; Middle Aged ; Russia/epidemiology ; *Breast Neoplasms/genetics/pathology/drug therapy/epidemiology ; Adult ; Erb-b2 Receptor Tyrosine Kinases/genetics/metabolism ; Aged ; Mutation ; Receptors, Estrogen/metabolism/genetics ; *Carcinoma, Ductal, Breast/genetics/pathology/drug therapy ; High-Throughput Nucleotide Sequencing ; Neoadjuvant Therapy ; }, abstract = {The analysis included 3,800 cases of breast cancer. Next-generation sequencing (NGS) of DNA extracted from peripheral blood leukocytes revealed mutations in the gPALB2 gene in 39 (1.03%) patients. The most frequent mutations were c.509_510del (25.64%), c.1592del (20.51%), and c.172_175del (10.26%). The predominant histological variant was invasive ductal carcinoma (84.62%) with moderate differentiation (G2) (48.72%). In most cases, luminal HER2[-] subtype (69.23%) was revealed, HER2[+] and triple-negative were less frequent (12.82 and 17.95%, respectively). Neoadjuvant chemotherapy was administered to 9 patients; a clinical response observed in 100% of cases. RCB-0 (pCR) was noted in 33.3%; RCB-I in 11.1%, RCB-II in 44.4%, and RCB-III in 11.1% of observations. All recorded cases of contralateral breast cancer (10.26%) were metachronous and presented as estrogen receptor-positive HER2[-] tumors.}, } @article {pmid40997111, year = {2025}, author = {Benmussa, C and Sanfeliu, E and Martínez-Romero, A and González-Farré, B and Pascual, T and Gavilá, J and Levy-Jurgenson, A and Shamir, A and Brasó-Maristany, F and Prat, A and Yakhini, Z}, title = {Latent representation of H&E images retains biological information in a breast cancer cohort.}, journal = {PloS one}, volume = {20}, number = {9}, pages = {e0329221}, pmid = {40997111}, issn = {1932-6203}, mesh = {Humans ; *Breast Neoplasms/pathology/diagnostic imaging ; Female ; Machine Learning ; Cohort Studies ; *Image Processing, Computer-Assisted/methods ; Ki-67 Antigen/metabolism ; Hematoxylin ; }, abstract = {Imaging technologies and staining based pathology are important components of common practice cancer care. Specifically, H&E imaging is standard for almost all cancer patients. Traditionally, H&E images can serve, when used by experienced trained pathologists, to infer important biological properties of the samples. Recent work demonstrated that machine learning and machine vision analysis of H&E images can further expand the scope of the inference. However, H&E images are high-resolution, making them difficult to analyze and possibly noisy. In this work, we propose an autoencoder-based pipeline that greatly reduces the dimension of the data representation while maintaining valuable properties. In particular, we investigate how different latent space dimensions affect bulk label predictions from H&E. We use autoencoders applied to image tiles as a tool in this investigation and also examine other information that may be inferred from image tiles. For example, we show classification results for tiles, such as Luminal A versus Luminal B, with an F1 score larger than 0.85. We also show that Ki67 levels can be inferred from H&E tiles, as shown before on other cohorts, and that inference is still possible when working with lower dimensional latent representations. The two main contributions of this paper are as follows. First, demonstrating that the use of image tiles can be informative, both at the global classification level, and, more importantly, to support the assessment of heterogeneity. Second, reasonably accurate inference can be performed with lower dimensional latent representations of the H&E images.}, } @article {pmid40995394, year = {2025}, author = {Satomi, H and Ryu, A and Murayama, S and Morimoto, Y and Kubo, C and Nagata, S and Tanada, S and Honma, K}, title = {Radiation-Associated Breast Angiosarcoma Versus Recurrent Invasive Ductal Carcinoma After Partial Mastectomy: A Diagnostic Dilemma.}, journal = {Clinical case reports}, volume = {13}, number = {9}, pages = {e70967}, pmid = {40995394}, issn = {2050-0904}, abstract = {Postradiation angiosarcoma (PRAS) of the breast occurs after irradiation. It is categorized separately from primary angiosarcoma (PAS) in the 2019 World Health Organization classification of tumors. PRAS diagnosis is challenging owing to its occurrence in circumstances similar to breast cancer recurrence, thus complicating cytomorphological analysis. In Japan, breast-conserving therapy is prevalent, with postoperative radiation therapy often employed to mitigate recurrence risk. Given that the number of PRAS cases is anticipated to increase, further research and understanding of this tumor are imperative. Although cytomorphological studies have provided some insights into PAS, similar comprehensive data for PRAS are lacking. In this case study, we report a case of a female in her 50s with a mass detected 8 years postradiotherapy for invasive ductal carcinoma (IDC). Fine needle aspiration cytology (FNAC) initially suggested IDC recurrence; however, histological and immunohistochemical analyses confirmed PRAS. This case highlights the challenge of distinguishing PRAS from IDC owing to overlapping cytomorphological features. Notably, the absence of benign components and distinctive endothelial wrapping observed on FNAC and imprinting cytology were crucial for accurate diagnosis. These findings highlight key cytomorphological features for PRAS differentiation: high-grade tumor features with monotonous appearance and abundant stromal component, which are essential given its poor response to conventional treatments and increasing incidence owing to standard breast-conserving therapies. Furthermore, recognizing PRAS as a differential diagnosis for neoplasms emerging postradiotherapy is crucial.}, } @article {pmid40994479, year = {2025}, author = {Altowairki, RS and Abubaker Mohammed, M and Aljalsi, MI}, title = {Thoracic epidural anesthesia combined with pecs 2 block for modified radical mastectomy: A safe and effective alternative to general anesthesia in high-risk patients.}, journal = {Saudi journal of anaesthesia}, volume = {19}, number = {4}, pages = {646-648}, pmid = {40994479}, issn = {1658-354X}, abstract = {Breast cancer is the most common malignancy among Saudi women, with Modified Radical Mastectomy (MRM) as a standard treatment, typically performed under general anesthesia (GA). However, GA poses significant risks to patients with multiple comorbidities. We present a 66-year-old female with invasive ductal carcinoma, complicated by scleroderma with interstitial lung disease, chemotherapy-induced heart failure, and hypertension, making GA a high-risk option. To optimize perioperative safety, thoracic epidural anesthesia (TEA) combined with a pectoralis nerve block (PECS2) was used instead. This approach provided effective surgical anesthesia, hemodynamic stability, and minimized opioid use. The patient tolerated the procedure well, with intraoperative hypotension managed by vasopressor support. She resumed oral intake within 6 hours, required minimal postoperative opioids, and was discharged on the third postoperative day without complications. This case highlights the feasibility and advantages of TEA with PECS2 block as a safe and effective alternative to GA in high-risk MRM patients. By reducing GA-related pulmonary and cardiac risks, improving postoperative pain control, and shortening hospital stays, this technique may enhance perioperative outcomes in select patients. Further studies are warranted to support the wider adoption of regional anesthesia in oncologic breast surgeries.}, } @article {pmid40993962, year = {2025}, author = {Aptaker Ben-Dori, S and Atzaba-Poria, N and Frenkel, TI}, title = {Individual differences in infants' expectations and preferences for responsive vs. unresponsive parent-puppets and their associations with early maternal behavior.}, journal = {Attachment & human development}, volume = {27}, number = {6}, pages = {868-892}, doi = {10.1080/14616734.2025.2562511}, pmid = {40993962}, issn = {1469-2988}, mesh = {Humans ; Female ; Infant ; Male ; *Object Attachment ; *Mother-Child Relations/psychology ; *Maternal Behavior/psychology ; *Infant Behavior/psychology ; Adult ; *Individuality ; Play and Playthings ; }, abstract = {Infants' mental representations of attachment are thought to develop across the first year. Due to methodological challenges, empirical attempts to assess these representations are scarce. The study presents a preliminary attempt to validate a measure of infants' attachment representations. Seventy-two mother-infant dyads (34 girls) were assessed. At 4-months, 60 dyads were observed during free-play interactions. At 10-months, 72 infants viewed a puppet-show depicting a responsive vs. an unresponsive parent-puppet. Looking-time patterns indexed infants' expectations, and puppet choice indexed infants' preference for parent-puppets' responsiveness. Infants generally expected (d = 0.42) and preferred (66%) parent-puppet-responsiveness. Moreover, maternal "responsive secure-base" behavior at 4-months was associated with infants' expectations (r = .29, p = .025) and preference (d = 0.6) for responsiveness at 10-months. Findings support theoretical concepts, providing preliminary evidence for infants' preverbal attachment representations and their roots in early social experience with their attachment figures. Future research using larger samples and standard attachment assessments is needed to validate this measure.}, } @article {pmid40993701, year = {2025}, author = {Cheng, X and Zeng, W and Yin, B and Gui, J and Zhang, H and Lv, Z and Zhang, S and Zhou, Y}, title = {Spatiotemporal microenvironment landscape and malignant epithelial pattern transition in breast ductal carcinoma progression.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {996}, pmid = {40993701}, issn = {1479-5876}, support = {Grant nos. 2020-133-11, 2020-133-16//Science and Technology Bureau of Nanchang Municipality/ ; }, mesh = {Humans ; *Tumor Microenvironment/genetics ; *Disease Progression ; Female ; *Breast Neoplasms/pathology/genetics ; *Carcinoma, Ductal, Breast/pathology/genetics ; Cell Movement ; Gene Expression Regulation, Neoplastic ; Neoplasm Invasiveness ; Lymphatic Metastasis ; Cell Line, Tumor ; Cell Proliferation ; *Spatio-Temporal Analysis ; Prognosis ; }, abstract = {BACKGROUND: Owing to the complexity of TME components and the heterogeneity of cancer cells, the relationship between the niches of TME and prognosis in breast ductal carcinoma remains unknown. The staged characteristics of corresponding cancer cell behaviors are unclear. Our study aims to reveal spatial structures and specific cellular information of TME and cancer cells subgroups during the progression from DCIS to IDC and lymph node metastasis.

METHODS: Single-cell sequencing, spatial transcriptomics, bulk RNA sequencing datasets were used to explore the changes in microenvironmental components and transcriptional programs of tumor cells during the progression of breast ductal carcinoma. Immunohistochemistry, multiplex immunofluorescence, flow cytometry cell cycle detection, invasion migration experiments, and WB imprinting were employed for validation.

RESULTS: Analysis of TME cell type subsets revealed the accumulation of TEX, iTreg, and stress-phenotype TAM in the mammary gland in situ during the invasion process. Lymphatic metastases exhibited enrichment of nTregs and a more naïve-like CD8 T cell population. Spatial analysis and survival analysis showed that the spatial niches of CD4 TN and phagocytic-phenotype macrophages were associated with a favorable prognosis, and these niches were lost during disease progression. The proliferative subpopulation of breast ductal carcinoma was enriched in lymphatic metastatic tissues, expressing high levels of FAM111B and exhibiting intense TCA and oxidative phosphorylation metabolism. Silencing FAM111B led to cell cycle arrest, decreased invasion and migration abilities, and downregulation of core mediator genes for cuproptosis and disulfidptosis.

CONCLUSIONS: The stage-specific microenvironmental characteristics of breast ductal carcinoma correspond to some extent to the behavior of tumor cells. During the progression of ductal carcinoma in breast tissue, the establishment of an immunosuppressive microenvironment occurs. The microenvironmental spectrum at lymph node metastases differs somewhat, corresponding to a more enriched turnover of cancer cell proliferation and death. Inhibitors of FAM111B and inducers of cuproptosis and disulfidptosis may serve as potential therapeutic targets for proliferative subgroups.}, } @article {pmid40990786, year = {2025}, author = {Tabassum, S and Saeed, U and Tahir, R and Khalid, Z and Piracha, ZZ and Uppal, R and Khan, AA and Ozsahin, DU and Waheed, Y and Ngozi, AJI and Ashraf, M}, title = {Estimating high mobility group box protein 1 (HMGB1) single nucleotide polymorphisms among hepatitis B virus infected patients of Pakistan origin.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {85}, number = {}, pages = {e284560}, doi = {10.1590/1519-6984.284560}, pmid = {40990786}, issn = {1678-4375}, mesh = {Humans ; Pakistan ; *Polymorphism, Single Nucleotide/genetics ; *HMGB1 Protein/genetics ; Male ; Female ; Genotype ; Adult ; Middle Aged ; Genetic Predisposition to Disease ; *Hepatitis B/genetics ; Young Adult ; Gene Frequency ; *Hepatitis B, Chronic/genetics ; }, abstract = {HMGB1 is nuclear non-histone protein and unique member of cytokines. In viral hepatitis infection HMGB1 serum level increases and translocates towards cytoplasm and extracellular spaces where it activates single stimulating hepatic stellate cell proliferation which induces fibrogenic protein expression and causes hepatocellular carcinoma. In this study, total 150 subjects were recruited to assess the association between HMGB1 SNPs and HBV. Three types of genotypes were found visible in rs3742305 of HMGB1; wild type homozygous GG with 65%, homozygous minor type CC with 6% and heterozygous minor type GC with 26% frequency distribution. High prevalence of GG genotype in the selected population presenting that GG genotype may have higher risk for susceptibility to HBV infection. Our results showed significant correlation of HMGB1 polymorphism with HBV infection in the selected Pakistani population.}, } @article {pmid40990784, year = {2025}, author = {Uppal, R and Saeed, U and Tahir, R and Uppal, MR and Khan, AA and Rahman, C and Uppal, MS and Ozsahin, DU and Gilani, SS and Waheed, Y and Piracha, ZZ}, title = {Lymphopenia as a diagnostic biomarker in clinical COVID-19: insights from a comprehensive study on SARS-CoV-2 variants.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {85}, number = {}, pages = {e284362}, doi = {10.1590/1519-6984.284362}, pmid = {40990784}, issn = {1678-4375}, mesh = {Humans ; *COVID-19/diagnosis/blood/complications ; *Lymphopenia/virology/blood/diagnosis ; *SARS-CoV-2/genetics ; Male ; Female ; Biomarkers/blood ; Adult ; Middle Aged ; Pakistan/epidemiology ; Young Adult ; Aged ; Adolescent ; Lymphocyte Count ; }, abstract = {The enduring SARS-CoV-2 pandemic necessitates robust tools for severity assessment. This study, conducted at Islamabad Diagnostic Center across Pakistan from January 2021 to August 2022, aimed to investigate hematological abnormalities among suspected SARS-CoV-2 subjects. Initial enrollment included 130,347 cases, with 53,078 confirmed positive and 77,269 negative. An additional 11,786 samples expanded the dataset to 142,133. The Omicron and Centaurus variants, in confirmed positive patients, exhibited a slightly higher frequency of hematological abnormalities (30.42%) than negative participants (27.01%). Notably, lymphocyte count reduction (40.95%) suggested its potential as an alternative diagnostic parameter for clinical COVID-19. Decreased levels of NA (37.99%), HGB (26.17%), MCV (20.60%), PLT (6.15%), and ALB (2.28%) were observed. Abnormally elevated NEU, CR, MONO, RBCs, WBC, and EOS levels affected 26.00%, 24.28%, 30.79%, 22.02%, 6.28%, and 5.53% of subjects, respectively. Comparatively, positive patients exhibited higher abnormal blood parameters-LYMP count (57.40%), NEU count (46.08%), EOS count (62.48%), MONO count (31.61%), RBC count (30.32%), ALC count (43.60%), CR count (30.91%), NA count (40.53%), CRP count (68.46%), and DD (63.08%) than negative counterparts. The study underscores lymphocytopenia's potential as a cost-effective, early diagnostic biomarker for clinical COVID-19, preceding real-time PCR diagnosis. This supports its consideration in resource-limited settings for strategic screening and policy-making in the ongoing SARS-CoV-2 battle.}, } @article {pmid40990674, year = {2025}, author = {Vera-Tizatl, CE and Vera-Hernández, A and Leija-Salas, L and Vega-López, MA and Ramírez-Estudillo, MDC and Fariña, GIG and Vera-Tizatl, AL}, title = {The Vietnamese swine as a translational model of invasive ductal carcinoma of the breast.}, journal = {Animal models and experimental medicine}, volume = {8}, number = {11}, pages = {1997-2007}, pmid = {40990674}, issn = {2576-2095}, mesh = {Animals ; Female ; *Breast Neoplasms/pathology/chemically induced ; *Carcinoma, Ductal, Breast/pathology/chemically induced ; *Disease Models, Animal ; *Mammary Neoplasms, Experimental/pathology/chemically induced ; Swine ; Tumor Microenvironment ; Vietnam ; }, abstract = {BACKGROUND: The Vietnamese swine represents a promising animal model due to its anatomical, physiological, and pathophysiological similarities to humans. Notably, the arrangement of lobes and ducts in the mammary glands is highly comparable to that of humans and is histologically indistinguishable. Leveraging these advantages through the chemical induction of carcinogenesis in this model offers a robust approach to mimic human exposure to carcinogenic compounds.

METHODS: This study elaborates on a protocol for developing a representative model of MNU-induced invasive breast carcinoma in three Vietnamese swine, validated histologically and immunologically. It evaluates not only the tissue similarity with humans, but also the development of chemically induced mammary tumors in an immunologically competent animal. Moreover, this study addresses the existing gap in histological knowledge regarding mammary tissue in the porcine model.

RESULTS: Our findings suggest that this model encompasses the full spectrum of cancer. It incorporates the key elements of a tumor microenvironment that enable tumor growth and propagation, such as immune cells, blood vessels, fibroblasts, extracellular matrix, fatty acids, and signaling molecules.

CONCLUSIONS: This model offers significant potential to advance the understanding of cancer pathogenesis and facilitate the development of innovative therapeutic strategies by closely replicating human tumor biology.}, } @article {pmid40985344, year = {2025}, author = {Hausmann, O and Schobert, PP and Ose, J and Himbert, C and Pletneva, M and Jedrzkiewicz, J and Nguyen, A and Lin, T and Warby, CA and Hardikar, S and Peoples, AR and Strehli, I and Huang, LC and Cohan, JN and Pickron, B and Scaife, C and Li, CI and Grady, WM and Shibata, D and Toriola, AT and Schneider, M and Figueiredo, JC and Siegel, EM and Gigic, B and Herzig, S and Ilozumba, MN and Ulrich, CM}, title = {Associations of Biomarkers of Systemic Inflammation, Angiogenesis, and Cell-to-Cell Adhesion With Tumor Budding Among Early-Onset and Later-Onset Colorectal Cancer Patients.}, journal = {Cancer medicine}, volume = {14}, number = {18}, pages = {e71267}, pmid = {40985344}, issn = {2045-7634}, support = {R01CA254108/NH/NIH HHS/United States ; R01 AG083580/AG/NIA NIH HHS/United States ; R01CA189184/NH/NIH HHS/United States ; //Stiftung LebensBlicke/ ; U01CA206110/NH/NIH HHS/United States ; R03CA270473/NH/NIH HHS/United States ; P30CA042014/CA/NCI NIH HHS/United States ; K07222060/NH/NIH HHS/United States ; R01CA207371/NH/NIH HHS/United States ; }, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; Age of Onset ; Angiogenesis ; *Biomarkers, Tumor/blood ; Cell Adhesion ; *Colorectal Neoplasms/pathology/blood ; *Inflammation/blood ; Intercellular Adhesion Molecule-1/blood ; Neoplasm Staging ; *Neovascularization, Pathologic/blood/pathology ; Prognosis ; }, abstract = {BACKGROUND: High tumor budding and elevated systemic inflammation are adverse prognostic indicators in colorectal cancer. Its underlying mechanisms remain poorly understood. It is unclear whether systemic inflammation, angiogenesis, and cell-to-cell adhesion influence tumor budding.

METHODS: We investigated n = 132 stage I-III colorectal cancer patients recruited at Huntsman Cancer Institute enrolled in the ColoCare Study. Tumor budding was evaluated using an evidence-based scoring system, and patient sera were analyzed for nine circulating biomarkers using the Meso Scale Discovery platform. We examined associations between biomarkers and tumor budding using multivariable linear regression models adjusted for age, sex, neoadjuvant treatment, stage, and non-steroidal anti-inflammatory drug use.

RESULTS: The study population was predominantly non-Hispanic White (95%), with a mean age of 61 years; 56% were male. Most tumors were stage III (47%), located in the colon (64%), and exhibited low-grade tumor budding (58%). Soluble intercellular adhesion molecule 1 was inversely associated with tumor budding overall (M1: β = -0.57, p = 0.03), among females (M1: β = -0.81, p-value = 0.03) and later-onset (≥ 50 years) colorectal cancer (M1: β = -0.71, p-value = 0.008). C-reactive protein was positively associated with tumor budding in males (M1: β = 0.23, p = 0.001), while interleukin-8 (M1: β = 0.96, p-value = 0.01) and soluble vascular adhesion molecule 1 (M2: β = 1.48, p-value = 0.04) were positively associated with tumor budding in early-onset patients. However, these associations did not remain statistically significant after correction for multiple testing.

CONCLUSION: Overall, our findings do not provide evidence of a significant association between biomarkers of systemic inflammation, angiogenesis, and cell-to-cell adhesion with tumor budding count. We observed patterns for some biomarkers, yet none remained statistically significant after correction for multiple testing. These findings provide preliminary insights for future studies.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT02328677.}, } @article {pmid40984893, year = {2025}, author = {Imran, M and Majeed, MA and Bin Naeem, S and Jamil, MA and Shahzad, M and Akhtar, F and Karim, A and Ahmad, A and Bano, S and Aqib, B and Abdullah Javaid Bukhari, S}, title = {Treatment Outcomes of HER2-Directed Therapy in Patients With HER2-Positive Non-metastatic Breast Cancer in Low-Resource Settings.}, journal = {Cureus}, volume = {17}, number = {8}, pages = {e90634}, pmid = {40984893}, issn = {2168-8184}, abstract = {Introduction This study aimed to evaluate treatment outcomes of human epidermal growth factor receptor 2 (HER2)-directed therapies in patients with non-metastatic HER2-positive breast cancer treated in a low-resource setting. Specifically, we assessed the impact of dual blockade (trastuzumab and pertuzumab), trastuzumab alone, or no HER2-targeted therapy on rates of residual disease, pathological complete response (pCR), progression-free survival (PFS), and overall survival (OS). Methods We conducted a retrospective cohort study at Shaukat Khanum Memorial Cancer Hospital, including 299 patients with non-metastatic HER2-positive breast cancer treated with neoadjuvant chemotherapy and either dual HER2 blockade, trastuzumab alone, or no HER2-targeted therapy due to financial constraints. Patient demographics, clinical features, treatments, and outcomes were analyzed using descriptive statistics, chi-square tests, and Kaplan-Meier survival analysis. Results The median age at diagnosis was 45.7 years (standard deviation±8.9). A majority of patients were premenopausal (n=222; 74.2%), and the majority presented with a palpable lump (n=275; 91.9%). Tumors were mainly located in the left (n=149; 49.8%) or right breast (n=147; 49.2%), with bilateral involvement in 3 (1.0%) cases. Invasive ductal carcinoma was the predominant histology (n=275; 91.9%), with estrogen receptor and progesterone receptor positivity observed in 185 (61.9%) and 179 (59.9%) patients, respectively. Grade III tumors were observed in 156 (52.2%) cases, and most tumors were T2 stage (n=236; 78.9%) with axillary nodal involvement in 232 (77.6%). Patients receiving dual HER2 blockade achieved a pCR in 45 (54.9%) of 82 cases, compared to 51 (45.9%) of 111 with trastuzumab alone, and 39 (36.8%) of 106 with no HER2 therapy (p=0.046). The docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) regimen had the highest pCR rate in 19 (65.5%) of 29 patients (p<0.001). Grade III tumors were associated with higher pCR than Grade II (n=96; 56.5% vs. n=39; 30.2%; p<0.001). At 60 months, PFS was 236 (79.0%) overall, highest in the dual blockade group (n=73; 89.0%), followed by trastuzumab (n=96; 86.5%) and no HER2 therapy (n=69; 65.1%). OS at 60 months was 271 (90.6%), highest in the dual blockade group (n=78; 95.1%), then trastuzumab (n=102; 91.9%) and no HER2 therapy (n=79; 74.5%). Achieving pCR was associated with improved PFS and OS. Differences in both outcomes across groups were statistically significant (p<0.001). Conclusion Dual HER2 blockade significantly improved pCR, PFS, and OS in non-metastatic HER2-positive breast cancer. These findings support the inclusion of HER2-targeted agents in standard neoadjuvant treatment, even in resource-limited settings. Addressing barriers to access remains essential to improving global outcomes in breast cancer care.}, } @article {pmid40984891, year = {2025}, author = {Albloshi, A and Samih, S and Alowami, S and Lovrics, P and Vasudev, P}, title = {Diagnostic Challenge of Nodal Nevi Mimicking Metastatic Melanoma in Axillary Lymph Nodes Following Neoadjuvant Therapy for Breast Cancer: A Case Report.}, journal = {Cureus}, volume = {17}, number = {8}, pages = {e90745}, pmid = {40984891}, issn = {2168-8184}, abstract = {Nodal nevi are benign melanocytic proliferations within lymph nodes that can closely mimic metastatic melanoma, posing a significant diagnostic challenge, particularly in breast cancer patients undergoing lymph node dissection after neoadjuvant chemotherapy. Accurate differentiation between nodal nevi and true melanoma metastases is essential to avoid misdiagnosis and overtreatment. Immunohistochemical (IHC) markers such as preferentially expressed antigen in melanoma (PRAME), p16, human melanoma black-45 (HMB-45), and Ki-67 are critical tools for diagnostic clarification. We present a diagnostically challenging case of multiple infiltrative nodal nevi in a 59-year-old female with triple-negative invasive ductal carcinoma, no special type, of the breast. The patient had a prior history of dysplastic nevus on the upper trunk and presented with a 1.5 cm palpable mass in the left breast and a 5 cm left axillary mass. Following neoadjuvant chemotherapy, both lesions demonstrated a clinical reduction in size. She subsequently underwent a partial mastectomy and axillary lymph node dissection. Histologic examination revealed no residual invasive carcinoma in the breast. However, four axillary lymph nodes contained atypical melanocytic-appearing cells in the subcapsular sinuses with extension into the nodal parenchyma, raising the differential diagnosis of residual carcinoma versus metastatic melanoma. Initial IHC showed these atypical cells to be melanocytic in origin (SOX10 and melanoma cocktail positive; AE1/AE3 negative). While initial interpretation favored metastatic melanoma, further IHC workup demonstrated low proliferative activity (Ki-67 <1%), diffuse p16 positivity, and negativity for both HMB-45 and PRAME. These findings, along with dermatopathology consultation, supported a diagnosis of multiple nodal nevi rather than melanoma. This case underscores the diagnostic pitfall posed by infiltrative nodal nevi, particularly when they mimic melanoma in the setting of breast cancer. It highlights the importance of comprehensive immunohistochemical panels, including PRAME, p16, HMB-45, and Ki-67, and the value of second opinions and dermatopathology consultation in avoiding diagnostic error.}, } @article {pmid40982417, year = {2025}, author = {Adenwalla, SF and Worboys, HM and Lawday, D and Gray, LJ and Hull, KL and Churchward, DR and Highton, PJ and Young, HML and Graham-Brown, MPM and Burton, JO and March, DS}, title = {The effect of a six-month programme of intradialytic cycling on survival and hospitalisations in people requiring haemodialysis: 5-year follow-up of the CYCLE-HD randomised controlled trial.}, journal = {PloS one}, volume = {20}, number = {9}, pages = {e0332389}, pmid = {40982417}, issn = {1932-6203}, mesh = {Humans ; *Renal Dialysis/methods/mortality ; Male ; *Hospitalization/statistics & numerical data ; Female ; Middle Aged ; Follow-Up Studies ; Aged ; *Kidney Failure, Chronic/therapy/mortality ; Cardiovascular Diseases/mortality ; Proportional Hazards Models ; Adult ; }, abstract = {We have previously shown that a six-month programme of intradialytic cycling (IDC) improved cardiovascular structure and function, it is unclear whether these changes are associated with long-term benefits. The aim of this post-trial analysis was to evaluate a programme of IDC on all-cause mortality, hospitalisations and cardiovascular events at five-years. Mortality and hospitalisation data were collected from Hospital Episode Statistics and death certificates. Models were fitted unadjusted and adjusted for age, sex, diabetes, duration of dialysis, and receiving a kidney transplant. Cox proportional hazard models were used for time-to-event analysis to evaluate all-cause mortality. Hospitalisations were analysed using a negative binomial regression model, and length of stay using a generalised linear model. A composite outcome of time to first cardiovascular event, combining cardiovascular mortality and hospitalisations, was evaluated using a Cox model. There was no evidence of a statistically significant effect of treatment allocation on survival (hazard ratio (HR) 1.09, 95% confidence interval (CI): 0.68-1.76, p = 0.71). After adjustment, results remained non-significant (HR 1.22, 95% CI: 0.74-2.01, p = 0.43). There was no evidence of a significant effect on all-cause hospitalisations for unadjusted (p = 0.20) or adjusted (p = 0.25) models. Similar results are reported for cardiovascular hospitalisations (p = 0.30 and p = 0.17). For time to first cardiovascular event there was no evidence of a statistically significant effect (HR 1.39, 95% CI: 0.79-2.72, p = 0.26). The main findings show no evidence that a six-month programme of IDC affected all-cause mortality, hospitalisations, cardiovascular events, or length of stay in hospital at five-years.}, } @article {pmid40979608, year = {2025}, author = {Shaikh, K and Arif, A and Mooghal, M and Vohra, L}, title = {Unveiling the Clinicopathological Outcomes of Breast Cancer in Young Women: A perspective from resource-limited settings.}, journal = {Sultan Qaboos University medical journal}, volume = {25}, number = {1}, pages = {658-665}, pmid = {40979608}, issn = {2075-0528}, mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/therapy/diagnosis ; Adult ; Retrospective Studies ; Adolescent ; Incidence ; Young Adult ; Risk Factors ; Registries/statistics & numerical data ; Resource-Limited Settings ; }, abstract = {OBJECTIVES: This study aimed to assess the incidence of breast cancer in young women over a ten-year period and examine its association with clinical characteristics, risk factors, treatment modalities, and survival outcomes.

METHODS: A retrospective analysis of the Breast Cancer Registry at our institution was conducted. Of the 2,238 women diagnosed with breast cancer between 2012 and 2021, 535 (23.9%) were aged 40 years or younger at the time of diagnosis. Cases with missing data for independent variables were excluded from the respective analyses.

RESULTS: The mean age at diagnosis was 34.5 years (range: 15-40). The most common clinical stage at presentation was IIB (25.2%), followed by IIA (24.4%), while 7.6% of patients presented with metastatic disease. Invasive ductal carcinoma was the predominant histological type (88.8%), and 57.4% of tumours were high grade. Triple-negative breast cancer accounted for 27.0% of cases, and 18.4% were ERBB2-enriched. Bilateral disease was observed in 2.5% of cases, and 7.5% were diagnosed during pregnancy. A family history of breast cancer was reported in 23.6%. Genetic testing was performed in 10.9% of patients, with BRCA1 mutations being the most frequently identified (12.1%). Modified radical mastectomy was performed in 38.2% of patients, and 8.2% underwent reconstructive surgery. Neoadjuvant chemotherapy was administered in 49.9% of cases, and 68.2% received adjuvant radiotherapy. The five-year overall survival rate was 93.9%, with 12 patients (2.4%) experiencing distant and one (0.2%) experiencing local recurrence within five years.

CONCLUSION: Young women with breast cancer in resource-limited settings demonstrate distinct sociodemographic and clinicopathological characteristics, underscoring the importance of early detection strategies and personalised treatment approaches.}, } @article {pmid40979420, year = {2025}, author = {Yoshioka, M and Shimoda, M and Abe, K and Masunaga, N and Tsukabe, M and Yoshinami, T and Sota, Y and Miyake, T and Tanei, T and Shimazu, K}, title = {Isolated splenic metastasis presenting at diagnosis of HER2-positive de novo metastatic breast cancer: a case report.}, journal = {Journal of surgical case reports}, volume = {2025}, number = {9}, pages = {rjaf751}, pmid = {40979420}, issn = {2042-8812}, abstract = {Splenic metastasis is uncommon, and truly isolated splenic metastasis (ISM) from breast cancer is a clinical rarity. Contemporary autopsy series reports splenic involvement in <1% of breast cancer-related deaths, and fewer than 15 well-documented ISM cases have been published. We report a 71-year-old woman presenting with a right-breast mass, regional lymphadenopathy, and a solitary splenic lesion detected on staging computed tomography (CT) and positron emission tomography-CT. Biopsy confirmed hormone receptor-negative, HER2-positive invasive ductal carcinoma. Six cycles of docetaxel, trastuzumab, and pertuzumab led to a 59% reduction in the primary tumour and complete radiological resolution of the splenic lesion. The patient remains progression-free 22 months after initiating therapy, maintained on trastuzumab and pertuzumab. Although extremely rare, ISM can present as the initial manifestation of de novo metastatic breast cancer. Awareness of this possibility may facilitate early systemic therapy and obviate the need for diagnostic splenectomy.}, } @article {pmid40978963, year = {2025}, author = {Alblowi, TM}, title = {Trends and Predictors of Re-excision Following Breast-Conserving Surgery: A Decade-Long Retrospective Study in Saudi Arabia.}, journal = {Cureus}, volume = {17}, number = {8}, pages = {e90508}, pmid = {40978963}, issn = {2168-8184}, abstract = {BACKGROUND: Breast-conserving surgery (BCS) is a widely used alternative to mastectomy for early-stage breast cancer. Achieving clear surgical margins is critical to reducing local recurrence, but re-excision is sometimes required, potentially delaying adjuvant therapy and affecting outcomes. Data on trends, predictors, and implications of re-excision in Saudi Arabia are limited.

METHODS: We conducted a retrospective cohort study of 1,248 women who underwent BCS for invasive breast cancer or ductal carcinoma in situ at tertiary hospitals in the Eastern Province from 2015 to 2024. Patient demographics, tumor characteristics, surgical details, margin status, and adjuvant therapy timelines were collected. The primary outcome was re-excision, defined as any subsequent breast operation to achieve negative margins. Univariable and multivariable logistic regression analyses were performed to identify predictors of re-excision. Temporal trends in re-excision rates and time to adjuvant therapy were analyzed.

RESULTS: The median patient age was 54 years (interquartile range (IQR): 46-63), and invasive ductal carcinoma was the most common histology (78.6%). Overall, 181 (14.5%) patients underwent re-excision, with rates declining from 18.6% in 2015 to 11.2% in 2024. Positive margin status at the index surgery was the strongest predictor of re-excision (adjusted odds ratio (OR): 4.52; 95% confidence interval (CI): 3.15-6.47). Other independent predictors included younger age (<45 years; OR: 1.82), lobular histology (OR: 1.94), tumor size > 2 cm (OR: 1.73), and multifocal disease (OR: 2.06). Preoperative MRI was associated with reduced odds of re-excision (OR: 0.66). Median time from index surgery to final margin clearance was 18 days for patients undergoing re-excision. Delays in radiotherapy beyond eight weeks occurred in 41.6% of re-excised patients versus 19.3% without re-excision (P<0.001). Three-year local recurrence did not differ significantly between groups (4.1% versus 2.7%; P=0.11).

CONCLUSIONS: Re-excision rates after BCS in Saudi Arabia have declined over the past decade. Positive margin status, younger age, lobular histology, larger tumors, and multifocal disease remain key risk factors. Re-excision is associated with delays in adjuvant radiotherapy, highlighting the importance of strategies to minimize repeat surgery while ensuring oncologic safety.}, } @article {pmid40978063, year = {2025}, author = {Luo, C and Wu, S and Zeng, Y and Zhao, S}, title = {Male accessory breast carcinoma: a rare case report and literature review.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1635515}, pmid = {40978063}, issn = {2234-943X}, abstract = {BACKGROUND: Accessory breast carcinoma, arising from embryologically persistent mammary tissue, is exceptionally rare in males, accounting for 2.4%-5.3% of all accessory breast malignancies. Due to limited clinical data, standardized diagnostic and therapeutic protocols remain undefined.

CASE PRESENTATION: A 72-year-old male presented with a 3-year history of a painless, mobile right axillary mass. Ultrasonography revealed a solid hypoechoic nodule with moderate vascularity. Histopathological examination confirmed invasive ductal carcinoma (grade II) with infiltrative growth, ER/PR/AR positivity (90%), and TRPS1 expression, confirming mammary origin. Adjuvant therapies were declined by the patient.

DISCUSSION: Differential diagnoses for axillary masses include fibroadenoma, lymphadenopathy, and cutaneous adnexal tumors. Immunohistochemistry (TRPS1, GATA-3) and histomorphology (absence of apocrine differentiation) are pivotal for distinguishing accessory breast carcinoma from mimics. Current management aligns with male breast cancer guidelines, emphasizing surgical resection, lymph node dissection, and adjuvant therapies tailored to molecular profiles. Over 90% of male breast cancers are hormone receptor-positive, warranting endocrine therapy.

CONCLUSION: Male accessory breast carcinoma poses significant diagnostic challenges due to its rarity and nonspecific presentation. Clinicians should consider this entity in differential diagnoses of axillary or inguinal masses, irrespective of patient sex. Core needle biopsy and advanced imaging aid preoperative evaluation. Multimodal treatment, including surgery and risk-stratified adjuvant therapies, is critical for optimizing outcomes. This case underscores the need for heightened clinical suspicion and evidence-based guidelines to address this understudied malignancy.}, } @article {pmid40978052, year = {2025}, author = {Gauthier, V and Simard, AJ and Desbiens, C and Poirier, B and Boudreau, D and Leblanc, D and Morin, C and Hogue, JC and Poirier, É}, title = {Neoadjuvant chemotherapy in invasive lobular carcinoma of the breast: perspectives based on the survival outcomes.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1655413}, pmid = {40978052}, issn = {2234-943X}, abstract = {Whether patients with invasive lobular carcinoma (ILC) can benefit from neoadjuvant chemotherapy (NAC) remains uncertain. In order to attempt to bring some light on the matter, the patients treated for ILC between 1998 and 2016 at a tertiary center specialized in breast diseases were examined according to NAC vs. adjuvant therapy. Among 265 eligible women treated for ILC, 72 received NAC and 193 received adjuvant chemotherapy. In the NAC group, only 4.2% of the patients with ILC achieved a pathological complete response after NAC. Over a mean follow-up of 8 years, after adjusting for confounders (age >55, T-stage, N-stage, surgery type, radiotherapy, and hormonal therapy), the two groups had similar 10-year locoregional recurrence rates (NAC: 90.6%; adjuvant: 93.5%, P=0.110), but the NAC group showed lower 10-year recurrence-free survival (51.8% vs. 72.7%, P=0.0004), 10-year progression-free survival (59.3% vs. 82.0%, P<0.0001), and 10-year overall survival (56.2% vs. 80.7%, P<0.0001). The results suggest that the response of ILC to NAC is poorer than to adjuvant chemotherapy. It is the authors' opinion that ILC should be considered separately from IDC in clinical trials and guidelines, and that patients with ILC might benefit from a more aggressive surgical approach followed by adjuvant chemotherapy no matter the severity of the disease.}, } @article {pmid40973282, year = {2025}, author = {Yang, R and Zheng, Q and Qiu, J and Zhao, S and Salam, A and Wu, P and Wu, J and Zhao, C and Zhang, Z}, title = {Prey-mimetic alginate microspheres for targeted control of red imported fire ants.}, journal = {Carbohydrate polymers}, volume = {369}, number = {}, pages = {124259}, doi = {10.1016/j.carbpol.2025.124259}, pmid = {40973282}, issn = {1879-1344}, mesh = {Animals ; *Alginates/chemistry ; *Ants/drug effects/physiology ; *Microspheres ; *Biomimetic Materials/chemistry/pharmacology ; *Insect Control/methods ; Fire Ants ; }, abstract = {The invasive red imported fire ant (Solenopsis invicta) poses a serious threat to ecology, agriculture, and public health. Existing baits are limited in their effectiveness due to behavioral resistance. To address this issue, we developed a biomimetic calcium alginate@indoxacarb microsphere bait (CA@IDC MBt) based on sodium alginate (SA) polysaccharides. SA polysaccharides form a matrix with specific mechanical properties and surface characteristics due to their unique β-D-mannuronic acid and α-L-guluronic acid block copolymer structure. The carboxyl cross-linked network not only provides structural stability (diameter 3.5 mm) but also enables precise loading of indoxacarb (loading rate 0.045 %, encapsulation efficiency 88.6 %). The CA@IDC MBt system effectively deceives ants by precisely mimicking both the chemical (epidermal alkanes) and physical (surface morphology) characteristics of natural insect larvae prey. Compared to commercial IDC MBt, CA@IDC MBt significantly improves bait recognition rates and group attack intensity. The sustained-release properties of SA polysaccharides (>80 h) effectively bypass the ants' vigilance mechanisms, achieving 100 % field efficacy without new nest formation. Behavioral experiments indicate that CA@IDC MBt can deplete 35-48 % of venom alkaloids within 21 days and completely eliminate ant colonies. This study reveals SA polysaccharide's key biomimetic role, advancing eco-friendly pest control with carbohydrate polymers.}, } @article {pmid40964799, year = {2025}, author = {Takahara, T and Taniguchi, N and Sassa, N and Tsuzuki, T}, title = {Spatial transcriptomics of intraductal carcinoma of the prostate.}, journal = {Histopathology}, volume = {87}, number = {5}, pages = {745-756}, doi = {10.1111/his.15551}, pmid = {40964799}, issn = {1365-2559}, support = {//21K06933/ ; //24K10131/ ; }, mesh = {Humans ; Male ; *Prostatic Neoplasms/genetics/pathology ; *Transcriptome ; Gene Expression Profiling ; DNA Copy Number Variations ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Biomarkers, Tumor/genetics ; Aged ; Middle Aged ; }, abstract = {AIMS: Intraductal carcinoma of the prostate (IDC-P) is a strong indicator of poor prognosis in prostate cancer (PCa). We utilized the Visium Spatial Gene Expression platform to characterize the gene expression profiles and copy number variations (CNVs) of IDC-P.

METHODS AND RESULTS: Manually annotated IDC-P components were relatively enriched in a single transcriptomic cluster identified by principal component analysis, which exhibited elevated expression of FOLH1 (PSMA), PSCA and PLA2G2A. Differential gene expression analysis between IDC-P and non-IDC-P cancer tissues revealed up-regulation of pathways related to chemotaxis and leukocyte migration, as well as gene sets associated with small cell lung carcinoma, suggesting a potential link to treatment-related neuroendocrine prostate carcinoma. In contrast, non-IDC-P components showed increased expression of genes associated with extracellular matrix organization. InferCNV analysis identified distinct CNV patterns differentiating IDC-P from non-IDC-P cancer components in four out of six cases. However, no common CNV alterations were shared across these cases, indicating molecular diversity among IDC-P lesions. In the remaining cases, IDC-P clustered with Gleason pattern 5 carcinoma, and no CNV alterations distinguishing IDC-P from adjacent non-IDC-P components were identified.

CONCLUSIONS: These findings suggest that IDC-P represents a biologically distinct component from conventional acinar adenocarcinoma and may reflect spatial tumour progression through pre-existing ductal structures. Our study also suggests that the molecular mechanisms underlying IDC-P progression may differ between patients, while the limited sample size (n = 6) warrants cautious interpretation and further validation in larger cohorts.}, } @article {pmid40960244, year = {2025}, author = {Nguyen, DL and Grimm, LJ and Wells, VA and Shpanskaya, K and Baker, JA}, title = {Echogenic Rind Associated With Suspicious Masses on Ultrasound: Performance for Breast Cancer Diagnosis and Associations With Pathologic Tumor Characteristics.}, journal = {AJR. American journal of roentgenology}, volume = {225}, number = {6}, pages = {e2533732}, doi = {10.2214/AJR.25.33732}, pmid = {40960244}, issn = {1546-3141}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology ; Middle Aged ; Retrospective Studies ; *Ultrasonography, Mammary/methods ; Adult ; Aged ; Sensitivity and Specificity ; Breast/diagnostic imaging/pathology ; Aged, 80 and over ; Image-Guided Biopsy ; }, abstract = {BACKGROUND. The 6th edition of the BI-RADS ultrasound lexicon is anticipated to include echogenic rind as a renamed associated feature, defined as a thick hyperechoic band partially or completely surrounding a mass and disrupting surrounding tissue texture. OBJECTIVE. The purpose of this study was to assess the performance of an echogenic rind associated with a suspicious mass on breast ultrasound for breast malignancy diagnosis as well as associations of echogenic rind with pathologic tumor characteristics. METHODS. This retrospective study included patients who underwent both diagnostic breast ultrasound that showed a suspicious mass (BI-RADS category 4 or 5) and subsequent ultrasound-guided biopsy from July 1, 2022, to June 30, 2023. Two radiologists independently reviewed the ultrasound examinations for echogenic rinds (requiring circumferential extent ≥ 25%) associated with masses; the readers also measured masses without and with inclusion of echogenic rinds. Diagnostic performance was evaluated using histopathology as the reference. RESULTS. The study included 511 patients (mean age, 52 years) with 583 suspicious masses; 249 masses were diagnosed as breast malignancy. The presence of echogenic rind yielded sensitivity and specificity, respectively, for breast malignancy of 58% and 81% for reader 1 and 51% and 85% for reader 2. An echogenic rind was associated with invasive cancer for reader 1 (invasive ductal carcinoma [IDC], 62%; invasive lobular carcinoma [ILC], 57%; ductal carcinoma in situ [DCIS], 24%; p = .003) and reader 2 (IDC, 53%; ILC, 53%; DCIS, 18%; p = .03). An echogenic rind was associated with invasive cancer molecular subtype for reader 1 (luminal A, 66%; luminal B, 48%; HER2-enriched, 100%; basal-like, 25%; p = .002) and reader 2 (luminal A, 62%; luminal B, 32%; HER2-enriched, 67%; basal-like, 19%; p < .001). In 168 resected malignancies, the difference between pathologic tumor size (mean, 19 mm) and ultrasound-based mass size, without and with the inclusion of echogenic rinds, was 4 and 3 mm for reader 1 and 7 and 5 mm for reader 2, respectively. CONCLUSION. An echogenic rind serves as a more specific than sensitive indicator of breast malignancy. Among breast malignancies, the finding is associated with invasive cancer. Inclusion of the rind decreases underestimation of tumor size relative to surgical pathology. CLINICAL IMPACT. These results provide insights into the clinical implications of an echogenic rind on ultrasound.}, } @article {pmid40957887, year = {2025}, author = {Kadri, S and Fischer, A and Mück-Häusl, M and Han, W and Kadri, A and Lin, Y and Yang, L and Hu, S and Ye, H and Ramesh, P and Ansari, M and Schiller, HB and Machens, HG and Rinkevich, Y}, title = {A mesothelial differentiation gateway drives fibrosis.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {8295}, pmid = {40957887}, issn = {2041-1723}, mesh = {Mice, Inbred C57BL ; Animals ; Mice ; Fibrosis ; *Epithelium/embryology/metabolism ; *Cell Differentiation ; Single-Cell Gene Expression Analysis ; Humans ; *Pulmonary Fibrosis/etiology ; Metabolic Reprogramming ; }, abstract = {Internal organs are encased by a supportive epithelial monolayer of mesodermal origin, termed mesothelium. The nature, evolution and function of mesothelial cells, and their genetic regulation impacting disease development are insufficiently understood. Here, we generate a comprehensive organ-wide single-cell transcriptomic compendium of mesothelium across healthy and diseased mouse and human organs, delineating the evolution of conserved activated states of mesothelial cells in response to disease. We uncover genetic drives behind each cell state and reveal a conserved metabolic gate into multipotent proteolytic, inflammatory and fibrotic cell differentiation, in mouse and human. Using lung injury models in mice, in combination with mesothelial cell-specific viral approaches, we show that direct metabolic reprogramming using Ifi27l2a and Crip1 on organ surfaces, blocks multipotent differentiation and protects mouse lungs from fibrotic disease. These findings place mesothelial cells as cellular exemplars and gateway to fibrotic disease, opening translational approaches to subvert fibrosis across a range of clinical indications.}, } @article {pmid40950543, year = {2025}, author = {Abon, JCR and Valparaiso, AP and Yuga, ACQ}, title = {Necrotizing Fasciitis of Bilateral Breasts following Unilateral Modified Radical Mastectomy for Invasive Ductal Carcinoma: A Case Report and Review of Literature.}, journal = {Acta medica Philippina}, volume = {59}, number = {11}, pages = {98-104}, pmid = {40950543}, issn = {2094-9278}, abstract = {Necrotizing fasciitis of the breast is a rare but potentially fatal soft tissue infection. It may occur primarily in patients without any direct cause, and less commonly after undergoing elective surgical procedures such as cosmetic mammoplasties and oncologic resections. This is a case of a 46-year-old female with stage IIIA invasive ductal carcinoma of the left breast treated with modified radical mastectomy presenting with a necrotizing infection involving the bilateral breast regions and left lateral abdomen six days after operation. She was managed with broad-spectrum antibiotics and radical debridement with right mastectomy, followed by wound coverage with split-thickness skin grafting. This is the eight case of breast necrotizing fasciitis occurring after mastectomy for breast cancer reported in the literature.}, } @article {pmid40947659, year = {2025}, author = {Goldhaber, NH and O'Keefe, TJ and Longo, L and Blair, SL and Grossi, S}, title = {Effect of Neoadjuvant Hormonal Therapy on Breast Conservation in Invasive Ductal Versus Lobular Carcinoma of the Breast: A Comparative Analysis.}, journal = {Journal of surgical oncology}, volume = {132}, number = {6}, pages = {1011-1018}, pmid = {40947659}, issn = {1096-9098}, support = {//The authors received no specific funding for this work./ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/drug therapy/surgery ; *Carcinoma, Lobular/pathology/drug therapy/surgery ; *Neoadjuvant Therapy/methods ; *Carcinoma, Ductal, Breast/pathology/drug therapy/surgery ; Middle Aged ; *Antineoplastic Agents, Hormonal/therapeutic use ; *Mastectomy, Segmental ; Aged ; Adult ; Retrospective Studies ; Follow-Up Studies ; Mastectomy ; }, abstract = {BACKGROUND: Comparative efficacy of neoadjuvant hormonal therapy in downstaging invasive ductal carcinoma (IDC) versus invasive lobular carcinoma (ILC) remains an area of uncertainty and may impact primary breast conservation rates.

METHODS: The National Cancer Database was used to identify women with IDC and ILC who underwent neoadjuvant hormonal therapy alone between 2004 and 2020. Clinical and pathological T-staging were examined and patients that downstaged before surgery were identified. Univariate and multivariate comparison analyses were performed. The effect of duration of neoadjuvant hormonal therapy was also examined.

RESULTS: Among women with IDC, 39.5% had lesions that downstaged compared to 30.0% with ILC (p < 0.001). Overall, the duration of neoadjuvant hormonal therapy was longer in patients with downstaged lesions compared to those that did not (mean = 126.9 v 99.4 days; p < 0.001). Of those who downstaged, 43% of patients with IDC and 57.8% of patients with ILC underwent mastectomy following neoadjuvant hormonal therapy.

CONCLUSIONS: Overall, ILC lesions are less likely to downstage after neoadjuvant hormonal therapy alone compared to IDC lesions. In both histologic subtypes, cancers were more likely to downstage after over 120 days of neoadjuvant hormonal therapy. Clinicians should be mindful when counseling patients that neoadjuvant hormonal therapy alone may not preclude the need for mastectomy in ILC.}, } @article {pmid40946623, year = {2025}, author = {AlGhuneem, AA and AlMoosa, NY and Awadh, MB}, title = {Occult breast cancer management with axillary lymph node dissection versus sentinel lymph node biopsy: Case reports and literature review.}, journal = {International journal of surgery case reports}, volume = {135}, number = {}, pages = {111896}, pmid = {40946623}, issn = {2210-2612}, abstract = {BACKGROUND: Breast cancer is the most common cancer worldwide. In patients with occult breast cancer, sentinel lymph node biopsy (SLNB) has been shown to reduce complications, shorter hospital stay, and improved quality of life compared to axillary lymph node dissection (ALND). This study presents two case reports comparing outcomes of ALND versus SLNB in the management of occult breast cancer. CASE 1: A 52-year-old female presented with a left axillary tail mass which showed invasive ductal carcinoma. Underwent left axillary lymph node dissection. She developed postoperative drain seroma. The patient was managed conservatively. CASE 2: A 65-year-old female known case of diabetes mellitus type 2, hypertension, and dyslipidemia presented with a right axillary tail mass which showed features suggestive of metastatic carcinoma, most arising from breast origin. The patient underwent uneventful right sentinel lymph node biopsy without any postoperative complications.

DISCUSSION: While ALND is associated with more complications including, seroma, lymphedema, paresthesia, infection, and nerve injury, SLNB offers a less invasive approach with favorable outcome.

CONCLUSION: SLNB is an effective and less morbid approach for managing occult breast cancer and warrants further study in larger cohorts.}, } @article {pmid40944124, year = {2025}, author = {Mrosewski, I and Fleming, T and Schulze-Tanzil, G and Werner, C and Gögele, C and Mantel, V and Kokozidou, M and Bertsch, T}, title = {Menaquinone-7 Supplementation Increases Multiple Advanced Glycation End-Products and Oxidation Markers in Zucker Diabetic Fatty Rats.}, journal = {Nutrients}, volume = {17}, number = {17}, pages = {}, pmid = {40944124}, issn = {2072-6643}, support = {SZ_FP_008.18//Kerscher´sche Stiftung/ ; SZ_FP_164.20//Kerscher´sche Stiftung/ ; }, mesh = {Animals ; *Glycation End Products, Advanced/blood/metabolism ; Rats, Zucker ; Male ; *Vitamin K 2/analogs & derivatives/pharmacology/administration & dosage ; Biomarkers/blood/urine ; *Oxidative Stress/drug effects ; *Diabetes Mellitus, Type 2/blood/metabolism/drug therapy ; *Dietary Supplements ; Oxidation-Reduction ; Rats ; Blood Glucose/metabolism ; *Diabetes Mellitus, Experimental/blood ; }, abstract = {Background: Dicarbonyls and advanced glycation end-products (AGEs) contribute to oxidative stress, inflammation, and complications in type 2 diabetes mellitus (T2DM). Menaquinone-7 (MK-7), a vitamin K2 subtype, has shown benefits for glucose tolerance and vascular health in some studies. We evaluated the impact of MK-7 on dicarbonyls, free AGEs, and protein nitration/oxidation adducts in a rat model of T2DM. Methods: Male heterozygous (fa/+, control) and homozygous (fa/fa, diabetic) Zucker Diabetic Fatty rats were fed a diabetogenic diet without or with MK-7 for 12 weeks. After sacrifice, plasma dicarbonyls as well as plasma and urinary levels of free AGEs and protein nitration/oxidation adducts were quantified by isotope dilution tandem mass spectrometry. Results: Diabetic rats showed significantly increased plasma glyoxal, 3-deoxyglucosone, and fructosyl-lysine with non-significant trends toward increased methylglyoxal-derived hydroimidazolone and methionine sulfoxide, as well as reductions in methylglyoxal and dityrosine. Urinary carboxyethyl-lysine, carboxymethyl-lysine, fructosyl-lysine (all significant), and dityrosine (non-significant) were elevated in diabetic rats; glucosepane (non-significant) was reduced. MK-7 supplementation reduced no measured parameter but was associated with non-significant further increases in plasma glyoxal-derived hydroimidazolone, carboxyethyl-lysine, carboxymethyl-lysine, fructosyl-lysine, 3-nitrotyrosine, and methionine sulfoxide, as well as in urinary glyoxal-derived hydroimidazolone, carboxyethyl-lysine, fructosyl-lysine, and 3-nitrotyrosine, in diabetic rats. Correlation analysis revealed significant associations between glucose, dicarbonyls, AGEs, and oxidative markers. Conclusions: High-dose MK-7 supplementation did not improve dicarbonyl stress, AGE burden, or protein nitration/oxidation. With respect to available scientific evidence and our observations, the combination of glycemia-driven amplification of glycation and oxidative stress, as well as MK-7-induced glutathione depletion, were likely causative.}, } @article {pmid40929383, year = {2025}, author = {Uppal, R and Rehan Uppal, M and Tahir, R and Saeed, U and Khan, AA and Uppal, MS and Ali, Z and Ozsahin, DU and Tariq, MN and Waheed, Y and Piracha, ZZ}, title = {Bacterial infections and antimicrobial resistance patterns: a comprehensive analysis of health dynamics across regions in Pakistan (2013-2023).}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {85}, number = {}, pages = {e285605}, doi = {10.1590/1519-6984.285605}, pmid = {40929383}, issn = {1678-4375}, mesh = {Pakistan/epidemiology ; Humans ; Female ; Male ; Adult ; Infant ; Middle Aged ; Adolescent ; *Bacterial Infections/epidemiology/microbiology/drug therapy ; Prevalence ; *Drug Resistance, Bacterial ; Young Adult ; Child, Preschool ; *Anti-Bacterial Agents/pharmacology ; Child ; Aged ; Infant, Newborn ; Escherichia coli/drug effects/isolation & purification ; Urinary Tract Infections/microbiology/epidemiology ; Salmonella/drug effects/isolation & purification ; }, abstract = {Antimicrobial resistance (AMR) is a significant public health concern globally, and Pakistan is no exception. The misuse and overuse of antibiotics, inadequate regulation of their sale, and a lack of awareness contribute to the rising levels of AMR in the country. study presents a detailed analysis of blood and urine samples collected in Pakistan over various periods, focusing on pathogen prevalence, gender distribution, and age-wise patterns. From January 2013 to 2017, the North region exclusively contributed to the blood sample dataset, with Salmonella emerging as the primary pathogen, particularly affecting infants and neonates. Subsequently, from January 2017 to December 2020, a significant dataset emerged from the North and Punjab regions, with Salmonella and E.coli prevalent across all age groups, notably impacting adults and infants. In the period from January 2021 to the present, blood samples predominantly originated from the North and Punjab regions, with Salmonella and E.coli remaining significant pathogens, affecting adults and the elderly. Regarding urine samples, from January 2013 to December 2017, E.coli was the dominant pathogen, with females showing a higher susceptibility to urinary tract infections (UTIs), particularly among the elderly. Similarly, from January 2017 to December 2020, E.coli remained predominant, with UTIs more prevalent in females and the elderly. In the most recent period, the North region significantly contributed to UTI cases, with E.coli remaining predominant and females exhibiting a higher susceptibility, especially among the elderly. This comprehensive analysis provides crucial insights into the epidemiology of blood and urinary tract infections in Pakistan, informing public health strategies and interventions aimed at addressing these health challenges.}, } @article {pmid40926949, year = {2025}, author = {Gmur, MK and Gajewski, M and Goliat, W and Haraziński, K and Dalski-Szelag, PR and Jastrzebska, I and Sławińska, B and Maryniak, N and Sysło, O and Błecha, Z and Rubik, N}, title = {A Case Report of Synchronous Multicentric Breast Carcinoma With Biologically Discordant Phenotypes: Luminal A and Triple-Negative Subtypes.}, journal = {Cureus}, volume = {17}, number = {8}, pages = {e89666}, pmid = {40926949}, issn = {2168-8184}, abstract = {We present the case of a 45-year-old Caucasian woman diagnosed with synchronous bicentric breast cancer of differing molecular phenotypes in the same breast. The first tumor, an invasive ductal carcinoma (G1), was estrogen and progesterone receptor-positive and HER2-negative, with a low proliferative index (Ki67 10%). A second lesion, located in a different quadrant and appearing within weeks after biopsy, exhibited a triple-negative phenotype and a higher proliferative index (Ki67 30%). Both tumors were classified as stage IA. Due to the multicentric nature of disease, the patient underwent mastectomy with sentinel node biopsy and immediate reconstruction. Genetic testing was negative for BRCA1/2, CHEK2, and PALB2 mutations, though familial cancer history suggested a possible hereditary syndrome (FCC suspicion). This case underscores the complexity of managing multicentric breast cancer with discordant receptor status and raises questions about the role of biopsy sites in tumor development.}, } @article {pmid40922956, year = {2025}, author = {Dahi, F and Shahbazi, S and Geranpayeh, L}, title = {mtDNA copy number/miR663/AATF axis in invasive ductal carcinoma of the breast.}, journal = {BioImpacts : BI}, volume = {15}, number = {}, pages = {30792}, pmid = {40922956}, issn = {2228-5652}, abstract = {INTRODUCTION: Mitochondrial DNA (mtDNA) copy number variations have been reported in multiple human cancers. Previous studies indicate that mitochondrial retrograde signaling regulates miR663, which plays a key role in tumorigenesis, including regulating apoptosis antagonizing transcription factor (AATF). This study investigates the expression of miR663 and AATF in relation to mtDNA copy number in invasive ductal carcinoma (IDC) of the breast.

METHODS: Paired primary tumors and adjacent non-tumor tissues were analyzed to assess changes in miR663 and AATF expression using fold-change analysis. The mtDNA copy number was quantified using COX1 as the mitochondrial gene and COX4 as the nuclear control gene. To validate the findings, publicly available data from The Cancer Genome Atlas (TCGA) were also analyzed.

RESULTS: A significant reduction in tumor miR663 expression was observed (fold change=0.139), with a strong correlation between miR663 and AATF expression. A significant Z-score difference was also detected between miR663 and mtDNA copy number. miR663 was predominantly expressed in grade I tumors but significantly downregulated in higher-grade tumors, whereas AATF expression increased with tumor grade. In silico analysis of TCGA data confirmed elevated AATF expression, with notable variations across breast cancer subtypes.

CONCLUSION: We observed reduced expression of miR663 and mtDNA copy number in breast tumors, along with variations in AATF levels across subtypes. The decrease in miR663 could be associated with lower mtDNA copy numbers and impaired retrograde signaling, impacting AATF expression and function. Our findings underscore the therapeutic promise of targeting the mtDNA/miR-663/AATF axis, which could lead to advancements in breast cancer treatment.}, } @article {pmid40921139, year = {2025}, author = {Xiao, Y and Song, L and Xie, WJ and Chen, RW and Lin, ZJ and Lin, XY and Liu, Y and Jiang, Y and Xu, S and Xu, JP}, title = {Histone Methyltransferase EHMT2 Promotes the Progression of Breast Ductal Carcinoma by Regulating the Hippo Pathway.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {44}, number = {3}, pages = {63-74}, doi = {10.1615/JEnvironPatholToxicolOncol.2025056721}, pmid = {40921139}, issn = {2162-6537}, mesh = {Humans ; *Histone-Lysine N-Methyltransferase/metabolism/genetics/antagonists & inhibitors ; Female ; Hippo Signaling Pathway ; *Breast Neoplasms/pathology/metabolism/genetics ; Animals ; Cell Line, Tumor ; *Protein Serine-Threonine Kinases/metabolism/genetics ; Mice ; *Carcinoma, Ductal, Breast/pathology/metabolism/genetics ; Signal Transduction ; Disease Progression ; Reactive Oxygen Species/metabolism ; Apoptosis ; Mice, Nude ; Cell Proliferation ; *Histocompatibility Antigens/metabolism/genetics ; }, abstract = {Invasive ductal carcinoma (IDC) is a major type of breast cancer. The utilization of inhibitors targeting histone methyltransferases introduces novel therapeutic avenues for the treatment of cancer. Immunohistochemistry, Western blot, and reverse transcription quantitative polymerase chain reaction experiments were applied to assess the levels of EHMT2 in IDC and adjacent tissues. HCC70 cells were treated with EHMT2 inhibitors (UNC0646 and BIX-01294), and assessed using Cell Counting Kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and transwell assays to evaluate cell viability, apoptosis, and migratory capacity, respectively. The reactive oxygen species (ROS) levels were assessed using the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe. The expressions of Hippo pathway were analyzed via Western blot assay. Immunofluorescence staining was employed to detect the subcellular localization changes in YAP expression. A xenograft tumor model of HCC70 cells was applied to validate the tumor-suppressive influences of EHMT2 inhibitors in vivo. We observed significant upregulation of EHMT2 in both IDC clinical samples and IDC cell lines, with high EHMT2 expression correlating with poor prognosis. After treatment with EHMT2 inhibitors UNC0646 or BIX-01294, HCC70 cells exhibited inhibition of proliferation and migratory capacity, alongside an increase in apoptosis rate and ROS production levels. UNC064 or BIX-01294 promoted the phosphorylation levels of MST1, LATS1, MOB1A, and YAP, indicating the activation of the Hippo pathway by EHMT2 inhibitors. Moreover, UNC0646 and BIX-01294 enhanced the cytoplasmic expression of YAP while inhibiting its nuclear localization, preventing its nuclear activation. EHMT2 was upregulated in IDC, and EHMT2 inhibitors suppressed IDC progression by modulating the Hippo signaling pathway.}, } @article {pmid40920319, year = {2025}, author = {Musa, DH}, title = {Hormonal receptor status and lymph nodes involvement in breast cancer: a retrospective study.}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {71}, number = {8}, pages = {67-71}, doi = {10.14715/cmb/2025.71.8.10}, pmid = {40920319}, issn = {1165-158X}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/metabolism ; Retrospective Studies ; Middle Aged ; *Receptors, Estrogen/metabolism ; Adult ; *Receptors, Progesterone/metabolism ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Lymphatic Metastasis/pathology ; *Lymph Nodes/pathology/metabolism ; Aged ; Ki-67 Antigen/metabolism ; Cross-Sectional Studies ; Carcinoma, Ductal, Breast/pathology/metabolism ; }, abstract = {Hormonal status and lymphatic invasion are two important prognostic factors among cases of breast cancer. This study aims to assess and evaluate the hormonal receptor status and lymph node involvement among female breast cancer patients in Duhok city, Kurdistan region, Iraq. A retrospective cross-sectional study was conducted, involving 156 diagnosed cases of breast cancer who had undergone surgical treatment and laboratory investigations at Azadi Teaching Hospital and Duhok Private Hospital for 30 months. Hormonal status (ER, PR, HER2 enriched, and Ki67), luminal staging, and lymphatic invasions were analyzed using SPSS version 26. Invasive ductal carcinoma not otherwise specified accounted for 87.8% of the total sample, with Luminal A being the most common form (42.31%), followed by Luminal B (37.17%). The prevalence of hormonal status among cases of breast cancer with lymphatic invasion was ER 42.5%, PR 41.2%, HER2 enriched 21.01%, and Ki67 36.8%; however, these differences were not statistically significant (P values: 0.586, 0.65, 0.253, and 0.469, respectively). In conclusion, invasive ductal carcinoma is the most common histological type of breast cancer, and the most frequent biological form is Luminal A. A significant number of breast cancer cases with positive lymphatic invasion show positive hormonal receptor levels; however, the number of lymphatic invasions is not correlated with the type of hormonal receptor positivity.}, } @article {pmid40919401, year = {2025}, author = {Xue, L and Sheng, Z}, title = {Triple-Negative Breast Cancer Presenting as Recurrent Cystic Lesions During Lactation: A Case Report.}, journal = {Clinical case reports}, volume = {13}, number = {9}, pages = {e70850}, pmid = {40919401}, issn = {2050-0904}, abstract = {Lactation-associated breast cancer poses diagnostic challenges due to physiological breast changes that may mask malignancies. Triple-negative breast cancer (TNBC) during lactation is rare and aggressive, requiring vigilant evaluation and treatment. This report highlights the diagnostic dilemma of recurrent cystic breast lesions during lactation, which can mimic benign conditions like galactoceles but may conceal aggressive TNBC, leading to potential delays in diagnosis despite initial conservative approaches such as aspiration. A 26-year-old lactating woman presented with recurrent complex cystic lesions initially mistaken for benign lactational changes. Despite multiple aspirations, the lesions enlarged, leading to surgical excision. Pathology confirmed TNBC (ER-, PR-, HER2-, Ki-67 ~40%). Core needle biopsy and extended resection with sentinel lymph node biopsy confirmed grade III invasive ductal carcinoma. The patient received 8 cycles of chemotherapy (4 cycles of pegylated liposomal doxorubicin and cyclophosphamide, followed by 4 cycles of taxane) without radiotherapy, achieving 6-year recurrence-free survival. Persistent complex cystic lesions during lactation require core needle biopsy to rule out malignancy. Multimodal TNBC treatment can yield favorable outcomes, including fertility preservation, as evidenced by the patient's subsequent pregnancy in 2024.}, } @article {pmid40918116, year = {2025}, author = {Li, H and Zhang, H and Dai, R and Zheng, D and Zhao, J and Jing, H and Ma, X and Zhang, L and Sun, W and Suo, Z}, title = {CD68 as a multi-omic prognostic biomarker in digestive system cancers: correlations with tumor-infiltrating immune cells and immune checkpoints.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1599677}, pmid = {40918116}, issn = {1664-3224}, mesh = {Humans ; *Biomarkers, Tumor/genetics/metabolism ; *Lymphocytes, Tumor-Infiltrating/immunology/metabolism ; Prognosis ; *Antigens, CD/genetics/metabolism/immunology ; *Antigens, Differentiation, Myelomonocytic/genetics/metabolism/immunology ; Female ; Male ; *Digestive System Neoplasms/immunology/mortality/metabolism/pathology/genetics ; *Immune Checkpoint Proteins/metabolism ; Middle Aged ; Tumor Microenvironment/immunology ; Multiomics ; CD68 Molecule ; }, abstract = {BACKGROUND AND OBJECTIVE: CD68 plays a crucial role in promoting phagocytosis. However, its expression level, prognostic value and the correlations with tumor-infiltrating immune cells (TIICs) or common tumor immune checkpoints (TICs) in human digestive system cancers (DSC) remain poorly understood. This study aims to investigate the expression levels, prognostic significance, and clinical implications of CD68, as well as its correlations with six TIICs and four common TICs in DSC.

MATERIALS AND METHODS: We analyzed CD68 mRNA and protein expression using online databases and immunohistochemistry (IHC) on tissue microarray (TMA) sections, comparing DSC tumor tissues with adjacent normal tissues. Overall survival (OS) was calculated to evaluate the prognostic value of CD68 in DSC. Additionally, correlations between CD68 expression and six TIICs (B cells, CD4+ T cells, CD8+ T cells, macrophages, NK cells, and cancer-associated fibroblasts) or four common TICs (PDCD1, CTLA4, IDO1, and CD40) were assessed using the Tumor Immune Estimation Resource (TIMER).

RESULTS: CD68 mRNA expression was significantly higher in esophageal carcinoma (ESCA) and stomach adenocarcinoma (STAD) tissues compared to adjacent normal tissues, but lower in colon adenocarcinoma (COAD), liver hepatocellular carcinoma (LIHC), and pancreas invasive ductal carcinoma (PAAD). Protein expression of CD68 was significantly higher in COAD than in adjacent normal tissues, but lower in ESCA, LIHC, PAAD, and STAD. CD68 protein expression served as a prognostic marker in COAD and STAD. Furthermore, CD68 expression showed strong positive correlations with the six TIICs and significant positive correlations with the four TICs in DSC.

CONCLUSION: CD68 may serve as an essential prognostic biomarker in COAD and STAD and could be a promising candidate for diagnostic, prognostic, and therapeutic targeting in human DSC.}, } @article {pmid40914542, year = {2025}, author = {Wang, Q and Huang, J and Wu, S and Wang, J and Yu, T and Wei, W and Yang, T and Wu, X and Zhai, J and Zhang, X}, title = {Neuro-immuno-stromal context in colorectal cancer: An enteric glial cell-driven prognostic model via machine learning predicts survival, recurrence, and therapy response.}, journal = {Experimental cell research}, volume = {452}, number = {1}, pages = {114733}, doi = {10.1016/j.yexcr.2025.114733}, pmid = {40914542}, issn = {1090-2422}, mesh = {Humans ; *Colorectal Neoplasms/pathology/genetics/immunology/mortality/therapy ; *Machine Learning ; Prognosis ; *Neoplasm Recurrence, Local/pathology/genetics ; *Neuroglia/pathology/metabolism/immunology ; Tumor Microenvironment/immunology ; Gene Expression Regulation, Neoplastic ; Male ; Female ; Biomarkers, Tumor/genetics ; }, abstract = {BACKGROUND: Enteric glial cells (EGCs) have been implicated in colorectal cancer (CRC) progression. This study aimed to develop and validate a prognostic model integrating EGC- and CRC-associated gene expression to predict patient survival, recurrence, metastasis, and therapy response.

METHODS: Bulk and single-cell RNA sequencing data were analyzed, and a machine learning-based model was constructed using the RSF random forest algorithm. The model's prognostic value was evaluated through survival analysis, pathway enrichment, immune profiling, and therapy response predictions.

RESULTS: The model effectively stratified patients into high- and low-risk groups, with high-risk patients exhibiting significantly worse overall survival (OS) and an increased likelihood of recurrence and metastasis. Gene Set Enrichment Analysis (GSEA) identified key pathways associated with tumor progression, immune regulation, and microenvironmental interactions. The model was significantly correlated with immune cell infiltration and chemokine signaling. High-risk patients exhibited reduced immune therapy efficacy and distinct drug sensitivity profiles, suggesting its potential to guide personalized treatment strategies.

CONCLUSION: This model serves as a valuable tool for CRC prognosis and treatment stratification, with potential clinical applications pending further validation.}, } @article {pmid40910488, year = {2025}, author = {Chen, DC and Alhamdani, Z and Papa, N and Shen, E and Kovaleva, N and Gao, M and Emmett, L and Hofman, MS and Ryan, A and Scott, AM and Lee, ST and Lawrentschuk, N and Perera, ML and Bolton, DM}, title = {The Blind Spot of Prostate-Specific Membrane Antigen Positron Emission Tomography Staging? Intraductal Carcinoma of the Prostate Is Overrepresented in Patients With No Uptake Pattern on Prostate-Specific Membrane Antigen Positron Emission Tomography and High-Grade Prostate Cancer.}, journal = {The Journal of urology}, volume = {214}, number = {6}, pages = {582-590}, doi = {10.1097/JU.0000000000004734}, pmid = {40910488}, issn = {1527-3792}, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/diagnostic imaging/surgery/metabolism ; Retrospective Studies ; Aged ; Neoplasm Staging/methods ; Middle Aged ; Neoplasm Grading ; *Positron-Emission Tomography/methods ; Prostatectomy ; *Glutamate Carboxypeptidase II/metabolism ; Gallium Radioisotopes ; Radiopharmaceuticals ; Prostate/pathology/diagnostic imaging ; *Antigens, Surface ; Gallium Isotopes ; }, abstract = {PURPOSE: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is increasingly used to diagnose and stage prostate cancer. A PRIMARY score uses anatomical localization and uptake patterns to improve diagnostic accuracy. We evaluated the histopathology of patients with no uptake pattern (PRIMARY score 1) and the prevalence of intraductal carcinoma of the prostate (IDC-P) in this subset compared with those with an uptake pattern (PRIMARY score ≥2).

MATERIALS AND METHODS: A 2-center, retrospective cohort study was conducted including consecutive patients imaged with intraprostatic [[68]Ga]Ga-PSMA-11 or [[18]F]DCFPyL PSMA PET before radical prostatectomy. All PSMA PET scans were centrally reviewed by nuclear medicine physicians, with PRIMARY scores and quantitative imaging parameters recorded. Perioperative characteristics, Prostate Imaging Reporting and Data System (PI-RADS), and histopathology were collected. The distribution of grade group and other histopathological findings, including IDC-P, were examined according to PSMA uptake patterns.

RESULTS: A total of 178 patients were analyzed. A PRIMARY score 1 finding on intraprostatic PSMA PET was seen in 30 (17%) patients. IDC-P in prostatectomy specimens was more frequent in these patients compared with PRIMARY score ≥ 2 patients (12/30, 40% vs 31/148, 21%; P = .026). In the PRIMARY score 1 subset, patients with IDC-P had considerably more pathological grade group ≥ 3 disease than those without IDC-P (100% vs 33%). Eighty-one percent of all patients had PI-RADS scores 4 or 5 on prebiopsy MRI. The study's generalizability is limited by the selection of patients with PRIMARY score 1 disease who subsequently proceeded to surgery.

CONCLUSIONS: In patients who are being considered for radical prostatectomy due to adverse clinical, PI-RADS, or biopsy features, a PSMA PET demonstrating no intraprostatic uptake pattern should not be considered inherently a marker for small-volume or lesser-grade disease. Some high-grade cancers, particularly those associated with IDC-P, may not be well visualized on PSMA PET.}, } @article {pmid40909583, year = {2025}, author = {Brown, AS and Llinás, M and Mahony, S}, title = {Chromatin state dynamics during the Plasmodium falciparum intraerythrocytic development cycle.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40909583}, issn = {2692-8205}, support = {R35 GM144135/GM/NIGMS NIH HHS/United States ; T32 GM152354/GM/NIGMS NIH HHS/United States ; }, abstract = {The interdependence of chromatin states and transcription factor (TF) binding in eukaryotic genomes is critical for the proper regulation of gene expression. In this study, we explore the connection between TFs and chromatin states in the human malaria parasite, Plasmodium falciparum, throughout its 48-hour asexual intraerythrocytic developmental cycle (IDC). Most P. falciparum genes are expressed in a periodic manner during the IDC, accompanied by dynamic shifts in histone modifications and chromatin accessibility. Leveraging genome-wide profiles of chromatin accessibility, histone modifications, and Heterochromatin Protein 1 (HP1) occupancy, we characterize chromatin state dynamics during the IDC. Our results indicate that several chromatin states remain stable throughout the lifecycle, while others are dynamic and are linked to gene activation or repression. We further characterize chromatin state dynamics at the genome-wide DNA binding sites for a selection of Plasmodium TFs, allowing us to group TFs according to their chromatin preferences. By correlating changes in chromatin accessibility, histone modifications, and TF binding, we provide a global overview of the chromatin state dynamics that coordinate P. falciparum asexual blood stage development.}, } @article {pmid40909459, year = {2025}, author = {Albayrak, NE}, title = {Case Report: Neuroendocrine carcinoma of the breast: a review of the literature and illustration of six cases.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1551309}, pmid = {40909459}, issn = {2296-858X}, abstract = {"Primary neuroendocrine breast carcinoma (NEBC) is an underdiagnosed subtype of breast cancer, which includes small cell (SCNEC) and large cell neuroendocrine carcinomas (LCNEC). Accurate diagnosis remains challenging given their low incidence; misclassification as invasive breast carcinoma of no special type (IBC-NST), invasive ductal carcinoma (IDC), or a metastatic neuroendocrine carcinoma may occur. Cases with any component of adenocarcinoma and well-differentiated neuroendocrine tumors were excluded. A search of the pathology database (2012-2024) revealed six female patients (27-85 years) with a final pathologic diagnosis of NEBC (stages IA-IV), including four diagnosed with LCNEC and two with SCNEC. Even though most NEBC cases (5 of 6; 83%) were of the luminal subtype, five of six patients (83%) developed distant metastases within 4 years of the initial diagnosis. Molecular profiling of six cases revealed common alterations in the FGF/FGFR and PI3K/AKT/mTOR pathways. In summary, primary neuroendocrine carcinomas of the breast display aggressive behavior. However, they are more likely to harbor certain alterations, such as activating PIK3CA mutations and FGFR1 amplification, which can be of therapeutic value. The Ki-67 index, unlike in the pancreas and gastrointestinal tract, is not suitable for grading neuroendocrine neoplasms (NENs) of the breast. However, it can still serve as a tool for risk stratification, similar to its use in luminal-type breast cancer.}, } @article {pmid40904548, year = {2025}, author = {Navaeipour, F and Sanderson, RW and Li, J and Rawlins, S and Hepburn, MS and Kennedy, BF}, title = {Development of breast-mimicking phantoms for use in optical coherence elastography.}, journal = {Journal of biomedical optics}, volume = {30}, number = {12}, pages = {124504}, pmid = {40904548}, issn = {1560-2281}, mesh = {*Phantoms, Imaging ; *Elasticity Imaging Techniques/methods/instrumentation ; *Tomography, Optical Coherence/methods/instrumentation ; Humans ; Female ; *Breast/diagnostic imaging ; Breast Neoplasms/diagnostic imaging ; Printing, Three-Dimensional ; }, abstract = {SIGNIFICANCE: Optical coherence elastography (OCE) is an emerging technique for mapping tissue mechanical properties into an image, known as an elastogram, with microscale resolution. Although system characterization phantoms are widely used in OCE development, there is a critical need for tissue-mimicking phantoms that can more accurately replicate the complex structural and mechanical properties of tissues, particularly for validating clinical applications, such as in breast cancer.

AIM: We aim to investigate the effects of tissue-like structures on elastogram formation in a controlled environment by developing and characterizing two types of breast tissue-mimicking phantoms, replicating invasive ductal carcinoma (IDC) morphology and the other mimicking breast ductal networks.

APPROACH: We present a comprehensive methodology for fabricating breast-mimicking phantoms using optical coherence tomography and ductography images to provide information on tissue structure. The method employs 3D-printed molds, casting different silicone materials for IDC-mimicking phantoms and implementing a dissolving mold technique to create duct-mimicking phantoms, which can be tested in both empty and fluid-filled states.

RESULTS: The IDC-mimicking phantom successfully replicates structural features as small as 100    μ m , revealing complex mechanical behaviors at tissue interfaces, including strain concentrations where tissues of different stiffness interact. The duct-mimicking phantom demonstrates distinct mechanical responses between configurations, with hollow ducts creating sharp discontinuities at boundaries, whereas fluid-filled ducts exhibit more gradual transitions in mechanical properties.

CONCLUSIONS: Our methodology demonstrates the capability to fabricate breast tissue-mimicking phantoms that reproduce both the structural and mechanical properties of breast tissue, providing a controlled environment for investigating OCE performance and understanding how tissue architecture influences elastogram formation, particularly at interfaces among different tissue types.}, } @article {pmid40901930, year = {2025}, author = {Jassim Ghrabat, MJ and Ghaib, AA and Al-Hossenat, A and Abduljabbar, ZA and Nyangaresi, VO and Ma, J and Aldarwish, AJY and Abduljaleel, IQ and Honi, DG and Neamah, HA}, title = {Effective SMOTE boost with deep learning for IDC identification in whole-slide images.}, journal = {PloS one}, volume = {20}, number = {9}, pages = {e0329078}, pmid = {40901930}, issn = {1932-6203}, mesh = {Humans ; *Deep Learning ; Female ; *Breast Neoplasms/pathology/diagnosis/diagnostic imaging ; *Carcinoma, Ductal, Breast/pathology/diagnosis/diagnostic imaging ; Neural Networks, Computer ; *Image Processing, Computer-Assisted/methods ; }, abstract = {Breast cancer is highlighted in recent research as one of the most prevalent types of cancer. Timely identification is essential for enhancing patient results and decreasing fatality rates. Utilizing computer-assisted detection and diagnosis early on may greatly improve the chances of recovery by accurately predicting outcomes and developing suitable treatment plans. Grading breast cancer properly, especially evaluating nuclear atypia, is difficult owing to faults and inconsistencies in slide preparation and the intricate nature of tissue patterns. This work explores the capability of deep learning to extract characteristics from histopathology photos of breast cancer. The research introduces a new method called SMOTE-based Convolutional Neural Network (CNN) technology to detect areas impacted by Invasive Ductal Carcinoma (IDC) in whole slide pictures. The trials used a dataset of 162 individuals with IDC, split into training (113 photos) and testing (49 images) groups. Every model was subjected to individual testing. The SMO_CNN model we developed demonstrated exceptional testing and training accuracies of 98.95% and 99.20% respectively, surpassing CNN, VGG19, and ResNet50 models. The results highlight the effectiveness of the created model in properly detecting IDC-affected tissue areas, showing great promise for improving breast cancer diagnosis and treatment planning. We surpassing other models as such, CNN, VGG19, ResNet50.}, } @article {pmid40896954, year = {2025}, author = {Ogita, M and Kumamaru, H and Kubo, M and Kinukawa, N and Niikura, N and Saji, S and Toi, M}, title = {Survival of patients with squamous cell carcinoma of the breast compared with invasive ductal carcinoma by biological subtype: A matched analysis of the Japanese national clinical database-breast cancer registry.}, journal = {Breast (Edinburgh, Scotland)}, volume = {83}, number = {}, pages = {104567}, pmid = {40896954}, issn = {1532-3080}, mesh = {Humans ; Female ; Middle Aged ; *Carcinoma, Squamous Cell/mortality/pathology/therapy ; Registries ; *Breast Neoplasms/mortality/pathology/therapy ; Japan/epidemiology ; Aged ; *Carcinoma, Ductal, Breast/mortality/pathology/therapy ; Triple Negative Breast Neoplasms/mortality/pathology ; Databases, Factual ; Prognosis ; Adult ; Neoplasm Recurrence, Local ; Aged, 80 and over ; Radiotherapy, Adjuvant ; Disease-Free Survival ; East Asian People ; }, abstract = {PURPOSE: Owing to the rarity of primary squamous cell carcinoma (SCC) of the breast, the prognosis of SCC remains uncertain. We aimed to investigate the clinical features and prognosis of breast SCC by subtype.

METHODS: A total of 350,977 patients with breast SCC or invasive ductal carcinoma (IDC) were identified from the National Clinical Database-Breast Cancer Registry from 2004 to 2014. SCC and IDC patients with triple-negative and luminal subtypes were matched 1:1 via exact matching. Overall survival (OS), breast cancer-specific survival (BCSS), and recurrence-free survival (RFS) were compared between patients with SCC and those with IDC. In-field area recurrence was analyzed among patients who received adjuvant radiotherapy.

RESULTS: The study included 452 SCC patients and 182,707 IDC patients. SCC patients were more likely than IDC patients to have advanced-stage disease. The crude 10-year OS, BCSS, and RFS were 70 %, 80 %, and 66 % for patients with SCC, and 88 %, 93 %, and 81 % for patients with IDC, respectively. After 204 patients with the triple-negative subtype and 68 patients with the luminal subtype in each group were matched, the 10-year BCSS was significantly worse for SCC (76.7 %) than for IDC (85.5 %) within the triple-negative subtype. There were no differences in OS, BCSS, or RFS for the luminal subtype. The rates of in-field area recurrence were similar between patients with SCC and those with IDC with either the triple-negative subtype or the luminal subtype.

CONCLUSIONS: Within the triple-negative subtype, SCC histology was associated with a significantly worse prognosis than IDC.}, } @article {pmid40895939, year = {2025}, author = {Correa Sandoval, DC and Guajardo Nieto, DA and Guzman Murguia, JL}, title = {Primary Breast Carcinoma in Ectopic Breast Tissue in the Suprapubic Region Presenting as a Subcutaneous Nodule: A Case Report and Review of the Literature.}, journal = {Cureus}, volume = {17}, number = {7}, pages = {e89015}, pmid = {40895939}, issn = {2168-8184}, abstract = {Ectopic breast tissue (EBT) is an uncommon congenital condition resulting from incomplete involution of the milk line. Primary carcinomas arising in EBT have been reported in a small number of cases, most frequently in the axilla, but they may occur anywhere along the mammary line. Here, we present the case of a 69-year-old woman who presented with an asymptomatic subcutaneous nodule located at the end of a Pfanneistein's laparotomy scar in the suprapubic region. Histopathological examination revealed invasive ductal carcinoma, compatible with no special type, originating from EBT. The patient underwent wide local excision of the lesion with clear margins, followed by adjuvant treatment with letrozole. This case highlights the importance of timely diagnosis and emphasizes the significance of recognizing the rare presentation of primary breast carcinoma in EBT. Early detection and appropriate treatment, including surgical intervention and targeted therapy, are essential for optimizing patient outcomes in such cases.}, } @article {pmid40895660, year = {2025}, author = {El Masadi, M and Elouaouch, S and Bouayed, FZ and BenSghier, A and Berhili, S and Moukhlissi, M and Mezouar, L}, title = {Apocrine Breast Carcinoma With an Atypical Immunohistochemical Profile: A Case Report.}, journal = {Cureus}, volume = {17}, number = {8}, pages = {e89193}, pmid = {40895660}, issn = {2168-8184}, abstract = {Breast cancer is the most common malignancy among women worldwide and encompasses a wide variety of histopathological subtypes. While invasive ductal carcinoma (IDC) represents the most prevalent form, rare variants such as apocrine carcinoma (AC) also warrant particular attention. Classically, AC of the breast is defined by apocrine morphology, negativity for hormonal receptors (estrogen receptor (ER), progesterone receptor (PR)), and strong positivity for the androgen receptor (AR). However, the present case involving a 37-year-old woman who detected a nodule at the junction of the lower quadrants of the right breast illustrates an atypical variant of this tumor subtype. Histological examination revealed two lesions displaying typical apocrine carcinomatous proliferation but with an unusual immunohistochemical profile: ER expression at 80%, PR expression at 5%, and human epidermal growth factor receptor 2 (HER2) overexpression. This deviation from the classical apocrine profile highlights the biological heterogeneity of these tumors and underscores the importance of thorough characterization to optimize therapeutic management.}, } @article {pmid40891975, year = {2025}, author = {Kim, HJ and Chae, EY and Eom, HJ and Choi, WJ and Shin, HJ and Cha, JH and Kim, HH}, title = {Node Reporting and Data System Evaluation of Axillary Nodes in Invasive Ductal and Lobular Carcinoma.}, journal = {Radiology}, volume = {316}, number = {3}, pages = {e243823}, doi = {10.1148/radiol.243823}, pmid = {40891975}, issn = {1527-1315}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/diagnostic imaging ; Middle Aged ; Axilla ; Retrospective Studies ; *Lymphatic Metastasis/diagnostic imaging/pathology ; *Carcinoma, Lobular/diagnostic imaging/pathology ; *Lymph Nodes/diagnostic imaging/pathology ; *Magnetic Resonance Imaging/methods ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Adult ; Aged ; Sensitivity and Specificity ; }, abstract = {Background Although the Node Reporting and Data System (Node-RADS) offers a standardized method for assessing lymph node metastasis, its performance may vary according to the histologic type of breast cancer. Purpose To evaluate the applicability of the Node-RADS score in assessing axillary lymph node involvement in patients with invasive ductal carcinoma (IDC) or invasive lobular carcinoma (ILC). Materials and Methods In this retrospective study, data from consecutive women with pathologically confirmed IDC or ILC who underwent preoperative breast MRI between January 2017 and December 2018 were analyzed. Axillary nodal status was assessed using Node-RADS, in which nodal size and configuration criteria are combined into a final assessment score ranging from 1 (very low suspicion) to 5 (very high suspicion). The performance of the Node-RADS score for predicting axillary lymph node metastasis was compared between the two histologic types using the χ[2] test. Results A total of 1602 women (mean age, 50.6 years ± 9.8 [SD]), including 25 with bilateral cancers, were included, yielding 1627 breast cancers. Among these cancers, 1486 were IDC and 141 were ILC. The frequency of lymph node metastasis was 25% (377 of 1486) for IDC and 28% (40 of 141) for ILC (P = .44). A Node-RADS score of 3 or greater yielded the highest Youden index for predicting axillary lymph node metastasis for both histologic types. At this cutoff, the sensitivity and specificity were 71.1% (268 of 377) and 86.5% (959 of 1109) for IDC and 52.5% (21 of 40) and 85.1% (86 of 101) for ILC, respectively. Although there was no evidence of a difference in specificity between the histologic types, sensitivity was significantly lower for ILC (P = .02). The area under the receiver operating characteristic curve (AUC) was 0.83 for IDC and 0.74 for ILC (P = .08). Multivariable logistic regression analyses confirmed Node-RADS score as an independent predictor of axillary lymph node metastasis (odds ratio, 3.1; P < .001). Conclusion The Node-RADS score demonstrated comparable performance in terms of AUC in axillary nodal evaluation for IDC and ILC but lower sensitivity for ILC. © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Freitas in this issue.}, } @article {pmid40888169, year = {2025}, author = {Zhou, S and Xiang, H and Huang, Z and Teng, Y and Xing, W}, title = {Feasibility and Prognostic Analysis of Neoadjuvant Therapy Followed by Breast-Conserving Surgery for Invasive Ductal Carcinoma Combined with Ductal Carcinoma in Situ.}, journal = {Journal of investigative surgery : the official journal of the Academy of Surgical Research}, volume = {38}, number = {1}, pages = {2547226}, doi = {10.1080/08941939.2025.2547226}, pmid = {40888169}, issn = {1521-0553}, mesh = {Humans ; Female ; *Breast Neoplasms/therapy/mortality/pathology ; *Mastectomy, Segmental/adverse effects ; Middle Aged ; Retrospective Studies ; *Neoadjuvant Therapy/adverse effects/methods ; *Carcinoma, Intraductal, Noninfiltrating/therapy/mortality/pathology ; Feasibility Studies ; *Carcinoma, Ductal, Breast/therapy/mortality/pathology ; Prognosis ; Adult ; *Neoplasm Recurrence, Local/epidemiology/prevention & control ; Aged ; Disease-Free Survival ; Treatment Outcome ; Breast/pathology/surgery ; }, abstract = {OBJECTIVE: This study aim to investigate the oncological safety of neoadjuvant therapy (NAT) followed by breast-conserving surgery (BCS) for invasive ductal carcinoma (IDC) patients with the presence of ductal carcinoma in situ (DCIS) on pre-NAT biopsy.

METHODS: The data of women with IDC who underwent radical surgery between January 2013 and December 2021 were retrospectively reviewed from two institutions. The study endpoints were 5-year disease-free survival (DFS) and local recurrence-fee survival (LRFS).

RESULTS: Overall, 994 eligible patients were enrolled. Patients with IDC with DCIS (n = 277) and patients undergoing BCS (n = 285) were selected separately for prognostic analysis. For patients with IDC with DCIS, the 5-year DFS (p = 0.517) and 5-year LRFS (p = 0.397) rates of the patients undergoing BCS were similar to those of patients undergoing mastectomy after propensity score matching. In addition, the 285 patients who underwent BCS were divided into the IDC + DCIS and IDC groups. The 5-year DFS (p = 0.394) and 5-year LRFS (p = 0.341) rates were similar between the IDC and IDC + DCIS groups.

CONCLUSION: NAT followed by BCS combined with adjuvant radiotherapy is a safe and feasible treatment option in patients with IDC with DCIS under the premise of strict adherence to the surgical indications and adequate incision margins.}, } @article {pmid40870508, year = {2025}, author = {Saray, S and Yılmaz, T and Kanmaz, H and İriağaç, Y}, title = {Androgen Receptor: Clinical Importance in Breast Cancer Patients Receiving CDK 4/6 Inhibitor Treatment.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {8}, pages = {}, pmid = {40870508}, issn = {1648-9144}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy ; Middle Aged ; *Receptors, Androgen/analysis ; Aged ; Adult ; *Cyclin-Dependent Kinase 4/antagonists & inhibitors/therapeutic use ; Cyclin-Dependent Kinase 6/antagonists & inhibitors/therapeutic use ; Prognosis ; Kaplan-Meier Estimate ; Retrospective Studies ; Protein Kinase Inhibitors/therapeutic use ; Receptors, Estrogen/analysis ; ROC Curve ; Clinical Relevance ; }, abstract = {Background and Objectives: The effect of AR expression on prognosis in hormone receptor-positive her2-negative breast cancer is controversial. There are studies showing that AR is a treatment target, a mechanism of resistance to endocrine treatments, and a prognostic indicator in these patients whose standard treatment is a CDK 4/6 inhibitor added to endocrine treatment. We aimed to investigate the effect of AR, the AR/ER ratio, and the AR/PR ratio on CDK4/6 inhibitor treatment response in breast cancer, as well as their effects on PFS, and to validate the hypothesis that AR is a target for research. Materials and Methods: Patients who were diagnosed with metastatic hormone receptor-positive her2-negative breast cancer and received cdk4/6 inhibitor + aromatase inhibitor in first-line therapy were included in this study conducted at Balıkesir Atatürk City Hospital. The tru-cut biopsy samples of the patients were evaluated immunohistochemically for AR, ER, and PR. Kaplan-Meier analysis was used to calculate the estimated median survival in PFS analyses, and the variables were compared with the Log-Rank test. Receiver Operating Characteristic (ROC) analysis was applied to determine the ideal cut-off. Cox regression analysis was used in univariate survival models, and the multivariate model was established with the "Forward: Likelihood Ratio (LR)" method. Hazard ratios (HRs) were also calculated as 95% confidence intervals (95% CIs). A p value below 0.05 was accepted for statistical significance. Results: In total, 41 patients were included in the study, and 73% (n = 30) of the patients were AR-positive. Increased AR (HR 1.014; 95% CI: 1.002-1.026; p = 0.023) was an unfavorable prognostic indicator. In our study, being ≥55 years old, being postmenopausal, not having visceral metastasis, having a non-IDC histology, having a low AR level (<50%), having an AR/ER ratio < 0.74, and having an AR/PR ratio < 1.00 were found to be associated with longer PFS. All factors were evaluated with univariate Cox regression analysis. Increasing AR (HR 1.014; 95% CI: 1.002-1.026; p = 0.023) was an unfavorable prognostic marker. Having an AR/ER ratio ≥ 0.74 (HR: 2.522; 95% CI: 1.004-6.336; p = 0.049) and having AR/PR ≥ 1 (HR: 2.659; 95% CI: 1.029-6.869; p = 0.043) were negative prognostic indicators. Conclusions: Our results were consistent with the literature and demonstrated the value of the androgen receptor as a therapeutic target, a mechanism explaining resistance to endocrine therapy, and an adverse prognostic indicator for creating resistance to endocrine therapy in breast cancer.}, } @article {pmid40868386, year = {2025}, author = {Liu, F and Chen, W and Zhang, J and Zou, J and Gu, B and Yang, H and Hu, S and Liu, X and Song, S}, title = {2.5D Deep Learning and Machine Learning for Discriminative DLBCL and IDC with Radiomics on PET/CT.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {12}, number = {8}, pages = {}, pmid = {40868386}, issn = {2306-5354}, support = {U23A2046//National Natural Science Foundation of China/ ; 82272035//National Natural Science Foundation of China/ ; 23DZ2291400//Shanghai Municipal Science and Technology Commission Projects/ ; 23TS1400800//Shanghai Municipal Science and Technology Commission Projects/ ; SACA-AX202316//Soaring Plan of the Anti-Cancer Association/ ; SHDC 12023103//Shanghai Shenkang Hospital Development Center Project/ ; }, abstract = {We aimed to establish non-invasive diagnostic models comparable to pathology testing and explore reliable digital imaging biomarkers to classify diffuse large B-cell lymphoma (DLBCL) and invasive ductal carcinoma (IDC). Our study enrolled 386 breast nodules from 279 patients with DLBCL and IDC, which were pathologically confirmed and underwent [18]F-fluorodeoxyglucose ([18]F-FDG) positron emission tomography/computed tomography (PET/CT) examination. Patients from two centers were separated into internal and external cohorts. Notably, we introduced 2.5D deep learning and machine learning to extract features, develop models, and discover biomarkers. Performances were assessed using the area under curve (AUC) and confusion matrix. Additionally, the Shapley additive explanation (SHAP) and local interpretable model-agnostic explanations (LIME) techniques were employed to interpret the model. On the internal cohort, the optimal model PT_TDC_SVM achieved an accuracy of 0.980 (95% confidence interval (CI): 0.957-0.991) and an AUC of 0.992 (95% CI: 0.946-0.998), surpassing the other models. On the external cohort, the accuracy was 0.975 (95% CI: 0.913-0.993) and the AUC was 0.996 (95% CI: 0.972-0.999). The optimal imaging biomarker PET_LBP-2D_gldm_DependenceEntropy demonstrated an average accuracy of 0.923/0.937 on internal/external testing. Our study presented an innovative automated model for DLBCL and IDC, identifying reliable digital imaging biomarkers with significant potential.}, } @article {pmid40868059, year = {2025}, author = {Pérez-Rodríguez, ND and Martín-Ramírez, R and González-Fernández, R and Maeso, MDC and Ávila, J and Martín-Vasallo, P}, title = {Functional Disruption of IQGAP1 by Truncated PALB2 in Two Cases of Breast Cancer: Implications for Proliferation and Invasion.}, journal = {Biomedicines}, volume = {13}, number = {8}, pages = {}, pmid = {40868059}, issn = {2227-9059}, support = {FIISIC EMER24/02//Gobierno de Canarias/ ; 87406381//Pfizer (General Research Pre-clinical/Clinical)/ ; }, abstract = {Background/Objectives: Truncating mutations in PALB2, a critical component of the BRCA1-PALB2-BRCA2 homologous recombination repair complex, are associated with increased risk and aggressiveness of breast cancer. The consequences of PALB2 truncation on the expression, localization, and functional dynamics of the scaffold protein IQGAP1 were investigated in this study based on two cases of truncated PALB2 human breast invasive ductal carcinoma (IDC), specifically, c.1240C>T (p.Arg414*) and c.2257C>T (p.Arg753*). Methods: Using confocal microscopy, we examined co-expression patterns of IQGAP1 with PALB2, PCNA, CK7, and β-tubulin in tumor tissues from both control cancer and PALB2-mutated cases. Results: In PALB2-truncated tumors, IQGAP1 exhibited enhanced peripheral and plasma membrane localization with elevated co-localization levels compared to controls, suggesting altered cytoskeletal organization. PALB2 truncation increased nuclear and cytoplasmic N-terminal PALB2 immunoreactivity, indicating the presence of truncated isoforms disrupting the homologous recombination repair system. Co-expression analyses with PCNA revealed an inverse expression pattern between IQGAP1 and proliferation markers, suggesting S-phase cell cycle-dependent heterogeneity. Furthermore, the loss of IQGAP1 dominance over CK7 and β-tubulin in mutant tumors, along with persistent intercellular spacing, implied a loss of cell-cell cohesion and the acquisition of invasive traits. Conclusions: These data support a model where PALB2 truncation triggers a reorganization of IQGAP1 that disrupts its canonical structural functions and facilitates tumor progression via enhanced motility and impaired cell-cell interaction. IQGAP1 thus serves as both a functional effector and potential biomarker in PALB2-mutated IDC, opening novel paths for diagnosis and targeted therapeutic intervention.}, } @article {pmid40881883, year = {2025}, author = {Xing, C and Li, P and Yang, S and Man, Q and Zhang, X and Yuan, Q and Hu, M and Bai, Y and Zhang, K}, title = {Investigation of the efficacy and safety of lung biopsy plus microwave ablation for a solitary suspected malignant pulmonary nodule after radical mastectomy.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1525114}, pmid = {40881883}, issn = {2234-943X}, abstract = {PURPOSE: To evaluate the safety and efficacy of CT-guided lung biopsy combined with microwave ablation (MWA) for solitary suspected malignant pulmonary nodules in post-radical surgery breast cancer patients.

MATERIALS AND METHODS: This retrospective study included 37 post-radical surgery breast cancer patients with solitary suspected malignant pulmonary nodules, treated with CT-guided lung biopsy and MWA between January 2014 and December 2018. Institutional review board approval was obtained. Clinical outcomes and complications were analyzed.

RESULTS: Pathological results identified primary lung cancer in 5 patients (13.5%, 5/37) and metastatic invasive ductal carcinoma (breast origin) in 30 patients (81.1%, 30/37). Major complications included pneumothorax (n=8, 21.6%), chest pain (n=6, 16.2%), and hemoptysis (n=4, 10.8%). For metastatic cases, 2-, 3-, and 5-year survival rates were 86.2%, 58.3%, and 35.3%, respectively. The median progression-free survival after MWA was 35 months (range: 4-72; 95% CI: 24.53-46.48), and median overall survival was 44 months (95% CI: 32.55-55.45).

CONCLUSION: CT-guided lung biopsy combined with MWA is a safe and effective approach for managing solitary suspected malignant pulmonary nodules in post-radical surgery breast cancer patients.}, } @article {pmid40877724, year = {2026}, author = {Chu, C and Goldman, J and Joung, H and Go, S and Jones, R and Stranix, JT}, title = {Breast Cancer Incidence Among Patients Undergoing Chest Masculinization Surgery: A Scoping Review.}, journal = {Annals of surgical oncology}, volume = {33}, number = {1}, pages = {138-145}, pmid = {40877724}, issn = {1534-4681}, mesh = {Humans ; *Breast Neoplasms/epidemiology/surgery/pathology ; Incidence ; Male ; Female ; *Gender-Affirming Surgery/adverse effects ; *Mastectomy ; *Transgender Persons/statistics & numerical data ; Prognosis ; United States/epidemiology ; }, abstract = {BACKGROUND: The incidence of breast cancer (BC) cases among transgender males undergoing gender-affirming mastectomy (GAM) and the future BC risk for this population are not well established. This scoping review aimed to explore breast cancer incidence rates before and after GAM in the United States.

METHODS: Following the Arskey and O'Malley framework, the search was conducted in Embase and PubMed using keywords "gender-affirming surgery" and "breast cancer." The initial search resulted in 405 articles, with 36 articles imported to Covidence for the screening and selection phase. The articles were limited to the United States alone and within the last 10 years.

RESULTS: For final inclusion, 13 articles were identified (11 observational/retrospective cohort studies and 2 case studies). Across all the studies, 42 cases of atypia, 6 cases of ductal carcinoma in situ (DCIS), 1 case of Paget's disease, and 10 cases of invasive ductal carcinoma (IDC) were reported. Nine studies reviewed routine GAM surgical specimens (3869 cases), identifying 42 cases of atypia, 5 cases of DCIS, 1 case of Paget's disease, and 3 cases of IDC. Seven invasive carcinomas and one DCIS case were detected pre-GAM during screening and involved concurrent treatment from breast and plastic surgery teams.

CONCLUSIONS: Standardization and best-practice screening protocols, including breast imaging before GAM and pathology performed on specimens collected during GAM, are needed. A shared decision-making approach and clinical coordination, including breast and plastic surgery for patients who receive a breast cancer diagnosis while pursuing GAM, can help achieve oncologic and cosmetic goals.}, } @article {pmid40852646, year = {2025}, author = {Elias, TM and Desa, DE and Brown, EB and Paul, S and Ramirez, GA and Turner, BM and Madden, K and Gonzalez, RS and Weiss, A and Brown, EB}, title = {Exploring racial differences in second-harmonic-generation-based prognostic indicators of metastasis in breast and colon cancer.}, journal = {Biophotonics discovery}, volume = {2}, number = {2}, pages = {}, pmid = {40852646}, issn = {3005-4745}, support = {R21 CA208921/CA/NCI NIH HHS/United States ; }, abstract = {SIGNIFICANCE: Second-harmonic generation (SHG) analysis of collagen internal structure and overall organization in the tumor microenvironment may enhance current metastasis prediction methods, which do not prognosticate with the same accuracy for patients of different races. For these optical tools to be clinically available, a multicenter trial is needed. We investigate if SHG-based prognostic signals vary with patient race, providing insight for designing such a trial.

AIM: SHG imaging was performed on colon adenocarcinoma (CRC) and invasive ductal carcinoma (IDC) patient samples to derive two prognostic indicators. We assessed the association between these indicators and patient race.

APPROACH: SHG images were analyzed as previously described to determine the forward- to backward-SHG scattering ratio (F/B) and fiber angle variability (FAV). Both prognostic measurements were compared between Black and White patients.

RESULTS: In the IDC cohort, F/B from the tumor-stroma interface differed significantly between demographic groups. For the CRC cohort, a trend was observed in the tumor-stroma interface and tumor bulk. FAV did not vary by race in either cohort.

CONCLUSIONS: F/B variation with patient race suggests the relationship between F/B and metastatic outcome may vary with patient race. These findings highlight the potential need for race-specific prognostic algorithms to improve metastasis prediction for all patients.}, } @article {pmid40875574, year = {2025}, author = {Perez, A and Schaverien, MV and George-Palop, M and Chang, EI and Barcenas, CH and Viola, GM}, title = {The Impact of Vascularized Lymph Node Transfer in Reducing the Rate of Cellulitis in Patients with Breast Cancer-Related Lymphedema.}, journal = {Plastic and reconstructive surgery}, volume = {}, number = {}, pages = {}, doi = {10.1097/PRS.0000000000012412}, pmid = {40875574}, issn = {1529-4242}, abstract = {BACKGROUND: Poorly managed breast cancer-related lymphedema (BCRL) may lead to recurrent cellulitis. Advances in the management of lymphedema have evolved beyond conservative decongestive therapy to include vascularized lymph node transfer (VLNT). Herein, we analyzed the impact of VLNT in the reduction of upper extremity cellulitis in breast cancer survivors.

METHODS: We reviewed all patients at our institution who had breast cancer, underwent mastectomy, experienced upper extremity lymphedema, and proceeded with VLNT from 2017 to 2021. Patients were included if they had 1 or more episodes of cellulitis within the year prior to VLNT and were followed for at least 12 months.

RESULTS: We included 66 patients that fulfilled our strict inclusion criteria with a median age of 57 years (IQR, 23-76 years). All patients were female and most were White (88%), with a mean (± SD) body mass index of 29.4 ± 6.7 kg/m2. Many presented with invasive ductal carcinoma (82%), had axillary lymph node dissection (98%), received chemotherapy (94%) and radiation therapy (86%). VLNT was performed at a median of 92 months after mastectomy (IQR, 32-156 months). Overall, 58 (88%) patients remained infection-free with an infection rate decrease from an average of 2.27 before the index VLNT to 0.17 (P < .0001) after VLNT.

CONCLUSIONS: VLNT is associated with significantly decreased cellulitis rates and should be considered as part of the infectious diseases armamentarium for the treatment of recurrent upper extremity cellulitis due to BCRL without adequate clinical improvement to conservative management alone.}, } @article {pmid40873579, year = {2025}, author = {Baena, JC and Victoria, JS and Toro-Pedroza, A and Aragón, CC and Ortiz-Guzman, J and Garcia-Robledo, JE and Torres, D and Rios-Serna, LJ and Albornoz, L and Rosales, JD and Cañas, CA and Adolfo Cruz-Suarez, G and Osorio, FO and Fleitas, T and Laponogov, I and Loukanov, A and Veselkov, K}, title = {Smart CAR-T Nanosymbionts: archetypes and proto-models.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1635159}, pmid = {40873579}, issn = {1664-3224}, mesh = {Humans ; *Immunotherapy, Adoptive/methods ; *Receptors, Chimeric Antigen/immunology/genetics ; Animals ; *Nanoparticles ; Artificial Intelligence ; Precision Medicine/methods ; *Neoplasms/therapy/immunology ; Nanotechnology/methods ; }, abstract = {Personalized medicine has redefined cancer treatment by aligning therapies with each patient's unique biological profile. A key example is chimeric antigen receptor T-cell (CAR-T) therapy, in which a patient's own T cells are genetically modified to recognize and destroy cancer cells. This approach has delivered remarkable results in hematologic malignancies and is beginning to show promise in solid tumors and autoimmune diseases. However, its broader adoption is limited by major challenges, including complex manufacturing, high costs, limited efficacy in solid tumors, and potentially severe toxicities. Nanotechnology offers exciting possibilities to overcome many of these barriers. Engineered nanoparticles can improve gene delivery, target tumors more precisely, enhance immune cell function, and enable in vivo CAR-T production, reducing the need for labor-intensive ex vivo processes. However, despite this promise, translation into clinical settings remains difficult due to regulatory hurdles, scalability issues, and inconsistent reproducibility in human models. At the same time, artificial intelligence (AI), with its powerful algorithms for data analysis and predictive modeling, is transforming how we design, evaluate, and monitor advanced therapies, including the optimization of manufacturing processes. In the context of CAR-T, AI holds strong potential for better patient stratification, improved prediction of treatment response and toxicity, and faster, more precise design of CAR constructs and delivery systems. Leveraging these three technological pillars, this review introduces the concept of Smart CART Nanosymbionts, an integrated framework in which AI guides the design and deployment of nanotechnology-enhanced CAR-T therapies. We explore how this convergence enables optimization of lipid nanoparticle formulations for mRNA transfection, specific targeting and modification of the tumor microenvironment, real-time monitoring of CAR-T cell behavior and toxicity, and improved in vivo CAR-T generation and overcoming barriers in solid tumors. Finally, it's important we also address the ethical and regulatory considerations surrounding this emerging interface of living therapies and computational driven systems. The Smart CART Nanosymbionts framework (Figure 1:) represents a transformative step forward, promising to advance personalized cancer treatment toward greater precision, accessibility, and overall effectiveness.}, } @article {pmid40865509, year = {2025}, author = {Yoneyama, K and Nakagawa, M and Hara, A}, title = {A case report of male breast cancer treated with breast-conserving surgery.}, journal = {International journal of surgery case reports}, volume = {135}, number = {}, pages = {111804}, pmid = {40865509}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Male breast cancer is a rare disease that accounts for less than 1 % of all breast cancer cases. The most common surgical treatment for male breast cancer is mastectomy, but breast-conserving surgery has been performed increasingly in recent years. This report describes a case of male breast cancer that was treated by breast-conserving surgery.

CASE PRESENTATION: A 61-year-old man visited our hospital complaining of a painless mass in his left breast. Imaging revealed a well-defined cystic mass, aspiration of which revealed bloody fluid. Cytology was inconclusive, but the findings were suggestive of malignancy. A left lumpectomy was performed for diagnostic purposes. Postoperative pathology revealed invasive ductal carcinoma with a predominant intraductal component. The surgical margins were negative. The patient declined adjuvant hormone therapy and radiotherapy and has been kept under follow-up in the year since surgery. There has been no recurrence during this time.

CLINICAL DISCUSSION: As in women, the goals of treatment for breast cancer in men are oncological safety and satisfactory cosmetic results. In the absence of specific guidelines for the treatment of male breast cancer, mastectomy is currently the standard treatment. However, in recent years, breast-conserving surgery has been performed for tumors that are discovered early and do not invade the nipple and areola. If curability and safety can be guaranteed, breast-conserving surgery can be considered for male breast cancer.

CONCLUSION: Breast-conserving surgery can be an effective treatment option in men with breast cancer.}, } @article {pmid40863403, year = {2025}, author = {Roshan, M and Mudrack, C and Sulaj, A and von Rauchhaupt, E and Fleming, T and Schimpfle, L and Seebauer, L and Flegka, V and Longo, VD and Kliemank, E and Herzig, S and Hohneck, A and Kender, Z and Szendroedi, J and Kopf, S}, title = {Exploring the Relationship Between Insulin Resistance, Liver Health, and Restrictive Lung Diseases in Type 2 Diabetes.}, journal = {Journal of personalized medicine}, volume = {15}, number = {8}, pages = {}, pmid = {40863403}, issn = {2075-4426}, support = {Collaborative Research Center 1118 (CRC1118)//Federal Ministry for Research (BMBF)/German Center for Diabetes Research (DZD), and by the Deutsche Forschungsgemeinschaft (DFG)./ ; }, abstract = {Background: Restrictive lung disease (RLD) is a potential complication in type 2 diabetes (T2D), but its relationship with insulin resistance and liver-related metabolic dysfunction remains unclear. This study evaluated the association between lung function and metabolic markers in T2D and retrospectively assessed whether metabolic improvements from dietary intervention were accompanied by changes in lung function. Methods: This cross-sectional analysis included 184 individuals (101 with T2D, 33 with prediabetes, and 50 glucose-tolerant individuals). Lung function parameters-vital capacity (VC), total lung capacity by plethysmography (TLC-B), and diffusion capacity for carbon monoxide (TLCO)-were assessed alongside metabolic markers including HOMA2-IR, fatty liver index (FLI), NAFLD score, and Fibrosis-4 index (FIB-4). In a subset of 54 T2D participants, lung function was reassessed after six months following either a fasting-mimicking diet (FMD, n = 14), Mediterranean diet (n = 13), or no dietary intervention (n = 27). Results: T2D participants had significantly lower VC and TLC-B compared to glucose-tolerant and prediabetic individuals, with 18-21% falling below clinical thresholds for RLD. Lung volumes were negatively correlated with HOMA2-IR, FLI, NAFLD score, and FIB-4 across the cohort and within the T2D group. Although the FMD intervention led to significant improvements in HOMA2-IR and FLI, no corresponding changes in lung function were observed over the six-month period. Conclusions: Restrictive lung impairment in T2D is associated with insulin resistance and markers of liver steatosis and fibrosis. While short-term dietary interventions can improve metabolic parameters, their effect on lung function may require a longer duration or additional interventions and targeted follow-up. These findings highlight the relevance of pulmonary assessment in individuals with metabolic dysfunction.}, } @article {pmid40863096, year = {2025}, author = {Cioroianu, RA and Schenker, M and Rădulescu, VM and Berisha, TC and Cioroianu, GO and Popescu, M and Ciofiac, CM and Petrescu, AM and Mogoantă, SȘ}, title = {Therapeutic Patterns and Surgical Decision-Making in Breast Cancer: A Retrospective Regional Cohort Study in Romania.}, journal = {Clinics and practice}, volume = {15}, number = {8}, pages = {}, pmid = {40863096}, issn = {2039-7275}, abstract = {Background: Breast cancer is the most prevalent malignancy among women globally. In Romania, it is the most frequent form of cancer affecting women, with approximately 12,000 new cases diagnosed annually, and the second most common cause of cancer-related mortality, second only to lung cancer. Methods: This study looked at 79 breast cancer patients from Oltenia, concentrating on epidemiology, histology, diagnostic features, and treatments. Patients were chosen based on inclusion criteria such as histopathologically verified diagnosis, availability of clinical and treatment data, and follow-up information. The analyzed biological material consisted of tissue samples taken from the breast parenchyma and axillary lymph nodes. Even though not the primary subject of this paper, all patients underwent immunohistochemical (IHC) evaluation both preoperatively and postoperatively. Results: We found invasive ductal carcinoma to be the predominant type, while ductal carcinoma in situ (DCIS) and mixed types were rare. We performed cross-tabulations of metastasis versus nodal status and age versus therapy type; none reached significance (all p > 0.05), suggesting observed differences were likely due to chance. A chi-square test comparing surgical interventions (breast-conserving vs. mastectomy) in patients who did or did not receive chemotherapy showed, χ[2] = 3.17, p = 0.367, indicating that chemotherapy did not significantly influence surgical choice. Importantly, adjuvant chemotherapy and radiotherapy were used at similar rates across age groups, whereas neoadjuvant hormonal (endocrine) therapy was more common in older patients (but without statistical significance). Conclusions: Finally, we discussed the consequences of individualized care and early detection. Romania's shockingly low screening rate, which contributes to delayed diagnosis, emphasizes the importance of improved population medical examination and tailored treatment options. Also, the country has one of the lowest rates of mammography uptake in Europe and no systematic population screening program.}, } @article {pmid40861718, year = {2025}, author = {Kawthalkar, A and Nayak, S and Jaiswal, K}, title = {Cytology in Mucinous Breast Carcinoma: Diagnostic Insights and a Rare Bilateral Case.}, journal = {Cureus}, volume = {17}, number = {7}, pages = {e88670}, pmid = {40861718}, issn = {2168-8184}, abstract = {Introduction Cytological evaluation of breast lumps is often conducted as part of the triple test for breast carcinomas and provides a confirmation of the clinical and radiological diagnosis. Mucinous carcinomas of the breast, while a relatively rare entity, are important to recognize due to their favorable prognosis. The present research has been designed to study and highlight the specific cytological features of mucinous carcinoma of the breast as well as present a rare case of cytologically diagnosed bilateral breast mucinous carcinoma. Materials and methods A two-year retrospective analysis of cytologically diagnosed and histopathologically confirmed cases of mucinous carcinoma of the breast was conducted. Relevant clinical and radiological details were noted and included in the study. All slides were assessed for specific features that assist in the final diagnosis of mucinous carcinoma based on cytology alone. Results A total of seven cases of mucinous carcinoma of the breast in a span of two years were identified on cytology. Fine-needle aspiration cytology (FNAC) yielded mucoid material in all cases. Abundant extracellular mucin was observed in all cases. In all cases, there was abundant cellularity. Most of the epithelial cells were seen to be arranged predominantly in clusters. In all cases, cells were uniform and had a moderate amount of cytoplasm and a round nucleus showing mild atypia. Branching, delicate capillary fragments (chicken-wire vascularity) were noted in six (85%) cases. Histopathological correlation was available for all cases, confirming mucinous carcinoma. There was a single case of metachronous bilateral breast mucinous carcinomas, with the right and left breast lesions being palpable five and three years back, respectively, by the patient. Discussion The mean size, age group, and cytological features were consistent with the findings of previous studies. Typically, pure mucinous subtypes show abundant extracellular mucin with floating islands and isolated tumor cells within on histopathology. Mixed mucinous carcinomas often show more solid areas with an invasive ductal carcinoma component. In the present study, there was a single case of bilateral mucinous carcinoma of the breast, making it only the third case to be reported so far. To the best of our knowledge, it is the first case of mucinous carcinoma presenting in bilateral breasts to be reported on FNAC. Conclusion Strict adherence to the above diagnostic cytologic criteria, which includes abundant pools of mucin, tight clusters of epithelial cells exhibiting mild atypia, and branching capillaries, is the key to a confident diagnosis of mucinous carcinoma of the breast on cytology. Though extremely rare, bilateral mucinous carcinoma of the breast does occur and can be reliably diagnosed on cytology.}, } @article {pmid40860639, year = {2025}, author = {Jassim, GA and AlMohri, MA and AlAsoomi, HY and AlNooh, A and AlDoseri, SF}, title = {Performance Metrics of Mammography Screening Programmes in Primary Health Care Centres in Bahrain.}, journal = {International journal of women's health}, volume = {17}, number = {}, pages = {2583-2593}, pmid = {40860639}, issn = {1179-1411}, abstract = {BACKGROUND: Mammography is the cornerstone of breast cancer screening. Its diagnostic performance, however, is influenced by population demographics such as age and breast density.

PURPOSE: The aim of this study was to establish contemporary performance benchmarks for mammography screening in Bahrain's primary health-care centres (PHCs) and to identify areas for quality improvement.

METHODS: A cross-sectional retrospective analysis was performed on mammograms from asymptomatic women aged ≥40 years who were screened in 2020 at primary health care centres. Screening outcomes were cross-referenced with subsequent breast cancer diagnoses recorded in the Bahrain Cancer Registry (2021-2022). Mammographic findings were categorised using the Breast Imaging Reporting and Data System (BI-RADS), and performance metrics including the cancer detection rate (CDR), sensitivity, and specificity were calculated.

RESULTS: A total of 2196 screening mammograms were included, with a mean patient age of 56.1 years. The cancer detection rate was 12.3 per 1000 screens, and the recall rate was 30.6%. Sensitivity and specificity were 69.2% and 71.2%, respectively, and the interval cancer rate was 5.4 per 1000. The most common breast density category was "scattered fibroglandular" (61.8%). Recall rates were significantly associated with breast density (p < 0.001). Among the 39 patients diagnosed with breast cancer, invasive ductal carcinoma was the most prevalent subtype (71.8%).

CONCLUSION: The findings highlight the moderate utility of mammography screening in Bahrain, characterised by a relatively high recall rate and a need to optimise reporting standards and recall criteria. Tailored strategies such as supplemental imaging for women with dense or high-risk breasts, strict adherence to BI-RADS guidelines, and implementing double reading or single reading with computer-aided detection could improve screening outcomes. These results establish important regional performance benchmarks and can inform policies to enhance breast cancer detection and management in the Arabian Gulf region.}, } @article {pmid40858478, year = {2026}, author = {Garcia-Tejedor, A and Julià, C and Ciria, J and Guevara-Peralta, R and Ortega-Expósito, C and Ortega, R and Stradella, A and Pérez-Montero, H and Reyes-Juncan, G and Benitez, A and Guma, A and Azcarate, J and Campos, M and Plà, MJ and Martinez, E and Pernas, S and Ponce, J and Falo, C}, title = {Prognostic Outcomes by Axillary Approach in Lobular and Ductal Breast Cancer With Sentinel Node Macrometastases: A Retrospective Cohort Study.}, journal = {Clinical breast cancer}, volume = {26}, number = {1}, pages = {262-275}, doi = {10.1016/j.clbc.2025.07.022}, pmid = {40858478}, issn = {1938-0666}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/mortality/surgery ; Retrospective Studies ; *Sentinel Lymph Node Biopsy ; *Carcinoma, Lobular/mortality/pathology/surgery ; Middle Aged ; Axilla ; *Carcinoma, Ductal, Breast/mortality/pathology/surgery ; Prognosis ; Lymphatic Metastasis/pathology ; *Sentinel Lymph Node/pathology/surgery ; Aged ; Lymph Node Excision/statistics & numerical data ; Adult ; Follow-Up Studies ; Mastectomy/statistics & numerical data ; Neoplasm Staging ; Survival Rate ; }, abstract = {PURPOSE: To compare survival outcomes between patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma non-special type (NST) presenting with sentinel lymph node biopsy (SLNB)-detected macrometastases in early-stage breast cancer.

MATERIALS AND METHODS: A retrospective cohort study was conducted including 364 cN0 breast cancer patients with SLNB-detected macrometastases who underwent surgical treatment between July 2011 and December 2023. Patients were categorized as NST (n = 250) or ILC (n = 108). SLNB was the primary axillary staging procedure, with axillary lymph node dissection (ALND) performed according to predefined clinical criteria. Univariate and multivariate Cox regression analyses were used to identify predictors of pN2-pN3. Survival outcomes were assessed using Kaplan-Meier curves and compared with log-rank tests.

RESULTS: ILC patients presented with larger tumors, higher rates of multifocality, and greater axillary nodal involvement compared to NST. Surgery was more frequently mastectomy and ALND. pN2-N3 was identified in 12% of cases, with pT3 stage, ILC histology, and lymphovascular invasion as independent predictors. After a median follow-up of 7.6 years, the ILC group exhibited higher overall mortality (19.4% vs. 9.6%) and deaths attributed to systemic progression (57% vs. 29%). Ten-year distant disease-free survival and breast cancer-specific survival were significantly lower in the ILC cohort (63% vs. 87% and 65% vs. 93%, respectively; P < .05). Although 10-year overall survival was lower in ILC (54% vs. 79%), statistical significance was only observed in patients with advanced nodal disease (pN2-N3).

CONCLUSIONS: ILC is associated with more advanced axillary burden and significantly worse long-term oncologic outcomes compared to NST carcinoma when macrometastases are present at SLNB.}, } @article {pmid40849879, year = {2025}, author = {Oolbekkink, S and Wolthaus, JWH and van Asselen, B and Stijnman, PRS and Raaymakers, BW}, title = {Development and demonstration of end-to-end testing for intra-fraction motion-managed workflows.}, journal = {Medical physics}, volume = {52}, number = {9}, pages = {e18042}, pmid = {40849879}, issn = {2473-4209}, support = {18495//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; }, mesh = {*Workflow ; Movement ; Radiotherapy Planning, Computer-Assisted/methods ; Radiotherapy Dosage ; Humans ; Radiometry ; }, abstract = {BACKGROUND: Intra-fraction motion management techniques, including beam gating and intra-fraction drift correction (IDC), have recently been introduced on the Unity MR-linac (Elekta AB, Stockholm, Sweden) to mitigate the dosimetric impact of motion during treatment. However, residual motion (e.g., within the gating window) still affects the delivered dose, causing deviations from the statically planned dose. Conventional end-to-end (E2E) testing does not incorporate such (known) motion, hampering evaluation of motion managed workflows.

PURPOSE: This study develops and demonstrates novel methods that incorporate known motion before treatment delivery. Using such a reference dose distribution allows for E2E testing of intra-fraction motion-managed workflows.

METHODS: A novel approach was developed to assess the E2E accuracy for motion-managed delivery techniques by comparing the measured dose distribution to a reference dose distribution that incorporates the applied motion during the delivery. Two motion-included reference dose distributions were generated and evaluated: (1) A Priori Motion-Included (APriMI) dose distribution which uses the known (periodic) motion to estimate the influence of anatomical motion on the dose distribution, and incorporates this into a new dose distribution; and (2) the Posteriori Motion-Included (PostMI) dose distribution, which adds an external trigger to relate the beam-on/off time to the motion of the setup. This allows for evaluation of non-periodic motion, or a drift motion during IDC workflows. In addition to these, the conventionally used static treatment planning system (TPS) dose distribution was used as a reference dose distribution. Several scenarios were evaluated: static (no phantom motion), two unmanaged, and two motion-managed scenarios using the Comprehensive Motion Management (CMM) software (Elekta AB, Stockholm, Sweden) for gated and IDC workflows, with cos 4 $\mathrm{cos^4}$ and linear drift motion patterns. All measurements were performed on a clinical Unity MR-linac equipped with CMM software, using film dosimeters for high spatial resolution dose distribution assessment. The geometric and dosimetric E2E accuracy of the workflow were evaluated for all scenarios.

RESULTS: First, the static benchmark scenario was evaluated and showed high agreement between the measured dose distribution and all reference dose distributions (i.e., static, APriMI, and PostMI). For the motion-included scenarios, excellent agreement was observed between the measured and calculated dose distributions in both unmanaged and managed cases when using either APriMI or PostMI. The largest geometric shift in the motion included scenarios was 0.3 mm, comparable to the static scenario. Dosimetric accuracy, evaluated using a global gamma index (2%/2 mm), exceeded 95.5%. As expected, larger deviations occurred when the static dose distribution was used as a reference, with geometric shifts up to 9.0 mm and gamma pass rates as low as 17.8%.

CONCLUSIONS: E2E testing of intra-fraction motion-managed workflows is possible using APriMI and PostMI dose distributions. Strong agreement was observed with these motion-included distributions, while larger deviations were seen with the static dose distribution. These findings highlight the need for reference dose files that account for actual motion in the measurement setup to assess E2E accuracy of motion-included workflows.}, } @article {pmid40841699, year = {2025}, author = {SeyedForootan, F and Mahdavi, N and Koopaie, M}, title = {Mandibular metastasis of invasive ductal carcinoma of the breast: a case report.}, journal = {Journal of medical case reports}, volume = {19}, number = {1}, pages = {423}, pmid = {40841699}, issn = {1752-1947}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/pathology ; *Mandibular Neoplasms/secondary/diagnostic imaging ; *Carcinoma, Ductal, Breast/secondary/pathology ; *Mandibular Fractures/etiology/diagnostic imaging ; Lung Neoplasms/secondary ; Liver Neoplasms/secondary ; Fatal Outcome ; *Fractures, Spontaneous/etiology ; }, abstract = {BACKGROUND: Metastasis of breast carcinoma to the oral cavity is an uncommon event, and mandibular involvement is even rarer. This case is notable owing to the delayed occurrence of mandibular metastasis 6 years after the primary diagnosis, highlighting its aggressive behavior, which resulted in a pathological mandibular fracture. Reporting such rare presentations can aid clinicians in identifying atypical metastatic patterns in breast cancer survivors.

CASE PRESENTATION: A 45 year-old Persian female with a history of invasive ductal breast carcinoma, diagnosed initially and treated 6 years earlier, presented with facial swelling and pain in the left lower jaw. She had been receiving bisphosphonate therapy for bone metastases. Clinical and radiographic evaluations revealed a radiolucent mandibular lesion with cortical bone perforation. Histopathological and immunohistochemical analyses confirmed metastasis from the primary breast cancer. Despite subsequent radiotherapy and chemotherapy, the lesion progressed, resulting in a pathological mandibular fracture and further metastases to the lungs and liver.

CONCLUSION: This case underscores the importance of considering metastatic disease in diagnosing oral lesions in patients with a history of malignancy. Early recognition of atypical presentations such as mandibular metastasis may facilitate timely intervention, although prognosis remains poor in such advanced stages.}, } @article {pmid40849199, year = {2025}, author = {Tank, P and Vora, S and D'Souza, F and Kamble, SS and Rameshkumar, N}, title = {Advanced mass spectrometry techniques for monitoring biopharmaceutical host cell proteins.}, journal = {Trends in biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tibtech.2025.07.026}, pmid = {40849199}, issn = {1879-3096}, abstract = {Residual host cell proteins (HCPs) in biologic drug products can compromise safety or stability and must be carefully monitored. While traditional immunoassays remain essential, they often lack specificity or coverage. Mass spectrometry (MS) offers a complementary approach by enabling direct identification and quantification of individual HCPs throughout development. This review highlights recent advances in MS technologies and workflows relevant to HCP detection, including new data acquisition strategies, software tools, and artificial intelligence applications. We also discuss regulatory perspectives and considerations for implementing MS in controlled environments. By integrating analytical innovations with risk-based strategies, MS-based approaches are becoming key components of modern biopharmaceutical quality control.}, } @article {pmid40840868, year = {2025}, author = {Chilumukuru, NS and Priyadarshini, P and Ezunkpe, Y}, title = {Deep Learning for the Early Detection of Invasive Ductal Carcinoma in Histopathological Images: Convolutional Neural Network Approach With Transfer Learning.}, journal = {JMIR formative research}, volume = {9}, number = {}, pages = {e62996}, pmid = {40840868}, issn = {2561-326X}, mesh = {Humans ; *Deep Learning ; Female ; *Breast Neoplasms/diagnosis/pathology ; *Carcinoma, Ductal, Breast/diagnosis/pathology ; *Early Detection of Cancer/methods ; *Neural Networks, Computer ; Convolutional Neural Networks ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is considered the most common form of breast cancer, accounting for a significant percentage of mortality worldwide. Therefore, its early detection is vital to further improve patients' outcomes and survival rates. However, conventional diagnostic methods in the form of manual histopathological examinations are time-consuming, subjective, and prone to errors. Therefore, there is an urgent need to develop automated solutions for accurate IDC detection in histopathology images to assist pathologists in clinical decision-making.

OBJECTIVE: We aim to develop and validate a convolutional neural network (CNN) model for early detection of IDC by analyzing histopathological images. The specific objectives are designing a deep learning-based technique for automated detection of IDC, assessing its performance compared to traditional diagnostic methods, and evaluating its utility in a clinical setup for early breast cancer diagnosis. These methods will be available to practitioners in underdeveloped countries via an open-source application.

METHODS: The dataset for the research included 277,524 publicly available histopathological images from Kaggle, comprising both IDC-positive and IDC-negative images. About 71.6% of images were IDC-positive (class 0), while 28.4% were IDC-negative (class 1). Since our data are unbalanced, we created a weighted loss function to overcome the class imbalance problem. Further development was based on a CNN using the approach of transfer learning with a pretrained architecture called Visual Geometry Group to uplift feature extraction so that performance may improve; hence, images were preprocessed and normalized to perform augmentation with robustness. The model was developed using a split of 80% for training and 20% for testing. Model performance was measured for accuracy, sensitivity, specificity, precision, recall, and F1-score in the confusion matrix and classification report.

RESULTS: From our CNN base model, we obtained an accuracy of 89% on the test set. Later, the base model was used with a weighted loss function to balance the class weights, giving a lower accuracy of 86% on the test set. Data augmentation was performed but did not improve the results. To deal with the class imbalance effectively, we performed transfer learning with a pretrained model, which gave an accuracy of 90% on the test set.

CONCLUSIONS: The CNN-based model thus showed accuracy and reliability for early detection of IDC from histopathological images. This technique will potentially act as an efficient and accurate assistant tool for pathologists, contributing to the early diagnosis of breast cancer and improving clinical outcomes. This paper provides an important contribution toward refining the performance of this model and widening its applications in a clinical setting by integrating it with other diagnostic techniques for better outcomes.}, } @article {pmid40836963, year = {2025}, author = {Osman, H and Hassan, M and Alfaki, M and Haj-Ali, G}, title = {Association between VEGF gene polymorphisms and breast cancer risk.}, journal = {Biochemistry and biophysics reports}, volume = {43}, number = {}, pages = {102202}, pmid = {40836963}, issn = {2405-5808}, abstract = {INTRODUCTION: Breast cancer (BC) poses a significant global health challenge. In Sudan, the absence of a national cancer registry has resulted in an underestimation of BC incidence. BC is notably the most common cancer among Sudanese women, especially affecting those under 50, with many cases diagnosed at advanced stages. Angiogenesis, driven by vascular endothelial growth factor (VEGF), plays a critical role in the progression and recurrence of BC. This study examines the relationship between the VEGF (rs699947) gene polymorphism and BC among Sudanese women in Khartoum State in 2022. Methodology: A case-control study was conducted with 30 BC patients, and tissue samples were collected for molecular analysis. DNA was extracted and genotyped for the VEGF (rs699947) polymorphism using allele-specific PCR.

RESULTS: No statistically significant association was found between the VEGF-2578 C > A polymorphism and BC risk in our study population. Although the A allele was more prevalent in tumor tissues compared to normal tissues, with no significant correlation with tumor stage or grade. The study revealed that BC in Sudanese women often presents at younger ages and is predominantly invasive ductal carcinoma, with stage II being the most common.

CONCLUSION: These findings emphasize the necessity for continued research to explore additional genetic factors and improve our understanding of BC and associated risks. Advancing early detection and prevention methods is vital, particularly for underrepresented populations. However, the small sample size in this study may limit the statistical power to detect significant associations, and thus, findings should be interpreted with caution.}, } @article {pmid40835571, year = {2025}, author = {Xu, W and Deng, S and Mao, G and Wang, N and Huang, Y and Zhang, C and Sa, G and Wu, S and An, Y}, title = {Differentiation of Suspicious Microcalcifications Using Deep Learning: DCIS or IDC.}, journal = {Academic radiology}, volume = {32}, number = {11}, pages = {6612-6622}, doi = {10.1016/j.acra.2025.07.062}, pmid = {40835571}, issn = {1878-4046}, mesh = {Humans ; Female ; *Deep Learning ; *Breast Neoplasms/diagnostic imaging/pathology ; *Calcinosis/diagnostic imaging ; Retrospective Studies ; Middle Aged ; *Mammography/methods ; Diagnosis, Differential ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging ; *Carcinoma, Ductal, Breast/diagnostic imaging ; Sensitivity and Specificity ; Aged ; Adult ; Radiographic Image Interpretation, Computer-Assisted/methods ; }, abstract = {RATIONALE AND OBJECTIVES: To explore the value of a deep learning-based model in distinguishing between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) manifesting suspicious microcalcifications on mammography.

MATERIALS: A total of 294 breast cancer cases (106 DCIS and 188 IDC) from two centers were randomly allocated into training, internal validation and external validation sets in this retrospective study. Clinical variables differentiating DCIS from IDC were identified through univariate and multivariate analyses and used to build a clinical model. Deep learning features were extracted using Resnet101 and selected by minimum redundancy maximum correlation (mRMR) and least absolute shrinkage and selection operator (LASSO). A deep learning model was developed using deep learning features, and a combined model was constructed by combining these features with clinical variables. The area under the receiver operating characteristic curve (AUC) was used to assess the performance of each model.

RESULTS: Multivariate logistic regression identified lesion type and BI-RADS category as independent predictors for differentiating DCIS from IDC. The clinical model incorporating these factors achieved an AUC of 0.67, sensitivity of 0.53, specificity of 0.81, and accuracy of 0.63 in the external validation set. In comparison, the deep learning model showed an AUC of 0.97, sensitivity of 0.94 and specificity of 0.92, accuracy of 0.93. For the combined model, the AUC, sensitivity, specificity and accuracy were 0.97, 0.96, 0.92 and 0.95, respectively. The diagnostic efficacy of the deep learning model and combined model was comparable (p>0.05), and both models outperformed the clinical model (p<0.05).

CONCLUSION: Deep learning provides an effective non-invasive approach to differentiate DCIS from IDC presenting as suspicious microcalcifications on mammography.}, } @article {pmid40829155, year = {2026}, author = {Wang, H and Huang, R and Huang, J and Feng, L and Zhang, W}, title = {Mandibular Osteosarcoma Mimicking Bisphosphonate-associated Osteonecrosis on 99m Tc-MDP Bone Scan in a Patient With Breast Cancer.}, journal = {Clinical nuclear medicine}, volume = {51}, number = {1}, pages = {68-69}, doi = {10.1097/RLU.0000000000006105}, pmid = {40829155}, issn = {1536-0229}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/complications ; Adult ; Diagnosis, Differential ; *Technetium Tc 99m Medronate ; *Osteosarcoma/diagnostic imaging/complications ; *Diphosphonates/adverse effects ; Radionuclide Imaging ; *Mandibular Neoplasms/diagnostic imaging ; *Bisphosphonate-Associated Osteonecrosis of the Jaw/diagnostic imaging ; }, abstract = {We present the case of a 27-year-old woman with a history of left breast invasive ductal carcinoma who developed mandibular osteosarcoma, as documented by 2 MDP bone scans. She had undergone a radical mastectomy, chemotherapy, radiotherapy, and intravenous zoledronic acid therapy. An initial bone scan 1 year later showed increased MDP uptake in the right mandible, suggesting drug-related osteonecrosis, but concurrent CT scans were normal. A follow-up bone scan performed 16 months later demonstrated increased MDP uptake in both mandibles. Subsequent partial mandibulectomy confirmed conventional osteosarcoma.}, } @article {pmid40826794, year = {2025}, author = {Li, S and Zhang, S}, title = {A case report of Chinese medicine combined with neoadjuvant chemotherapy in the treatment of human epidermal growth factor receptor 2 breast cancer.}, journal = {Medicine}, volume = {104}, number = {33}, pages = {e43387}, pmid = {40826794}, issn = {1536-5964}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/pathology/therapy ; Middle Aged ; *Neoadjuvant Therapy/methods ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; *Carcinoma, Ductal, Breast/drug therapy/pathology ; *Drugs, Chinese Herbal/therapeutic use ; *Medicine, Chinese Traditional/methods ; Chemotherapy, Adjuvant ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; }, abstract = {RATIONALE: According to Chinese medicine, surgical trauma and chemotherapy aggravate patients' qi and blood deficiency and damage to the veins and channels. The combination of Chinese medicine and neoadjuvant chemotherapy (NACT) can not only improve the above symptoms, but also is expected to alleviate the adverse effects of breast cancer chemotherapy, such as nausea and vomiting, thereby improving patient compliance to achieve tumor reduction or even tumor-free, and providing a new diagnostic and therapeutic idea for the clinical treatment of breast cancer. This paper reported a case of human epidermal growth factor receptor 2 (HER-2) invasive breast cancer treated with traditional Chinese medicine combined with NACT. The lesion disappeared after 2 months of treatment and effectively reduced nausea and the symptoms of loss of appetite during NACT.

PATIENT CONCERNS: The patient was a female, 54-year-old, unintentionally found a double breast lump with tingling pain over 1 year. During this period, the patient did not pay attention to any treatment, the mass increased progressively, hard texture, unclear boundary. Denied family genetic history of breast cancer. The patient was diagnosed with invasive ductal carcinoma of both breasts (multiple metastases in right axillary and supraclavicular lymph nodes), T4N3M0 (tumour staging basis), stage IIC, HER-2 positive by breast needle biopsy. In the course of NACT, the patient complained of severe nausea and vomiting, which seriously affected the quality of life and chemotherapy confidence.

DIAGNOSES: The patient was diagnosed with invasive ductal carcinoma of both breasts (multiple metastases in right axillary and supraclavicular lymph nodes), T4N3M0, stage IIC, HER-2 positive.

INTERVENTIONS: The patient was treated with NACT, and traditional Chinese medicine was taken orally.

OUTCOMES: After 2 months of combination therapy, the breast mass shrank, the symptoms of nausea and vomiting were significantly relieved, and the appetite became better. The biopsy of the breast tissue cut at the completion of NACT showed no upper, lower, internal, outer, and basal lesions.

LESSONS: Chinese medicine internal effect is remarkable and safe, new adjuvant chemotherapy combined with Chinese medicine internal effectively improve nausea, vomiting symptoms, and effectively inhibit tumor hyperplasia, shrink tumor lesions, this case allows us consider whether in breast cancer new adjuvant chemotherapy combined Chinese medicine internal effect can be better, and provide new ideas for clinical treatment.}, } @article {pmid40824984, year = {2025}, author = {An, T and Dong, X and Dong, B and Jiang, H and Liu, L and Ma, B}, title = {Event-Triggered Mixed Nonzero-Sum Game Optimal Control for Modular Robotic Manipulator Performing Coordinated Operation Tasks.}, journal = {IEEE transactions on neural networks and learning systems}, volume = {36}, number = {12}, pages = {20371-20385}, doi = {10.1109/TNNLS.2025.3595563}, pmid = {40824984}, issn = {2162-2388}, abstract = {Taking advantage of high-performance intelligent robots to solve the coordination control problem such as assembly, handling, and installation, transportation is gradually becoming a kind of frontier subject with great scientific research value in the field of robotics. However, due to possible conflicts and inconsistencies between the manipulator and the operating object, it is challenging to design the optimal coordination control scheme between human and robot. This article presents an event-triggered mixed nonzero-sum game optimal control method, which considers both nonzero-sum game and cooperative game cases, for modular robotic manipulator (MRM) systems performing coordinated operation tasks. First, the joint torque feedback technique and joint task assignment method are employed to establish the dynamic model of MRM subsystem, and then, the global state-space description is deduced. For the unknown information containing interconnected dynamic coupling (IDC) terms and friction modeling errors, an adaptive neural network (NN) identifier is established by utilizing the measured input-output data of each joint module. The adaptive updating law guarantees that the NN weight error finally converged to a minimum neighborhood of zero. To ensure the optimality of system overall performance, the corresponding value functions reflecting the interconnectedness among each joint subsystem and manipulated object are constructed. Based on the idea of differential game, the coordination control problem of MRM system is transformed into a mixed nonzero-sum game problem among each joint module and the operated object. Next, by constructing a single critic NN with learning structure, the optimal value function is approximated to solve the event-based Hamiltonian equations, and then, the optimal control strategy of each player is obtained. Finally, the Lyapunov theory is used to analyze system stability, and the effectiveness of the presented method is reinforced by experimental results.}, } @article {pmid40824585, year = {2026}, author = {Sakata, S and Hisa, T and Ito, Y and Nishiyama, S and Kudo, A and Yamada, T and Osera, S and Fukushima, H and Hamura, R and Shiozawa, S}, title = {Pancreatic ductal adenocarcinoma originating from focal pancreatic parenchymal atrophy demonstrated by transabdominal ultrasonography.}, journal = {Clinical journal of gastroenterology}, volume = {19}, number = {1}, pages = {8-15}, pmid = {40824585}, issn = {1865-7265}, mesh = {Humans ; Male ; Atrophy ; Aged, 80 and over ; *Pancreatic Neoplasms/diagnostic imaging/pathology/surgery ; *Carcinoma, Pancreatic Ductal/diagnostic imaging/pathology/surgery/etiology ; *Pancreas/pathology/diagnostic imaging ; Ultrasonography ; }, abstract = {In this report, we present an 80-year-old man referred for evaluation of a pancreatic mass detected by transabdominal ultrasonography during health screening. Additional examinations revealed severe, long-segment focal atrophy from the pancreatic head to the body, appearing as a cord-like hypoechoic lesion on transabdominal and endoscopic ultrasonography. Although cytological examination of pancreatic juice was recommended, the patient opted for a follow-up. Three years later, a hypoechoic mass with upstream main pancreatic duct dilatation developed in the atrophic region. Cytological examination of pancreatic juice revealed adenocarcinoma, and pancreaticoduodenectomy was performed. Histopathology revealed Stage IIB invasive ductal carcinoma and carcinoma in situ within the atrophic region. Retrospective review showed that focal atrophy was present on transabdominal ultrasonography 11 years before the invasive carcinoma mass appeared, progressing without main pancreatic duct dilatation until its development. During follow-up of focal atrophy, early diagnosis of carcinoma in situ or microinvasive carcinoma before main pancreatic duct dilatation is crucial. The present case suggests that severe, long-segment focal pancreatic parenchymal atrophy can be detected by transabdominal ultrasonography and that carcinoma in situ within the focal pancreatic parenchymal atrophy may progress to invasive carcinoma.}, } @article {pmid40823661, year = {2025}, author = {van Veen, FEE and Scheepe, JR and Blok, BFM}, title = {[Regional variation in urinary catheter use in the Netherlands: a population-based cohort from 2012 to 2021].}, journal = {Tijdschrift voor urologie}, volume = {15}, number = {5}, pages = {88-96}, pmid = {40823661}, issn = {2211-4718}, abstract = {INTRODUCTION: Clean intermittent catheterization (CIC) is often preferred over indwelling catheters (IDC) due to fewer complications and improved quality of life. This study investigated trends and regional differences in CIC and IDC use in the Netherlands between 2012 and 2021.

METHODS: Data were collected from the Drug and Medical Devices Information System and regional differences were assessed using negative binomial regression (NBR).

RESULTS: The number of CIC users increased by 27.3%, from 34,204 to 43,528 and the number of ID users by 44.6%, from 41,619 to 60,172. The most significant increases were among male CIC users > 65 years and IDC users > 85 years. NBR showed significant regional variations, with higher CIC use in the northern Netherlands and variable IDC use across the country.

CONCLUSION: There is a growing number of catheter users in the Netherlands and there are regional differences, which may be explained by variations in patient populations, healthcare provider preferences, and adherence to guidelines.}, } @article {pmid40821286, year = {2025}, author = {Silva, MJ and Patel, J and Huang, A and Lo Gullo, R and Pinker-Domenig, K}, title = {Breast Plasmacytoma as the Initial Manifestation of Multiple Myeloma in a 36-Year-Old Woman.}, journal = {Cureus}, volume = {17}, number = {7}, pages = {e87929}, pmid = {40821286}, issn = {2168-8184}, abstract = {Extramedullary plasmacytomas (EMPs) of the breast are extremely rare and may present as the initial manifestation of multiple myeloma (MM). We report the case of a 36-year-old woman who presented with a rapidly growing right breast mass. Mammography and ultrasound revealed an oval, circumscribed, heterogeneous, vascular mass, measuring up to 4.2 cm, categorized as Breast Imaging Reporting and Data System (BI-RADS) 4. Core needle biopsy revealed a plasmablastic/plasmacytic neoplasm with strong CD138 expression, lambda light chain restriction, high Ki-67 index, and negative Epstein-Barr virus early RNA in situ hybridization (EBER-ISH), consistent with plasmablastic plasmacytoma. Systemic staging confirmed the diagnosis of MM, and the patient underwent chemotherapy followed by autologous stem cell transplantation. This case illustrates how breast plasmacytoma (BP) can mimic primary breast malignancies on imaging, particularly triple-negative invasive ductal carcinoma, lymphoma, or malignant phyllodes tumor. Although rare, it should be considered in younger patients with atypical breast masses. Diagnosis relies on biopsy with histopathological and immunophenotypic confirmation. Early recognition and biopsy are key, as BP may mimic aggressive breast malignancies and carry prognostic significance in MM.}, } @article {pmid40821164, year = {2025}, author = {Iwaisako, N and Oura, S}, title = {Bilateral Breast Reconstruction Using Extended Latissimus Dorsi Musculocutaneous Flaps for Metachronous Bilateral Breast Cancer: A Case Report.}, journal = {Cureus}, volume = {17}, number = {7}, pages = {e88024}, pmid = {40821164}, issn = {2168-8184}, abstract = {A 49-year-old woman had undergone radiofrequency ablation (RFA) therapy and sentinel lymph node biopsy (SNB), followed by radiation therapy for her right breast cancer at the age of 31. The patient had further undergone nipple-sparing mastectomy (NSM), SNB, and immediate breast reconstruction using an extended latissimus dorsi musculocutaneous flap (eLDMCF) for her left breast cancer at the age of 43. Follow-up mammography further revealed widespread linear calcifications in the right breast. Core needle biopsy pathologically showed atypical cells growing in trabecular and tubular fashions with connective tissue proliferation, leading to the diagnosis of invasive ductal carcinoma. Due to the patient's strong preference for not using silicone prosthesis on right breast reconstruction, the patient underwent NSM and SNB, followed by immediate breast reconstruction using the right eLDMCF after obtaining full informed consent about the unknown bilateral eLDMCF harvesting effect on respiratory function. The patient recovered uneventfully and showed respiratory function as follows: preoperative 2.69 L to postoperative 2.46 L in vital capacity and preoperative 2.1 L to postoperative 1.83 L in forced expiratory volume in one second. The patient reported no respiratory symptoms and has been fully satisfied with the cosmetic outcomes of the reconstructed right breast. These results suggest that bilateral breast reconstruction using eLDMCFs can be a good therapeutic option for metachronous bilateral breast cancer.}, } @article {pmid40814164, year = {2025}, author = {Volfson, E and Moshkovich, M and Yakubov, R and Dalson, J and Kirshen, C}, title = {Dermatologic Mimickers of Paget's Disease of the Breast: A Systematic Review.}, journal = {Journal of cutaneous medicine and surgery}, volume = {}, number = {}, pages = {12034754251364870}, doi = {10.1177/12034754251364870}, pmid = {40814164}, issn = {1615-7109}, abstract = {Mammary Paget disease (MPD) is a rare form of breast cancer that accounts for just 1% to 4% of all cases and is often associated with underlying malignancies such as ductal carcinoma in situ and invasive ductal carcinoma. Its clinical presentation frequently mimics benign dermatologic conditions or malignant melanoma, leading to diagnostic confusion and significant treatment delays. This review explores the diagnostic challenges and patterns of misdiagnosis in MPD, as well as the consequences of delayed recognition. A comprehensive search of Embase and MEDLINE identified 29 studies reporting on 32 cases of MPD, all of which were initially misdiagnosed-most commonly as melanoma (44.4%) and atopic dermatitis (25.0%). The average diagnostic delay was 2.3 years. Most lesions were unilateral (93.8%) and involved the nipple-areolar complex (87.5%). Imaging modalities demonstrated limited sensitivity, reinforcing the importance of early biopsy for timely diagnosis. Surgical intervention was the predominant treatment approach, employed in 75% of cases, and no recurrences were reported during a mean follow-up of 1.3 years. These findings underscore the urgent need for heightened clinical suspicion, earlier tissue sampling, and the development of standardized diagnostic pathways to reduce misdiagnosis and improve outcomes in patients with MPD.}, } @article {pmid40812028, year = {2025}, author = {Khesali, M and Yazdi, SAM}, title = {Spontaneous migration of a port catheter tip to the pulmonary vein: A case report of an uncommon complication.}, journal = {International journal of surgery case reports}, volume = {134}, number = {}, pages = {111777}, pmid = {40812028}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Port catheters are commonly used for chemotherapy in cancer patients. However, complications such as spontaneous catheter tip migration can occur, leading to symptoms like pain, infection, or venous thrombosis, with factors like Changes in thoracic pressure potentially contributing to this rare phenomenon.

CASE PRESENTATION: This report details the case of a 44-year-old woman with invasive ductal carcinoma of the right breast who developed a cough following six chemotherapy sessions.

CLINICAL SISCUSSION: Imaging revealed that the catheter tip had migrated from the superior vena cava (SVC) to the right pulmonary vein.

CONCLUSION: The catheter was successfully removed using minimally invasive intravascular techniques under angiography guidance.}, } @article {pmid40810087, year = {2025}, author = {Suzuki, D and Oshi, M and Nishikawa, A and Kawashima, K and Sasamoto, M and Shibata, Y and Adachi, S and Narui, K and Takase, H and Yamada, A and Fujii, S and Endo, I}, title = {Breast Cancer With Airway Edema Caused by Metastatic Fracture of the Cervical Vertebra.}, journal = {World journal of oncology}, volume = {16}, number = {4}, pages = {422-425}, pmid = {40810087}, issn = {1920-454X}, abstract = {Bone is a common site of breast cancer metastasis, with the spine showing a particularly high affinity. An 83-year-old Japanese woman with Alzheimer's disease presented with a palpable mass in her left breast. A needle biopsy revealed invasive ductal carcinoma of the breast, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, with lymph node metastasis. Chest dynamic computed tomography showed no distant metastases. She was diagnosed with luminal-type, stage IIB (T2N1M0) breast cancer and underwent surgery. During induction of general anesthesia, intubation was difficult due to airway edema, necessitating bronchoscopy. The day after surgery, she reported neck pain, and radiography revealed a compression fracture of the third cervical vertebra. Magnetic resonance imaging confirmed a metastatic lesion in the third cervical vertebra. Postoperatively, she received endocrine therapy with letrozole, radiation therapy with zoledronic acid, and a cervical collar for cervical metastases. Seven months later, the osteolytic lesion calcified, and her pain improved. This case is unique because solitary cervical vertebral metastases from breast cancer, leading to compression fractures and airway edema, are rare. The case highlights the importance of considering cervical metastases in patients with breast cancer who develop airway difficulties or unexplained neck pain, particularly in the perioperative setting. Early recognition and intervention are crucial for preventing complications and optimizing patient outcomes.}, } @article {pmid40809963, year = {2025}, author = {Bellesini, JA and Foo, KY and Li, J and Sanderson, RW and Zilkens, R and Gale, L and Hardie, M and Hamza, S and Rijhumal, A and Saunders, CM and Kennedy, BF}, title = {Three-dimensional dynamic optical coherence tomography for breast tumor margin assessment.}, journal = {Biomedical optics express}, volume = {16}, number = {8}, pages = {3061-3074}, pmid = {40809963}, issn = {2156-7085}, abstract = {Intraoperative margin assessment techniques are needed to reduce the re-excision rate in breast-conserving surgery. Optical coherence tomography (OCT) is a non-invasive imaging technique capable of rapid three-dimensional (3-D) imaging of the internal microstructure of tissues. However, there is often low contrast between morphological features in breast tissue. Dynamic OCT (d-OCT), which provides additional contrast derived from the temporal variance of the OCT signal caused by intrinsic motion within the tissue, may provide a solution. However, few studies have applied it to breast tumor margin assessment. In this study, we acquired 3-D d-OCT images of ten human mastectomy specimens and three wide local excisions from breast-conserving surgery (BCS) procedures and, in each case, performed co-registered histology for validation. To optimize the trade-off between spatial resolution, temporal resolution, and acquisition time, we considered a range of acquisition settings. Several methods for visualizing d-OCT images were investigated, including Fourier weighted mean frequency, Fourier power spectral analysis, using red-green-blue (RGB) and hue-saturation-value (HSV) color spaces, and phase variance. We present d-OCT images of invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS), invasive lobular carcinoma (ILC), and lobular carcinoma in situ (LCIS), and show that the contrast between malignant and benign regions is consistently higher with d-OCT than using OCT intensity alone. The improved contrast may derive from increased proliferation rates and collagen deposition in cancerous tissue compared to benign tissue. We believe that our results demonstrate that d-OCT has the potential to improve intraoperative tumor margin assessment during breast-conserving surgery.}, } @article {pmid40809661, year = {2025}, author = {Vulasala, SR and Louviere, CD and Navarro, F and Adler, GA and Gopireddy, DR and Hatch, P and Abu Hana, R}, title = {Systemic Sarcoidosis Mimicking Metastatic Invasive Ductal Carcinoma of the Breast.}, journal = {Cureus}, volume = {17}, number = {7}, pages = {e87860}, pmid = {40809661}, issn = {2168-8184}, abstract = {Sarcoidosis is a granulomatous inflammatory disorder of uncertain etiology that can closely mimic metastatic malignancies, particularly when it presents with multi-organ involvement. In patients with a confirmed diagnosis of cancer, to avoid misdiagnosis and subsequent inappropriate treatment, distinguishing between sarcoidosis and metastatic disease is essential. Histologic confirmation through tissue sampling and correlation with tumor markers are critical tools in this process. We report a case of a 36-year-old female with invasive ductal carcinoma of the breast who presented with suspicious findings that indicated metastatic disease involving her lungs, liver, and bones. However, tumor marker levels and histopathology revealed systemic sarcoidosis, not metastatic spread.}, } @article {pmid40807127, year = {2025}, author = {McMahon, JE and Craig, A and Cameron, ID}, title = {Development of Cut Scores for Feigning Spectrum Behavior on the Orebro Musculoskeletal Pain Screening Questionnaire and the Perceived Stress Scale: A Simulation Study.}, journal = {Journal of clinical medicine}, volume = {14}, number = {15}, pages = {}, pmid = {40807127}, issn = {2077-0383}, abstract = {Background/Objectives: Feigning spectrum behavior (FSB) is the exaggeration, fabrication, or false imputation of symptoms. It occurs in compensable injury with great cost to society by way of loss of productivity and excessive costs. The aim of this study is to identify feigning by developing cut scores on the long and short forms (SF) of the Orebro Musculoskeletal Pain Screening Questionnaire (OMPSQ and OMPSQ-SF) and the Perceived Stress Scale (PSS and PSS-4). Methods: As part of pre-screening for a support program, 40 injured workers who had been certified unfit for work for more than 2 weeks were screened once with the OMPSQ and PSS by telephone by a mental health professional. A control sample comprised of 40 non-injured community members were screened by a mental health professional on four occasions under different aliases, twice responding genuinely and twice simulating an injury. Results: Differences between the workplace injured people and the community sample were compared using ANCOVA with age and gender as covariates, and then receiver operator characteristics (ROCs) were calculated. The OMPSQ and OMPSQ-SF discriminated (ρ < 0.001) between all conditions. All measures discriminated between the simulation condition and workplace injured people (ρ < 0.001). Intraclass correlation demonstrated the PSS, PSS-4, OMPSQ, and OMPSQ-SF were reliable (ρ < 0.001). Area Under the Curve (AUC) was 0.750 for OMPSQ and 0.835 for OMPSQ-SF for work-injured versus simulators. Conclusions: The measures discriminated between injured and non-injured people and non-injured people instructed to simulate injury. Non-injured simulators produced similar scores when they had multiple exposures to the test materials, showing the uniformity of feigning spectrum behavior on these measures. The OMPSQ-SF has adequate discriminant validity and sensitivity to feigning spectrum behavior, making it optimal for telephone screening in clinical practice.}, } @article {pmid40805222, year = {2025}, author = {Kwong, A and Ho, CYS and Au, CH and Ma, ESK}, title = {Germline BARD1 Mutation in High-Risk Chinese Breast and Ovarian Cancer Patients.}, journal = {Cancers}, volume = {17}, number = {15}, pages = {}, pmid = {40805222}, issn = {2072-6694}, support = {NA//Dr. Ellen Li Charitable Foundation/ ; NA//Kerry Kuok Foundation/ ; 03143406//Health and Medical Research Fund/ ; NA//Asian Fund for Cancer Research/ ; NA//Hong Kong Hereditary Breast Cancer Family Registry/ ; }, abstract = {BACKGROUND: The prevalence of BARD1 mutations in breast and ovarian cancers varies across different ethnic groups. Evaluating the cancer risk and clinical significance of BARD1 mutations in the local Chinese patients with breast cancer, ovarian cancer, or both is clinically important for designing an appropriate surveillance scheme.

METHODS: This study used a 30 gene panel to identify BARD1 germline mutations in 2658 breast and ovarian cancer patients.

RESULTS: Among this cohort, the BARD1 mutation prevalence was 0.45% for breast cancer and 0.29% for ovarian cancer. In our 12 mutation carriers, we identified eight types of mutation variants, including three novel mutations. BARD1 mutation carriers were more likely to have a family history of liver, prostate, and cervical cancers (p-values = 0.004, 0.018, and 0.037, respectively) than patients who tested negative for mutations. Among the BARD1 mutants, the majority of the breast tumors were invasive ductal carcinoma (NOS type) (10/11, 90.9%) of high-grade disease (9/9, 100%) and half of them were triple-negative breast cancer (5/10, 50%).

CONCLUSIONS: Although the prevalence of BARD1 mutations is low and the penetrance is incomplete, we recommend including BARD1 in the test panel for breast cancer patients. Our data suggest that more comprehensive surveillance management may be considered in mutation carriers due to the familial aggregation of a relatively wide spectrum of cancers.}, } @article {pmid40805194, year = {2025}, author = {Tsai, MY and Yu, ZH and Chou, CP}, title = {AI-Based Ultrasound Nomogram for Differentiating Invasive from Non-Invasive Breast Cancer Masses.}, journal = {Cancers}, volume = {17}, number = {15}, pages = {}, pmid = {40805194}, issn = {2072-6694}, support = {KSVGH112-108//Kaohsiung Veterans Hospital/ ; }, abstract = {Purpose: This study aimed to develop a predictive nomogram integrating AI-based BI-RADS lexicons and lesion-to-nipple distance (LND) ultrasound features to differentiate mass-type ductal carcinoma in situ (DCIS) from invasive ductal carcinoma (IDC) visible on ultrasound. Methods: The final study cohort consisted of 170 women with 175 pathologically confirmed malignant breast lesions, including 26 cases of DCIS and 149 cases of IDC. LND and AI-based features from the S-Detect system (BI-RADS lexicons) were analyzed. Rare features were consolidated into broader categories to enhance model stability. Data were split into training (70%) and validation (30%) sets. Logistic regression identified key predictors for an LND nomogram. Model performance was evaluated using receiver operating characteristic (ROC) curves, 1000 bootstrap resamples, and calibration curves to assess discrimination and calibration. Results: Multivariate logistic regression identified smaller lesion size, irregular shape, LND ≤ 3 cm, and non-hypoechoic echogenicity as independent predictors of DCIS. These variables were integrated into the LND nomogram, which demonstrated strong discriminative performance (AUC = 0.851 training; AUC = 0.842 validation). Calibration was excellent, with non-significant Hosmer-Lemeshow tests (p = 0.127 training, p = 0.972 validation) and low mean absolute errors (MAE = 0.016 and 0.034, respectively), supporting the model's accuracy and reliability. Conclusions: The AI-based comprehensive nomogram demonstrates strong reliability in distinguishing mass-type DCIS from IDC, offering a practical tool to enhance non-invasive breast cancer diagnosis and inform preoperative planning.}, } @article {pmid40804863, year = {2025}, author = {Cantisani, C and Caruso, G and Taliano, A and Longo, C and Rizzuto, G and D'Andrea, V and Pietkiewicz, P and Bortone, G and Gargano, L and Suppa, M and Pellacani, G}, title = {Multimodal Imaging Detection of Difficult Mammary Paget Disease: Dermoscopy, Reflectance Confocal Microscopy, and Line-Field Confocal-Optical Coherence Tomography.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {15}, pages = {}, pmid = {40804863}, issn = {2075-4418}, abstract = {Mammary Paget disease (MPD) is a rare cutaneous malignancy associated with underlying ductal carcinoma in situ (DCIS) or invasive ductal carcinoma (IDC). Clinically, it appears as eczematous changes in the nipple and areola complex (NAC), which may include itching, redness, crusting, and ulceration; these symptoms can sometimes mimic benign dermatologic conditions such as nipple eczema, making early diagnosis challenging. A 56-year-old woman presented with persistent erythema and scaling of the left nipple, which did not respond to conventional dermatologic treatments: a high degree of suspicion prompted further investigation. Reflectance confocal microscopy (RCM) revealed atypical, enlarged epidermal cells with irregular boundaries, while line-field confocal-optical coherence tomography (LC-OCT) demonstrated thickening of the epidermis, hypo-reflective vacuous spaces and abnormally large round cells (Paget cells). These non-invasive imaging findings were consistent with an aggressive case of Paget disease despite the absence of clear mammographic evidence of underlying carcinoma: in fact, several biopsies were needed, and at the end, massive surgery was necessary. Non-invasive imaging techniques, such as dermoscopy, RCM, and LC-OCT, offer a valuable diagnostic tool in detecting Paget disease, especially in early stages and atypical forms.}, } @article {pmid40804756, year = {2025}, author = {Gato, J and Vázquez, I and Coimbra, S and Santos, I and Dore, I and Shenkman, G and Janowicz, K and Ciesielski, P and Tasker, F}, title = {To build a family: exploring preferred paths to parenthood among plurisexual individuals without children.}, journal = {Journal of reproductive and infant psychology}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/02646838.2025.2547920}, pmid = {40804756}, issn = {1469-672X}, abstract = {AIMS/BACKGROUND: Limited research has examined family-building strategies among plurisexual individuals. Culture and gender are essential determinants of parenthood prospects among individuals with minoritized sexual identities. For plurisexual individuals, the partner's gender also seems to play a critical role. Our investigation aimed to explore cisgender plurisexual individuals' preferred paths to parenthood considering their country of origin, gender, and partner's gender.

DESIGN/METHOD: We examined associations between preferred pathways to parenthood and country, gender, and partner's gender among 405 cisgender plurisexual individuals aged between 18 and 45 years (M = 25.76; SD = 5.57), from Portugal (n = 140; 34.9%), Israel (n = 78; 19.3%), Poland (n = 85; 21%), and the UK (n = 102; 25.2%).

RESULTS: Overall, couple adoption and sexual intercourse were the most chosen pathways to parenthood, and self-insemination and co-parenting were the least chosen. Participants from Poland and the United Kingdom were less likely to choose artificial insemination, single adoption, and self-insemination than their Portuguese counterparts. Women were more likely than men to choose artificial insemination. Individuals in different-gender relationships were more likely to choose sexual intercourse as a means of having children than were those in same-gender relationships, and the opposite was true for artificial insemination.

CONCLUSION: Country, gender, and the partner's gender influence plurisexual individuals' choice of some parenthood pathways. Psychological and reproductive counselling should consider these aspects.}, } @article {pmid40804747, year = {2025}, author = {Awan, UA and Bashir, S and Hassan, U and Khan, SN and Awan, FM and Jabbar, A and Khan, S and Guo, X}, title = {HPV-driven breast carcinogenesis: associations with tumor severity, Ki67 expression and metastasis.}, journal = {Infectious agents and cancer}, volume = {20}, number = {1}, pages = {55}, pmid = {40804747}, issn = {1750-9378}, abstract = {OBJECTIVE: Breast cancer (BC) poses a significant global health challenge, and its potential link to HPV warrants investigation. This study investigates the prevalence, genotype distribution, and clinicopathological associations of human papillomavirus (HPV) in breast cancer patients from Pakistan.

METHODS: This single-institutional cross-sectional study included 501 FFPE BC specimens from female patients and 110 benign controls, collected between January 2019 and December 2023. High-risk (HR) HPV DNA was detected via highly sensitive real-time PCR, with genotyping conducted using the INNO-LiPA Genotyping Extra II assay. Clinicopathological data, including tumor grade, size, lymph node metastasis, and receptor status, were analyzed for associations with HPV infection. Statistical analyses employed the Kruskal-Wallis test for continuous variables and Fisher's exact or chi-square tests for categorical variables, as appropriate (p < 0.05).

RESULTS: HPV DNA was detected in 10.5% of BC cases (n = 53/501) compared to other statuses, with HR genotypes predominating (91%). HPV-16 (26%) and HPV-18 (15%) were the most frequent genotypes. HPV-positive cases exhibited aggressive tumor characteristics, including 58.5% grade III tumors, a mean tumor size of 65.6 ± 46.4 mm, and 32.1% N3 disease, with an increasing prevalence of HR-HPV associated with tumor stage and significance (p < 0.05). Invasive ductal carcinoma (34%) and invasive lobular carcinoma (28.3%) were the most common histological subtypes. Metaplastic carcinomas, with the largest mean tumor size (86.4 ± 74.6 mm), showed the highest HPV-16 prevalence (28.6%) and were linked to HR-HPV infection. Peak HPV incidence occurred in patients aged 51-60 years (37.7%). Geographically, HPV-16 predominated in Lahore (50%) and Peshawar (60%).

CONCLUSION: This study links HR-HPV to aggressive BC, with HPV-16 and -18 predominating in urban areas. Additionally, it highlights the importance of targeted vaccination and research into subtype-specific oncogenesis.}, } @article {pmid40797027, year = {2025}, author = {Kliemank, E and von Rauchhaupt, E and Seebauer, L and Roshan, M and Ansmann, M and Flegka, V and Schimpfle, L and Tsilingiris, D and Bartl, H and Fleming, T and Kender, Z and Jende, JME and Mooshage, CM and Schwarz, D and Bendszus, M and Schirmacher, P and Herzig, S and Nawroth, PP and Kopf, S and Szendroedi, J and Sulaj, A}, title = {Cohort profile of the Heidelberg study on diabetes and complications HEIST-DiC.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {29580}, pmid = {40797027}, issn = {2045-2322}, mesh = {Humans ; Male ; Middle Aged ; Female ; Prospective Studies ; Aged ; Longitudinal Studies ; *Diabetes Complications/epidemiology/physiopathology ; Adult ; Germany/epidemiology ; }, abstract = {The Heidelberg Study on Diabetes and Complications (HEIST-DiC) is a prospective longitudinal study focused on the development and progression of diabetes-associated complications. Participants with/without diabetes mellitus undergo annual phenotyping of diabetes-associated complications over 11 years. Assessments include: albuminuria, estimated glomerular filtration rate for chronic kidney disease; clinical neuropathy scores, Purdue Pegboard test, electrophysiological examination, transcutaneous electrical nerve fiber stimulation, quantitative sensory testing and high-resolution magnetic resonance neurography for distal sensorimotor polyneuropathy; heart rate variability for cardiovascular autonomic neuropathy; funduscopic examination of undilated pupils for retinopathy; the 6-minute walk test, spirometry, body plethysmography, and carbon monoxide-based diffusing capacity measurements for respiratory lung disease; non-invasive scores, transient elastography and hepatic ultrasound for metabolic dysfunction-associated steatotic liver disease; ankle-brachial index and carotid intima-media thickness for peripheral atherosclerosis; hand grip strength for muscle function; bioelectrical impedance analysis for body composition; skin autofluorescence for measurement of advanced glycation end products. Beta-cell function and tissue-specific insulin sensitivity are evaluated using oral glucose tolerance test or euglycemic hyperinsulinemic clamp. The biobank stores specimens of blood, urine, skeletal muscle, subcutaneous adipose tissue, and skin. Health-related quality of life, physical health, and somatic and depression symptoms are measured via standardized questionnaires. HEIST-DiC explores diabetes onset in high-risk individuals, disease progression and the development of complications, aiming to design personalized strategies to prevent, mitigate, or reverse diabetes-related complications.Trial registration: The study was retrospectively registered at Clinicaltrials.gov (NCT03022721, date of registration 20170112).}, } @article {pmid40796841, year = {2025}, author = {Chen, J and Liu, K and Cheng, Q and Wang, L}, title = {Modeling health literacy intentions: a structural equation analysis of community residents' willingness to acquire infectious disease specific health literacy.}, journal = {BMC public health}, volume = {25}, number = {1}, pages = {2734}, pmid = {40796841}, issn = {1471-2458}, support = {LGF21H260007 and LGF21H19000//Basic Public Welfare Research Project of Zhejiang Province/ ; 2020PY064, 2020KY238, and 2021PY065//Medical Science and Technology Project of Zhejiang Province/ ; 20220919Y059//Hangzhou City Science and Technology Bureau Project/ ; 0020190783//Health Science and Technology Project of Hangzhou Municipality/ ; }, mesh = {Humans ; *Health Literacy/statistics & numerical data ; Female ; Male ; Cross-Sectional Studies ; Adult ; Middle Aged ; China ; *Intention ; Latent Class Analysis ; *Health Knowledge, Attitudes, Practice ; *Communicable Diseases ; Surveys and Questionnaires ; Aged ; Young Adult ; }, abstract = {BACKGROUND: How the willingness to acquire infectious-disease-specific health literacy (IDSHL) can be promoted is unknown among community residents. Community residents' willingness to acquire IDSHL (CRWAI) and its impact on health status is a multifaceted phenomenon that encompasses many factors, including socio-demographic characteristics, cognition, attitude, health behavior, perceived-efficacy, and knowledge needs related to infectious diseases. Early identification of associated-factors for CRWAI is essential. The objective of this research is to construct analytical models and examine the influencing factors relevant to CRWAI.

METHODS: In this multi-center cross-sectional study, we included 3,921 subjects from Hangzhou City using the method of stratified cluster sampling. We applied a structural equation modeling (SEM) to examine the factors that affect the CRWAI.

RESULTS: The findings from the SEM indicated that socio-demographic factors (SDF) (β =0.017, p =0.021), infectious disease cognition (IDC) (β =0.105, p <0.001), infectious disease perceived-efficacy (IDPE) (β =0.109, p <0.001), and infectious disease knowledge needs (IDKN) (β =0.097, p <0.001) was positively correlated with CRWAI. There was no significant association between the attitude and health behavior regarding infectious disease and CRWAI (p>0.05). The results indicated that IDC and IDKN served as mediators in the connection between SDF and CRWAI. Moreover, it was found that IDPE played a mediating part in the relationship of IDC and CRWAI. IDKN functioned as a mediator in the link between IDPE and CRWAI.

CONCLUSION: Our findings have indicated potential mechanistic pathways and intervention targets for CRWAI. We have introduced the SEM to analyze the CRWAI. Given that SDF, IDC, IDPE, and IDKN demonstrate direct and interactive associations with CRWAI, strategic interventions targeting these determinants are critical for enhancing population health outcomes in community settings.}, } @article {pmid40796089, year = {2025}, author = {Tassot, J and Ahlstrom, A and Capalbo, A and Cheong, Y and Coticchio, G and Delbaere, I and Fadler, C and Gameiro, S and Goddijn, M and Kirkman-Brown, J and Laganà, AS and Moura-Ramos, M and Nordhoff, V and Orlić, A and Pinborg, A and Rives, N and Sousa-Leite, M and Nielsen, HS and Thorn, P and Vermeulen, N and Viville, S and Sermon, K}, title = {ESHRE's key research priorities in infertility: maximizing impact on science, people and society†.}, journal = {Human reproduction (Oxford, England)}, volume = {40}, number = {10}, pages = {1829-1842}, pmid = {40796089}, issn = {1460-2350}, support = {//ESHRE/ ; }, mesh = {Humans ; Female ; Male ; *Infertility/therapy/prevention & control ; *Biomedical Research ; *Reproductive Medicine ; Societies, Medical ; Pregnancy ; Europe ; *Research ; }, abstract = {STUDY QUESTION: Which research topics in the area of infertility should be prioritized in the allocation of research resources?

SUMMARY ANSWER: Twelve research priorities were formulated, spanning the following areas: preventing infertility and preserving fertility, gynaecological diseases, male infertility, optimizing fertility treatments, optimizing psychosocial support and deepening knowledge on preimplantation development and early pregnancy.

WHAT IS KNOWN ALREADY: Many research gaps related to infertility and its management remain understudied and underfunded, making it important to set priorities to ensure appropriate allocation of research resources.

STUDY DESIGN, SIZE, DURATION: The European Society of Human Reproduction and Embryology (ESHRE) appointed a multidisciplinary working group, including a patient representative, to develop a list of research priorities related to infertility, which are relevant to researchers and institutions that fund research.

A list of research topics was collated based on the recommendations for future research formulated in ESHRE's evidence-based guidelines and suggestions submitted by ESHRE's Special Interest Groups as call topics for the ESHRE research grants. A scoring tool was developed to assess the expected impact of research on each topic on individuals, society and scientific advancement. Topics were scored independently by the working group members and the 12 topics with the highest scores were selected for presentation in this paper.

Using our newly developed scoring tool, we have identified 12 research priorities that broadly fall under six areas. These are preventing infertility and preserving fertility, gynaecological diseases, male infertility, optimizing fertility treatments (two priorities per area selected), optimizing psychosocial support (one priority selected) and deepening knowledge on preimplantation development and early pregnancy (three priorities selected).

The impact scoring tool would benefit from further testing and refinement in future projects. The scoring of some impact indicators is heavily based on the judgment and expertise of the scorers, which was accounted for by ensuring representation of knowledge and experience from all relevant disciplines and subject areas as well as the patient perspective within the working group.

This paper may serve to stimulate further thought and discussion within the infertility research community on the potential impact of proposed and ongoing research. It will furthermore inform and encourage policy makers involved in research funding allocation and contribute to a more efficient and purposeful allocation of research resources towards infertility research.

The technical support for this project was provided by ESHRE. A.C. reports employment at Juno Genetics. Y.C. reports a grant from Guerbet and honoraria from Ferring, Merck, Abbot, Nordic Pharma and Organon. G.C. reports consulting fees from Gedeon Richter and honoraria from Cooper Surgical. S.G. reports the development of www.myjourney.pt licensed under a CC BY-NC-SA 4.0 licence. J.K.-B. reports grants from the NIHR Evaluation and Studies Coordinating Centre, the Gates Foundation, the Economic and Social Research Council, BAYER Consumer Health and MRC Confidence in Concept; honoraria from Ferring and Cooper Surgical; travel support from Ferring, Cooper Surgical, Congressworks LLP, Deutsche Gesellschaft für Andrologie e. V., BAYER, University of Munster and ESHRE; a patent for microchannel sperm cell preparation; and a leadership or fiduciary role in the Association of Clinical and Reproductive Scientists. A.P. reports grants (to her institution) and consulting fees from Gedeon Richter, Ferring, Merck A/S and Cryos; honoraria from Gedeon Richter, Ferring, Merck A/S and Organon; and travel support (to her institution) from Gedeon Richter. H.S.N. reports grants from Freya Biosciences ApS, Ferring Pharmaceuticals, BioInnovation Institute, Ministry of Education, Novo Nordic Foundation, Augustinus Fonden, Oda og Hans Svenningsens Fond, Demant Fonden, Ole Kirks Fond and the Independent Research Fund Denmark; speaker's fees from Ferring, Merck A/S, Astra Zeneca, Cook Medical, Gedeon Richter, Ibsa Nordic, Novo Nordisk A/S; co-development of an app with the Maternity Foundation; and co-founding a project with Lulu Health. The remaining authors (J.T., A.A., I.D., C.F., M.G., A.S.L., M.M.-R., V.N., A.O., N.R., M.S.-L., P.T., N.V., S.V. and K.S.) have nothing to declare.

TRIAL REGISTRATION NUMBER: N/A.}, } @article {pmid40791519, year = {2025}, author = {Hoffmann, RJ and Bensen, A and Dane, M and Arterberry, J and Smith, R and Korkola, J and Schedin, P}, title = {S-Nitrosylated COX-2 is a TME-regulated breast cancer biomarker of mesenchymal phenotypes.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.07.15.664474}, pmid = {40791519}, issn = {2692-8205}, abstract = {COX-2 is an inducible enzyme key to the production of inflammatory prostaglandins. COX-2 also has tumor intrinsic oncogenic activity in mouse models of breast cancer. Previously, we reported increased expression of Cys-526-nitrosylated COX-2 (SNO-COX-2), but not non-nitrosylated COX-2, with progression of early-stage human breast cancer to invasive ductal carcinoma. Here, we used a 3D culture model of early-stage human breast cancer (MCF10DCIS cells) to investigate the relationship between SNO-COX-2 expression and mesenchymal/invasive tumor cell morphology. We find that SNO-COX-2, but not non-nitrosylated COX-2, closely associated with mesenchymal phenotypes induced by fibrillar type I collagen. Interestingly, invasive phenotypes did not associate with induction of the classic epithelial-to-mesenchymal transition (EMT) markers SNAIL , CDH2 (N-cadherin), and VIM (vimentin). By contrast TGFβ-1 strongly induced EMT-related transcripts, but not SNO-COX-2 protein expression or mesenchymal phenotypes. These observations suggest that in MCF10DCIS cells, SNO-COX-2 associates with mesenchymal phenotypes more strongly than non-nitrosylated COX-2 protein, or expression of classic EMT transcripts. In a mouse model with breast tumor heterogeneity, mesenchymal tumor regions also have increased SNO-COX-2 expression. Testing 300 distinct tumor microenvironment conditions, we find SNO-COX-2 protein expression is driven by inflammation, wound resolution, and cancer-associated factors, especially TNC, SPP1, decorin, fibrillar type I and III collagens, INF-γ, and IL-4/13, with evidence for specific extracellular matrix-ligand interactions driving both high and low SNO-COX-2 expression. In sum, in MCF10DCIS cells, expression of SNO-COX-2 is highly microenvironment-dependent and strongly associated with invasive/mesenchymal growth, indicating potential for SNO-COX-2 as a biomarker to assess risk of early-stage breast cancer progression.}, } @article {pmid40789889, year = {2025}, author = {Pintican, R and Duma, MM and Spada, AM and Szep, M and Eniu, D and Chiorean, A}, title = {COVID-19 pandemic resulted in more metastatic breast cancer cases at diagnosis.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {29296}, pmid = {40789889}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/epidemiology/virology ; Female ; *Breast Neoplasms/diagnosis/pathology/epidemiology ; Middle Aged ; Retrospective Studies ; Aged ; Adult ; SARS-CoV-2 ; Neoplasm Staging ; Pandemics ; Neoplasm Metastasis ; }, abstract = {The study aimed to assess the impact of the COVID-19 pandemic on breast cancer diagnosis, tumor characteristics, and staging in an Eastern-European country. This retrospective study included 11,635 breast cancer patients and clients presenting between March 2019 and March 2022. Patients were categorized into pre-pandemic, pandemic, and post-pandemic groups. Data included age, sex, pathology, tumor characteristics (histologic type, grade, ER/PR/HER2 status), and TNM staging. Statistical analysis compared these parameters across the three-time intervals.During the pandemic, breast cancer diagnosis decreased significantly compared to the pre-pandemic period (9.1% vs. 13.17%, p < 0.001) but increased post-pandemic (11%, p = 0.013). Invasive ductal carcinoma of non-special type (IDC-NST) was predominant in all three-time periods. Aggressive tumors (Nottingham grade 3, ER negative) increased during the pandemic and post-pandemic times. Molecular subtypes showed variations across time intervals, with triple-negative tumors rising significantly. Larger tumors, increased lymph node involvement (9-19%), and distant metastasis characterized the pandemic and post-pandemic periods. Compared to pre-pandemic patients, post-pandemic ones were 7 times more likely to be metastatic at diagnosis (p < 0.05). The COVID-19 pandemic led to a significant decrease in breast cancer diagnosis, particularly during the pandemic period. Tumors appeared more aggressive, with higher lymph node and distant metastatic involvement. The long-term prognosis and healthcare cost implications remain uncertain. These findings emphasize the need for adapted cancer screening programs and healthcare system readiness during pandemics.COVID-19 pandemic has resulted in a lower detection rate among patients diagnosed with breast cancer and increased TNM stage.}, } @article {pmid40787784, year = {2025}, author = {Köker, SC and Tsokanos, FF and El-Merahbi, R and Jha, AK and Cicatelli, K and Weber, P and Mhamane, A and Kaltenecker, D and Morigny, P and Loft, A and Klepac, K and Maida, A and Molocea, CE and Hass, D and Vogl, ES and Alfaro, AJ and Sun, W and Zitzelsberger, H and Unger, K and Szendrödi, J and Li, Y and Diaz, MB and Wolfrum, C and Bartelt, A and Herzig, S and Georgiadi, A}, title = {The TBLR1/TBL1 Co-Factor Complex Acts as a Transcriptional Checkpoint in the Brown Adipose Tissue Response to Prolonged Cold Exposure.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {39}, number = {15}, pages = {e70886}, pmid = {40787784}, issn = {1530-6860}, support = {450149205-TRR333/1//Deutsche Forschungsgemeinschaft (DFG)/ ; //Deutsches Zentrum für Herz-Kreislaufforschung (DZHK)/ ; J4224-B34//Austrian Science Fund (FWF)/ ; }, mesh = {Animals ; *Adipose Tissue, Brown/metabolism ; Mice ; *Cold Temperature ; Thermogenesis/physiology ; *Transducin/metabolism/genetics ; Histone Deacetylases/metabolism/genetics ; Energy Metabolism ; Male ; *Nuclear Proteins/metabolism/genetics ; Mice, Transgenic ; Mice, Inbred C57BL ; Lipolysis ; Adipocytes, Brown/metabolism ; Mice, Knockout ; *Transcription, Genetic ; Histone Deacetylase 3 ; }, abstract = {Brown adipose tissue (BAT) is a key thermogenic organ, whose activation in response to cold environmental temperatures and β-adrenergic stimulation requires the proper function of the NCOR/HDAC3 corepressor complex in brown adipocytes. The NCOR/HDAC3 complex is large and multi-component, including the transducin beta-like 1 (TBL1) and TBL1-related 1 (TBLR1) proteins. Loss of TBL1 in the hepatocytes and TBLR1 in the white adipocytes has been shown to impair fasting- and β-adrenergic-induced lipolysis. However, their roles in BAT thermogenesis remain unknown. Here, we report that deletion of TBLR1 alone in brown adipocytes does not impair the adaptive thermogenic response to prolonged cold exposure. In contrast, simultaneous deletion of TBL1 and TBLR1 dampens β-adrenergic-induced lipolysis and mitochondrial respiration in cultured mouse brown adipocytes. Transgenic mice with UCP1-Cre mediated double deletion of TBLR1 and TBL1 exhibit reduced whole-body energy expenditure during prolonged cold exposure, lower core body temperature, increased appearance of unilocular adipocytes in BAT, and suppressed expression of metabolic and myogenic PRDM16 target genes. Also, we present some evidence that TBLR1 and TBL1 interact with HDAC3 and PRDM16 in brown adipocytes, potentially suggesting a direct involvement in the PRDM16-controlled transcriptional program. These findings identify the TBLR1/TBL1 complex as a critical regulator of BAT adaptation to prolonged cold and systemic energy homeostasis, shedding light on the context-dependent functions of corepressor complexes.}, } @article {pmid40778244, year = {2025}, author = {Ho, KC and Huffman, KN and O'Connor, MJ and Sparks, P and Bozigar, C and Sterbling, H and Hansen, N}, title = {Triple-Positive PALB-2 Breast Cancer in a 27-Year-Old Male-to-Female Patient.}, journal = {Eplasty}, volume = {25}, number = {}, pages = {e27}, pmid = {40778244}, issn = {1937-5719}, abstract = {INTRODUCTION: There is a paucity of literature describing breast cancer prevention and screening guidelines in transgender patients. As more patients undergo gender-affirming care, breast cancer screening guidelines must be solidified for transgender patients. While there are no published incidence rates of breast cancer in the transgender population, case reports continue to underscore the prevalence of breast cancer in transgender females.

METHODS: A 27-year-old transgender woman with a family history of breast cancer and personal gender-affirming hormone therapy for 9 years was diagnosed with stage 3 invasive ductal carcinoma. The patient presented with a palpable breast lump and had never undergone breast imaging.

CONCLUSIONS: Breast cancer risk in transgender patients with long-term hormone therapy use is not well understood. Individuals, both male and female, with a family history of breast cancer; increased cumulative lifetime estrogen and progesterone use; or mutations in BRCA1, BRCA2, CHEK2, PTEN, or PALB2 genes have an increased risk for breast cancer. Hormonal treatment is often used alongside gender-affirming surgeries for development of female secondary sex characteristics in male-to-female patients. Although hormone therapy can have gender-affirming benefits, the increased lifetime exposure to estrogen and progesterone can increase the risk of breast cancer. Mammography guidelines for transgender patients vary by age, familial and genetic risk, as well as duration of hormone therapy. Three current organizations have published mammographic screening guidelines for transgender patients: the University of California San Francisco, the World Professional Association for Transgender Health, and the American College of Radiology. Future research should focus on substantiating these guidelines with greater data to produce evidence-based recommendations to guide the care of transgender patients.}, } @article {pmid40773373, year = {2025}, author = {Tucunduva, TCM and Zanetta, VC and Chala, LF and Torres, US and Viana, MP and Lee, MV and Silva, MM and Shimizu, C and Aguillar, VLN and de Mello, GGN}, title = {Advancements in Detection and Management of Ductal Carcinoma in Situ.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {45}, number = {9}, pages = {e240174}, doi = {10.1148/rg.240174}, pmid = {40773373}, issn = {1527-1323}, mesh = {Humans ; *Breast Neoplasms/therapy/diagnostic imaging/pathology/diagnosis ; Female ; *Carcinoma, Intraductal, Noninfiltrating/therapy/diagnostic imaging/pathology ; Mammography/methods ; }, abstract = {Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer characterized by neoplastic epithelial cells confined to the ductal system by the basement membrane without invasion of adjacent tissue. Its progression to invasive carcinoma is not understood fully, and currently, DCIS is considered a nonobligatory precursor of invasive breast cancer. However, DCIS is challenging because it includes a heterogeneous group of lesions with varied histologic, immunohistochemical, genetic, radiologic, and clinical characteristics. This heterogeneity is reflected in its natural progression, with some lesions remaining indolent, whereas others may develop into invasive ductal carcinoma. As DCIS detection rates rise due to mammographic screening, concerns about overdiagnosis and overtreatment have emerged, which has lead to a greater focus on understanding the biologic characteristics of DCIS. Radiologists need to understand the various imaging techniques used to evaluate DCIS. These include mammography, contrast-enhanced mammography, tomosynthesis, US, and MRI. By familiarizing themselves with each modality's various strengths and limitations, radiologists can effectively assess DCIS and develop the appropriate treatment plan. Although current guidelines advise treating all cases of DCIS with surgery, radiation therapy, and hormonal therapy, ongoing trials are investigating the safety of active surveillance for women with low-risk DCIS. There is interest in improving the risk stratification of DCIS lesions, and new advanced tools, such as radiomics, artificial intelligence, and other emerging techniques, are showing positive initial results and have the potential to become valuable solutions in the future. However, further studies and development still are needed before they can be widely adopted in clinical practice. Published under a CC BY 4.0 license See the invited commentary by Chikarmane in this issue.}, } @article {pmid40762843, year = {2025}, author = {Metser, U and Ali Mirshahvalad, S and Dayes, IS and Parpia, S and Levine, MN}, title = {[18]F-FDG PET/CT of Oligometastatic Disease in Locally Advanced Breast Cancer: PETABC Trial Post Hoc Analysis.}, journal = {Radiology}, volume = {316}, number = {2}, pages = {e243788}, doi = {10.1148/radiol.243788}, pmid = {40762843}, issn = {1527-1315}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/diagnostic imaging ; *Positron Emission Tomography Computed Tomography/methods ; *Fluorodeoxyglucose F18 ; Middle Aged ; Radiopharmaceuticals ; Prospective Studies ; Aged ; Adult ; *Neoplasm Metastasis/diagnostic imaging ; Neoplasm Staging ; }, abstract = {Background The optimal treatment of patients with oligometastatic breast cancer and the methods for selecting individuals who may benefit from metastasis-directed therapies are controversial. Purpose To determine the prevalence of oligometastatic disease (OMD; defined as five or fewer distant metastases) in patients with locally advanced breast cancer initially staged at fluorine 18 ([18]F) fluorodeoxyglucose (FDG) PET/CT or at CT and bone scintigraphy (CTBS), and to compare patterns of local-regional and distant metastatic disease. Materials and Methods This is a post hoc analysis of data from a prospective, multicenter randomized trial including participants with stage IIb (T3N0) or III invasive ductal carcinoma in the breast between December 2016 and April 2022. Participants were randomized for staging at [18]F-FDG PET/CT or at conventional chest, abdomen, and pelvis CTBS. The prevalence of OMD, sites of distant metastases, and extent of local-regional disease were compared using the χ[2] test or Fisher exact test. Logistic regression was used to assess the association between imaging and disease extent, with P < .05 indicating a statistically significant difference. Results The study included 369 participants (mean age, 53 years ± 13 [SD]). OMD was more common on [18]F-FDG PET/CT scans (19 of 180; 11%; 95% CI: 6.9, 15.9) than on CTBS scans (eight of 185; 4%; 95% CI: 2.2, 8.3; P = .03). Polymetastatic disease (more than five distant metastases) was also more common on [18]F-FDG PET/CT scans (24 of 180; 13%) than on CTBS scans (13 of 185; 7%; P = .04). Patients with OMD that was depicted on [18]F-FDG PET/CT and CTBS scans had axillary lymph node metastases, but [18]F-FDG PET/CT helped to detect extra-axillary regional lymphadenopathy, extra-regional lymph node metastases, and liver metastases more frequently than did CTBS (six of 19 [32%] vs one of eight [13%], three of 19 [16%] vs 0 of eight [0%], and six of 19 [32%] vs one of eight [13%], respectively; P = .63, .53, and .63, respectively). Conclusion At patient presentation, [18]F-FDG PET/CT helped to detect OMD in more than one in 10 participants with locally advanced breast cancer, which was more than 2.5 times more often than CTBS, and [18]F-FDG PET/CT helped to detect more extensive local-regional metastatic disease. ClinicalTrials.gov Identifier: NCT02751710 © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Ulaner in this issue.}, } @article {pmid40761960, year = {2025}, author = {Rios Herrera, O and De La Torre, M and Melnikau, S and Bogati, N and Debebe, K and Melhem, A and Johnson, RW and Pagé, J and Zamaro, A and Raeburn, T}, title = {Necrotizing Soft Tissue Infection of the Breast: A Unique Presentation of Underlying Invasive Breast Cancer.}, journal = {Cureus}, volume = {17}, number = {7}, pages = {e87310}, pmid = {40761960}, issn = {2168-8184}, abstract = {Necrotizing soft tissue infections (NSTIs) are life-threatening infections that most commonly affect the extremities, perineum, and abdominal wall. These infections begin with the presence of toxin-producing bacteria that invade through a defect in the skin barrier, such as a wound, laceration, trauma, or recent surgical incision. These bacteria cause subsequent tissue destruction and necrosis that can involve the superficial skin, subcutaneous tissue, fascia, and/or muscle. NSTIs can progress quickly, leading to severe sepsis, shock, and even death. NSTIs associated with the breast are an exceedingly rare occurrence, requiring early diagnosis and prompt surgical intervention. In this article, we report the case of a 46-year-old woman with an NSTI of the left breast, which required serial debridement initially, and subsequently a modified radical mastectomy given a pathological diagnosis of invasive ductal carcinoma.}, } @article {pmid40761476, year = {2025}, author = {Takahashi, A and Fujiwara, S and Takahashi, Y and Isoda, M and Yasukawa, M and Goda, K and Yamanaka, T and Yamashita, T and Yuguchi, S}, title = {A Case of Drug-Induced Pancytopenia due to Tamoxifen.}, journal = {Surgical case reports}, volume = {11}, number = {1}, pages = {}, pmid = {40761476}, issn = {2198-7793}, abstract = {INTRODUCTION: Tamoxifen (TAM) is a well-established treatment for hormone receptor-positive breast cancer with a known side-effect profile that includes hot flashes, genital bleeding, and diarrhea (0.1%-5%). Other notable side effects include liver damage, abnormal vaginal discharge, depression, dizziness, and headaches of unknown frequency. However, blood cell count reduction has not yet been reported as a side effect in Japan.

CASE PRESENTATION: A 46-year-old female patient was diagnosed with right breast cancer (cT1N0M0). The patient underwent partial right breast resection and sentinel lymph node biopsy. Owing to the positive surgical resection margin, a mastectomy was performed. Pathological analysis of the surgical specimen confirmed invasive ductal carcinoma (estrogen receptor [ER]: 95%, progesterone receptor [PgR]: 85%, HER2: 2+ [fluorescence in situ hybridization, FISH negative]), with macrometastasis in one sentinel lymph node. Postoperative treatment included chemotherapy (dose-dense adriamycin and cyclophosphamide [AC] to dose-dense paclitaxel [PTX]), irradiation, and TAM. While initial blood test results before starting TAM showed mild anemia (Hb: 8.9 g/dL Grade 2), a follow-up blood test 5 months after initiating TAM revealed a significant decrease in blood cell counts (white blood cell [WBC]: 2600/μL Grade 2, neutrophil [neu]: 0.55 × 10³/μL Grade 3, Hb: 7.7 g/dL Grade 2, platelet [PLT]: 13.3 × 10⁴/μL). Considering the onset of symptoms following TAM administration, drug-induced pancytopenia was suspected. TAM and its concomitant medication pregabalin were discontinued. However, the blood cell counts continued to decline, necessitating further investigation. Myelodysplastic syndrome (MDS) was suspected, leading to multiple bone marrow biopsies. However, no definitive hematological disorder was diagnosed. The patient received transfusions and granulocyte colony-stimulating factor (G-CSF) injections based on the blood cell count. Approximately 4 months after the onset of neutropenia, gradual recovery was observed and spontaneous remission occurred. Given the rarity of spontaneous recovery from MDS, TAM is considered a potential causative agent of the observed decline in blood cell counts.

CONCLUSIONS: We report a case of suspected drug-induced cytopenia associated with tamoxifen administration.}, } @article {pmid40757683, year = {2024}, author = {Cushman, CJ and Abaleka, F and Ibrahim, AF and Yalamanchili, K and Thirumala, S and Quick, D}, title = {Pembrolizumab Induced Recall Dermatitis Occurring 5 Years After Radiotherapy.}, journal = {Reports (MDPI)}, volume = {7}, number = {4}, pages = {}, pmid = {40757683}, issn = {2571-841X}, abstract = {Background and Clinical Significance: Radiation recall dermatitis (RRD) following immune checkpoint inhibitor (ICI) therapy has been infrequently reported. Case Presentation: We present a 47-year-old female patient who developed RRD of the breast following three doses of pembrolizumab administered as an adjuvant treatment post-nephrectomy for Stage III renal cell carcinoma (RCC). Notably, the affected breast had previously undergone external beam radiotherapy 247 weeks earlier for Stage IA invasive ductal carcinoma. She had received no prior chemotherapy at any point. RRD manifested as breast induration, erythema, and peau d'orange, and contraction of breast volume was noted following three cycles of pembrolizumab on week 17 (400 mg dose every 6 weeks). The dermatitis responded rapidly to systemic corticosteroids and no treatment interruption was needed. Conclusions: To date, this is the longest reported interval from completion of radiotherapy to RRD. A literature search underscores the variability in presentation and management of ICI-associated RRD.}, } @article {pmid40755326, year = {2025}, author = {Arshad, U and Rizvi, SF and Sohail, SK and Qamar, S and Sarfraz, R and Akhlaq, M}, title = {Expression of C-terminal tensin-like in breast carcinoma and its correlation with known prognostic factors.}, journal = {Polish journal of pathology : official journal of the Polish Society of Pathologists}, volume = {76}, number = {1}, pages = {10-15}, doi = {10.5114/pjp.2025.149282}, pmid = {40755326}, issn = {1233-9687}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/metabolism ; *Biomarkers, Tumor/analysis ; Middle Aged ; *Tensins/analysis/biosynthesis ; Prognosis ; *Carcinoma, Ductal, Breast/pathology/metabolism ; Aged ; Adult ; Immunohistochemistry ; }, abstract = {C-terminal tensin-like (Cten) is a marker for poorly differentiated breast cancer. We evaluated the immunohistochemical expression of Cten in invasive breast carcinoma in our population and correlated it with known histopathologic prognostic variables. Fifty-seven specimens of modified radical mastectomy diagnosed as invasive ductal carcinoma were collected. The histopathologic findings were noted independent of the result of Cten. According to the results of Cten immunohistochemistry, the tumors were categorized as negative/mild, moderate, or high expression and were statistically corelated with histologic findings. In our study, 47 (82.5%) cases showed negative/mild expression, 2 (3.5%) cases showed moderate staining, and 8 (14%) cases showed strong expression of Cten. Positive Cten was present in pT4 stage tumors. Similarly, grade III tumor showed moderate expression in 2 (3.5%) cases and strong staining in 8 (14%) cases. Posi-tive expression of Cten was observed in cases with lymphovascular invasion (LVI) and high axillary lymph nodal involvement (N3). All these poor prognostic factors were significantly associated with moderate to high expression of Cten. We found that tumor size and extent, histologic grade, LVI, and lymph node status were significantly associated with Cten expression. C-terminal tensin-like can be used as marker of poor prognosis in breast carcinoma.}, } @article {pmid40754350, year = {2025}, author = {Represa, M and Lima, O and Ávila, M and Rubiñán, P and Torres, C and Sansón-León, S and Lugo, J and Álvarez-Fernández, M and Rubianes, M and Legarra, JJ and Pérez-Rodríguez, MT}, title = {Impact of infectious diseases consultation and oral sequential therapy in the management of post-surgical mediastinitis.}, journal = {Enfermedades infecciosas y microbiologia clinica (English ed.)}, volume = {43}, number = {7}, pages = {383-388}, doi = {10.1016/j.eimce.2025.06.005}, pmid = {40754350}, issn = {2529-993X}, mesh = {Humans ; *Mediastinitis/drug therapy/microbiology/etiology ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; *Anti-Bacterial Agents/administration & dosage/therapeutic use ; *Referral and Consultation ; *Postoperative Complications/drug therapy/microbiology ; Administration, Oral ; *Cardiac Surgical Procedures/adverse effects ; Length of Stay/statistics & numerical data ; Treatment Outcome ; }, abstract = {INTRODUCTION: Post-cardiac surgery mediastinitis (PSM) is a serious, complex, and multifactorial complication of surgical procedures. Infectious diseases consultation (IDC) has demonstrated improvement in other complex infectious diseases. The objective of the study was to evaluate the impact of IDC in the management and outcome of patients with PSM.

METHODS: Observational retrospective study, of adult patients with PSM between January 2010 and June 2021. After January 2016, IDC was performed in all the patients with PSM. The primary endpoint was clinical success, a composite variable of clinical cure, and absence of adverse events, or recurrence. Also, in-hospital stay, and clinical cure was evaluated in patients that received oral sequential therapy (OST).

RESULTS: A total of 84 patients with PSM were included, 48 pre-IDC and 36 in IDC period. No differences in clinical success were observed between the two periods (pre-IDC 60% vs, IDC 77%, p=0.104). During the IDC period the rate of adequate targeted antibiotic treatment was higher (pre-IDC 71% vs. IDC 94%, p=0.016). Gram-negative bacilli infections (pre-IDC 42% vs. IDC 78%, p=0.002) and polymicrobial infections (pre-IDC 37% vs. IDC 63%, p=0.004) increased in the IDC period. Multivariate analysis did not show any variable associated with clinical success. OST was similar in both periods, and a shorter in-hospital stay was observed in the patients who underwent OST (no-OST, 70 days vs. OST, 44 days, p=0.003).

CONCLUSIONS: IDC was related with a higher adequate targeted antimicrobial therapy. We observed that OST offers a promising strategy in the management of this infection.}, } @article {pmid40750235, year = {2025}, author = {Makkawi, M and Alasiri, L and Alasmari, S}, title = {Assessing the Prevalence of Breast Tumors and Associated Abnormalities in Hematological and Coagulation Parameters in the Asir Region, Saudi Arabia.}, journal = {Annals of clinical and laboratory science}, volume = {55}, number = {3}, pages = {373-379}, pmid = {40750235}, issn = {1550-8080}, mesh = {Humans ; Saudi Arabia/epidemiology ; *Breast Neoplasms/epidemiology/blood/pathology ; Female ; Middle Aged ; Adult ; Retrospective Studies ; Prevalence ; *Blood Coagulation ; Aged ; Fibroadenoma/epidemiology/blood ; Young Adult ; }, abstract = {OBJECTIVE: This study investigates the prevalence and classifications of breast tumors in the Asir region over the last five years, together with abnormal hematological parameters and coagulation profiles prior to cancer therapy.

METHODS: This retrospective analysis, covering the period from 2018 to 2022, was conducted at Asir Central Hospital in Abha, Saudi Arabia. Data on demographics and tumor types were obtained from the medical records of 764 patients. Hematological parameters and coagulation profiles of 94 malignant breast cancer patients and control samples were compared using GraphPad Prism.

RESULTS: The majority of cases were benign breast disease (61%, 473), followed by malignant tumors (38%, 292). The most common benign subtypes were fibroadenoma (53.2%, 252 patients), fibrocystic breast alterations (12.6%, 60 patients), and fibroadenosis (9.9%, 47 patients). Among malignant tumors, invasive ductal carcinoma (82.1%, 240 patients), ductal carcinoma in situ (7.1%, 21 patients), and invasive lobular carcinoma (3.7%, 11 patients) predominated. Malignancy patients had lower HB, RBC, MCHC, MCH, MCV, and HCT, and higher RDW. In addition, INR was significantly lower than the control group.

CONCLUSIONS: Over the five-year period ending in 2022, the incidence rate of malignant breast cancer increased in the Asir region. Patients with such cancers show significant abnormalities in hematological parameters and coagulation profiles prior to treatment.}, } @article {pmid40748488, year = {2025}, author = {Christiaans, CHH and van Veen, FEE and Scheepe, JR and Blok, BFM}, title = {Patient satisfaction, quality of life, and catheter-related complications in long-term urinary catheter users: a nationwide survey.}, journal = {World journal of urology}, volume = {43}, number = {1}, pages = {470}, pmid = {40748488}, issn = {1433-8726}, support = {10310012110004//ZonMw,The Netherlands/ ; 10310012110004//ZonMw,The Netherlands/ ; }, mesh = {Humans ; Male ; *Quality of Life ; Female ; *Patient Satisfaction ; Aged ; *Urinary Catheterization/adverse effects/methods ; Middle Aged ; *Urinary Catheters/adverse effects ; Time Factors ; Surveys and Questionnaires ; Aged, 80 and over ; *Catheter-Related Infections/epidemiology ; Netherlands/epidemiology ; Catheters, Indwelling/adverse effects ; }, abstract = {PURPOSE: To compare patient satisfaction, quality of life, catheter-related complications between three types of catheterization in long-term urinary catheter users. To improve clinical decision-making for long-term urinary catheter users.

METHODS: A nationwide survey study was conducted from August to September 2024. Patients who apply clean intermittent catheterization (CIC), have an urethral indwelling catheter (IDC), or a suprapubic catheter (SPC), were identified through the MediReva database, a Dutch medical supplier. The survey was developed by structured consensus meeting and consisted of the ICIq-LTCqol and the EQ-5D-5 L.

RESULTS: 3320 patients participated in the study (response rate 33%). 2634 performed CIC, 383 had an IDC, and 303 had an SPC. 75.9% was male and the mean age was 72 years. CIC patients reported the best patient satisfaction and QoL scores. When corrected for multiple confounders IDC and SPC were independently associated with lower patient satisfaction and QoL scores. There was no difference in UTI incidence in the last 6 months between the groups.

CONCLUSIONS: This study shows differences in patient satisfaction, QoL and, catheter-related complications between three types of catheterization. Healthcare providers should be aware of the impact of bladder drainage methods on the patient satisfaction and QoL, especially for those using an IDC or SPC. This information can be of added value in the decision-making process of long-term bladder management.}, } @article {pmid40746925, year = {2025}, author = {Ayatollahi, H and Jafarian, AH and Pakize Moghadam, Z and Ayatollahi, Y and Ghayyem Hassankhani, G and Mehrad-Majd, H}, title = {Clinicopathological Characteristics of Breast Cancer Patients with Equivocal Immunohistochemistry: A Prevalence-Based Statistical Analysis.}, journal = {Iranian journal of pathology}, volume = {20}, number = {3}, pages = {273-279}, pmid = {40746925}, issn = {1735-5303}, abstract = {BACKGROUND & OBJECTIVE: Although the concordance between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) is generally high for HER2 scores of 3+ and 1+, discrepancies remain in cases scored as IHC 2+. This study aimed to evaluate HER2/neu gene amplification using FISH in breast cancer patients with IHC 2+ and to examine associated clinicopathological characteristics.

METHODS: This retrospective study included tissue samples from 369 women diagnosed with invasive ductal carcinoma of the breast and an equivocal HER2 IHC score (2+). These samples were further assessed for HER2 gene amplification using FISH. Demographic and clinicopathological data were collected and analyzed.

RESULTS: The mean age of patients was 51.6 ± 2.6 years. FISH analysis revealed no HER2 amplification in 72.6% of IHC 2+ cases, while 27.4% demonstrated amplification. HER2 amplification was significantly associated with younger age, higher histological grade, lymph node involvement, larger tumor size, and reduced survival rate. No significant association was observed between HER2 amplification and margin involvement.

CONCLUSION: HER2 amplification is a significant predictor of aggressive tumor behavior and may necessitate targeted therapy. In cases with IHC 2+, both FISH results and relevant clinicopathological features should be considered prior to initiating trastuzumab treatment.}, } @article {pmid40744681, year = {2025}, author = {Moradi, G and Ahmadinejad, N and Zarei, D and Sadighi, N}, title = {Sonographic Correlations With Histological Grade and Biomarker Profiles in Breast Invasive Ductal Carcinoma.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {8}, number = {8}, pages = {e70288}, pmid = {40744681}, issn = {2573-8348}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/diagnostic imaging/metabolism ; Middle Aged ; *Carcinoma, Ductal, Breast/pathology/diagnostic imaging/metabolism ; *Biomarkers, Tumor/analysis/metabolism ; Retrospective Studies ; Neoplasm Grading ; Adult ; Receptors, Estrogen/metabolism/analysis ; Erb-b2 Receptor Tyrosine Kinases/metabolism/analysis ; Receptors, Progesterone/metabolism/analysis ; *Ultrasonography, Mammary/methods ; Aged ; Prognosis ; Ki-67 Antigen/metabolism ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC), the most common breast cancer subtype, exhibits significant heterogeneity, limiting traditional prognostic markers. Molecular profiles improve precision, but imaging features may also reflect tumor biology.

AIMS: This study evaluates the predictive potential and clinical applicability of ultrasound features for determining tumor grade and molecular profiles in IDC.

METHODS AND RESULTS: A blinded radiologist retrospectively analyzed 109 IDC cases using the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) classification, evaluating ultrasound features such as lesion shape, margins, orientation, echo pattern, calcifications, vascularity, and lymph node involvement. Tumors were graded histologically (Scarff-Bloom-Richardson system) as low (grades 1 and 2) or high (grade 3). Immunohistochemistry determined estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 status. ER and PR positivity were defined as > 10% nuclear staining, HER2 graded on a 0-3+ scale, and Ki-67 positivity as ≥ 10% staining. Statistical analyses, including logistic and linear regression, examined correlations between ultrasound features and histological/molecular profiles. Among 109 women (mean age 48.4 ± 12.5 years), the mean tumor length and width were 21.83 ± 11.22 mm and 15.3 ± 6.97 mm, respectively. Histopathological grading revealed that grade 2 tumors were predominant (51%), while grade 1 and grade 3 tumors were observed in 25% and 24% of cases, respectively. ER and PR positivity were observed in 76.4% and 67.6% of cases, respectively. High-grade tumors were significantly associated with ER and PR negativity (p-value < 0.05). Ultrasound features associated with high-grade tumors included larger tumor length (p-value = 0.029). ER positive tumors had smaller axillary lymph nodes (p-value < 0.05). Likewise, PR positive tumors exhibited smaller suspicious axillary lymph nodes compared to PR negative cases (p-value = 0.004).

CONCLUSION: Sonographic features may correlate with histological grades and hormone receptor statuses in breast IDC, suggesting that ultrasound could aid in predictive assessment.}, } @article {pmid40743788, year = {2025}, author = {Broitman, S and Golan, O and Menes, TS and Freitas, VAR and Kessner, R and Neeman, R and Mauda-Havakuk, M and Nechyporenko, Y and Stav, D and Lazar, S and Mercer, D and Amitai, Y}, title = {Outcomes following pre-operative MRI-guided bracketing in breast cancer patients.}, journal = {Clinical imaging}, volume = {125}, number = {}, pages = {110567}, doi = {10.1016/j.clinimag.2025.110567}, pmid = {40743788}, issn = {1873-4499}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery/diagnostic imaging/pathology ; Middle Aged ; Retrospective Studies ; *Mastectomy, Segmental/methods ; *Magnetic Resonance Imaging/methods ; Margins of Excision ; Adult ; Aged ; Preoperative Care/methods ; Treatment Outcome ; }, abstract = {INTRODUCTION: This study aimed to evaluate the surgical outcomes of patients undergoing magnetic resonance imaging-guided bracketing (MRI-B) prior to breast-conserving therapy (BCT).

MATERIALS AND METHODS: This retrospective study included consecutive patients treated with BCT at our institution for invasive or in situ breast cancer between January 2016 and December 2022 and requiring MRI-B before surgery. Bracketing was performed by either inserting MRI-compatible wires or deploying clips under MRI guidance, with subsequent localization using mammography. Clinical, radiological, and pathological data were collected and correlated with positive surgical margins and imaging overestimation.

RESULTS: Among the 57 patients included, 10 (18 %) had positive surgical margins. Younger age (Mean: 56 vs 49 years) and the presence of ductal carcinoma in-situ (DCIS) or infiltrative lobular carcinoma (ILC) component (100 % vs 82 %) were most strongly associated with positive margins, although statistical significance was not reached (P = 0.11 and P = 0.149, respectively). MRI overestimated disease extent in 13 of 49 eligible patients (27 %). Overestimation was most strongly linked to isolated infiltrating ductal carcinoma (IDC; 38 % vs. 3 %, P = 0.008) and bracketed enhancing foci (54 % vs. 22 %, P = 0.084). During long-term follow-up, 2 patients (4 %) had local recurrence, and 3 patients (5 %) experienced distant recurrence.

CONCLUSIONS: MRI-B before BCT is associated with a clinically manageable rate of positive margins and local recurrence. However, optimizing patient selection is essential to minimize unnecessary bracketing and improve surgical outcomes.}, } @article {pmid40742538, year = {2026}, author = {Macedo, M and Agustí, E and Ganau, S and Úbeda, B and Sitges, C and Ribera-Perianes, J and Oses, G and Pascual, T and Mension, E and Vidal-Sicart, S and Bargalló, X}, title = {Preoperative localization of metastatic axillary lymph nodes using radioactive iodine seed before neoadjuvant chemotherapy. A one-step marking method for targeted axillary dissection.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {53}, number = {2}, pages = {890-898}, pmid = {40742538}, issn = {1619-7089}, mesh = {Humans ; *Iodine Radioisotopes ; Middle Aged ; Female ; *Breast Neoplasms/pathology/diagnostic imaging/surgery/drug therapy ; Axilla ; Lymphatic Metastasis ; Male ; *Neoadjuvant Therapy ; *Lymph Node Excision/methods ; Aged ; Adult ; Prospective Studies ; Preoperative Care ; }, abstract = {OBJECTIVE: To evaluate the reliability and effectiveness of using the radioactive iodine seed (RIS) as one-step target axillary dissection (TAD) procedure in breast cancer patients.

MATERIALS AND METHODS: This was a non-randomized, single-center, prospective study. Consecutive patients between May-2022 and November-2023 with breast cancer and axillary involvement (cN1) planned to receive NAC and TAD surgery were marked with RIS in the pathologically proven ALN. Radiation levels emitted by the patient were measured. On the day of surgery, the marked lymph node (MLN) and sentinel lymph node (SLN) were removed. We studied the identification rate (IR) and the concordance rate (CR) between the MLN and SLN.

RESULTS: Forty patients participated in the study (39 females, 1 male; mean age 53). Most of the patients included were diagnosed with invasive ductal carcinoma (92.5%). Half of the patients were hormone receptor positive and HER2 negative, and the other half were triple negative or HER2 positive. There was one suspicious ALN in the majority of breast cancer cases (72.5%). Average time from RIS placement to surgery was 157 days. IR of RIS were 100% and IR of SLN was 95%. CR between SLN and MLN was 52.5%. No complications in RIS placement and carriage were reported. No breast or axillary relapse were reported in a 16-34 month follow-up period. The radiation levels were low at distances greater than 0.5 m.

CONCLUSIONS: The use of RIS for TAD as a one-step procedure for axillary staging of cN1 breast cancer patients in a pre-NAC context is a reliable and effective radiologic marker placement procedure.}, } @article {pmid40736024, year = {2025}, author = {Fang, W and Kozai, Y and Acevedo, DS and Brodine, R and Gorrepati, HS and Arviso, N and Cote, P and Thompson, A and Gerdes, Z and Espinoza, A and Bergeron, N and Brownfield, A and Cheng, N}, title = {Cooperative CCL2/CCR2 and HGF/MET signaling enhances breast cancer growth and invasion associated with metabolic reprogramming.}, journal = {Cancer biology & therapy}, volume = {26}, number = {1}, pages = {2535824}, pmid = {40736024}, issn = {1555-8576}, support = {P30 CA168524/CA/NCI NIH HHS/United States ; R01 CA172764/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/metabolism/genetics ; *Chemokine CCL2/metabolism/genetics ; Animals ; *Proto-Oncogene Proteins c-met/metabolism/genetics ; Signal Transduction ; *Receptors, CCR2/metabolism/genetics ; Mice ; *Hepatocyte Growth Factor/metabolism/genetics ; Cell Proliferation ; Cell Line, Tumor ; Neoplasm Invasiveness ; Xenograft Model Antitumor Assays ; Metabolic Reprogramming ; }, abstract = {With over 60,000 cases diagnosed in women annually, ductal carcinoma in situ (DCIS) is the most common form of pre-invasive breast cancer in the US. Despite standardized therapy, under-treatment and over-treatment are prevailing concerns. By understanding the mechanisms regulating DCIS progression, we may develop tailored strategies to improve treatment. CCL2/CCR2 and HGF/MET signaling pathways are upregulated in breast cancers. Our studies indicate that these pathways cooperate to promote DCIS progression and metabolism. DCIS and IDC tissues were immunostained for CCL2 and HGF expression. DCIS.com and HCC1937 cells were analyzed for cell proliferation through PCNA immunostaining, apoptosis through cleaved caspase-3 immunostaining, and invasion through Matrigel transwell assays. AKT, AMPK, p42/44MAPK and PKC activities were analyzed in vitro through immunoblot and pharmacologic inhibition. CCL2 and HGF-mediated metabolism were analyzed by LC-MS. Glucose uptake and lactate production were measured biochemically. CCR2 and MET were targeted in breast xenografts through CCR2 knockout and treatment with Merestinib. Significant associations between CCL2 and HGF were detected in DCIS and IDC tissues. CCL2 and HGF co-treatment enhanced breast cancer cell growth, survival, and invasiveness over individual CCL2 or HGF treatment. These CCL2/HGF-mediated phenotypes were associated with metabolic changes including glycolysis and increased AKT, AMPK, p42/44MAPK and PKC signaling. CCL2/HGF-mediated glycolysis was reduced with AKT, AMPK and p42/44MAPK inhibition. CCR2 knockout combined with Merestinib treatment inhibited growth, survival, and stromal reactivity of breast xenografts more than CCR2 or MET targeting alone. CCL2/CCR2 and HGF/MET cooperate to enhance breast cancer progression and metabolic reprogramming.}, } @article {pmid40734184, year = {2025}, author = {Bai, Y and Guo, X and Liu, K and Zheng, B and Wei, Y and Wang, Y and Zhang, W and Luo, Q and Yin, J and Wu, L and Li, Y and Zhang, Y and Chen, A and Wang, X and Xu, X and Liu, C and Jin, X}, title = {SpaSEG: unsupervised deep learning for multi-task analysis of spatially resolved transcriptomics.}, journal = {Genome biology}, volume = {26}, number = {1}, pages = {230}, pmid = {40734184}, issn = {1474-760X}, support = {2022YFC3400400//National Key Research and Development Program of China/ ; }, mesh = {Humans ; *Deep Learning ; *Gene Expression Profiling/methods ; *Transcriptome ; Breast Neoplasms/genetics ; *Unsupervised Machine Learning ; Female ; Carcinoma, Ductal, Breast/genetics ; }, abstract = {Spatially resolved transcriptomics (SRT) for characterizing spatial cellular heterogeneities in tissue environments requires systematic analytical approaches to elucidate gene expression variations within their physiological context. Here, we introduce SpaSEG, an unsupervised deep learning model utilizing convolutional neural networks for multiple SRT analysis tasks. Extensive evaluations across diverse SRT datasets generated by various platforms demonstrate SpaSEG's superior robustness and efficiency compared to existing methods. In the application analysis of invasive ductal carcinoma, SpaSEG successfully unravels intratumoral heterogeneity and delivers insights into immunoregulatory mechanisms. These results highlight SpaSEG's substantial potential for exploring tissue architectures and pathological biology.}, } @article {pmid40730795, year = {2025}, author = {Murugesan, GK and McCrumb, D and Soni, R and Kumar, J and Nuernberg, L and Pei, L and Wagner, U and Granger, S and Fedorov, AY and Moore, S and Van Oss, J}, title = {AI generated annotations for Breast, Brain, Liver, Lungs, and Prostate cancer collections in the National Cancer Institute Imaging Data Commons.}, journal = {Scientific data}, volume = {12}, number = {1}, pages = {1317}, pmid = {40730795}, issn = {2052-4463}, support = {75N91019D00024/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; National Cancer Institute (U.S.) ; Male ; United States ; *Artificial Intelligence ; Tomography, X-Ray Computed ; Magnetic Resonance Imaging ; Female ; *Neoplasms/diagnostic imaging ; Prostatic Neoplasms/diagnostic imaging ; Breast Neoplasms/diagnostic imaging ; }, abstract = {The Artificial Intelligence in Medical Imaging (AIMI) initiative aims to enhance the National Cancer Institute's (NCI) Image Data Commons (IDC) by releasing fully reproducible nnU-Net models, along with AI-assisted segmentation for cancer radiology images. In this extension of our earlier work, we created high-quality, AI-annotated imaging datasets for 11 IDC collections, spanning computed tomography (CT) and magnetic resonance imaging (MRI) of the lungs, breast, brain, kidneys, prostate, and liver. Each nnU-Net model was trained on open-source datasets, and a portion of the AI-generated annotations was reviewed and corrected by board-certified radiologists. Both the AI and radiologist annotations were encoded in compliance with the Digital Imaging and Communications in Medicine (DICOM) standard, ensuring seamless integration into the IDC collections. By making these models, images, and annotations publicly accessible, we aim to facilitate further research and development in cancer imaging.}, } @article {pmid40730731, year = {2025}, author = {Pratt, CG and McClelland, PH and Long, SA and Moore, AN and Lewis, JD and Heelan, AA}, title = {The Metaplastic Conundrum: A National Cancer Database Analysis of Metaplastic versus Triple-Negative Ductal Breast Cancer.}, journal = {Annals of surgical oncology}, volume = {32}, number = {11}, pages = {8448-8460}, pmid = {40730731}, issn = {1534-4681}, mesh = {Humans ; Female ; *Triple Negative Breast Neoplasms/pathology/therapy/mortality ; Middle Aged ; Survival Rate ; Databases, Factual ; *Carcinoma, Ductal, Breast/pathology/therapy/mortality ; *Neoadjuvant Therapy/mortality ; Metaplasia/pathology ; Prognosis ; Follow-Up Studies ; Aged ; Adult ; Mastectomy/mortality ; Chemotherapy, Adjuvant/mortality ; Breast Neoplasms/pathology ; }, abstract = {BACKGROUND: Historically, treatment approaches for metaplastic breast cancer (MpBC) have mirrored that of triple-negative ductal breast cancer (TN-IDC), yet MpBC has persistently worse survival. This study describes rates and response to neoadjuvant systemic therapy (NAC) for MpBC and evaluates survival between triple-negative MpBC (TN-MpBC), biomarker-positive MpBC (nTN-MpBC), and TN-IDC by treatment approach.

METHODS: The National Cancer Database was queried for females diagnosed with clinically non-metastatic MpBC or TN-IDC from 2011 to 2021. One-to-one propensity score matching between TN-MpBC and TN-IDC patients was performed.

RESULTS: Of 5575 MpBC patients, surgery and chemotherapy rates were high. For patients who received systemic therapy and surgery, an adjuvant approach was favored; however, NAC for TN-MpBC increased from 18.3 to 31.5% by 2021. Higher rates of NAC non-response and lower overall survival were found among MpBC cohorts compared with TN-IDC. For MpBC, an adjuvant approach had significantly better survival than other systemic therapy sequences. When evaluated by pathologic response to NAC, a partial or non-response had worse survival compared with complete response or not undergoing NAC. On Cox proportional hazard regression of matched patients, NAC had an adjusted hazard ratio of 2.56 (1.36-4.79) compared with not undergoing NAC.

CONCLUSION: MpBC is predominantly treated with surgery and systemic therapy, with increasing rates of NAC for TN-MpBC. However, patients with MpBC have inferior survival to TN-IDC, and NAC for MpBC is associated with worse survival compared with other systemic therapy sequences, unless a complete pathologic response is achieved. These findings reinforce the need for systemic treatment sequence optimization for MpBC.}, } @article {pmid40727978, year = {2025}, author = {Kahlon, N and Baddam, S and Bansal, N and Qureshi, Z and Maradana, J}, title = {Dynamic Changes in Breast Cancer Receptor Status: A Case Report Highlighting the Importance of Repeat Biopsies in Guiding Treatment Strategies.}, journal = {Journal of investigative medicine high impact case reports}, volume = {13}, number = {}, pages = {23247096251362974}, pmid = {40727978}, issn = {2324-7096}, mesh = {Humans ; Female ; Middle Aged ; *Receptors, Estrogen/metabolism ; *Erb-b2 Receptor Tyrosine Kinases/metabolism ; *Breast Neoplasms/pathology/therapy/metabolism ; Receptors, Progesterone/metabolism ; Biopsy ; *Carcinoma, Ductal, Breast/pathology/metabolism ; Immunohistochemistry ; Neoplasm Recurrence, Local/pathology ; *Triple Negative Breast Neoplasms/pathology ; }, abstract = {Breast cancer receptor status plays a critical role in treatment selection, yet receptor evolution throughout disease progression remains a significant challenge. This case describes a 58-year-old female initially diagnosed with estrogen receptor (ER)-positive (95%), progesterone receptor (PR)-negative (<5%), human epidermal growth factor receptor 2 (HER2)-negative (immunohistochemistry [IHC] 0, fluorescence in situ hybridization-negative) invasive ductal carcinoma. Over 6 years, her tumor transitioned to triple-negative breast cancer at recurrence, then reacquired ER expression (80%) in metastatic mediastinal lymph nodes. HER2 status evolved from IHC 0 → HER2-low (IHC 1+ → IHC 2+), directly influencing therapy selection. These receptor changes led to major systemic treatment modifications, including endocrine therapy, immunotherapy, CDK4/6 inhibitors, and antibody-drug conjugates. Given the extended response duration and improved tolerability of targeted therapies, accurate receptor assessment is essential to ensure that patients receive the most effective treatment. Literature reports receptor discordance rates of ER loss (19%), PR loss (34%), and HER2 fluctuations (15%), reinforcing the necessity of biopsy-driven treatment adaptation. While serial biopsies remain invasive, they provide essential molecular insights that optimize systemic therapy choices, allowing patients to remain on the most appropriate, well-tolerated regimen for as long as possible. This case highlights the clinical significance of receptor evolution and advocates for biopsy-guided precision oncology in metastatic breast cancer management. Ensuring accurate receptor reassessment through periodic molecular profiling can maximize therapeutic efficacy, improving response rates, treatment tolerability, and overall patient outcomes.}, } @article {pmid40727474, year = {2025}, author = {Gu, W and Yuan, J and Dong, M and Sheng, J and Jiang, K}, title = {Case Report: Advanced breast invasive ductal carcinoma with erysipeloid cutaneous metastasis misdiagnosed as erysipelas.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1535421}, pmid = {40727474}, issn = {2234-943X}, abstract = {BACKGROUND: Breast cancer has become the second most common cancer after lung cancer. Patients may present with skin manifestations at the time of initial diagnosis, while erysipel-like carcinoma typically appears later, following initial treatment. This delay increases the risk of misdiagnosis.

CASE PRESENTATION: The patient was a 51-year-old female. A modified radical mastectomy for left breast carcinoma (pT2N3M0, stage IIIC; tumor size 4.6 cm × 4.5 cm × 1.6 cm, 14/21 axillary lymph nodes involved), HER2-positive type, was performed on April 21, 2021. In April 2024 (three years post-surgery), the patient developed unexplained redness and swelling in the skin of the left upper limb, accompanied by increased skin temperature. This was misdiagnosed as erysipelas of the upper limb. After one week of antibiotic treatment, the redness and swelling slightly subsided. In May 2024, the patient experienced dizziness and headaches without any obvious cause. Enhanced cranial MRI revealed multiple brain metastases, with possible lymph node metastasis in the left cervical region. The patient underwent whole-brain radiotherapy. During radiotherapy, erysipelas-like rashes developed on the left chest wall, upper limb, and right breast skin. In June 2024, a skin biopsy of the chest wall confirmed cutaneous metastasis. Following systemic anti-tumor treatment, both the skin and brain metastasis improved.

CONCLUSION: Pathological biopsy should be emphasized when breast cancer patients develop localized rashes. Understanding the unique inflammatory manifestations of cutaneous metastasis is crucial for breast oncologists to enable early diagnosis, timely treatment, and improved overall survival.}, } @article {pmid40727336, year = {2025}, author = {Yang, Y and Cheng, L}, title = {Correlation between ultrasonic features and expression of immunohistochemical factors in invasive ductal carcinoma of the breast.}, journal = {Quantitative imaging in medicine and surgery}, volume = {15}, number = {7}, pages = {6044-6052}, pmid = {40727336}, issn = {2223-4292}, abstract = {BACKGROUND: Breast cancer is the most common malignancy among women globally, with invasive ductal carcinoma (IDC) accounting for approximately 80% of all breast cancer cases. IDC exhibits significant heterogeneity in terms of pathological manifestations and prognosis, which are largely influenced by the expression of immunohistochemical (IHC) factors. The study aimed to investigate the correlation between ultrasonic features and the expression of IHC factors in IDC of the breast.

METHODS: A retrospective analysis was conducted of the clinical data of patients with IDC confirmed by surgery and pathology from January 2019 to December 2022, with ultrasonography performed pre-operation and standard sonograms retained. Specifically, the correlation between sonographic signs and the expression of IHC factors such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), E-cadherin, and Ki-67 was investigated using the univariate and binary logistic regression analyses. E-cadherin was included due to its role in epithelial-mesenchymal transition and metastasis in IDC. Key sonographic features (e.g., Adler grade, morphology, posterior echo) and IHC factors were analyzed.

RESULTS: The study identified significant associations between specific ultrasonic features and IHC factor expression. For ER expression, irregular shape [odds ratio (OR) =1.694, 95% confidence interval (CI): 1.032-2.309, P=0.011], reduced posterior echo (OR =1.904, 95% CI: 1.211-2.901, P=0.008), and hyperechoic halo (OR =3.705, 95% CI: 1.277-7.903, P=0.003) were associated with ER-positive expression, while Adler grade II-III was associated with ER-negative expression (OR =0.390, 95% CI: 0.127-0.745, P<0.001). For PR expression, hyperechoic halo (OR =4.905, 95% CI: 2.664-11.231, P=0.01) was associated with PR-positive expression, while smooth margin (OR =0.513, 95% CI: 0.132-0.784, P<0.001) and maximum diameter ≥2 cm (OR =0.622, 95% CI: 0.267-0.874, P=0.005) were associated with PR-negative expression. Calcification (OR =1.806, 95% CI: 1.237-4.584, P=0.002) and maximum diameter ≥2 cm (OR =1.409, 95% CI: 1.194-2.385, P=0.01) were associated with HER-2-positive expression. Lymphatic metastasis (OR =1.450, 95% CI: 1.057-2.328, P=0.03) and Adler grade II-III (OR =0.704, 95% CI: 0.406-1.242, P=0.02) were associated with E-cadherin-positive expression. Reduced posterior echo was associated with Ki-67-negative expression (OR =0.307, 95% CI: 0.106-0.684, P=0.02). The areas under the ROC curves for each IHC factor were as follows: ER, 0.832; PR, 0.756; HER-2, 0.675; E-cadherin, 0.684; Ki-67, 0.703.

CONCLUSIONS: Since IHC factors are correlated with ultrasonic features to some extent, their biological behaviors can be preliminarily identified through analyses of their sonographic features, thereby providing a reference for clinically individualized treatment regimens and prognosis evaluation of patients.}, } @article {pmid40726055, year = {2025}, author = {Blaas, L and Matta, L}, title = {SAF-guarding the cuff: Could shoulder fat cells combat fibrosis?.}, journal = {The Journal of physiology}, volume = {603}, number = {23}, pages = {7631-7633}, doi = {10.1113/JP289055}, pmid = {40726055}, issn = {1469-7793}, } @article {pmid40722501, year = {2025}, author = {Güler, M and Sart, G and Algorabi, Ö and Adıguzel Tuylu, AN and Türkan, YS}, title = {Breast Cancer Classification with Various Optimized Deep Learning Methods.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {14}, pages = {}, pmid = {40722501}, issn = {2075-4418}, abstract = {Background/Objectives: In recent years, there has been a significant increase in the number of women with breast cancer. Breast cancer prediction is defined as a medical data analysis and image processing problem. Experts may need artificial intelligence technologies to distinguish between benign and malignant tumors in order to make decisions. When the studies in the literature are examined, it can be seen that applications of deep learning algorithms in the field of medicine have achieved very successful results. Methods: In this study, 11 different deep learning algorithms (Vanilla, ResNet50, ResNet152, VGG16, DenseNet152, MobileNetv2, EfficientB1, NasNet, DenseNet201, ensemble, and Tuned Model) were used. Images of pathological specimens from breast biopsies consisting of two classes, benign and malignant, were used for classification analysis. To limit the computational time and speed up the analysis process, 10,000 images, 6172 IDC-negative and 3828 IDC-positive, were selected. Of the images, 80% were used for training, 10% were used for validation, and 10% were used for testing the trained model. Results: The results demonstrate that DenseNet201 achieved the highest classification accuracy of 89.4%, with a precision of 88.2%, a recall of 84.1%, an F1 score of 86.1%, and an AUC score of 95.8%. Conclusions: In conclusion, this study highlights the potential of deep learning algorithms in breast cancer classification. Future research should focus on integrating multi-modal imaging data, refining ensemble learning methodologies, and expanding dataset diversity to further improve the classification accuracy and real-world clinical applicability.}, } @article {pmid40716754, year = {2025}, author = {Nguyen, NJ and Liu, K and Lajkosz, K and Bernardino, R and Yin, LB and Hollemans, E and Kroon, LJ and Fleshner, N and van Leenders, GJLH and Iczkowski, KA and van der Kwast, TH and Downes, MR}, title = {Magnetic Resonance Imaging (MRI)-Adapted Prostate Cancer Risk Tool Incorporating Cribriform and Intraductal Carcinoma.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {38}, number = {12}, pages = {100852}, doi = {10.1016/j.modpat.2025.100852}, pmid = {40716754}, issn = {1530-0285}, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/diagnostic imaging/surgery ; Middle Aged ; Aged ; Risk Assessment/methods ; *Magnetic Resonance Imaging ; Neoplasm Grading ; Prostatectomy ; Image-Guided Biopsy ; *Carcinoma, Intraductal, Noninfiltrating/pathology/diagnostic imaging ; }, abstract = {Current prostate cancer risk stratification tools are not adapted for magnetic resonance imaging (MRI)-targeted biopsies and do not include the presence of cribriform carcinoma/intraductal carcinoma (CC/IDC), an independent predictor of adverse clinical outcomes. We developed an MRI-adapted prostate cancer risk tool (MAPCaRT), which incorporates CC/IDC presence to the Cancer of the Prostate Risk Assessment (CAPRA) tool. We compared the prognostic power of MAPCaRT with that of CAPRA in MRI-targeted biopsies (n = 266, 2015-2023) and systematic-only biopsies (n = 1291, 2010-2018) that had matched radical prostatectomy. MAPCaRT employs the aggregate core count method for MRI-targeted lesions to calculate percent positive biopsy cores and uses the radiological stage when assessing MRI-targeted biopsies. Point attribution for CC/IDC presence and Gleason score was determined using a Cox proportional hazards model that included the CAPRA score, Gleason score, and CC/IDC status. Based on calculated MAPCaRT and CAPRA scores, patients were classified into the low-risk (0-2), intermediate-risk (3-5), or high-risk (6+) group. Model performance was assessed via the Kaplan-Meier curves, Harrell C-indices, and decision curve analysis for biochemical recurrence-free survival (BCR-FS) and event-free survival (EFS) (metastasis/cancer-specific death). CC/IDC was present in 84 of 266 (32%) MRI-targeted biopsies and 293 of 1291 systematic-only biopsies (23%). The median follow-up time was 3.4 years (IQR, 2.3-5.5 years) for the MRI-targeted biopsy cohort and 5.9 years (IQR, 3.4-8.1 years) for the systematic biopsy cohort. In the MRI-targeted biopsy cohort, MAPCaRT showed substantial improvement of the C-index compared with CAPRA (0.635 vs 0.574, P = .045) and greater net clinical benefit for 4-year BCR-FS. In the systematic biopsy cohort, MAPCaRT demonstrated improved C-index for BCR-FS (0.696 vs 0.655, P < .001) and greater net clinical benefit for 5-year BCR-FS and EFS. Other model performance metrics were marginally better with MAPCaRT. In summary, we developed MAPCaRT (prostatecancercalculator.lmp.utoronto.ca), a modified version of CAPRA incorporating CC/IDC presence, which demonstrated improved BCR-FS and EFS predictions. This may result in better clinical guidance for disease management decisions.}, } @article {pmid40719068, year = {2025}, author = {Kim, Y and Chae, SH and Lee, D and Lee, BS and Lim, J and Jung, HI and Kim, KH and Kwak, B}, title = {Alternative Models for Anticancer Drug Discovery From Natural Products Using Binary Tumor-Microenvironment-on-a-Chip.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {40}, pages = {e07944}, pmid = {40719068}, issn = {2198-3844}, support = {RS-2025-02223058//Korea Ministry of Environment (MOE)/ ; RS-2019-NR040057//Ministry of Science, ICT and Future Planning/ ; RS-2021-NR059240//Ministry of Science, ICT and Future Planning/ ; }, mesh = {*Tumor Microenvironment/drug effects ; *Biological Products/pharmacology ; *Antineoplastic Agents/pharmacology ; *Drug Discovery/methods ; Animals ; Humans ; *Lab-On-A-Chip Devices ; Mice ; Cell Line, Tumor ; }, abstract = {The efficacy evaluation of anticancer drugs derived from natural products has traditionally relied on animal models, highlighting the need for more efficient preclinical assessment platforms. In this study, a binary tumor-microenvironment-on-a-chip (T-MOC) system is introduced to assess the therapeutic potential of illudin S and roridin E, two cytotoxic compounds derived from Omphalotus japonicus and Podostroma cornu-damae, respectively. The binary T-MOC model integrates independently developed vascular and invasive ductal carcinoma compartments, effectively mimicking in vivo drug delivery barriers and physiological dynamics. Using this model, illudin S demonstrates strong anticancer effects but exhibits high toxicity, particularly in the lung and liver, indicating a narrow therapeutic window. Roridin E demonstrates potent activity at low concentrations but exhibits high toxicity, especially in the liver and skin. Additionally, morphological analysis is performed to predict drug delivery and distribution characteristics, revealing anisotropic remission and the influence of microenvironmental factors on drug response. This study underscores the potential of the binary T-MOC system as an alternative platform for anticancer drug evaluation, enabling efficient preclinical validation while reducing reliance on animal models.}, } @article {pmid40717412, year = {2025}, author = {Rattanapitoon, SK and La, N and Rattanapitoon, NK}, title = {Superb Microvascular Imaging and Angiogenesis Markers in IDC: Further Considerations.}, journal = {Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine}, volume = {44}, number = {12}, pages = {2383}, doi = {10.1002/jum.70016}, pmid = {40717412}, issn = {1550-9613}, } @article {pmid40709968, year = {2025}, author = {Pascual-Vera, B and Doron, G and Inozu, M and García, F and Belloch, A}, title = {The Mediating Role of Misinterpretations and Neutralizing Responses to Unwanted Intrusive Thoughts in Obsessive-Compulsive Spectrum Disorders.}, journal = {European journal of investigation in health, psychology and education}, volume = {15}, number = {7}, pages = {}, pmid = {40709968}, issn = {2254-9625}, support = {RTI2018-098349-B-I00//The study was partially supported by the Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigación (Spain) & Fondos FEDER UE [RTI2018-098349-B-I00). This research received no external funding./ ; RTI2018-098349-B-I00//The study was partially supported by the Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigación (Spain) & Fondos FEDER UE [RTI2018-098349-B-I00). This research received no external funding./ ; }, abstract = {Background. Cognitive-behavioral theories suggest that obsessions in obsessive-compulsive disorder (OCD) develop from maladaptive misinterpretations and coping strategies of unwanted intrusive thoughts (UITs). Models of Body Dysmorphic Disorder (BDD) and Illness Anxiety Disorder (IAD) propose that these symptoms stem from similar misinterpretations of common UITs relating to perceived defects in appearance and illness. This study examines whether maladaptive misinterpretations and control strategies leading to the escalation of obsessional UITs to OCD symptoms also have a similar effect on the development of BDD and IAD. More specifically, we examined whether misinterpretations and neutralizing responses mediate the associations between the frequency of disorder-specific UITs and symptoms of these disorders. Method. A total of 625 non-clinical participants from four countries completed the Questionnaire of Unpleasant Intrusive Thoughts (QUIT) that assesses OCD, BDD and IAD-related UITs and their associated misinterpretations and neutralizing strategies, as well as self-report measures of OCD, BDD, and IAD symptoms. Parallel multiple mediation models were conducted. Results. The frequency of OCD, BDD and IAD-related UITs predicted symptoms of each disorder. Dysfunctional appraisals and neutralizing behaviors mediated the associations between disorder-specific UITs and symptoms in OCD and IAD. The IAD model accounted for a smaller proportion of variance than the OCD model. No mediating effects were found for BDD symptoms. Conclusions. Experiencing disturbing UITs is a transdiagnostic risk factor of OCD, BDD and IAD, and is associated with symptoms of these disorders. Maladaptive interpretation of UITs and neutralizing strategies should be specific targets in the assessment and treatment of OCD and IAD. The absence of mediation effects for BDD could be due to the limitations observed on the self-report used to assess BDD symptoms and/or the low relevance of the misinterpretations and control strategies assessed by the QUIT, which are more typically endorsed by individuals with OCD.}, } @article {pmid40707709, year = {2025}, author = {Bareket, O and Reifen-Tagar, M and Saguy, T}, title = {Ambivalent sexism predicts Israelis' gendered preferences in the Gaza hostage crisis.}, journal = {Communications psychology}, volume = {3}, number = {1}, pages = {113}, pmid = {40707709}, issn = {2731-9121}, abstract = {Gender-based prioritization in life-or-death decisions has long shaped crisis responses, from natural disasters to wartime evacuations. This study examined psychological predictors of public support for such prioritization, using the case of Israeli hostages abducted by Hamas terrorist organization on October 7, 2023. Across two hostage release deals-one in November 2023 and another in January 2025-women were systematically prioritized, leaving abducted men in captivity. Analyses of a representative Jewish Israeli sample (N = 1171) regarding the November 2023 deal, reveal that hostile sexism, marked by resentment toward women, predicts opposition to prioritizing women's release. Conversely, benevolent sexism, casting women as needing protection, predicts support for women's prioritization (particularly for mothers). Even after accounting for demographics and broader ideologies, sexist attitudes emerge as key predictors of gender-based preferences in public opinion. Hostile and benevolent sexism operate here largely independently, with no credible evidence for an interaction, suggesting distinct psychological pathways. Respondent's gender plays a minor role, though benevolent sexism predicts a stronger protective bias toward women hostages among men than among women. These findings underscore how hostile sexism can disadvantage women, while benevolent sexism can reinforce women's vulnerability but demands men's sacrifice. Although decisions about hostage release may appear purely pragmatic on the surface, divergent public views on the matter may reflect gendered biases that emerge in high-stakes, life-or-death contexts-potentially more than impartial, need-based considerations.}, } @article {pmid40705266, year = {2025}, author = {Mukhtar, RA and Dimitroff, K and Yau, C and Chien, AJ and Connolly, EP and Howard-McNatt, M and Rao, R and Ladores, V and Golshan, M and Sauder, CA and Ahmed, K and Lancaster, R and Fox, J and Gutnik, L and Lee, MC and Tchou, J and Prionas, N and Arciero, CA and Reyna, C and Kuerer, H and Switalla, K and Taunk, N and Tuttle, TM and Moran, MS and Postlewait, LM and Perlmutter, J and DeMichele, A and Yee, D and Hylton, N and Symmans, WF and Rugo, HS and Shatsky, R and Isaacs, C and Esserman, LJ and Van't Veer, L and Boughey, JC}, title = {Impact of Neoadjuvant Chemotherapy on Surgical Outcomes and Conversion to Node-Negativity in Invasive Lobular Breast Cancer: Analysis of Molecularly High-Risk Tumors by Histologic Subtype on the I-SPY2 Clinical Trial.}, journal = {Annals of surgical oncology}, volume = {32}, number = {11}, pages = {8243-8253}, pmid = {40705266}, issn = {1534-4681}, support = {K08 CA256047/CA/NCI NIH HHS/United States ; P01 CA210961/CA/NCI NIH HHS/United States ; K08CA256047/CA/NCI NIH HHS/United States ; P01CA210961/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/analysis/genetics/metabolism ; *Breast Neoplasms/drug therapy/genetics/pathology/surgery ; *Carcinoma, Ductal, Breast/drug therapy/genetics/pathology/surgery ; *Carcinoma, Lobular/drug therapy/genetics/pathology/surgery ; Chemotherapy, Adjuvant ; Follow-Up Studies ; Lymph Node Excision ; *Lymph Nodes/pathology ; Lymphatic Metastasis ; *Mastectomy ; *Neoadjuvant Therapy ; Neoplasm Invasiveness ; Prognosis ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) has lower response rates to neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma. While ILC often has low-risk biology, there is a high-risk subset within this heterogeneous tumor type. We compared surgical treatment and response rates by histology in I-SPY2, a multicenter NAC trial.

METHODS: We evaluated 1329 patients with stage II-III breast cancer and high-risk 70-gene assay. Patients with classic, pleomorphic, or mixed lobular/ductal histology were included in the lobular cohort. We evaluated rates of mastectomy, positive margins, axillary dissection, and conversion from clinical node-positive (cN+) to pathologic node-negative (ypN-) status after NAC.

RESULTS: Overall, 124 patients (9.3%) had lobular histology, with 69% being hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-). There was no difference in mastectomy rate (57.2% for lobular vs. 55.8% for non-lobular). The ILC cohort had more positive margins after lumpectomy than the non-ILC cohort (21.2% vs. 7.9%; p = 0.023). Within cN0 cases, axillary dissection was significantly more common among the lobular cases (24.1% vs. 14.0%; p = 0.039). Conversion from cN+ to ypN0 did not differ statistically between lobular and non-lobular cases (40.9% vs. 51.2%; p = 0.11). The nodal conversion rate among cN+lobular tumors was 30.6% in HR+/HER2-, 72.7% in HER2+, and 66.7% in triple-negative cases.

CONCLUSIONS: These data demonstrate the challenges of surgical management for ILC but hold promise that molecular classification can improve treatment selection. While high genomic risk is generally less common among ILC, our findings suggest that gene expression assays in cN+ILC patients can identify a subset who may benefit from NAC.}, } @article {pmid40695279, year = {2025}, author = {Kaltenecker, D and Fisker Schmidt, S and Weber, P and Loft, A and Morigny, P and Machado, J and Geppert, J and Saul, KB and Benedikt, P and Molocea, CE and Scott, R and Haase, K and Martignoni, ME and Alfaro, AJ and Chow, KK and Simoes, E and Pinhata Otoch, J and Lima, JDCC and Swanton, C and Spielmann, N and Hrabé de Angelis, M and Elsner, M and Ertürk, A and Dyar, KA and Rohm, M and Prokopchuk, O and Jamal-Hanjani, M and Seelaender, M and Backs, J and Herzig, S and Berriel Diaz, M}, title = {Functional liver genomics identifies hepatokines promoting wasting in cancer cachexia.}, journal = {Cell}, volume = {188}, number = {17}, pages = {4549-4566.e22}, doi = {10.1016/j.cell.2025.06.039}, pmid = {40695279}, issn = {1097-4172}, mesh = {*Cachexia/metabolism/genetics/pathology ; Humans ; Animals ; *Liver/metabolism ; *Neoplasms/complications/metabolism/genetics ; Mice ; Hepatocytes/metabolism ; Male ; Nuclear Receptor Subfamily 1, Group D, Member 1/metabolism/genetics ; Genomics ; Female ; Transcriptome ; Mice, Inbred C57BL ; }, abstract = {In cancer cachexia, the presence of a tumor triggers systemic metabolic disruption that leads to involuntary body weight loss and accelerated mortality in affected patients. Here, we conducted transcriptomic and epigenomic profiling of the liver in various weight-stable cancer and cancer cachexia models. An integrative multilevel analysis approach identified a distinct gene expression signature that included hepatocyte-secreted factors and the circadian clock component REV-ERBα as key modulator of hepatic transcriptional reprogramming in cancer cachexia. Notably, hepatocyte-specific genetic reconstitution of REV-ERBα in cachexia ameliorated peripheral tissue wasting. This improvement was associated with decreased levels of specific cachexia-controlled hepatocyte-secreted factors. These hepatokines promoted catabolism in multiple cell types and were elevated in cachectic cancer patients. Our findings reveal a mechanism by which the liver contributes to peripheral tissue wasting in cancer cachexia, offering perspectives for future therapeutic interventions.}, } @article {pmid40693684, year = {2025}, author = {Liu, Y and Liu, J}, title = {Male Breast Cancer Complicated With Leukocytosis Resembling Leukemia Reaction After Chemotherapy: A Case Report.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {8}, number = {7}, pages = {e70280}, pmid = {40693684}, issn = {2573-8348}, mesh = {Humans ; Male ; Middle Aged ; *Breast Neoplasms, Male/drug therapy/pathology/complications ; *Leukocytosis/chemically induced/diagnosis/drug therapy ; *Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Diagnosis, Differential ; *Carcinoma, Ductal, Breast/drug therapy/pathology/surgery ; *Filgrastim/adverse effects/administration & dosage ; Polyethylene Glycols/adverse effects/administration & dosage ; Mastectomy, Modified Radical ; *Leukemia/diagnosis/chemically induced ; Granulocyte Colony-Stimulating Factor/adverse effects ; }, abstract = {INTRODUCTION: Male breast cancer (MBC) accounts for less than 1% of all cancers in men, with invasive ductal carcinoma being the most common type. The chemotherapy regimens used for MBC are similar to those for female breast cancer. However, the incidence of chemotherapy-induced complications such as leukocytosis resembling leukemia reaction is not well documented in MBC. This case highlights a rare complication in an MBC patient, induced by prophylactic PEG-rhG-CSF following chemotherapy.

CASE PRESENTATION: A 51-year-old male with left breast invasive ductal carcinoma underwent modified radical mastectomy. Postoperative pathology revealed high-risk features, and the patient received 8 cycles of chemotherapy with the ddAC-T regimen, followed by PEG-rhG-CSF for febrile neutropenia prevention. After the fifth chemotherapy cycle, the patient developed leukocytosis resembling leukemia reaction, characterized by a white blood cell count exceeding 50 × 10[9]/L, along with intermittent fever up to 42.5°C. The condition was attributed to the PEG-rhG-CSF administration, and the patient was treated with NSAIDs and dexamethasone. Leukocytosis resolved after adjusting the PEG-rhG-CSF dose.

CONCLUSION: Leukocytosis resembling leukemia reaction induced by PEG-rhG-CSF post-chemotherapy is a rare complication, particularly in MBC patients. This case underscores the importance of careful monitoring and differential diagnosis to avoid misdiagnosis and unnecessary interventions. Personalized treatment strategies and dose adjustments for PEG-rhG-CSF are crucial in managing this rare reaction, emphasizing the need for awareness and individualized care in MBC patients undergoing chemotherapy.}, } @article {pmid40693510, year = {2025}, author = {Shahid, U and Haya, N and Baessler, K and Christmann-Schmid, C and Yeung, E and Chen, Z and Maher, C}, title = {Perioperative interventions in pelvic organ prolapse surgery.}, journal = {The Cochrane database of systematic reviews}, volume = {7}, number = {7}, pages = {CD013105}, pmid = {40693510}, issn = {1469-493X}, mesh = {Humans ; Female ; Randomized Controlled Trials as Topic ; *Pelvic Organ Prolapse/surgery ; Postoperative Complications/epidemiology/prevention & control ; Reoperation/statistics & numerical data ; *Perioperative Care/methods ; }, abstract = {BACKGROUND: Pelvic organ prolapse (POP) is a common condition, with a significant proportion of women requiring surgical treatment. While the evidence supporting the surgical management of pelvic organ prolapse is well established, the evidence for perioperative interventions remains porous. The main goal of perioperative interventions is to reduce the rate of adverse events while improving women's outcomes following surgical intervention for prolapse.

OBJECTIVES: To compare the safety and effectiveness of a range of perioperative interventions versus other interventions or no intervention (control group) at the time of surgery for POP.

SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Register, which contains trials identified from CENTRAL, MEDLINE, two major international clinical trials registers, and handsearching of journals and conference proceedings (searched 30 April 2024). We also contacted researchers in the field.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) of women undergoing surgical treatment for symptomatic POP that compared a perioperative intervention related to POP surgery versus no treatment or another intervention.

DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. Our primary outcomes were awareness of prolapse, repeat surgery for prolapse and objective failure at any site. We also measured adverse events and patient-reported outcomes. We used the GRADE approach to assess the certainty of the evidence.

MAIN RESULTS: This review includes 49 RCTs that compared 19 different intervention groups versus a control. The trials were conducted in 15 countries, and involved 5657 women. The certainty of the evidence ranged from low to moderate. Most interventions could not be blinded, thus introducing a risk of bias. POP surgery with or without pelvic floor muscle training (PFMT): seven RCTs with 1032 women There may be no clinically relevant difference in awareness of prolapse following POP surgery with or without PFMT (odds ratio (OR) 1.07, 95% confidence interval (CI) 0.61 to 1.87; 1 study, 305 women; low-certainty evidence). This suggests that if 20% of women are aware of prolapse after surgery without PFMT, 13% to 31% are likely to be aware after POP surgery with PFMT. Similarly, there may be no clinically relevant difference in repeat surgery for prolapse with or without PFMT (OR 0.86, 95% CI 0.23 to 3.26; 1 study, 316 women; low-certainty evidence). Additionally, there may be no clinically relevant difference in objective failure at any site with or without PFMT (OR 1.24, 95% CI 0.67 to 2.29; P = 0.49; 1 study, 307 women; low-certainty evidence). Finally, there may be no clinically relevant difference in patient-reported outcomes measures with or without PFMT, including Pelvic Floor Distress Inventory-20 (PFDI-20) scores (mean difference (MD) -4.11, 95% CI -8.97 to 0.76; I² = 0%; 3 studies, 512 women; low-certainty evidence), Urinary Distress Inventory (UDI) (MD -0.23, 95% CI -4.59 to 4.14; I² = 81%, 3 studies, 289 women; low-certainty evidence), Pelvic Organ Prolapse - Distress Inventory (POP-DI) (MD 0.00, 95% CI -1.22 to 1.22; I² = 0%; 2 studies, 143 women; low-certainty evidence) and Colorectal Anal Distress Inventory (CRADI) (MD -1.70, 95% CI -7.91 to 4.51; I² = 96%; 3 studies, 291 women; low-certainty evidence). POP surgery with in-dwelling catheter (IDC) removal before 24 hours versus at 24 hours postoperatively: five RCTs with 478 women There was probably no clinically relevant difference in urinary tract infections (UTIs) between women with IDC removal before 24 hours versus at 24 hours postoperatively (OR 0.63, 95% CI 0.37 to 1.08; I² = 61%; 4 studies, 381 women; moderate-certainty evidence). Similarly, there may be no clinically relevant difference in the number of women discharged with a catheter between the two groups (OR 0.80, 95% CI 0.22 to 2.95; 1 study, 64 women; low-certainty evidence). Furthermore, there may be no clinically relevant difference in the length of stay (days) between women with IDC removal before 24 hours versus at 24 hours postoperatively (MD 0.00, 95% CI -0.10 to 0.11; I² = 45%; 3 studies, 181 women; low-certainty evidence). Finally, there may be little to no difference in total catheter days between the two groups (MD 0.10, 95% CI -0.64 to 0.84; 2 studies, 124 women; low-certainty evidence). POP surgery with IDC removal day at more than 24 hours postoperatively versus at 24 hours: two RCTs with 277 women Women may be more likely to have a large increase in UTI risk if they had an IDC for longer than one day (OR 9.25, 95% CI 3.60 to 23.75; I² = 0%; 2 studies, 274 women; low-certainty evidence). This suggests that if 4% of women get a UTI with IDC removal at 24 hours, 12% to 47% will get a UTI with IDC removal at more than 24 hours following POP surgery. Similarly, having an IDC for longer than 24 hours probably increases the length of hospital stay (MD 1.18, 95% CI 0.92 to 1.44; 2 studies, 274 women; moderate-certainty evidence). Finally, having an IDC for longer than 24 hours may result in a large increase in total catheter days (MD 2.45, 95% CI 2.14 to 2.76; 1 study, 197 women; low-certainty evidence). There were no clinically relevant differences between study groups in the few available results for the following interventions at the time of POP surgery: with or without bowel preparation, short-acting versus long-acting bupivacaine, with or without vasoconstrictors, with chlorhexadine 2% vaginal preparation versus other vaginal antiseptic solutions, with or without vaginal packing, with restricted versus liberal postoperative activity instructions, with or without vaginal oestrogen, and with or without cranberry supplementation.

AUTHORS' CONCLUSIONS: There remains a paucity of data on perioperative interventions in POP surgery. We were unable to establish a clinically meaningful reduction in adverse events or increase in patient satisfaction across most of the perioperative interventions. Women may be more likely to have a large increase in UTI risk if they have an IDC for longer than one day.}, } @article {pmid40690467, year = {2025}, author = {Kretzmann, HG and Adeniyi, OV}, title = {Clinicopathological and molecular subtypes of breast cancer in the Eastern Cape, South Africa: A two-year retrospective study.}, journal = {PloS one}, volume = {20}, number = {7}, pages = {e0325387}, pmid = {40690467}, issn = {1932-6203}, mesh = {Humans ; Female ; South Africa/epidemiology ; Middle Aged ; Retrospective Studies ; *Breast Neoplasms/pathology/epidemiology/classification/metabolism/genetics ; Adult ; Aged ; Cross-Sectional Studies ; Triple Negative Breast Neoplasms/pathology/epidemiology ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most common cancer in women worldwide and the most frequent cause of cancer death in women in low- and middle-income countries (LMIC). The incidence of BC in Africa is on the rise, expected to double by 2050, primarily owing to late presentation and weak health infrastructure in sub-Saharan Africa (SSA). This study addresses the lack of recent data on BC cases in the Eastern Cape Province of South Africa.

OBJECTIVE: The objectives of this study were to describe the clinicopathological characteristics and molecular subtypes of BC and, in addition, to examine the association between the clinicopathological characteristics and the molecular subtypes of BC in a single tertiary hospital in the Eastern Cape Province of South Africa.

METHODS: A two-year (2022-2023) retrospective cross-sectional clinical record review study was conducted on patients treated for invasive BC at a tertiary hospital in the Eastern Cape Province, South Africa. The demographic, clinical and pathological characteristics and molecular subtypes were reported. Associations were investigated between the BC molecular subtypes identified and the clinicopathological characteristics of the patients.

RESULTS: A total of 282 patients met the study's inclusion criteria. Most patients were female (98.6%) and African (88.1%). The mean age of the patients was 58.7 years, with BC most prevalent in the age group >70 (25.2%) and postmenopausal (77.4%). Breast lump was the most common presenting complaint (98.6%), with 61% of patients presenting three months after noticing the anomaly. The most common tumour size (59.4%) was > 5 cm (mean = 6.37 ± 3.6), with the most common clinical T stage being T4 (50.4%). Lymph node involvement was seen in 50.4% of cases. Patients mostly presented in Stages III and IV of the disease (60.1%). Invasive ductal carcinoma not otherwise specified (NOS) was the most common histopathological subtype (86.2%). Grade 2 (56.2%) and Grade 3 (29.5%) BC accounted for the majority of cases. Luminal B was found in 47.4% of cases, Luminal A in 28.5%, triple negative breast cancer (TNBC) in 18.6% and human epidermal growth factor receptor 2 (HER2) enriched in 5.5% of cases, respectively.

CONCLUSION: In our setting, most patients consulted at a late stage of the disease with a large tumour size, positive lymph node status and a high histological grade. Luminal B tumours are the most common molecular subtype. These results indicate the need for more intensive breast cancer awareness campaigns, early detection, and timely referral and treatment.}, } @article {pmid40681988, year = {2025}, author = {Nasir, J and Han, B and Hu, X and Ling, H}, title = {Retrospective insights: clinical characteristics and survival in 403 ILC cases from China.}, journal = {BMC cancer}, volume = {25}, number = {1}, pages = {1188}, pmid = {40681988}, issn = {1471-2407}, mesh = {Humans ; Female ; Middle Aged ; China/epidemiology ; *Breast Neoplasms/mortality/pathology/therapy ; Retrospective Studies ; *Carcinoma, Lobular/mortality/pathology/therapy ; *Carcinoma, Ductal, Breast/mortality/pathology/therapy ; Adult ; Aged ; Kaplan-Meier Estimate ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Disease-Free Survival ; Prognosis ; Receptors, Progesterone/metabolism ; }, abstract = {BACKGROUND: The objective of this study was to compare the demographic characteristics, clinicopathological factors, and survival outcomes between Invasive Lobular Carcinoma (ILC) and Invasive Ductal Carcinoma (IDC) using the Fudan University Shanghai Cancer Center (FUSCC) database.

METHODS: Over 12,000 patients were treated at FUSCC from January 2000 to December 2019. We identified 403 patients diagnosed with ILC and 11,829 with IDC. The chi-square test was employed to compare clinical demographics, tumor characteristics, and treatments, while Kaplan-Meier survival analysis was used to obtain Disease-Free Survival (DFS) and Overall Survival (OS) curves. Cox proportional hazard regression models established hazard ratios (HR), reported with a 95% confidence interval (CI).

RESULTS: ILC exhibited distinctive characteristics compared to IDC, including older age, larger tumor size, higher estrogen receptor and progesterone receptor expression, and significantly lower HER-2 expression. The disease-free survival (DFS: ILC 86.6% vs. IDC 90.2%, P = 0.007) and overall survival (OS: ILC 90.5% vs. IDC 92.4%, P = 0.038) were worse for ILC than IDC. After applying Propensity Score Matching (PSM), the overall survival (OS: ILC 90.5% vs. IDC 93.2%, P = 0.046) was worse for ILC compared to IDC.

CONCLUSION: Patients diagnosed with Invasive Lobular Carcinoma (ILC) encounter distinct challenges, characterized by a lower survival rate, an elevated risk of metastasis when compared to those with Invasive Ductal Carcinoma (IDC). In order to gain a comprehensive understanding of ILC and to develop tailored, effective treatment strategies, it is imperative to investigate a variety of influencing factors in future research endeavors.}, } @article {pmid40679946, year = {2025}, author = {Yıldırım, S and Mhamane, A and Lösch, S and Wieder, A and Ermis, E and König, AC and Yilmaz, S and Hauck, SM and Kocabas, F and Szendroedi, J and Herzig, S and Ekim, B}, title = {TSC22D1 is a newly identified inhibitor of insulin secretion in pancreatic beta cells.}, journal = {The FEBS journal}, volume = {292}, number = {23}, pages = {6307-6329}, pmid = {40679946}, issn = {1742-4658}, support = {EK108-1/1//Deutsche Forschungsgemeinschaft/ ; //Scientific and Technological Research Council of Turkey (TUBITAK)/ ; }, mesh = {*Insulin-Secreting Cells/metabolism ; *Insulin Secretion/genetics ; Animals ; Glucose/metabolism/pharmacology ; *Insulin/metabolism/genetics ; Humans ; Rats ; Mice ; Gene Expression Regulation ; Cell Line ; }, abstract = {The loss of pancreatic beta cell function leads to chronically high blood glucose levels, contributing to diabetes mellitus, one of the leading causes of morbidity and mortality worldwide. Understanding the molecular mechanisms that regulate beta cell function could pave the way for the development of more effective antidiabetic treatments. In this study, we identify the evolutionarily conserved transforming growth factor β-1 stimulated clone D1 (TSC22D1) protein as a previously unknown regulator of beta cell function. TSC22D1 depletion in INS-1E cells enhances the expression of key beta cell identity genes, including Ins1, Ins2, Pdx1, Slc2a2, and Nkx6.1, and promotes glucose-stimulated insulin secretion without altering intracellular insulin content. Mechanistically, TSC22D1 and Forkhead box protein O1 (FoxO1) interact and regulate each other in a reciprocal manner to control beta cell function. Our follow-up interactome and RNA-Seq analyses reveal that TSC22D1 is crucial for glucose-responsive cellular processes in beta cells, including mRNA processing, ribonucleoprotein complex biogenesis, and Golgi vesicle transport. Overall, our findings indicate that TSC22D1 plays a significant role in regulating beta cell function at multiple levels, with potential implications for metabolic diseases, such as diabetes.}, } @article {pmid40679713, year = {2025}, author = {Bae, SY and Kim, CW and Chin, J and Lee, JA and Kim, D and Lee, YJ and Yoon, CI and Park, WC}, title = {Clinical subtypes and prognosis of invasive breast cancer with Paget's disease: a SEER study.}, journal = {Breast cancer research and treatment}, volume = {213}, number = {2}, pages = {281-289}, pmid = {40679713}, issn = {1573-7217}, mesh = {Humans ; Female ; *Paget's Disease, Mammary/pathology/mortality/epidemiology/metabolism/genetics ; SEER Program ; *Breast Neoplasms/pathology/mortality/metabolism/epidemiology ; Prognosis ; Erb-b2 Receptor Tyrosine Kinases/metabolism/genetics ; Aged ; Middle Aged ; Receptors, Estrogen/metabolism/genetics ; *Carcinoma, Ductal, Breast/pathology/mortality/metabolism ; Aged, 80 and over ; Adult ; Receptors, Progesterone/metabolism ; Biomarkers, Tumor ; Neoplasm Staging ; }, abstract = {PURPOSE: Paget's disease of the breast is rare but commonly associated with underlying carcinoma. Despite frequent HER2 overexpression, its clinical relevance in Paget's disease remains unclear. We evaluated the prognostic impact of ER and HER2 expression in invasive ductal carcinoma (IDC) with Paget's disease and assessed whether clinical subtypes affect survival outcomes.

METHODS: Using SEER 17 data, we identified patients with IDC and HER2 status available, diagnosed from 2010 onward. Two groups were analyzed: IDC with Paget's disease (ICD-O-3 code 8541/3, n = 1,000) and IDC alone (ICD-O-3 code 8500/3, n = 487,162).

RESULTS: Compared to IDC alone, patients with Paget's disease had lower ER (60.5% vs. 82.0%) and PR (45.5% vs. 71.7%) expression, and higher HER2 overexpression (52.5% vs. 15.4%) (all P < 0.001). The ER + HER2 - subtype was less common in the Paget's group (34.9% vs. 71.6%), while ER - HER2 + was more frequent (29.2% vs. 4.8%) (P < 0.001). Among ER + HER2 - and ER + HER2 + subtypes, those with Paget's disease had worse breast cancer-specific survival (BCSS) than those with IDC alone (HR 1.519, 95% CI 1.074-2.149; HR 1.030, 95% CI 1.027-1.033, respectively). No BCSS differences were observed in ER - HER2 - and ER - HER2 + subtypes.

CONCLUSION: ER + HER2 - subtype in IDC with Paget's disease is linked to worse BCSS, differing from IDC alone. These findings suggest distinct tumor biology in IDC with Paget's disease, highlighting the need for subtype-specific management strategies.}, } @article {pmid40679712, year = {2025}, author = {Zhan, H and Chan, NNN and Khaimova, R and Aung, TN and Gaule, P and Robbins, CJ and Rimm, DL}, title = {Quantitative assessment of HER2 expression in invasive ductal carcinoma and co-existing DCIS.}, journal = {Breast cancer research and treatment}, volume = {213}, number = {2}, pages = {273-279}, pmid = {40679712}, issn = {1573-7217}, support = {BCRF 23-138//Breast Cancer Research Foundation/ ; }, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/pathology/metabolism/genetics ; *Erb-b2 Receptor Tyrosine Kinases/metabolism/genetics ; *Breast Neoplasms/pathology/metabolism/genetics ; Middle Aged ; *Carcinoma, Ductal, Breast/pathology/metabolism/genetics ; *Biomarkers, Tumor/metabolism ; Aged ; Neoplasm Grading ; Adult ; Immunohistochemistry ; }, abstract = {PURPOSE: Previous studies have demonstrated that ductal carcinoma in situ (DCIS) component often exhibits higher HER2 expression than the invasive component when assessed by immunohistochemistry, while some other studies showed concordant HER2 expression between these two components. In this study, we used our high-sensitivity HER2 (HS-HER2) quantitative immunofluorescence assay to compare HER2 expression in IDC and co-existing DCIS and correlate with clinicopathologic characteristics.

METHODS: We included 36 IDC + DCIS cases from the Yale Pathology department. DCIS was classified according to the three-tier nuclear grading system: low (grade 1), intermediate (grade 2), and high (grade 3) nuclear grade. Invasive carcinoma was graded according to the modified Bloom-Richardson histologic grading system. Cases were divided into two groups: low to intermediate-grade DCIS (G1-2) with co-existing invasive carcinoma (n = 26) and high-grade DCIS (G3) with co-existing invasive carcinoma (n = 10). Separate regions of interest for IDC and DCIS were annotated by two board-certified pathologists. Serial sections of FFPE tumor specimens were used to accurately measure the HER2 protein expression by the HS-HER2 assay in attomole/mm[2] unit and the acquisition by QuPath v.04 with the Qymia extension.

RESULTS: Low to intermediate-grade DCIS expressed higher HER2 levels (4295 ± 449 amol/mm[2]) than co-existing invasive carcinoma (2880 ± 413 amol/mm[2]). Similarly, high-grade DCIS expressed higher HER2 levels (4953 ± 700 amol/mm[2]) than co-existing invasive carcinoma (3560 ± 688 amol/mm[2]). Neither of these trends toward lower expression levels in the IDC were statistically significant. Additionally, no significant statistic difference was noted between low to intermediate-grade DCIS versus high-grade DCIS or between their corresponding co-existing invasive carcinomas in this cohort.

CONCLUSION: Using the HS-HER2 assay, our results demonstrated comparable HER2 expression levels in DCIS and paired invasive carcinoma regardless of histopathological grade or HER2 immunohistochemical score. These findings contributed to a more nuanced understanding of HER2 biology in early breast carcinogenesis and may inform future biomarker-driven therapeutic strategies.}, } @article {pmid40677494, year = {2025}, author = {Saurborn, E and Adkins, J and Mahmud, W and Lawrence, LM and Denning, KL and Legenza, M and Krutzler-Berry, D}, title = {Rare Presentation of Metastatic Breast Cancer Involving the Peritoneal Cavity: Two Cases Arising From Stage 0/1 Disease.}, journal = {Cureus}, volume = {17}, number = {6}, pages = {e86236}, pmid = {40677494}, issn = {2168-8184}, abstract = {Ductal cell carcinoma in situ (DCIS) is a noninvasive stage 0 breast cancer that arises from an abnormal proliferation of ductal epithelial cells. If untreated, it can progress to invasive ductal carcinoma (IDC), the most common form of breast cancer. A minority of women with early-stage breast cancer may experience recurrent advanced cancer, which can progress to metastatic disease, commonly in the bone, liver, lung, and brain. Improved surveillance and raised awareness over the last three decades have resulted in an increased incidence of disease; however, early detection and treatment of DCIS and IDC have a favorable prognosis. We present two cases of well-treated early-stage breast cancer with late recurrence of distal metastasis involving the peritoneal cavity and liver, with ascites as a primary presentation. In Case one, Stage 1 IDC was detected on a routine mammogram and was well-treated with lumpectomy and sentinel lymph node biopsies, chemotherapy, and radiation, with repeat mammograms negative for any evidence of recurrence. One year following treatment, the patient presented with dull epigastric pain and ascites positive for malignancy, with primary breast origin. In Case two, the patient presented to the emergency department with right upper quadrant pain and abdominal distension. A CT scan identified multiple liver lesions, and a biopsy revealed primary breast origin. A subsequent mammography detected DCIS in the right breast. One month later, the patient presented with abdominal and pelvic ascites and rapid decline of mental status before treatment was initiated. These cases underscore the importance of educating patients on self-examinations and yearly mammograms. Additionally, it is essential to educate providers on risk factors of metastatic disease and their possible presentations, including metastasis into the peritoneal cavity, to ensure optimal clinical outcomes.}, } @article {pmid40675644, year = {2025}, author = {Aguiar-Leiva, VP and Leiva-Fernández, F and Martín-Roselló, ML and Gomez-Garcia, R and Fernandez-Lopez, A and Barnestein-Fonseca, P and Morales-Asencio, JM}, title = {Validation of a questionnaire to assess complexity of palliative care needs in primary care in Malaga, Spain: a study protocol.}, journal = {BMJ open}, volume = {15}, number = {7}, pages = {e102040}, pmid = {40675644}, issn = {2044-6055}, mesh = {Adult ; Humans ; Cross-Sectional Studies ; Delphi Technique ; *Needs Assessment ; *Palliative Care ; *Primary Health Care ; Reproducibility of Results ; Spain ; Surveys and Questionnaires/standards ; Observational Studies as Topic ; Validation Studies as Topic ; }, abstract = {INTRODUCTION: The needs of patients in palliative care (PC) are multiple and changing. Several tools assess them, but there is a lack of homogeneity among them. A specific diagnostic tool to assess complexity in PC (IDC-Pal: Instrumento Diagnóstico de la Complejidad en Cuidados Paliativos, in Spanish) was created in community and hospital settings with 36 items to diagnose PC complexity, but its application in primary care is difficult.

AIMS: (1) To generate an adapted version to primary care of the IDC-Pal tool to identify and stratify PC complexity in the adult population. (2) To determine face, content, criterion and construct validity and reliability of the new instrument.

METHODS AND ANALYSIS: There are three phases of clinimetric cross-sectional observational validation study: Phase 0: Review of the original tool structure suitability for its use in primary care setting by a committee (researchers and the original developer team). Phase 1: Expert consensus phase by Delphi technique with physicians, nurses and social workers from primary care and PC. Phase 2: Empirical validation of the resulting tool in primary care using a cross-sectional descriptive design involving physicians and case manager nurses from across Andalucia, who will recruit adult patients with PC needs from healthcare centres that accept to participate in the study. Reliability (Cronbach's alpha, McDonald's omega, interclass correlation coefficient) and construct validity (exploratory factor analysis) analysis will be carried out; convergent criterion validity will be assessed with the NEC-PAL (Necesidades Paliativas Questionnaire, in Spanish) instrument. Differences by gender, type of professional and place where it is administered will be explored. Interobserver reliability analyses will be carried out using intraclass correlation coefficient, Bland-Altman plots and concordance analysis. Phase 0-1 results were expected by 2025 and Phase 2 results by 2026. Reporting method: CRISP checklist. This protocol was conducted without patient or public participation.

ETHICS AND DISSEMINATION: This study evaluates a novel, co-designed tool to diagnose PC complexity to inform practice recommendations for a more efficient allocation of resources that may be included in future clinical practice guidelines. The study has been approved by the Provincial Research Ethics Committee of Málaga as of July 2023 and will be conducted in accordance with the principles established in the Declaration of Helsinki, the Council of Europe Convention on Human Rights and Biomedicine, and the requirements established in Spanish legislation. The study conforms to the norms of good clinical practice. All participants in the Delphi study must express their agreement to participate in the survey by providing informed consent (IC) before beginning the questionnaire. For the development of Phase 2, the primary care professionals who agree to participate will sign a researcher commitment, and the patients included in the study will sign a written IC before the data collection. Dissemination of the results will inform future research on the appropriate diagnosis of PC complexity in the primary care setting, which is of paramount importance due to its gatekeeper position. Dissemination will be aimed at academics and healthcare professionals through publications, presentations and training workshops on the use of the diagnostic tool.}, } @article {pmid40672349, year = {2025}, author = {Ghiarone, T and Hansen, E and Holaska, JM}, title = {Emerin expression stratification across breast cancer subtypes.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40672349}, issn = {2692-8205}, support = {R15 AR069935/AR/NIAMS NIH HHS/United States ; }, abstract = {Nuclear dysmorphism is a critical indicator of tumor aggressiveness, influencing cancer cell invasion and metastasis. Emerin, an integral nuclear envelope protein involved in nuclear architecture, is important for maintaining nuclear integrity. Our previous work demonstrated an inverse correlation between nuclear envelope-localized emerin expression and breast cancer aggressiveness. However, it failed to have the power to assess whether emerin loss correlates with cancer stage, grade, proliferation, or molecular phenotype. Here we analyzed emerin expression at the nuclear envelope across 243 breast cancer patient samples encompassing various tumor grades, stages, and molecular phenotypes. We found significantly reduced emerin expression in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and ductal carcinoma in situ (DCIS), compared to normal breast tissue. Notably, emerin loss correlated with advanced tumor stage, higher Ki-67 proliferation rates, elevated human epidermal growth factor receptor 2 (HER2) levels, and decreased estrogen receptor (ER) and progesterone receptor (PR) expression-markers associated with more aggressive breast cancers. Emerin expression was consistently reduced in triple-negative breast cancer (TNBC) and other receptor-negative subtypes, underscoring its potential role in tumor dedifferentiation and progression. These findings highlight emerin as a promising prognostic biomarker and therapeutic target for aggressive breast cancer subtypes.}, } @article {pmid40669200, year = {2025}, author = {Akbari Rad, M and Sheybani, F and Gharib, M and Aghel, E and Emadzadeh, M and Mottaghi, M}, title = {Coexistence of lobular granulomatous mastitis and breast cancer: Case report and case-based literature review.}, journal = {International journal of surgery case reports}, volume = {133}, number = {}, pages = {111628}, pmid = {40669200}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: This study aims to provide insights into the characteristics of patients who experience both conditions of lobular granulomatous mastitis (LGM) and breast carcinoma. This patient was the only case among our 246 consecutive patients with LGM who experienced both LGM and malignancy.

CASE PRESENTATION: A 46-year-old Persian woman was diagnosed with left-sided LGM via core-needle biopsy, which resolved following two years of prednisone and subsequent methotrexate therapy. Three months after remission, she developed stiffness in the contralateral breast, and biopsy revealed grade 3 invasive ductal carcinoma that was estrogen receptor (ER)-positive, progesterone receptor (PR)-negative, and HER2 (1+).

CLINICAL DISCUSSION: The prevalence of coexisting LGM and breast cancer among LGM cases was 0.41 %. In our review of 20 patients, LGM occurred prior to breast cancer in nine cases (45 %), concurrently in nine cases (45 %), and subsequent to breast cancer in two cases (10 %). Among the 20 reviewed cases, invasive ductal carcinoma (IDC) was the most frequently identified malignancy, observed in 15 patients (75 %), while ductal carcinoma in situ (DCIS) was reported in five cases (25 %). Hormone receptor positivity (estrogen and/or progesterone receptor) was noted in 11 patients (55 %), and HER2 overexpression was present in seven cases (35 %).

CONCLUSION: New breast findings in individuals previously diagnosed with LGM should not be readily interpreted as a disease recurrence. To minimize the risk of misdiagnosis, bilateral assessment-including bilateral mammography or biopsy-is recommended, particularly in older patients, postmenopausal women, those with recurrent episodes, or when the contralateral breast is involved.}, } @article {pmid40667287, year = {2025}, author = {Wang, R and Fridman, G}, title = {Ionic Direct Current Enables Millimeter- and Millisecond-Scale Cortical Gain Control in vivo.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40667287}, issn = {2692-8205}, support = {R01 NS110893/NS/NINDS NIH HHS/United States ; }, abstract = {Precise, reversible modulation of cortical gain at mesoscale resolution remains a major challenge for neuroscience. Here, we introduce ionic direct current (iDC) delivered through non-penetrating electrolyte-filled microcatheters on the cortical surface as a method for targeted neuromodulation at millimeter spatial scales and millisecond onset/offset. In rat primary somatosensory cortex (S1HL), laminar recordings under urethane revealed that cathodic iDC attenuated and anodic iDC amplified both spontaneous delta oscillations and sensory-evoked responses, without causing time-locked spiking or state disruption. Computational modeling reproduced these effects and implicated dendritic summation at the axon initial segment as the mechanism for bidirectional gain control. In awake animals, iDC modulation of S1HL altered tactile sensitivity to Von Frey stimulation, demonstrating behavioral relevance. Together, these results establish iDC as a versatile platform for precise, rapidly reversible, and non-disruptive manipulation of cortical gain in vivo, enabling new approaches for dissecting mesoscale circuit interactions and linking column-scale physiology to behavior.}, } @article {pmid40665951, year = {2025}, author = {Taraschi, F and Cossa, A and Maggi, S and Lombardi, A and Nicodemi, EM}, title = {18 Years Experience of an Italian Breast Unit Among Male Breast Cancer: A Retrospective Observational Study.}, journal = {Annali italiani di chirurgia}, volume = {96}, number = {7}, pages = {950-955}, doi = {10.62713/aic.3888}, pmid = {40665951}, issn = {2239-253X}, mesh = {Humans ; *Breast Neoplasms, Male/surgery/mortality/diagnosis ; Retrospective Studies ; Male ; Italy/epidemiology ; Middle Aged ; Aged ; *Carcinoma, Ductal, Breast/surgery/mortality/diagnosis ; Adult ; *Carcinoma, Lobular/surgery/mortality/diagnosis ; Lymph Node Excision ; Mastectomy ; Time Factors ; Aged, 80 and over ; Survival Rate ; }, abstract = {AIM: Male breast cancer has increased by approximately 26% over the past 25 years, there is a need to research specific treatment options. Currently, there is no established standard treatment which is therefore based on female disease. The purpose of this study is to analyze the clinical characteristics, survival outcomes, and the need for tailored treatment strategies in male breast cancer patients.

METHODS: This is an observational, retrospective, single-center clinical study. The research involved 21 male patients who underwent surgery for breast cancer from 2003 to 2020 in our hospital. In order to strengthen the statistical value of the results obtained, the survival curves of three selected studies in the literature were compared with that obtained in the present study.

RESULTS: All our patients underwent total mastectomy and axillary lymph node dissection. Twenty patients were diagnosed with invasive ductal carcinoma, while only one patient with invasive lobular carcinoma. The 5-year survival was 71.4% with a median survival for metastatic patients of 5.7 years. A statistically significant difference was found when comparing 5-year survival with one of the other three studies (p = 0.048).

CONCLUSIONS: Our findings highlight the delayed clinical presentation of male breast cancer and a 5-year overall survival of 71.4%, underscoring the need for targeted screening strategies to improve early diagnosis and outcomes.The lack of knowledge of this disease at sociocultural and health level is the main reason for delay in diagnosis, a factor that strongly affects the prognosis.}, } @article {pmid40656598, year = {2025}, author = {Yang, C and Wang, H and Tong, Y and Wang, Z and Sun, X and Li, A and Lu, Y and Han, M and Zhu, S and Dong, L and Shen, K and Chen, X}, title = {Clinicopathological and molecular significance of HER2-low expression in Asian women with triple-negative breast cancer.}, journal = {Therapeutic advances in medical oncology}, volume = {17}, number = {}, pages = {17588359251353083}, pmid = {40656598}, issn = {1758-8340}, abstract = {BACKGROUND: Heterogeneity of human epidermal growth factor receptor 2 (HER2) expression exists in triple-negative breast cancer (TNBC). The evolution of the HER2 testing algorithm has led to the new classification of the HER2-low category, with unclear clinicopathological and molecular features in Asian women with HER2-low TNBC.

OBJECTIVES: This study aimed to assess the clinicopathological and molecular characteristics of HER2-low TNBC in Asian women.

DESIGN: Our study prospectively included 3376 patients with TNBC diagnosed from 2009 to 2021 in the Shanghai Jiao Tong University Breast Cancer Database (a multicenter dataset), and 92 patients from The Cancer Genome Atlas (TCGA) cohort were enrolled.

METHODS: Two different independent TNBC cohorts were included, a multicenter cohort (Whole cohort, n = 3376) and the TCGA cohort (n = 92). Genomic profiling covering 32 mutations for Homologous Recombination Repair and other cancer predisposition genes was obtained. Clinicopathological features, genomic status of the above genes, treatment response, and disease prognosis were compared between HER2-low and HER2-zero TNBC patients.

RESULTS: In Asian females, 1611 (47.72%) TNBC patients were HER2-low. HER2-low was associated with a higher percentage of postmenopausal status (odds ratio (OR) = 1.64, p < 0.001), lymph node positivity (OR = 1.14, p = 0.003), and invasive ductal carcinoma histology (OR = 1.21, p = 0.012). HER2-low group had less BRCA1 mutation (7.02% vs 13.76%, p = 0.038) but was associated with a higher rate of PIK3CA mutation (28.07% vs 12.17%, p < 0.001) compared with HER2-zero TNBC. No significant difference in breast pathologic complete response rate, breast cancer-free interval, or overall survival was observed between HER2-low and HER2-zero TNBC. In the TCGA cohort, lipid metabolism genes were upregulated in the HER2-low TNBC, enriched in alpha-linolenic acid metabolism (normalized enrichment score = 1.51, p = 0.019).

CONCLUSION: Our results show that HER2-low TNBC had specific clinicopathological, genomic profiling, and biological features compared with HER2-zero TNBC in Asian women, but without significant differences in treatment response and prognosis, warranting exploring better treatment strategies to improve disease outcomes.}, } @article {pmid40656431, year = {2025}, author = {Malik, M and Mirza, ZR and Idrees, RB and Nawaz, S and Arif, J and Ahmad, B and Chaudry, SS and Chaudhary, MH}, title = {Interplay of Receptor Status, Age, and Stage in Breast Cancer: A Prospective Analysis.}, journal = {Cureus}, volume = {17}, number = {6}, pages = {e85925}, pmid = {40656431}, issn = {2168-8184}, abstract = {Background Breast cancer is the most prevalent cancer among women globally, with significant variations in incidence and characteristics across different age groups and regions. Understanding the relationship between age, hormone receptor status, and breast cancer stage is crucial for developing effective treatment strategies. Objectives This study aimed to: (1) categorize the relationship between receptor status and the stage of breast cancer, (2) determine the frequency of different receptor statuses according to patient age, and (3) correlate the relationship between age and the stage of breast cancer among Pakistani women. Materials and methods A prospective analysis was conducted on 1003 breast cancer patients from a semi-government-run hospital in Lahore, Pakistan, between October 2021 to October 2023 using systematic sampling to recruit every fourth patient of breast cancer. Data on age, tumor grade, histopathological subtype, and hormone receptor status (estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2/NEU (HER2/NEU), Ki-67) were collected and analyzed using SPSS v26 (IBM Corp., Armonk, USA). Chi-squared test was employed to explore associations between age groups and receptor status. Results The mean age of patients was 50.5 years, with a concentration of cases between 41 and 60 years. Invasive ductal carcinoma (IDC) was the most common subtype (91%). Grade II tumors were most prevalent (50.6%), followed by Grade III (45.5%). The majority of patients were ER-positive (62.4%), followed by PR-positive (52.3%), while HER2/NEU positivity was 44%. The most common receptor status was HER2/NEU negative and ER/PR positive (28.9%). Receptor status distribution varied significantly among age groups (p < 0.000), with younger patients more likely to have triple-negative breast cancers and older patients more likely to have ER/PR-positive, HER2/NEU-negative cancers. Ki-67 levels were assessed in 41.5% of patients, with higher levels observed in younger patients. Younger patients (20-30 years) had a higher prevalence of Grade III tumors, whereas older patients (over 60 years) more frequently had Grade II tumors. There were no significant differences in hormone receptor status distribution across cancer stages (p = 0.76). The stage of carcinoma did not significantly differ across age groups (p = 0.05). Conclusion The study highlights significant age-related differences in breast cancer pathology, particularly in tumor grade and receptor status, underscoring the need for age-specific treatment strategies. Younger patients tend to present with more aggressive tumors, necessitating tailored therapeutic approaches to improve outcomes.}, } @article {pmid40644582, year = {2025}, author = {Wang, G and Liu, X and Si, Z and Wang, Z and Wang, X}, title = {A Scallop-shaped Photopenic Region in the Urinary Bladder Area on Tc-99m MDP Bone Scan Caused by a Uterine Cervical Leiomyoma.}, journal = {Clinical nuclear medicine}, volume = {50}, number = {12}, pages = {1243-1244}, doi = {10.1097/RLU.0000000000006049}, pmid = {40644582}, issn = {1536-0229}, mesh = {Humans ; Female ; Middle Aged ; *Technetium Tc 99m Medronate ; *Leiomyoma/diagnostic imaging ; *Urinary Bladder/diagnostic imaging ; *Uterine Cervical Neoplasms/diagnostic imaging ; Radionuclide Imaging ; *Bone and Bones/diagnostic imaging ; }, abstract = {A 46-year-old woman with right breast invasive ductal carcinoma and sternalgia underwent Tc-99m methylene diphosphonate (MDP) whole-body bone scintigraphy, on which a scallop-shaped photopenic region in the urinary bladder area was found, besides increased radioactivity in the sternum region and both breasts. By reviewing a previous CT scan, a pelvic mass oppressing the right wall of the urinary bladder was noted, which was confirmed to be a rare uterine cervical leiomyoma by biopsy.}, } @article {pmid40642685, year = {2025}, author = {Takaoka, K and Oura, S}, title = {A Case of Breast Cancer Arising From a Florid Adenosis Nodule.}, journal = {Cureus}, volume = {17}, number = {6}, pages = {e85725}, pmid = {40642685}, issn = {2168-8184}, abstract = {A 42-year-old woman noticed a left breast mass and was diagnosed with florid adenosis by vacuum-assisted biopsy (VAB) 10 years before. Semiannual ultrasound follow-ups showed gradual shrinkage of the florid adenosis nodule as time passed after VAB, but showed a slight increase in size after her marriage at the age of 40. Thereafter, the sudden rapid growth of the nodule made us again examine it in detail. Magnetic resonance imaging of the masses, including a daughter nodule in the nipple direction, showed low signals on T1-weighted images, slightly high signals on fat-suppressed T2-weighted images, and persistent rim enhancement on subtraction images. The patient underwent core needle biopsy under the tentative diagnosis of breast cancer. Pathological study showed atypical cells growing in a papillary fashion with bleeding and necrosis, leading to the diagnosis of invasive ductal carcinoma. Immunostaining showed estrogen and progesterone receptor negativity, human epidermal growth factor receptor type 2 negativity, and a high Ki-67 labeling index of 60%. The patient, therefore, underwent nipple-preserving mastectomy and sentinel biopsy followed by immediate breast reconstruction using an extended latissimus dorsi musculocutaneous flap. Postoperative pathological study showed that the breast cancer had similar pathological findings to those of the core needle biopsy specimen and a higher Ki-67 labeling index of 70%. The patient recovered uneventfully and was discharged on the 9th day after the operation. The patient has received dose-dense chemotherapy and is scheduled for periodical checkups on an outpatient basis. Breast specialists should note that even pathologically proven florid adenosis nodules might develop breast cancer.}, } @article {pmid40639624, year = {2025}, author = {Borella, F and Gallio, N and Giurdanella, M and Capella, G and Cassoni, P and Castellano, I}, title = {Triple-negative lobular breast cancer: focus on pathology and clinical challenges.}, journal = {Human pathology}, volume = {162}, number = {}, pages = {105871}, doi = {10.1016/j.humpath.2025.105871}, pmid = {40639624}, issn = {1532-8392}, mesh = {Humans ; *Triple Negative Breast Neoplasms/pathology/genetics/therapy ; Female ; *Carcinoma, Lobular/pathology/genetics/therapy ; *Biomarkers, Tumor/genetics ; Prognosis ; }, abstract = {Triple-negative invasive lobular carcinoma is a rare and under-characterized subtype of breast cancer, distinct from the more common triple-negative invasive ductal carcinoma. While triple-negative invasive ductal carcinoma is generally recognized for its aggressive clinical behavior and lack of targeted treatment options, triple-negative invasive lobular carcinoma presents unique histopathological and molecular features that may influence its prognosis and therapeutic responsiveness. Despite these differences, triple-negative invasive lobular carcinoma remains poorly studied, leading to a reliance on treatment strategies adapted from ductal histotype, which may not fully address its biological complexities. This review aims to provide a comprehensive overview of triple-negative invasive lobular carcinoma by analyzing its clinicopathological characteristics, prognostic factors, and emerging therapeutic approaches. We explore the genetic alterations commonly observed in triple-negative invasive lobular carcinoma, their potential implications for treatment selection, and the challenges in current management strategies. Furthermore, we discuss the need for specialized research efforts and clinical trials to define treatment paradigms better. As precision oncology continues to evolve, understanding the biological distinctions of triple-negative invasive lobular carcinoma will be essential for optimizing patient outcomes and developing more effective treatment strategies.}, } @article {pmid40637704, year = {2025}, author = {Umezu, M and Kondo, Y and Ichikawa, S and Sasaki, Y and Kaneko, K and Ozaki, T and Koizumi, N and Seki, H}, title = {Recurrence prediction of invasive ductal carcinoma from preoperative contrast-enhanced computed tomography using deep convolutional neural network.}, journal = {Biomedical physics & engineering express}, volume = {11}, number = {4}, pages = {}, doi = {10.1088/2057-1976/adeab5}, pmid = {40637704}, issn = {2057-1976}, mesh = {Humans ; Female ; *Tomography, X-Ray Computed/methods ; *Breast Neoplasms/diagnostic imaging/pathology/surgery ; Retrospective Studies ; *Neural Networks, Computer ; Middle Aged ; *Contrast Media ; *Neoplasm Recurrence, Local/diagnostic imaging ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology/surgery ; Aged ; ROC Curve ; Adult ; Preoperative Period ; Area Under Curve ; Convolutional Neural Networks ; }, abstract = {Predicting the risk of breast cancer recurrence is crucial for guiding therapeutic strategies, including enhanced surveillance and the consideration of additional treatment after surgery. In this study, we developed a deep convolutional neural network (DCNN) model to predict recurrence within six years after surgery using preoperative contrast-enhanced computed tomography (CECT) images, which are widely available and effective for detecting distant metastases. This retrospective study included preoperative CECT images from 133 patients with invasive ductal carcinoma. The images were classified into recurrence and no-recurrence groups using ResNet-101 and DenseNet-201. Classification performance was evaluated using the area under the receiver operating curve (AUC) with leave-one-patient-out cross-validation. At the optimal threshold, the classification accuracies for ResNet-101 and DenseNet-201 were 0.73 and 0.72, respectively. The median (interquartile range) AUC of DenseNet-201 (0.70 [0.69-0.72]) was statistically higher than that of ResNet-101 (0.68 [0.66-0.68]) (p < 0.05). These results suggest the potential of preoperative CECT-based DCNN models to predict breast cancer recurrence without the need for additional invasive procedures.}, } @article {pmid40636692, year = {2025}, author = {Zhang, Q and Xiong, Z and Gao, Y and Zeng, M and Yang, H and Lyu, G}, title = {Rare case report: non-mass invasive ductal carcinoma presenting with rectal and cervical lymph node metastasis as the initial symptom.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1606116}, pmid = {40636692}, issn = {2234-943X}, abstract = {It is uncommon for breast cancer to present with distant metastasis as the initial symptom. This study reported a 67-year-old female patient with breast non-mass invasive ductal carcinoma, who sought medical attention due to abdominal distention, lower abdominal pain, constipation, hematochezia, and left-sided neck swelling. After a thorough examination, pathology confirmed the diagnosis of breast invasive ductal carcinoma, along with cervical lymph node and rectal metastasis. The non-specific breast symptoms in this case posed challenges for the early diagnosis of breast cancer. This also suggests that for breast cancer patients without a history of gastrointestinal disease, the presence of changes in bowel habits should raise suspicion for metastatic lesions. Imaging combined with biopsy pathology plays an important role in the diagnosis and treatment of non-mass breast cancer. This case also underscores the importance of breast health awareness and routine breast cancer screening among women, both for clinical practice and public health initiatives. Notably, early identification and diagnosis of non-mass breast cancer, coupled with the development of personalized treatment plans through multidisciplinary collaboration, are essential for enhancing treatment efficacy.}, } @article {pmid40630196, year = {2025}, author = {Zhang, T and Cui, T and Cao, Z and Hu, J and Ma, J}, title = {Deep learning-based risk stratification of ductal carcinoma in situ using mammography and abbreviated breast magnetic resonance imaging.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1587882}, pmid = {40630196}, issn = {2234-943X}, abstract = {BACKGROUND: Current management of ductal carcinoma in situ lacks robust risk stratification tools, leading to universal surgical and radiotherapy interventions despite heterogeneous progression risks. Optimizing therapeutic balance remains a critical unmet clinical need.

MATERIALS AND METHODS: We retrospectively analyzed two patient cohorts. The first included 173 cases with BI-RADS category 3 or higher findings, used to compare the diagnostic accuracy of four abbreviated MRI protocols against the full diagnostic MRI. The second cohort involved 210 patients who had both mammography and abbreviated MRI. We developed two separate predictive models-one for pure ductal carcinoma in situ and another for invasive ductal carcinoma with associated ductal carcinoma in situ-by integrating clinical, imaging, and pathological features. Deep learning and natural language processing techniques were used to extract relevant features, and model performance was assessed using bootstrap validation.

RESULTS: Abbreviated Magnetic Resonance Imaging protocols demonstrated similar diagnostic accuracy to the full protocol (P > 0.05), offering a faster yet effective imaging option. The pure group incorporated features like nuclear grade, calcification morphology, and lesion size, achieving an Area Under the Curve of 0.905, with 86.8% accuracy and an F1 score of 0.853. The model for invasive cases incorporated features Ki-67 status, lymph vascular invasion, and enhancement patterns, achieved an Area Under the Curve of 0.880, with 86.2% accuracy and an F1 score of 0.834. Both models showed good calibration and clinical utility, as confirmed by bootstrap resampling and decision curve analysis.

CONCLUSION: Deep Learning-driven multimodal models enable precise ductal carcinoma in situ risk stratification, addressing overtreatment challenges. abbreviated Magnetic Resonance Imaging achieves diagnostic parity with full diagnostic protocol, positioning Magnetic Resonance Imaging as a viable ductal carcinoma in situ screening modality.}, } @article {pmid40629357, year = {2025}, author = {Xiao, C and Zhang, Y and Li, J}, title = {The prognostic differences between breast-conserving surgery and mastectomy in patients with invasive ductal carcinoma who achieved complete response following neoadjuvant chemotherapy: a propensity score matched analysis based on the SEER database.}, journal = {World journal of surgical oncology}, volume = {23}, number = {1}, pages = {269}, pmid = {40629357}, issn = {1477-7819}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/mortality/therapy/surgery ; Propensity Score ; *Carcinoma, Ductal, Breast/pathology/mortality/therapy/surgery ; SEER Program/statistics & numerical data ; Middle Aged ; *Mastectomy, Segmental/mortality ; *Neoadjuvant Therapy/mortality ; Prognosis ; *Mastectomy/mortality ; Survival Rate ; Follow-Up Studies ; Adult ; Aged ; Retrospective Studies ; Chemotherapy, Adjuvant ; }, abstract = {BACKGROUND: The study investigates the prognostic differences between breast-conserving surgery (BCS) and mastectomy in patients with invasive ductal carcinoma of the breast who achieve a complete response (CR) after neoadjuvant chemotherapy.

METHODS: This study analyzed data from 9,411 patients diagnosed with invasive ductal carcinoma of the breast who achieved complete response following neoadjuvant chemotherapy, using data from the SEER database between 2010 and 2019, comprising 4,219 patients in the BCS group and 5,192 in the mastectomy group. Propensity score matching (PSM) was employed to control for confounding variables, and univariate and multivariate analyses were performed to identify variables associated with overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier survival curves were used to evaluate the prognosis of patients in the two groups.

RESULTS: The multivariate Cox regression analysis demonstrated that histological subtype, T stage, N stage, surgical method, and radiotherapy were risk factors for CSS, while age, histological subtype, T stage, and N stage were associated with OS (p < 0.05). Following matching, the Kaplan-Meier survival analysis curve suggested that the BCS group had higher CSS than the mastectomy group (p < 0.05), although there was no statistically significant difference in OS between the two groups (p = 0.16). Subgroup analysis revealed that, among patients aged ≤ 50, of White ethnicity, with grade 3 tumors, and HR+/HER-2- subtype, the BCS group exhibited superior CSS compared to the mastectomy group (p < 0.05).

CONCLUSION: Patients with invasive ductal carcinoma of the breast who achieve complete response following neoadjuvant chemotherapy experience better CSS benefits with BCS compared to undergoing mastectomy.}, } @article {pmid40629116, year = {2025}, author = {Wang, R and Zhao, F and Yan, T and Li, Y and Cheng, D and Wang, W and Tian, C and Yu, H}, title = {Gallbladder metastasis in invasive ductal breast cancer with concurrent gallstones and gallbladder carcinoma.}, journal = {Discover oncology}, volume = {16}, number = {1}, pages = {1287}, pmid = {40629116}, issn = {2730-6011}, support = {AHWJ2023A10015//2023 Health research project of Anhui Health Commission/ ; YZ2023H2A006//Anhui University of Science and Technology 2023 medical special cultivation project/ ; NO. 2023AH040405//Scientific research project (Natural science) of Anhui University/ ; NO.2023szsfkc069//2023 Provincial new era education quality engineering (graduate education) project/ ; }, abstract = {The gallbladder is an uncommon location for tumor metastases. Breast cancer seldom spreads to the gallbladder, although melanoma and renal cell tumors typically do. We report a case of a 58-year-old woman with chronic cholecystitis caused by gallstones. Following a laparoscopic cholecystectomy, a nodule was discovered on the gallbladder wall. Based on her medical history and pathological tissue molecular typing, the diagnosis was determined to be gallbladder metastasis of invasive breast ductal carcinoma, with a negative hormone receptor. Two years prior, the patient had undergone a modified radical mastectomy for left breast cancer. The postoperative pathology revealed grade III invasive ductal carcinoma, pT2N1M0, and a negative hormone receptor. This case report highlights the rare occurrence of invasive breast ductal carcinoma metastasizing to the gallbladder.}, } @article {pmid40625130, year = {2025}, author = {Grimaldi, L and Garcia-Uzquiano, R and de la Banda, MG and Oulhissane-Omar, A and Tard, C and Saugier-Veber, P and Laugel, V and Desguerre, I and Cintas, P and Vuillerot, C and Audic, F and Cances, C and Stojkovic, T and Urtizberea, JA and Attarian, S and Ropars, J and Quijano-Roy, S and , }, title = {REGISTRE SMA FRANCE: A nationwide observational registry of patients with spinal muscular atrophy in France.}, journal = {Journal of neuromuscular diseases}, volume = {12}, number = {6}, pages = {793-803}, doi = {10.1177/22143602251353446}, pmid = {40625130}, issn = {2214-3602}, mesh = {Humans ; *Registries ; France/epidemiology ; *Muscular Atrophy, Spinal/therapy/epidemiology/drug therapy ; Male ; Child ; Female ; Adult ; Adolescent ; Child, Preschool ; Middle Aged ; Young Adult ; Retrospective Studies ; Infant ; Oligonucleotides/therapeutic use ; Biological Products/therapeutic use ; Quality of Life ; Aged ; Azo Compounds ; Pyrimidines ; }, abstract = {BackgroundSpinal muscular atrophy (SMA) is a severe neurodegenerative disease affecting children. Three innovative disease-modifying therapies (DMTs)-nusinersen, risdiplam, and onasemnogene abeparvovec-are available for treatment.ObjectiveTo provide a descriptive overview of patients enrolled in the Registre SMA France until July 22, 2024.MethodsRegistre SMA France is a multicenter, national observational registry that includes patients with SMA-children and adults, treated or untreated. Data collection began retrospectively in 2016 and prospectively in 2020, with a 10-year follow-up plan. The coordinating center is the neuropediatric department of Garches Hospital (AP-HP), while methodological and, regulatory and operational management, are provided by the Clinical Research Unit of AP-HP Paris-Saclay. Financial support is provided through unrestricted grants from Biogen, Novartis, and Roche. Data on patient characteristics, medical and surgical follow-up, treatments, adverse events, and quality of life are recorded via structured forms, with additional modules developed as required (e.g., hematological monitoring post-gene therapy in 2021). Data quality is ensured through routine checks and periodic monitoring.ResultsBy July 22, 2024, 1299 patients from 59 centers were enrolled (299 SMA1, 502 SMA2, 469 SMA3, 19 SMA4, 10 presymptomatic). Of these, 76.2% received DMT (nusinersen: 46.1%, risdiplam: 23.2%, onasemnogene abeparvovec: 9.2%), with 21.5% undergoing sequential or combination therapy. Major complications included ventilatory support (SMA1: 69.9%, SMA2: 64.5%, SMA3: 18.1%), enteral feeding (SMA1: 56.2%SMA1), and spine surgery (SMA2: 24.5%). Survival was significantly higher in treated SMA1 and SMA2 cases.ConclusionThis registry serves as a key resource for understanding the clinical course and treatment outcomes of SMA in the real world, supporting future research and informing clinical and policy decisions in the era of DMTs.Trial registrationNCT04177134.}, } @article {pmid40622486, year = {2025}, author = {Kaindal, S and Venkataramana, B}, title = {Demographic and clinical predictors of treatment outcomes in invasive lobular carcinoma breast cancer: insights from Cox regression analysis.}, journal = {Discover oncology}, volume = {16}, number = {1}, pages = {1273}, pmid = {40622486}, issn = {2730-6011}, abstract = {Invasive lobular carcinoma (ILC) ranks as the second most prevalent type of breast cancer after invasive ductal carcinoma (IDC). Understanding the demographics, clinical, and treatment outcomes of patients with ILC is essential for developing personalized treatment strategies. The purpose of this study is to evaluate the risk factors, treatment efficacy, demographics, and effects of marital status on treatment approaches for patients with lobular carcinoma. The data retrieved from the SEER program included 2,085 patients with lobular carcinoma. Descriptive statistics describe their clinical and demographical characteristics, while inferential statistics, including the Pearson chi-square test and Cox regression models, assess treatment outcomes based on age and clinicopathological factors. Among the cohort, 7.9% of patients were aged 30-44, 40.1% were aged 45-59, and 52% were aged 60-74. The analysis indicated that patients aged 45-59 predominantly received radiation therapy, while those aged 60-74 primarily underwent chemotherapy. Compared to older individuals, younger patients demonstrated a more favorable response to chemotherapy (HR = 0.653, 95% CI: 0.261-1.633) and radiation therapy (HR = 0.625, 95% CI: 0.249-1.565). Age at diagnosis was an independent factor in breast cancer of lobular carcinoma. The Cox regression models revealed significant disparities in treatment effects across different age groups and clinicopathological characteristics. The chi-square analysis showed no significant associations for most variables, indicating that unmeasured factors influence chemotherapy and radiation therapy. A frailty model better captures risk factors, improving treatment decision-making and patient outcome analysis. This study emphasizes the need to evaluate demographic and clinical factors in treatment planning for lobular carcinoma patients. The findings suggest that personalized treatment strategies should be developed to address the varying responses to treatment among different patient cohorts.}, } @article {pmid40619853, year = {2025}, author = {Brunetta, HS and Mori, MA and Bartelt, A}, title = {Oxidative Phosphorylation in Uncoupled Mitochondria.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {47}, number = {9}, pages = {e70038}, pmid = {40619853}, issn = {1521-1878}, support = {DFG 4925/5-1 AOBJ 704031//Deutsche Forschungsgemeinschaft/ ; }, mesh = {*Oxidative Phosphorylation ; *Mitochondria/metabolism ; Animals ; Thermogenesis/physiology ; Humans ; Uncoupling Protein 1/metabolism ; Adipose Tissue, Brown/metabolism ; Energy Metabolism ; Adipocytes, Brown/metabolism ; }, abstract = {Mitochondrial membrane potential is highly dependent on coupled as well as uncoupled respiration. While brown adipose tissue (BAT) mediates non-shivering thermogenesis (NST), a highly adaptive bioenergetic process critical for energy metabolism, the relationship of coupled and uncoupled respiration in thermogenic adipocytes remains complicated. Uncoupling protein 1 (UCP1)-mediated proton leak is the primary driver of NST, but recent studies have shown that oxidative phosphorylation may be an underappreciated contributor to UCP1-dependent NST. Here, we highlight the role of ATP synthase for BAT thermogenesis and discuss the implications of fine-tuning adrenergic signaling in brown adipocytes by the protein inhibitory factor 1 (IF1). We conclude by hypothesizing future directions for mitochondrial research, such as investigating the potential role of IF1 for mitochondrial substrate preference, structural dynamics, as well as its role in cell fate decision and differentiation.}, } @article {pmid40614127, year = {2025}, author = {Grant, RS and Kakani, P and Movva, P and Daskivich, TJ and Raman, SS and Sisk, AE and Brisbane, WG and Reiter, RE and Weiner, AB}, title = {Identifying cribriform and intraductal histology on magnetic resonance imaging-assisted biopsy for patients with intermediate-grade prostate cancer: Implications for active surveillance.}, journal = {Cancer}, volume = {131}, number = {14}, pages = {e35968}, pmid = {40614127}, issn = {1097-0142}, support = {P50 CA092131/CA/NCI NIH HHS/United States ; T32 CA009213/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/diagnostic imaging/surgery ; *Magnetic Resonance Imaging/methods ; Aged ; Retrospective Studies ; Middle Aged ; Neoplasm Grading ; Watchful Waiting ; *Image-Guided Biopsy/methods ; Prostatectomy ; Sensitivity and Specificity ; Prostate/pathology/diagnostic imaging ; }, abstract = {BACKGROUND: Nearly 12% of patients in the United States with intermediate-risk prostate cancer (PCa) opt for surveillance as their initial management strategy. Patients with aggressive histologic variants, such as cribriform and intraductal carcinoma (IDC), are considered poor candidates for surveillance. The objective of this study was to determine the sensitivity and specificity of magnetic resonance imaging (MRI)-assisted biopsy for detecting cribriform PCa and IDC.

METHODS: In this retrospective cohort study, patients who underwent prostate MRI before biopsy within 6 months of prostatectomy at a single institution (2018-2024) were identified. All patients had grade group 2-3 (GG2-3) PCa on biopsy. The primary outcome was the sensitivity of MRI-assisted biopsy for detecting cribriform PCa and IDC by patient in the prostatectomy specimen.

RESULTS: The authors identified 641 patients who had 1186 tumors that were GG2-3 PCa on biopsy. The median time between MRI and biopsy was 31 days, and the median time between biopsy and surgery was 91 days. Cribriform PCa was identified in 35 patients (5.5%) at the time of biopsy and in 119 patients (18.6%) at surgery. IDC was present in 22 patients (3.4%) at biopsy and in 71 patients (11.1%) at surgery. By patient, the sensitivity for detecting cribriform PCa, IDC, or either was 21.8%, 26.8%, and 29.3%, respectively. The sensitivity by tumor for cribriform PCa, IDC, or either was 20.5%, 27.3%, and 28%, respectively.

CONCLUSIONS: The sensitivity of MRI-assisted biopsy for detecting cribriform PCa and IDC in patients with GG2-3 PCa is poor. This work should encourage improvements in detecting variant histologies with optimized biopsy, imaging, and adjunct biomarkers.}, } @article {pmid40612485, year = {2025}, author = {Câmara, B and Florindo, C and de Lima, CB and Correia, N and Fernandes, I and Batista, M and Gaspar, A and Janeiro, P}, title = {Rethinking phenylalanine levels in phenylketonuria for optimal neurocognitive development beyond childhood.}, journal = {Frontiers in pediatrics}, volume = {13}, number = {}, pages = {1488809}, pmid = {40612485}, issn = {2296-2360}, abstract = {INTRODUCTION: Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism that disrupts neurotransmitter balance. Although early intervention has improved outcomes, neurocognitive challenges persist, particularly during adolescence. Metabolic control guidelines for patients aged >12 years differ between the European Union and the United States, with recommended blood Phe levels below 600 µM and 360 µM, respectively.

METHODS: This study evaluated the relationship between blood Phe levels, intelligence quotient (IQ), and executive functions using the Wechsler Intelligence Scale for Children-Third Edition and the d2 Test of Attention. Blood Phe levels were monitored longitudinally and summarized using the Index of Dietary Control (IDC), calculated as the mean of individual annual median Phe concentrations, both before and after 12 years of age.

RESULTS: The study included 14 early-treated PKU patients aged 12-17 years, all diagnosed through newborn screening programs. Participants maintained good metabolic control (IDC <360 µM) prior to 12 years of age, with a mean IDC of 302 µM. Higher IQ scores before the age of 12 years were observed only among patients with consistent dietary compliance. After that age, attentional performance declined in those who were noncompliant with dietary recommendations. Additionally, occasional elevations in blood Phe levels at the time of cognitive assessments were associated with poorer cognitive performance.

DISCUSSION: These findings underscore the detrimental effects of elevated Phe levels on executive functions during adolescence and highlight the need for larger studies to determine whether blood Phe levels between 360 and 600 µM are safe for patients aged >12 years.}, } @article {pmid40611065, year = {2025}, author = {Zhou, L and Wu, Y and Wen, X and Guo, X and Zhang, L and Zhao, T and Song, W and Xin, Y and Su, Z and Sun, L and Tian, J}, title = {Prediction model for assessing HER2 status patient with invasive ductal carcinoma based on clinical parameters and ultrasound features: a dual-center study.}, journal = {BMC women's health}, volume = {25}, number = {1}, pages = {291}, pmid = {40611065}, issn = {1472-6874}, support = {2025KY564//Medical Science and Technology Project of Zhejiang Province/ ; 82371984, 82202168, and 82272001//National Natural Science Foundation of China/ ; ZH22036201210064PWC//The Science and Technology Plan Medical and Health Project of Zhuhai/ ; YQ2022H010//Outstanding Youth Program of the Heilongjiang Natural Science Foundation/ ; 2024C03069//Major Scientific and Technological Project of Zhejiang Province/ ; }, mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; *Breast Neoplasms/diagnostic imaging/pathology/metabolism ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology/metabolism ; *Nomograms ; *Erb-b2 Receptor Tyrosine Kinases/metabolism/analysis ; Retrospective Studies ; ROC Curve ; *Ultrasonography, Mammary ; }, abstract = {OBJECTIVE: The assessment of Human Epidermal Growth Factor Receptor 2 (HER2) expression status is crucial for determining the eligibility of breast cancer (BC) patients for HER2-targeted therapies. This study aims to develop a nomogram model that incorporates multimodal ultrasound imaging features alongside clinicopathological characteristics to evaluate HER2 status.

METHODS: A retrospective analysis was conducted on 456 breast cancer patients who underwent breast ultrasound between January 2019 and December 2021. The dataset was randomly divided into a training cohort (n = 319) and a validation cohort (n = 137) in a 7:3 ratio. Independent factors predicting HER2 status in the training cohort were evaluated using univariate and multivariate logistic regression. Subsequently, a combined model was developed and validated in the validation cohort. Model performance was assessed through receiver operating characteristic (ROC) curves, decision curve analysis (DCA) and calibration curves to evaluate discrimination, net clinical benefit, and calibration, respectively.

RESULTS: Of the 456 patients enrolled, 120 (26.32%) were HER2-positive and 336 (73.68%) were HER2-negative. The area under the ROC curve (AUC) for the combined model distinguishing HER2-negative from HER2-positive patients was 0.864 (95% CI: 0.823-0.904) in the training cohort and 0.874 (95% CI: 0.815-0.933) in the validation cohort. Significant predictors included estrogen receptor (ER) status, Ki67, ultrasound lesion size, calcification, and posterior acoustic features. Additionally, the calibration curves for the combined model indicated good fit in both the training and validation cohorts.

CONCLUSION: A nomogram constructed from clinical and ultrasound features may serve as a promising non-invasive tool for determining HER2 expression status, aiding in the prediction of eligibility for HER2-targeted therapy in clinical practice.

CLINICAL TRIAL NUMBER: Not applicable.}, } @article {pmid40604374, year = {2025}, author = {Pardo, J and Capdevila-Lacasa, C and Segura, B and Pané, A and Moreno, PJ and Garrabou, G and Grau-Junyent, JM and Junqué, C and , }, title = {Diffusivity alterations related to cognitive performance and phenylalanine levels in early-treated adults with phenylketonuria.}, journal = {Journal of neurodevelopmental disorders}, volume = {17}, number = {1}, pages = {37}, pmid = {40604374}, issn = {1866-1955}, mesh = {Humans ; *Phenylketonurias/blood/diagnostic imaging/psychology/diet therapy/pathology/complications ; *Phenylalanine/blood ; Adult ; Male ; Female ; Diffusion Tensor Imaging ; *White Matter/diagnostic imaging/pathology ; *Cognition/physiology ; Young Adult ; *Brain/diagnostic imaging ; Neuropsychological Tests ; }, abstract = {BACKGROUND: Altered white matter (WM) is consistently reported in patients with phenylketonuria (PKU). However, the knowledge about WM microstructural integrity in early-treated adults with classical PKU and its relationship with cognition and metabolic parameters is inconclusive. This study aims to explore the cerebral WM microstructural alterations in adult patients with early-treated classical PKU and their association with blood phenylalanine (Phe) levels and neuropsychological performance using whole-brain diffusion tensor imaging (DTI).

METHODS: Twenty-nine patients with early-treated classical PKU (mean age = 30.86, SD = 7.74) and 31 healthy controls (mean age = 32.45, SD = 9.40) underwent neuropsychological assessment and MRI. Phe dry blood spot (DBS-Phe) samples, along with venous Phe levels, were collected from the PKU sample to calculate the index of dietary control (IDC). Tract-based spatial statistics (TBSS) of the mean diffusivity (MD), and fractional anisotropy (FA), were carried out with FSL v6.0.4 to assess between-group differences and to explore associations with both cognitive and clinical data.

RESULTS: Patients exhibited a widespread white matter tract involvement, with lower MD and higher FA values compared to controls. The most affected tracts were the inferior longitudinal fasciculus and inferior fronto-occipital fasciculus for MD, and the anterior corona radiata, uncinate fasciculus and forceps minor for FA. MD negatively correlated with IDC and venous Phe levels, whereas FA negatively correlated with full-scale intelligence quotient (FSIQ) (p-value ≤0.05 FWE-corrected).

CONCLUSIONS: Microstructural WM alterations were present in adults with early-treated classical PKU, and these abnormalities were related to global intelligence and metabolic control markers. Although our results suggest the importance of proper disease management, further studies are needed to determine its long-term relevance.}, } @article {pmid40603576, year = {2025}, author = {Marchesi, S and Marinello, A and Ambrosini, P and Cavalli, C and Lo Russo, G and Occhipinti, M}, title = {Immune-checkpoint targeting drug conjugates: a novel class of promising therapeutic agents for cancer treatment.}, journal = {NPJ precision oncology}, volume = {9}, number = {1}, pages = {219}, pmid = {40603576}, issn = {2397-768X}, abstract = {Immune-checkpoint targeting Drug Conjugates (IDCs) are a novel class of therapeutics that combine an immune checkpoint-targeting moiety, a cleavable linker, and a cytotoxic payload. By integrating features and functions of antibody-drug conjugates and immunotherapy, IDCs represent a promising strategy to remodel the tumor microenvironment and enhance antitumor efficacy. Several IDCs targeting checkpoints such as PD-L1, B7-H3, and B7-H4 are in early-phase clinical trials. This review summarizes available data on IDC efficacy and toxicity in human. Although current evidence is limited, ongoing phase III trials and biomarker studies will clarify their optimal clinical role, including potential for tumor-agnostic use.}, } @article {pmid40599636, year = {2025}, author = {Usluca, S and Bakir, A and Arikok, AT and Korkut, G and Yagiz, GC and Alper, M}, title = {Detection of Toxoplasma gondii and High-Risk Human Papillomaviruses in FFPE Malignant and Benign Breast Lesions Using Real-Time PCR.}, journal = {Infection and drug resistance}, volume = {18}, number = {}, pages = {3149-3155}, pmid = {40599636}, issn = {1178-6973}, abstract = {OBJECTIVE: Breast cancer is the most prevalent malignancy among women. In recent years, it has been suggested that various pathogens such as Toxoplasma gondii (T. gondii) and human papillomavirus (HPV) may play a potential role in the development of breast cancer. This study aimed to determine the prevalence of T. gondii and HPV infections in formalin-fixed paraffin-embedded tissue samples of breast cancer patients using real-time PCR.

METHODS: The study included 136 paraffin-embedded biopsy samples with w confirmed malignant breast tumor diagnosis and 50 breast tissue samples diagnosed as benign breast lesions, serving as controls. The presence of T. gondii DNA and high-, medium-, and low-risk HPV genotype DNAs were investigated using the real-time PCR method. First, deparaffinization was performed using xylene and alcohol, followed by DNA extraction and real-time PCR amplification.

RESULTS: The most common histopathological types of malignant breast carcinoma were invasive carcinoma (n=82; 60.3%), invasive lobular carcinoma (n=26; 19.1%), invasive ductal carcinoma (n=8; 5.9%), and mixed invasive carcinoma (n=8; 5.9%). According to the Modified Bloom-Richardson classification, 55.15% of malignant breast tumor samples were grade 2, 32.4% were grade 3, and 12.5% were grade 1. Real-time PCR analysis did not detect T. gondii DNA or HPV DNA in any of these samples.

CONCLUSION: Our findings do not support a role of T. gondii and HPV in breast cancer development. To better understand the possible relationship between breast cancer and these pathogens, further studies with larger sample sizes, diverse diagnostic methods, and broder geographical coverage are necessary.}, } @article {pmid40598506, year = {2025}, author = {Raouf, M and Kamal, S and Elsayed, R and Zaki, I and Kholeif, D}, title = {Detection of bovine leukemia virus, Epstein-Barr virus and human papillomavirus in breast cancer tissues of Egyptian patients.}, journal = {Infectious agents and cancer}, volume = {20}, number = {1}, pages = {43}, pmid = {40598506}, issn = {1750-9378}, abstract = {BACKGROUND: Breast cancer (BC) remains one of the most common malignancies worldwide. Many viruses have been linked to BC; namely, Human papillomavirus (HPV), Epstein-Barr virus (EBV) and Bovine leukemia virus (BLV). However, a causal role is yet to be established.

OBJECTIVES: To detect the prevalence of BLV, EBV and HPV sequences in BC tissue compared to BC-free tissue and correlate their presence with different pathological features of BC.

SUBJECTS AND METHODS: A retrospective case-control study was conducted on 75 FFPE (formalin fixed paraffin embedded) blocks of BC tissues and 25 of BC-free tissues obtained from Alexandria Main University Hospital pathology department archive. Demographic, medical, pathological data were retrieved from patients' archival records. Hormonal receptor status, Real-time PCR for viral detection and HPV genotyping were done. Statistical analysis was done using SPSS software. The Chi-square test, Fisher's Exact correction and Monte Carlo simulation were used for quantitative variables.

RESULTS: Invasive ductal carcinoma was the most predominant histologic type (85.3%). BLV, EBV and HPV were detected in (22.7% vs. 16%, 14.7% vs. 8%, 6.7% vs. 0%) BC vs. non-BC tissues respectively with HR HPV 16 detection. Lymphovascular invasion (LVI) and stage III were more commonly seen among tissues with positive viral detection vs. those which were negative (64.3% vs. 53% and 39% vs. 17% respectively). However, no single viral detection was found to be statistically significant in relation to clinicopathological parameters. Multiple viral co-existence was found in 18% of PCR positive cases which was significantly associated with younger age (P = 0.026).

CONCLUSION: Low rate of viral presence was found in BC tissues. Nevertheless, LVI and stage III were more commonly seen in tissues with positive viral detection. Moreover, a synergetic relation between multiple viral existence and BC development in young age could be possible yet to be verified.}, } @article {pmid40598288, year = {2025}, author = {Idc, G and Gy, W and Klmd, S}, title = {Knowledge and attitudes on cancer pain management among nurses at National Cancer Institute Sri Lanka.}, journal = {BMC nursing}, volume = {24}, number = {1}, pages = {690}, pmid = {40598288}, issn = {1472-6955}, abstract = {BACKGROUND: Effective pain management is crucial in oncology nursing, yet gaps in knowledge and attitudes may affect the quality of care.

OBJECTIVE: To describe knowledge and attitudes on cancer pain management among nurses at NCI Sri Lanka.

METHODS: A cross-sectional survey was conducted at the NCI in Sri Lanka among 340 nurses selected using stratified random sampling. Knowledge and attitudes on cancer pain management was assessed using self-administered 41-item Knowledge and Attitudes Survey Regarding Pain (KASRP) questionnaire. Scoring was carried out as per the recommended guidelines and knowledge and attitudes were categorized into three groups as good, moderate, poor using > 75%, 75%- 50% and < 50% as cut-offs. The collected data were analyzed using IBM SPSS version 26.0. Descriptive statistics were calculated, and independent sample t-test followed by one way ANOVA was used to identify associated factors. P-value of < 0.05 were considered statistically significant. Ethical approval was obtained by the Research Ethics Committee of the Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Lanka (REC/NSG 06).

RESULTS: The response rate was 80.56%. The majority of participants were females (n = 285, 83.8%), < 35 years (n = 252, 74.1%). Majority (n = 266, 66.5%) had a poor level of knowledge and attitudes on cancer pain management, 31.2% (n = 106) had a moderate level, and only 2.4% (n = 8) had a good level. The mean knowledge and attitude score was 19.2 (4.35). Nurses with a BSc degree or higher (p = .011) and nurses working in wards (p = .003) exhibited a significantly higher knowledge and attitudes score. Significant differences were also found across educational levels (p = .038), with BSc nurses outperforming Diploma holders. However, age, gender, total working experience, experience at NCI, and previous training on pain management did not show any significant associations. Multinomial logistic regression showed educational level and current working station as significant predictors.

CONCLUSION: Significant gaps in knowledge and attitudes towards cancer pain management existed among nurses at the NCI in Sri Lanka. These findings highlight the need for targeted educational interventions to improve the knowledge and attitudes of nurses in managing cancer pain to enhance the quality of oncology care.}, } @article {pmid40597443, year = {2025}, author = {Bullock, E and Rozyczko, A and Shabbir, S and Tsoupi, I and Young, AIJ and Travnickova, J and Gómez-Cuadrado, L and Mabruk, Z and Carrasco, G and Morrow, E and Pennel, K and Kloosterman, P and Houthuijzen, JM and Jonkers, J and Avalle, L and Poli, V and Iggo, R and Xiao, X and Guo, J and Zhu, X and Mallon, E and Edwards, J and Patton, EE and Brunton, VG}, title = {Cancer-associated fibroblast driven paracrine IL-6/STAT3 signaling promotes migration and dissemination in invasive lobular carcinoma.}, journal = {Breast cancer research : BCR}, volume = {27}, number = {1}, pages = {121}, pmid = {40597443}, issn = {1465-542X}, support = {Pakistan-Programme 2020-2024//Punjab Educational Endowment Funds/ ; MC_UU_00035/13/MRC_/Medical Research Council/United Kingdom ; C157/A24837/CRUK_/Cancer Research UK/United Kingdom ; NO. 2022YFS0601//Sichuan Provincial Science and Technology Support Program/ ; 68730/MRA/Melanoma Research Alliance/United States ; S3181//NHS Lothian Charity/ ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {*STAT3 Transcription Factor/metabolism/genetics ; *Interleukin-6/metabolism/genetics ; Humans ; Animals ; Female ; Mice ; Cell Movement ; *Breast Neoplasms/pathology/metabolism/genetics ; *Carcinoma, Lobular/pathology/metabolism/genetics ; *Cancer-Associated Fibroblasts/metabolism/pathology ; Zebrafish ; Signal Transduction ; Paracrine Communication ; Cell Line, Tumor ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer after invasive ductal carcinoma of no special type (NST), accounting for 10-15% of diagnoses. Despite the myriad molecular, histological and clinical differences between ILC and NST tumors, patients are treated in the same way, and although prognosis initially is good, ILC patients have poorer long-term outcomes. Understanding the differences between these two subtypes and identifying ILC-enriched therapeutic targets is necessary to improve patient care.

METHODS: Human and mouse cancer-associated fibroblasts (CAFs), ILC cell lines and patient-derived organoids were used for in vitro and in vivo studies, including western blotting, migration, organotypic invasion assays and dissemination in zebrafish embryos. RNASeq was used to identify CAF and interleukin-6 (IL-6)-derived gene signatures. Bioinformatic analysis of public databases and immunohistochemical of human tumor microarrays was carried out.

RESULTS: We identified IL-6 as a paracrine CAF-derived factor that activates Signal-Transducer-and-Activator-of-Transcription-3 (STAT3) in human and mouse ILC models. Analysis of human breast tumors showed that the IL-6/JAK/STAT3 pathway is enriched in ER + ILC compared to ER + NST. A 42-gene CAF dependent IL-6 gene signature and 64-gene consensus IL-6 gene signature were generated and were significantly enriched in ER + ILC, with many of the genes overexpressed in ILC tumors. IL-6 treatment suppressed downstream estrogen signaling and also led to the acquisition of a more mesenchymal-like phenotype associated with increased migration and invasion. Finally, IL-6 treatment significantly increased ILC cell dissemination following injection into zebrafish embryos.

CONCLUSIONS: CAF-derived IL-6 drives paracrine activation of the IL6/JAK/STAT3 signaling pathway which is enriched in ILC. This leads to the acquisition of pro-tumorigenic phenotypes, highlighting the pathway as a potential therapeutic target in ILC.}, } @article {pmid40596034, year = {2025}, author = {Yang, Q and Xi, L and Huang, M and Zhang, H and Zhou, F}, title = {Nomogram for the prediction of the prognosis of patients with triple-negative invasive ductal carcinoma of breast after neoadjuvant chemotherapy.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {21666}, pmid = {40596034}, issn = {2045-2322}, mesh = {Humans ; *Nomograms ; Female ; *Triple Negative Breast Neoplasms/drug therapy/pathology/mortality ; Middle Aged ; Neoadjuvant Therapy ; Prognosis ; Adult ; *Carcinoma, Ductal, Breast/drug therapy/pathology/mortality ; Aged ; ROC Curve ; Chemotherapy, Adjuvant ; SEER Program ; }, abstract = {Triple-negative breast cancer (TNBC) represents a subtype of breast cancer with a poor prognosis because of limited treatment options at present. Therefore, this study aimed to use nomograms to forecast the prognosis of patients with triple-negative invasive ductal carcinoma of the breast (TN-IDC) undergoing neoadjuvant chemotherapy (NCT). 3573 TNBC patients from the SEER database who received NCT between 2010 and 2015 were selected and randomized in 7:3 into the training or the testing group. Then, nomograms for overall survival (OS) and cancer-specific survival (CSS) of the two groups were created via univariate and multivariate analyses. Consistency index (C-index), calibration curve, and area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA) were employed to evaluate the reliability and accuracy of the model. As demonstrated by univariate and multivariate Cox regression analyses, 8 indicators (AJCC_M, AJCC_N, AJCC_T, positive lymph nodes [LNs] and the number of positive LNs, liver metastases, response to NCT, and radical surgery) were incorporated in the nomogram. The results indicated that the C-index of the OS prediction model was 0.776 for the training group and 0.779 for the testing group. In the training group, the AUC for forecasting 1-, 3-, and 5-year OS was 0.840, 0.822, and 0.817, respectively; in the testing group, the AUC was 0.889, 0.821, and 0.813, respectively. The C-index of the CSS prediction model was 0.790 for the training group and 0.789 for the testing group. In the training group, the AUC for forecasting 1-, 3-, and 5-year CSS was 0.853, 0.829, and 0.827, respectively; in the testing group, the AUC was 0.887, 0.800, and 0.820, respectively. Both C-index and AUC of OS and CSS prediction models were above or close to 0.8, indicating good predictability of the model. DCA consistently indicated that using the nomogram for OS and CSS prediction yielded favorable net clinical benefit, and the nomogram outperformed the AJCC TNM staging system in decision-making. T2-4 (maximum tumor diameter > 2 cm or invasion of the chest wall/skin), N3, M1, liver metastasis, incomplete remission after chemotherapy, and breast-conserving surgery were prognostic risk factors in TN-IDC patients receiving NCT. Higher T stage (T3-4, maximum tumor diameter > 5 cm or invasion of the chest wall/skin), N stage (N3), liver metastasis, non-remission (NR) after NCT, and positive LNs after chemotherapy were linked to worse OS and CSS. After NCT, the number of positive LNs ≥ 4 and NR for lesion exhibited the greatest impact on OS and CSS.}, } @article {pmid40595592, year = {2025}, author = {Mello, RM and Gomez Ceballos, D and Sandate, CR and Wang, S and Jouffe, C and Agudelo, D and Uhlenhaut, NH and Thomä, NH and Simon, MC and Lamia, KA}, title = {BMAL1 and ARNT enable circadian HIF2α responses in clear cell renal cell carcinoma.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {5834}, pmid = {40595592}, issn = {2041-1723}, support = {UL1TR002550//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; CA271500//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R01 CA211187/CA/NCI NIH HHS/United States ; R01 CA271500/CA/NCI NIH HHS/United States ; 450149205//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; UL1 TR002550/TR/NCATS NIH HHS/United States ; DK136780//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; CA211187//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; }, mesh = {*ARNTL Transcription Factors/metabolism/genetics ; *Basic Helix-Loop-Helix Proteins/metabolism/genetics/antagonists & inhibitors ; *Carcinoma, Renal Cell/genetics/metabolism/pathology/drug therapy ; Humans ; *Kidney Neoplasms/genetics/metabolism/pathology/drug therapy ; *Aryl Hydrocarbon Receptor Nuclear Translocator/metabolism/genetics ; Animals ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; *Circadian Rhythm/genetics ; Mice ; Xenograft Model Antitumor Assays ; Cell Proliferation/drug effects ; Female ; Endothelial PAS Domain-Containing Protein 1 ; }, abstract = {Circadian disruption enhances cancer risk, and many tumors exhibit disordered circadian gene expression. We show rhythmic gene expression is unexpectedly robust in clear cell renal cell carcinoma (ccRCC). The core circadian transcription factor BMAL1 is closely related to ARNT, and we show that BMAL1-HIF2α regulates a subset of HIF2α target genes in ccRCC cells. Depletion of BMAL1 selectively reduces HIF2α chromatin association and target gene expression and reduces ccRCC growth in culture and in xenografts. Analysis of pre-existing data reveals higher BMAL1 in patient-derived xenografts that are sensitive to growth suppression by a HIF2α antagonist (PT2399). BMAL1-HIF2α is more sensitive than ARNT-HIF2α is to suppression by PT2399, and the effectiveness of PT2399 for suppressing xenograft tumor growth in vivo depends on the time of day at which it is delivered. Together, these findings indicate that an alternate HIF2α heterodimer containing the circadian partner BMAL1 influences HIF2α activity, growth, and sensitivity to HIF2α antagonist drugs in ccRCC cells.}, } @article {pmid40593019, year = {2025}, author = {Saha, D and Dutta, S}, title = {Introducing electric spring in the voltage frequency regulation of a multi area multi source integrated power system network.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {22373}, pmid = {40593019}, issn = {2045-2322}, abstract = {The present work demonstrates the application of an electric spring in a multi-source interconnected power system in which coordinated control of frequency and voltage loop is investigated. A two-area power system is considered with non-linearity for the thermal power system, such as generation rate constraint and governor dead band, so that the developed model is realistic. A novel cascade controller, namely a two-degree-of-freedom proportional-integral-derivative controller cascaded with a proportional-integral-derivative controller (2DOFPID-PID), is utilized for the first time for reducing the area control error to zero in both the control areas. A powerful algorithm known as the Golden Jackal Algorithm (GJA) is considered for tuning the controller parameters and achieving the minimum performance index. System dynamic responses are observed for the coordinated automatic load frequency control and automatic voltage regulator during step load perturbations and random load perturbations. Selection of the best performance index (PI) among integral of squared error (ISE), integral of time multiplied by absolute error (ITAE), integral of time multiplied by squared error (ITSE), and Integral of absolute error (IAE) proves that ITAE serves the best among others. To model an AC/DC bus, system responses are also investigated with a parallel AC/DC link that depicts satisfactory results in terms of overshoot, undershoot, and settling time. Modelling of the electric spring in the proposed system is integrated to check the terminal voltage deviation and frequency deviation, and mitigate them. Results show reduced generator terminal deviation in both the control areas. Comparison of different powerful algorithms with the proposed one infers the superiority of the proposed golden jackal algorithm with reference to the performance index vs. number of iterations.}, } @article {pmid40592998, year = {2025}, author = {Almohanna, H and Almsned, F and Alharbi, H and Al Dossary, N and Alrasheed, A and Alzayer, R and Alwosaibai, K}, title = {A comprehensive epidemiological analysis of breast cancer in the Eastern Province of Saudi Arabia.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {20816}, pmid = {40592998}, issn = {2045-2322}, mesh = {Humans ; Saudi Arabia/epidemiology ; Female ; Middle Aged ; *Breast Neoplasms/epidemiology/pathology ; Adult ; Retrospective Studies ; Incidence ; Aged ; Receptors, Estrogen/metabolism ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {Breast cancer is a leading health concern in Saudi Arabia, characterized by unique demographic and clinical profiles. This study analyzed breast cancer cases at King Fahad Specialist Hospital-Dammam (KFSH-D), focusing on age at diagnosis, disease stage, histological type, and hormonal receptor status. A retrospective cohort study included 5,954 breast cancer patients diagnosed between 2006 and 2022 from the KFSH-D database. Data were extracted via a Real-World Evidence Digital Platform adhering to international standards. Statistical analyses included descriptive statistics, Chi-square tests, t-tests, incidence and mortality rate calculations, survival analysis, and predictive modeling for future incidence trends. The cohort had a mean age at diagnosis of 49 years (SD = 12.0), with most patients aged 40-59 years. Over 99% were female and predominantly Saudi nationals. Approximately two-thirds presented with locally advanced disease, with invasive ductal carcinoma being the most common type (81%). Al Ahsa region accounted for 31% of referral cases. Hormonal receptor status showed 59% HER2-negative, 61% ER-positive, and 56% PR-positive. Predictive modeling forecasted an 80% increase in new cases by 2028, with incidence rates expected to double. This study highlights a younger median age at diagnosis and a high prevalence of late-stage disease. These findings underscore the urgent need for improved screening programs, targeted public health interventions, and better healthcare access in Saudi Arabia.}, } @article {pmid40591177, year = {2025}, author = {Muroyama, Y and Miyashita, M and Miura, T and Sato, S and Watanabe, M and Suzuki, T}, title = {Malignant phyllodes tumor of the breast with osteosarcoma component: a diagnostic dilemma - a case report.}, journal = {Discover oncology}, volume = {16}, number = {1}, pages = {1191}, pmid = {40591177}, issn = {2730-6011}, abstract = {Osteosarcoma component in the breast is rare and can present as a rapidly growing mass with calcification in imaging studies. Differential diagnosis includes metaplastic carcinoma, malignant phyllodes tumor with osteosarcoma component, and exceptionally rare osteosarcoma. Distinguishing these tumors is critical for determining therapeutic strategies, especially in differentiating metaplastic carcinoma, as only the former is indicated for adjuvant chemoradiotherapy. Diagnosis can be challenging, however, particularly when the dominant stromal and/or sarcomatous components mask the epithelial component. Here, we present a rare case of breast tumor with osteosarcoma component determined as malignant phyllodes tumor after extensive pathological examination. A 55-year-old woman presented with a left breast mass rapidly growing over the past 3 months. FDG-PET/CT revealed a calcified tumor in the left breast, nearly exposed to the skin, as well as an incidentally found small right breast tumor. Bilateral total mastectomy with sentinel and left axillary lymph node dissection was performed. Microscopic examination of the left breast tumor revealed osteosarcoma components with the atypical cells producing osteoid/neoplastic bone, chondrosarcoma-like components, and massive overgrowth of atypical spindle cells. Extensive pathological examination revealed a small amount of compressed mammary glands without atypia. Collectively, the diagnosis of malignant phyllodes tumor with osteosarcoma component, was made. The patient was discharged without major postsurgical complications and initiated on anastrozole for the concurrently identified hormone-receptor-positive, HER2-negative right breast invasive ductal carcinoma. Breast tumor with osteosarcoma component warrants not only diligent pathological examination to determine the indication for chemoradiotherapy, but also multidisciplinary collaboration to develop effective therapeutic strategies.}, } @article {pmid40589310, year = {2025}, author = {Shan, M and Chen, L and Wang, J and Wen, L}, title = {Dual-Channel Off-Axis Ion Funnel With a Deflection Electrode.}, journal = {Rapid communications in mass spectrometry : RCM}, volume = {39}, number = {20}, pages = {e10103}, doi = {10.1002/rcm.10103}, pmid = {40589310}, issn = {1097-0231}, support = {2023ZY01073//Ministry of Industry and Information Technology/ ; 2022S012//Public welfare project in Ningbo/ ; 2024S002//Public welfare project in Ningbo/ ; 2021Z055//Major projects in Ningbo/ ; //K.C. Wong Magna Fund in Ningbo University/ ; }, abstract = {RATIONALE: In electrospray ionization mass spectrometry (ESI-MS) systems, two critical challenges persist: (1) under-expanded supersonic jets at the atmospheric pressure interface (API) cause ion losses and reduced transmission efficiency; (2) residual solvents and charged droplets entering vacuum stages lead to contamination and elevated chemical noise, degrading analysis accuracy.

METHODS: A dual-channel off-axis ion funnel with a deflection electrode (DC-OFIDE) was developed to address these challenges. This device integrates three core components: an ion drift channel (IDC), an ion funnel channel (IFC), and a deflection electrode. The IDC and IFC are separated by conjoined gaps. Ions within the gas stream emanating from the API are extracted from the IDC via a deflection field, while a retarding axial field prolongs ions' residence time, ensuring efficient transfer to the IFC. This DC-OFIDE features an enlarged entrance aperture (Φ18 mm) to accommodate a multi-capillary interface, enhancing compatibility with high-conductance sample introduction systems.

RESULTS: Compared with the original conventional ion funnel (CIF), the DC-OFIDE achieved a threefold enhancement in caffeine ion intensity and a broader m/z transmission window. It demonstrated robust neutral and droplet suppression, maintaining 80% ion intensity even under tripled serum volume infused. In drug screening of hair samples, baseline noises in drug ion peaks were reduced by 36%-82%, with a quadrupled signal-to-noise ratio improvement observed for 6-monoacetylmorphine.

CONCLUSIONS: This DC-OFIDE significantly enhances ion transmission efficiency and chemical noise suppression in ESI-MS, establishing its potential for high-fidelity analysis of complex samples.}, } @article {pmid40585989, year = {2025}, author = {Song, W and Wang, J and Gong, S and Wang, X and Xu, J and Wu, R and Jiang, Z and Zhang, H and Wu, L and Wang, Y and Su, Y and Wang, H and Gu, Y}, title = {FAK signaling suppression by OCT4-ITGA6 mediates the effectively removal of residual pluripotent stem cells and enhances application safety.}, journal = {Theranostics}, volume = {15}, number = {14}, pages = {7127-7153}, pmid = {40585989}, issn = {1838-7640}, mesh = {Animals ; *Octamer Transcription Factor-3/metabolism/genetics ; Mice ; *Pluripotent Stem Cells/metabolism/cytology ; Signal Transduction ; Humans ; Cell Differentiation ; Coculture Techniques ; Teratoma/pathology ; *Focal Adhesion Kinase 1/metabolism ; }, abstract = {Rationale: Pluripotent stem cells (PSCs) serve as a critical source of seed cells for regenerative therapies due to their unlimited proliferative capacity and ability to differentiate into all three germ layers. Despite their potential, the risk of teratoma formation caused by residual PSCs within differentiated cell populations poses a significant barrier to clinical applications. This study aims to develop a novel strategy to selectively remove residual PSCs while preserving the safety and functionality of PSC-derived differentiated cells (iDCs). Methods: The calcium- and magnesium-free balanced salt solution (BSS(Ca-Mg-)) was employed to selectively target PSCs in a co-culture system comprising PSCs and four types of iDCs. The effect of BSS(Ca-Mg-) treatment on teratoma formation was evaluated in immunodeficient mice following cell transplantation. Comparative analysis and gene knockdown experiments were conducted to explore the molecular mechanisms underlying the differential response of PSCs and iDCs to BSS(Ca-Mg-), focusing on FAK signaling and its interaction with OCT4 and ITGA6. Results: The BSS(Ca-Mg-) treatment effectively induced the detachment of PSCs in the co-culture system without disrupting iDC adhesion. In vivo experiments confirmed that cells treated with BSS(Ca-Mg-) did not form teratomas upon implantation into immunodeficient mice. Mechanistic studies revealed that PSCs exhibit lower activation of FAK signaling compared to iDCs, contributing to their selective detachment. Additionally, OCT4 and ITGA6 were found to maintain each other's protein expression, forming a feedback loop that suppressed FAK signaling, while FAK suppression further enhanced OCT4 expression. Conclusions: The study presents a safe, effective, and cost-efficient method for the selective removal of residual PSCs. This approach enhances existing safety measures for iDC applications, improving the clinical feasibility of iDC-based cell therapies.}, } @article {pmid40581674, year = {2026}, author = {Liu, G and Yang, N and Qu, Y and Chen, G and Wen, G and Li, G and Deng, L and Mai, Y}, title = {Developing ultrasound-based machine learning models for accurate differentiation between sclerosing adenosis and invasive ductal carcinoma.}, journal = {European radiology}, volume = {36}, number = {1}, pages = {33-44}, pmid = {40581674}, issn = {1432-1084}, support = {2023QN37//The 19th Batch of Jilin Province Innovation and Entrepreneurship Talent Funding Project, China/ ; 2024B011//Health Technology Capability Enhancement Project of Jilin Province/ ; LH2021H109//Joint Guidance Project of the Natural Science Foundation of Heilongjiang/ ; }, mesh = {Humans ; *Machine Learning ; Female ; Diagnosis, Differential ; *Breast Neoplasms/diagnostic imaging ; *Ultrasonography, Mammary/methods ; Middle Aged ; *Carcinoma, Ductal, Breast/diagnostic imaging ; *Fibrocystic Breast Disease/diagnostic imaging ; Adult ; Aged ; Image Interpretation, Computer-Assisted/methods ; }, abstract = {OBJECTIVE: This study aimed to develop a machine learning model using breast ultrasound images to improve the non-invasive differential diagnosis between Sclerosing Adenosis (SA) and Invasive Ductal Carcinoma (IDC).

MATERIALS AND METHODS: 2046 ultrasound images from 772 SA and IDC patients were collected, Regions of Interest (ROI) were delineated, and features were extracted. The dataset was split into training and test cohorts, and feature selection was performed by correlation coefficients and Recursive Feature Elimination. 10 classifiers with Grid Search and 5-fold cross-validation were applied during model training. Receiver Operating Characteristic (ROC) curve and Youden index were used to model evaluation. SHapley Additive exPlanations (SHAP) was employed for model interpretation. Another 224 ROIs of 84 patients from other hospitals were used for external validation.

RESULTS: For the ROI-level model, XGBoost with 18 features achieved an area under the curve (AUC) of 0.9758 (0.9654-0.9847) in the test cohort and 0.9906 (0.9805-0.9973) in the validation cohort. For the patient-level model, logistic regression with 9 features achieved an AUC of 0.9653 (0.9402-0.9859) in the test cohort and 0.9846 (0.9615-0.9978) in the validation cohort. The feature "Original shape Major Axis Length" was identified as the most important, with its value positively correlated with a higher likelihood of the sample being IDC. Feature contributions for specific ROIs were visualized as well.

CONCLUSION: We developed explainable, ultrasound-based machine learning models with high performance for differentiating SA and IDC, offering a potential non-invasive tool for improved differential diagnosis.

KEY POINTS: Question Accurately distinguishing between sclerosing adenosis (SA) and invasive ductal carcinoma (IDC) in a non-invasive manner has been a diagnostic challenge. Findings Explainable, ultrasound-based machine learning models with high performance were developed for differentiating SA and IDC, and validated well in external validation cohort. Critical relevance These models provide non-invasive tools to reduce misdiagnoses of SA and improve early detection for IDC.}, } @article {pmid40578985, year = {2025}, author = {Woo, HY and Jung, YY and Kim, HS}, title = {Metastatic Invasive Lobular Breast Carcinoma Involving Tamoxifen-related Endometrial Polyp in a Patient With Metachronous Bilateral Breast Carcinomas: A Case Report.}, journal = {In vivo (Athens, Greece)}, volume = {39}, number = {4}, pages = {2456-2463}, pmid = {40578985}, issn = {1791-7549}, mesh = {Humans ; Female ; *Tamoxifen/adverse effects/therapeutic use ; *Breast Neoplasms/pathology/drug therapy/diagnosis ; Adult ; *Polyps/pathology/diagnosis/chemically induced ; *Carcinoma, Lobular/pathology/drug therapy/diagnosis ; *Endometrial Neoplasms/secondary/diagnosis/pathology ; Antineoplastic Agents, Hormonal/adverse effects ; *Neoplasms, Second Primary/pathology ; }, abstract = {BACKGROUND/AIM: Metastasis of extragenital malignancies to the female genital tract, particularly the uterus, is exceedingly rare. Invasive lobular carcinoma (ILC) is the most common histological type of breast carcinoma that metastasizes to gynecologic organs.

CASE REPORT: A 42-year-old woman receiving tamoxifen presented with an irregularly thickened endometrium on transvaginal ultrasonography. She had previously undergone bilateral partial mastectomies - eight years prior for right-sided invasive ductal carcinoma, and three years prior for left-sided ILC. Hysteroscopic evaluation revealed an endometrial polyp. Microscopic examination of the polypectomy specimen showed variably sized, irregularly shaped branching glands embedded in densely fibrotic stroma. Within the stroma, monomorphic tumor cells with hyperchromatic, eccentrically located nuclei were arranged in single files, thin cords, or nests. Immunostaining revealed that the tumor cells were positive for GATA-binding protein 3 and negative for paired box 8, supporting a diagnosis of metastatic carcinoma from the breast. The final pathological diagnosis was metastatic ILC involving a tamoxifen-associated endometrial polyp.

CONCLUSION: Although rare, breast carcinoma may metastasize to endometrial polyps. Clinicians and pathologists should consider this possibility when evaluating abnormal ultrasonographic findings in the female genital tract, particularly in patients with a history of breast carcinoma receiving tamoxifen therapy. Abnormal ultrasonographic findings in the uterus of such patients warrant a comprehensive diagnostic workup to exclude metastatic disease.}, } @article {pmid40574925, year = {2025}, author = {Lin, YT and Hong, ZJ and Liao, GS and Dai, MS and Chao, TK and Tsai, WC and Sung, YK and Chiu, CH and Chang, CK and Yu, JC}, title = {Unexpected contralateral axillary lymph node metastasis without ipsilateral involvement in triple-negative breast cancer: A case report and review of literature.}, journal = {World journal of clinical cases}, volume = {13}, number = {18}, pages = {103571}, pmid = {40574925}, issn = {2307-8960}, abstract = {BACKGROUND: Breast cancer is a leading cause of cancer-related mortality among women worldwide, with invasive ductal carcinoma (IDC) being the most prevalent subtype. Lymph node metastasis is the primary prognostic indicator, typically evaluated via biopsy of the ipsilateral sentinel or axillary lymph nodes. Contralateral axillary metastasis (CAM) without ipsilateral involvement is exceedingly rare, particularly in early-stage breast cancer. This report presents a case of CAM in a patient with triple-negative breast cancer (TNBC), underscoring diagnostic and therapeutic complexities.

CASE SUMMARY: A 73-year-old female presented with left-sided early-stage IDC in February 2023. Despite a modified radical mastectomy and pathologically negative ipsilateral lymph nodes, a postoperative positron emission tomography (PET) scan detected fluorodeoxyglucose-avid nodes in the contralateral axilla. Biopsy confirmed metastatic ductal carcinoma with triple-negative status, resulting in an upstaged diagnosis of metastatic breast cancer, stage IV, M1. The patient underwent six cycles of adjuvant chemotherapy, with follow-up PET imaging showing regression of the contralateral lesion. This case highlights the importance of advanced imaging in TNBC for precise staging and treatment optimization.

CONCLUSION: This case highlights the aggressive nature of TNBC and the need for advanced imaging to ensure accurate staging and effective management.}, } @article {pmid40574914, year = {2025}, author = {Wei, L and Tian, Z and Wang, ZY and Liu, WJ and Li, HB and Zhang, Y}, title = {Concurrent invasive ductal carcinoma and ductal carcinoma in situ arising inside and outside a breast hamartoma: A case report.}, journal = {World journal of clinical cases}, volume = {13}, number = {18}, pages = {101882}, pmid = {40574914}, issn = {2307-8960}, abstract = {BACKGROUND: Breast hamartomas are rare benign breast tumors, with an incidence rate of 0.8%-4.8%. Further, the coexistence of hamartomas and carcinoma is also uncommon. Our case report presents a unique instance where invasive ductal carcinoma (IDC) and ductal carcinoma in situ were found both inside and outside a breast hamartoma. This is the second case reported in the literature.

CASE SUMMARY: A 51-year-old woman presented with a 6.0 cm breast tumor on mammography and ultrasound, with suspicious areas indicative of malignant transformation. Biopsy of the suspicious area confirmed IDC with intraductal carcinoma. Breast magnetic resonance imaging showed typical hamartoma changes with irregular areas of abnormal enhancement both inside and outside. A breast-conserving surgery was performed, and postoperative pathology confirmed mammary hamartoma, concurrent with IDC and intraductal carcinoma occurring both inside and outside the hamartoma. Subsequently, appropriate adjuvant therapy was initiated. Currently, the patient is in good condition. Breast cancer may be located both inside and outside the ipsilateral mammary hamartoma, which is difficult to detect preoperatively, especially when there is a focus of intraductal carcinoma, requiring accurate assessment of the tumor extent by modern imaging techniques. Early detection of the coexistence of cancer is clinically important as it can alter patient management.

CONCLUSION: This case emphasizes the importance of modern imaging techniques in accurately evaluating mammary hamartomas associated with malignancies prior to surgery.}, } @article {pmid40574868, year = {2024}, author = {Cobb, AN and Czaja, R and Jorns, J and Cortina, CS}, title = {Breast Cancer Subtypes: Clinicopathologic Features and Treatment Considerations.}, journal = {Current breast cancer reports}, volume = {16}, number = {2}, pages = {150-160}, pmid = {40574868}, issn = {1943-4588}, support = {K08 CA276706/CA/NCI NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: The purpose of this review is to provide an overview of ten unique breast cancer subtypes and their clinicopathologic features and treatment implications.

RECENT FINDINGS: Recent findings show that while many subtypes (mucinous, papillary, tubular, apocrine) have favorable biology, with better overall survival than invasive ductal carcinoma, some (metaplastic, adenoid cystic) are more aggressive portending worse prognosis for patients.

SUMMARY: The differences in histology represented in these breast cancer subtypes often impacts biology, behavior, and prognosis. Due to their rarity, additional research is needed to implement clear treatment protocols for each subtype.}, } @article {pmid40566345, year = {2025}, author = {Chang, SP and Braun, KL and Yanagihara, R and De Heer, H and Wu, YY and Chen, Z and Cox, MB and Gorniak, SL and Haddad, G and Hohmann, CF and Lee, ES and Stiles, JK and Teufel-Shone, NI and Nerurkar, VR}, title = {Science Speed Dating to Spur Inter-Institutional Collaborative Research.}, journal = {International journal of environmental research and public health}, volume = {22}, number = {6}, pages = {}, pmid = {40566345}, issn = {1660-4601}, support = {U54 MD012388/MD/NIMHD NIH HHS/United States ; U54 MD007582/MD/NIMHD NIH HHS/United States ; U54 MD007586/MD/NIMHD NIH HHS/United States ; U54 MD007597/MD/NIMHD NIH HHS/United States ; U54 MD007601/MD/NIMHD NIH HHS/United States ; U54 MD007602/MD/NIMHD NIH HHS/United States ; U54 MD015946/MD/NIMHD NIH HHS/United States ; U54 MD007592/MD/NIMHD NIH HHS/United States ; U54 MD013376/MD/NIMHD NIH HHS/United States ; U54MD007582, U54MD007586, U54MD007592, U54MD007597, U54MD007601, U54MD007602, U54MD012388, U54MD013376, U54MD015946/GF/NIH HHS/United States ; U24 MD015970/MD/NIMHD NIH HHS/United States ; }, mesh = {Humans ; *Cooperative Behavior ; *Biomedical Research ; *Interinstitutional Relations ; United States ; Research Personnel ; }, abstract = {A principal strategic goal of the RCMI Coordinating Center (RCMI-CC) is to improve the health of minority populations and to reduce ethnic and geographic disparities in health by coordinating the development and facilitating the implementation of clinical research across the RCMI Consortium. To more effectively spur inter-institutional collaborative research, the RCMI-CC supports a Clinical Research Pilot Projects Program for hypothesis-driven clinical research projects proposed by postdoctoral fellows, early-career faculty and/or early-stage investigators from two or more RCMI U54 Centers. The purpose of this brief report is to summarize the Science Speed Dating sessions to facilitate cross-site collaboration at the RCMI Investigator Development Core (IDC) Workshop, held in conjunction with the 2024 RCMI Consortium National Conference. RCMI investigators and IDC Directors from 20 RCMI U54 Centers participated in two rounds of highly interactive small-group presentations of research ideas and resource needs in search of new collaborative and mentoring partnerships. Workshop participants expressed a high level of satisfaction with the speed-networking format and strongly agreed that the workshop was beneficial to their professional-development goals.}, } @article {pmid40564583, year = {2025}, author = {Galily, Y and Tenenbaum, G}, title = {Emotional and Cognitive Perspectives in Physical Activity and Sport: An Introduction.}, journal = {Behavioral sciences (Basel, Switzerland)}, volume = {15}, number = {6}, pages = {}, pmid = {40564583}, issn = {2076-328X}, abstract = {In the rapidly evolving world of physical activity and sport science, researchers and practitioners alike are increasingly recognizing that the path to optimal performance and well-being is paved not just with physical conditioning and technical skill but also with emotional regulation and cognitive acuity (Lepers et al [...].}, } @article {pmid40563575, year = {2025}, author = {Prajzendanc, K}, title = {DCIS Progression and the Tumor Microenvironment: Molecular Insights and Prognostic Challenges.}, journal = {Cancers}, volume = {17}, number = {12}, pages = {}, pmid = {40563575}, issn = {2072-6694}, abstract = {Ductal carcinoma in situ (DCIS) is the most common form of non-invasive breast cancer and a recognized precursor to invasive ductal carcinoma (IDC). Although DCIS itself is confined to the milk duct and not immediately life-threatening, its potential for progression to invasive disease necessitates careful clinical management. The increased detection of DCIS due to advancements in imaging and widespread screening programs has raised critical questions regarding its classification, prognosis, and optimal treatment strategies. While most cases exhibit indolent behavior, others harbor molecular characteristics that drive malignant transformation. A key challenge lies in distinguishing low-risk DCIS, which may never progress, from aggressive cases requiring intervention. Tumor microenvironment dynamics, immune cell infiltration, and molecular alterations, including hormone receptor (HR) status, human epidermal growth factor 2 (HER2) expression, and genetic mutations, play crucial roles in determining disease trajectory. This review explores the biological and molecular mechanisms underlying DCIS progression, with an emphasis on myoepithelial cells, tumor-infiltrating lymphocytes, and microenvironmental factors. By integrating recent findings, this article aims to refine risk stratification approaches and guide future strategies for personalized DCIS management. Improved prognostic biomarkers and targeted therapeutic interventions could help optimize treatment decisions, balancing the need for effective cancer prevention while minimizing overtreatment in low-risk patients.}, } @article {pmid40563551, year = {2025}, author = {Bahmad, HF and Wegner, C and Nuraj, J and Avellan, R and Gonzalez, J and Mendez, T and Jabbour, D and Gomez-Fernandez, C}, title = {Perineural Invasion in Breast Cancer: A Comprehensive Review.}, journal = {Cancers}, volume = {17}, number = {12}, pages = {}, pmid = {40563551}, issn = {2072-6694}, abstract = {Perineural invasion (PNI) is a well-recognized histopathologic feature in multiple malignancies; however, its significance in breast cancer remains relatively underexplored. This review provides a synopsis of the current knowledge on PNI in breast cancer, discussing its histopathologic features, molecular mechanisms, diagnostic challenges, and clinical relevance. PNI is most frequently observed in high-grade invasive ductal carcinoma (IDC), particularly in triple-negative and HER2-positive subtypes. It is also seen in special histological subtypes such as mixed, metaplastic, and invasive micropapillary carcinomas. Mechanistically, PNI involves tumor-neural interactions, including neurotrophic factor signaling and epithelial-mesenchymal transition, contributing to tumor progression and potential locoregional recurrence (LRR). While PNI is linked to adverse prognosis in other tumors, its independent role remains unclear in breast cancer due to limited large-scale studies. Therefore, further investigation into its prognostic significance and potential therapeutic implications is needed. Future research should focus on refining diagnostic criteria and assessing targeted therapies to mitigate PNI-associated progression. This review summarizes the current knowledge on perineural invasion (PNI) in breast cancer, addressing its histological features, molecular mechanisms, diagnostic challenges, and clinical implications.}, } @article {pmid40561128, year = {2025}, author = {Deng, M and March, DS and Churchwood, DR and Young, HML and Highton, PJ and Denniff, MJ and Graham-Brown, MPM and Burton, JO and Baker, LA}, title = {Exploring a role for Chemerin in the cardiovascular and musculoskeletal benefits of intradialytic exercise in the hemodialysis population.}, journal = {PloS one}, volume = {20}, number = {6}, pages = {e0321497}, pmid = {40561128}, issn = {1932-6203}, mesh = {Humans ; *Chemokines/blood ; *Renal Dialysis ; Male ; Female ; Middle Aged ; *Intercellular Signaling Peptides and Proteins/blood ; *Cardiovascular Diseases/blood/prevention & control ; Aged ; *Exercise/physiology ; Adult ; *Exercise Therapy/methods ; Retrospective Studies ; }, abstract = {BACKGROUND: Cardiovascular disease is the leading cause of death for people receiving hemodialysis. Intradialytic cycling (IDC) has been shown to improve cardiovascular health in the hemodialysis population, but specific mechanisms require elucidation. Chemerin is an adipokine which contributes to the inflammatory process and may be associated with the cardiovascular benefits of IDC and physical function in hemodialysis population.

METHODS: Adults undertaking ≥3 months hemodialysis were randomized to either IDC (30 min each time, moderate intensity, thrice weekly) and usual care; or usual care only (control group). 88 blood samples were retrospectively analyzed for chemerin concentrations using ELISA. Unadjusted and adjusted linear regression was used to understand how changes in chemerin are associated with changes in cardiovascular and musculoskeletal health in response to IDC.

RESULTS: There was a significant increase of plasma chemerin concentration after 6 months in both groups. A positive association was detected between chemerin and short physical performance battery at baseline (β = 0.264, p = 0.017). There was no correlation of chemerin with cardiovascular, body composition, and other physical function markers.

CONCLUSIONS: This study is the first to show plasma level of chemerin increases with time on hemodialysis. No evidence was found to support a role for chemerin in modifying cardiac structure and function in people undertaking IDC. Further studies should investigate the associations between chemerin and physical performance.}, } @article {pmid40556807, year = {2024}, author = {Bourassa-Blanchette, S and Biesheuvel, MM and Lam, JC and Kipp, A and Church, D and Carson, J and Dalton, B and Parkins, MD and Barkema, HW and Gregson, DB}, title = {Candidemia Treatment is Improved by Infectious Disease Consultation: A Population-Based Cohort Study.}, journal = {Journal of the Association of Medical Microbiology and Infectious Disease Canada = Journal officiel de l'Association pour la microbiologie medicale et l'infectiologie Canada}, volume = {9}, number = {3}, pages = {129-139}, pmid = {40556807}, issn = {2371-0888}, abstract = {INTRODUCTION: Candidemia is a common bloodstream infection with morbidity and mortality. Both the European Society of Clinical Microbiology and Infectious Diseases and Infectious Diseases Society of America have evidence-based recommendations for its management. While infectious diseases consultation (IDC) reduced mortality, effects on guideline concordance remain unclear.

METHODS: We conducted a multicentre retrospective cohort study (2010-2018) in Canada to characterize the role of IDC in attaining evidence-based recommendations for adults with candidemia. Such recommendations include follow-up blood cultures to document blood clearance, prompt antifungal initiation and selection, source control, treatment duration determination, and ancillary investigations. We measured associations between IDC and adherence to evidence-based recommendations.

RESULTS: Patients with candidemia who received IDC were more likely not to be left without antifungal therapy (26% versus 4.8%). Echocardiograms were more common in noncritically ill patients with IDC (64% versus 44%; P < 0.01) and in all critically ill patients, irrespective of IDC status (75% versus 63%; P = 0.08). In patients with uncomplicated candidemia, treatment duration ≥14 days was similar with or without IDC (78% versus 70%; P = 0.15). Patients with complicated candidemia and IDC were more likely treated for ≥42 days (an appropriate duration; 100% versus 47%; P = 0.06). Fluconazole (transition therapy) was not affected by IDC for critically ill (41% and 29%; P = 0.34) or noncritically ill patients (34% versus 24%; P = 0.51). Mortality rates at 30 and 60 days after candidemia diagnosis were lower in patients receiving IDC (P < 0.05).

CONCLUSIONS: Best practice guidelines were issued for patients with candidemia; adherence varied, but involvement of an infectious disease physician increased implementation and was associated with considerably decreased mortality.}, } @article {pmid40554446, year = {2025}, author = {Wang, Y and Chen, Y and Zhang, B and Liu, X}, title = {Bilateral Primary Breast Cancer: A Case of Synchronous Diagnosis and Management of Ductal Carcinoma In Situ and Invasive Ductal Carcinoma.}, journal = {British journal of hospital medicine (London, England : 2005)}, volume = {86}, number = {6}, pages = {1-9}, doi = {10.12968/hmed.2024.1013}, pmid = {40554446}, issn = {1750-8460}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/therapy/pathology/diagnosis ; *Carcinoma, Ductal, Breast/therapy/pathology/diagnosis ; Mastectomy, Segmental ; *Carcinoma, Intraductal, Noninfiltrating/therapy/pathology/diagnosis ; *Neoplasms, Multiple Primary/therapy/pathology/diagnosis ; Mastectomy, Modified Radical ; Neoadjuvant Therapy ; }, abstract = {Aims/Background Bilateral breast cancer (BBC) is an uncommon subtype of breast cancer which occurs either synchronously or metachronously. Synchronous BBC with distinct histological types in the left and right breasts is particularly rare. Case Presentation This report presents a case of a 57-year-old female patient diagnosed with bilateral primary breast cancer, characterized by ductal carcinoma in situ (DCIS) in one breast and invasive ductal carcinoma (IDC) in the other. The patient initially sought medical attention due to a palpable mass and pain in her left breast, leading to a diagnosis confirmed through imaging studies and biopsy. The patient was treated with three cycles of neoadjuvant therapy, followed by a modified radical mastectomy on the left breast and a lumpectomy on the right breast. Postoperatively, the patient received endocrine therapy and radiotherapy, with no evidence of recurrence observed to date. Conclusion Further research and clinical advancements are necessary to optimize treatment and care strategies for patients with bilateral breast cancer, ensuring that their unique therapeutic needs are effectively addressed.}, } @article {pmid40545966, year = {2025}, author = {Iczkowski, KA and De Marzo, AM and Agarwal, N and Berman, DM and Cimadamore, A and Fine, SW and Greenland, N and Khani, F and Loda, M and Lotan, TL and Varma, M and Chinnaiyan, A and Giannarini, G and Huang, J and Montironi, R and Netto, GJ and Osunkoya, AO and Ratliff, T and Kristiansen, G and Cheng, L and van Leenders, GJLH and , }, title = {International Society of Urological Pathology Consensus on Cancer Precursor Lesions. Working Group 1: The Prostate.}, journal = {The American journal of surgical pathology}, volume = {49}, number = {12}, pages = {e33-e45}, pmid = {40545966}, issn = {1532-0979}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Male ; Consensus ; Neoplasm Grading ; *Precancerous Conditions/pathology/diagnosis ; *Prostate/pathology ; *Prostatic Intraepithelial Neoplasia/pathology ; *Prostatic Neoplasms/pathology/diagnosis ; }, abstract = {Working Group 1 at ISUP's Cancer Precursors meeting (September 2024) evaluated 5 putative precursors of invasive prostate cancer: high-grade prostatic intraepithelial neoplasia (HGPIN), intraductal carcinoma (IDC), atypical intraductal proliferation (AIP), atypical adenomatous hyperplasia (AAH)/adenosis, and proliferative inflammatory atrophy (PIA). Objectives were to compile recent evidence, interrogate current practices, and vote on recommendations, with 67% approval defined as consensus. Consensus was reached against the reporting of the low-grade form of PIN. HGPIN need not be reported when concomitant cancer or atypical small acinar proliferation suspicious for cancer exists adjacent to it, for biopsy or prostatectomy specimens. Finally, while the clinical significance of unifocal HGPIN in biopsies remains uncertain, there is stronger evidence for multifocal isolated HGPIN as a predictor of subsequent cancer detection. By consensus, multifocal HGPIN should continue being reported. Slight refinement was achieved regarding IDC criteria. The consensus opinion was that a dense cribriform to solid proliferation need not demonstrate marked nuclear atypia/ pleomorphism to qualify as IDC. The inverse scenario of marked atypia without dense cribriform/solid proliferation fell just short (65%) of consensus for IDC. Redesignating cribriform HGPIN as AIP achieved consensus. AIP found alone or with grade group 1 cancer warrants an explanatory comment. However, agreement was not attained to report AIP in the presence of invasive cancer, in either needle biopsy or prostatectomy. Finally, the optional reporting of PIA or AAH/adenosis in biopsies as pertinent negatives both fell short of consensus. This guidance should help pathologists standardize reporting, staying focused on the clinically actionable aspects of these lesions.}, } @article {pmid40544078, year = {2025}, author = {Ao, Y and Li, X and Mu, L and Zhao, J and Chen, H and Wang, Y and Zhang, S and Yang, S and Zhang, N and Qiu, L}, title = {Time-Dependent Apparent Diffusion Coefficient Changes in Breast MR Images With Contrast for Tumor Characterization.}, journal = {Clinical breast cancer}, volume = {25}, number = {8}, pages = {817-825}, doi = {10.1016/j.clbc.2025.05.019}, pmid = {40544078}, issn = {1938-0666}, mesh = {Humans ; Female ; *Contrast Media/administration & dosage ; *Breast Neoplasms/pathology/diagnostic imaging/diagnosis ; *Diffusion Magnetic Resonance Imaging/methods ; Middle Aged ; Adult ; Aged ; Breast/diagnostic imaging/pathology ; Time Factors ; Diagnosis, Differential ; ROC Curve ; Retrospective Studies ; *Carcinoma, Ductal, Breast/pathology/diagnostic imaging ; Aged, 80 and over ; }, abstract = {BACKGROUND: To assess the effect of scan time after contrast injection on breast MRI DWI sequence ADC values and its role in lesion differentiation.

PATIENTS AND METHODS: Between 2022 and 2023, two hundred and fifty-one breast magnetic resonance (MR) images were collected from 251 patients, who had a total of 258 lesions. Pathology results obtained within 1 month of the MR imaging were utilized. Apparent diffusion coefficient (ADC) values were measured at 3 time-points: precontrast, 3 minutes postcontrast, and 6 minutes postcontrast. For the analysis, statistical methods including the Friedman test, linear mixed models, Bonferroni correction, receiver operating characteristic (ROC) curve analysis, and DeLong test were applied.

RESULTS: Contrast agents cause ADC values to decrease within 3 minutes after injection and recover within 6 minutes (e.g., invasive ductal carcinoma). ADC can distinguish between benign tumors and cancers but not between carcinoma in situ and invasive carcinoma. Time-dependent changes do not affect the differentiation of benign from malignant lesions.

CONCLUSION: Contrast injection time has little effect on the effectiveness of ADC in differentiating benign from malignant lesions on DWI sequences. The findings support the feasibility of postcontrast DWI without compromising diagnostic accuracy.}, } @article {pmid40543242, year = {2025}, author = {Bunte, K and Ituarte, B and Warikoo, G and Morales-Ramírez, P}, title = {Regional disparities in incidence and outcomes of invasive ductal carcinoma of the breast among Asian and Pacific Islander women in the United States.}, journal = {Cancer epidemiology}, volume = {97}, number = {}, pages = {102861}, doi = {10.1016/j.canep.2025.102861}, pmid = {40543242}, issn = {1877-783X}, mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; *Asian American Native Hawaiian and Pacific Islander/statistics & numerical data ; *Breast Neoplasms/epidemiology/mortality/therapy/pathology/ethnology ; *Carcinoma, Ductal, Breast/epidemiology/mortality/therapy/pathology/ethnology ; *Health Status Disparities ; Incidence ; SEER Program/statistics & numerical data ; Survival Rate ; United States/epidemiology ; }, abstract = {BACKGROUND: Asian women have experienced a disproportionate increase in breast cancer incidence over the past four decades when compared to patients of other races. We aim to determine the variation of incidence and survival rates for Asian women based on their residential status by region of the United States.

METHODS: The Surveillance, Epidemiology and End Results (SEER) 17-State database was used to identify cases of ductal carcinoma and its subtypes (ICD-O-3/3 codes: 8500, 8521, 8503, 8507, 8514, 8522, 8523; C50.0-50.9) among Asian and Pacific Islander (API) women during 2000-2020. Chi square tests were used for comparison of clinical and socioeconomic variables and Kolmogorov-Smirnov and Kruskal Wallis tests were used to assess differences between mean time to treatment and diagnosis. Incidence was analyzed via Joinpoint Regression Software with Kaplan-Meier survival curves for evaluation of survival by region, measured in months. Multivariate Cox proportional hazards regression identified independent predictors of survival. All statistical analyses were conducted using SPSS Version 29.0.2, with significance at p < 0.05.

RESULTS: The West represented the largest incidence over the 20-year study period with 89.6 per 100,000 (95 % CI: 88.9-90.2). There were notable differences in both 5-year and 10-year survival rates with the south having the largest decline, dropping from 84 % at 5 years and 54 % at 10 years. This is despite the south being found to have the shortest time to treatment, 0.97 months (95 % CI: 0.95-0.99; p = 0.009). Multivariate Cox regression showed API women in the South had a 24 % increased risk of mortality compared to those in the West (aHR 1.244, 95 % CI: 1.176-1.315; p < 0.001).

CONCLUSIONS: The results of this study demonstrate significant disparities in incidence, treatment patterns, and survival outcomes amongst API women by residential status.}, } @article {pmid40539820, year = {2025}, author = {Zhang, X and Yin, Y and Ye, Z and Zhang, X and Wei, W and Hao, Y and Zeng, L and Yang, T and Li, D and Wang, J and Zhao, D and Chen, Y and Lei, S and Jiang, Y and Zhang, Y and Xu, S and Nanding, A and Gong, Y and Li, S and Yu, Y and Zhao, S and Liu, S and Zhao, Y and Chen, Z and Yu, S and Fan, JB and Pang, D}, title = {An Approach for Differential Diagnosis of Breast Tumors by ctDNA Methylation Sequencing.}, journal = {Cancer medicine}, volume = {14}, number = {12}, pages = {e71004}, pmid = {40539820}, issn = {2045-7634}, support = {2019B121205010//Science and Technology Program of Guangdong Province/ ; GA20C016//Heilongjiang Province Applied Technology Research and Development/ ; 201909010010//Scheme of Guangzhou for Leading Team in Innovation/ ; 82073410//China National Science Foundation/ ; 82272623//China National Science Foundation/ ; 82173235//China National Science Foundation/ ; 202201010943//Guangzhou Basic and Applied Basic Research Project/ ; 2016007//Scheme of Guangzhou for Leading Talents in Innovation and Entrepreneurship/ ; 2023ZX06C10//Key Special Projects of Heilongjiang Province Key Research and Development Program/ ; Nn10//Nn10 Program of Harbin Medical University Cancer Hospital/ ; JJZD2020-08//Haiyan Foundation of Harbin Medical University Cancer Hospital/ ; 2020GH15//2020 Guangzhou Development Zone International Science and Technology Cooperation Project/ ; 2017-L152//Scheme of Guangzhou Economic and Technological Development District for Leading Talents in Innovation and Entrepreneurship/ ; JD22C004//Key R&D Plan Projects of Heilongjiang Province, Da Pang/ ; }, mesh = {Humans ; *Breast Neoplasms/genetics/diagnosis/blood ; Female ; *DNA Methylation ; Diagnosis, Differential ; *Biomarkers, Tumor/genetics/blood ; *Circulating Tumor DNA/genetics/blood ; Middle Aged ; Mammography ; Aged ; Adult ; }, abstract = {BACKGROUND: Breast ultrasonography and mammography remain predominant in breast tumor evaluations, yet they often result in false positives, particularly for tumors classified as BI-RADS 4a or those no more than 10 mm, which are not ideal for core needle biopsy (CNB). Early-stage breast cancer detection via circulating tumor DNA (ctDNA) methylation holds potential to bridge these diagnostic gaps.

METHODS: We curated a breast cancer-specific panel by harnessing methylation profiles from in-house and public databases. Leveraging breast tissue-plasma-leukocyte samples, we identified breast cancer-specific markers, culminating in a 103-marker methylation model which underwent rigorous validation in two independent cohorts. To assess its performance, we compared it against the accuracy of ultrasonography, mammography, and CNB.

RESULTS: The 103-marker model exhibited remarkable proficiency in discerning benign from malignant breast tumors in plasma, with AUCs of 0.838, 0.838 and 0.823 in the validation set and two independent test sets, respectively. In BI-RADS 4a breast cancer, when compared to ultrasonography or mammography, the model augmented breast cancer diagnostic accuracy by 40.58% and 25.49%, separately. Retrospective analyses suggested that our model achieved a sensitivity of 66.67% (4/6) and a specificity of 80.36% (45/56) for surgical patients in the BI-RADS 4a category with tumors ≤ 10 mm, who did not undergo CNB, potentially sparing 45 benign patients from overtreatment. Notably, significant differences emerged in cancer scores between DCIS and invasive ductal carcinoma (p < 0.05). Higher cancer scores correlated with a more unfavorable prognosis (p < 0.05).

CONCLUSIONS: The 103-marker methylation model demonstrates impressive performance in distinguishing between malignant and benign tumors, facilitating precise early diagnosis of BC, and holds promise as a prognostic tool.}, } @article {pmid40538452, year = {2025}, author = {Whitney, HM and Drukker, K and Edwards, A and Giger, ML}, title = {Sureness of classification of breast cancers as pure ductal carcinoma in situ or with invasive components on dynamic contrast-enhanced magnetic resonance imaging: application of likelihood assurance metrics for computer-aided diagnosis.}, journal = {Journal of medical imaging (Bellingham, Wash.)}, volume = {12}, number = {Suppl 2}, pages = {S22012}, pmid = {40538452}, issn = {2329-4302}, abstract = {PURPOSE: Breast cancer may persist within milk ducts (ductal carcinoma in situ, DCIS) or advance into surrounding breast tissue (invasive ductal carcinoma, IDC). Occasionally, invasiveness in cancer may be underestimated during biopsy, leading to adjustments in the treatment plan based on unexpected surgical findings. Artificial intelligence/computer-aided diagnosis (AI/CADx) techniques in medical imaging may have the potential to predict whether a lesion is purely DCIS or exhibits a mixture of IDC and DCIS components, serving as a valuable supplement to biopsy findings. To enhance the evaluation of AI/CADx performance, assessing variability on a lesion-by-lesion basis via likelihood assurance measures could add value.

APPROACH: We evaluated the performance in the task of distinguishing between pure DCIS and mixed IDC/DCIS breast cancers using computer-extracted radiomic features from dynamic contrast-enhanced magnetic resonance imaging using 0.632+ bootstrapping methods (2000 folds) on 550 lesions (135 pure DCIS, 415 mixed IDC/DCIS). Lesion-based likelihood assurance was measured using a sureness metric based on the 95% confidence interval of the classifier output for each lesion.

RESULTS: The median and 95% CI of the 0.632+-corrected area under the receiver operating characteristic curve for the task of classifying lesions as pure DCIS or mixed IDC/DCIS were 0.81 [0.75, 0.86]. The sureness metric varied across the dataset with a range of 0.0002 (low sureness) to 0.96 (high sureness), with combinations of high and low classifier output and high and low sureness for some lesions.

CONCLUSIONS: Sureness metrics can provide additional insights into the ability of CADx algorithms to pre-operatively predict whether a lesion is invasive.}, } @article {pmid40536116, year = {2026}, author = {Nechyporenko, Y and Golan, O and Menes, TS and Freitas, VAR and Kessner, R and Neeman, R and Mauda-Havakuk, M and Broitman, S and Stav, D and Lazar, S and Mercer, D and Amitai, Y}, title = {T2 Hyperintense Lesions on Breast MRI - Is the Assumption of Benignity Justified?.}, journal = {Canadian Association of Radiologists journal = Journal l'Association canadienne des radiologistes}, volume = {77}, number = {1}, pages = {180-186}, doi = {10.1177/08465371251346137}, pmid = {40536116}, issn = {1488-2361}, mesh = {Humans ; Female ; Middle Aged ; Retrospective Studies ; *Breast Neoplasms/diagnostic imaging/pathology ; *Magnetic Resonance Imaging/methods ; Aged ; Breast/diagnostic imaging/pathology ; Adult ; *Image-Guided Biopsy/methods ; *Magnetic Resonance Imaging, Interventional/methods ; Aged, 80 and over ; }, abstract = {Introduction: This study aims to evaluate the outcomes of breast MRI-guided vacuum assisted biopsies (MVAB) performed on lesions with high T2 signal. Materials and Methods: We retrospectively collected of all MVAB performed at our institution between January 2016 and December 2021 for high T2 lesions. T2 hyperintensity was defined as equal or higher signal than normal lymph node. The correlation between various demographic and imaging characteristics and the binary pathological outcome (benign vs malignant) was evaluated. Results: In total, 174 biopsies from 165 women met the inclusion criteria and were included in the cohort. Malignancy was detected in 35 lesions (20%), most commonly ductal carcinoma in situ (DCIS, 57%), followed by infiltrating ductal carcinoma (IDC, 40%). The most common benign diagnosis was fibrocystic changes (FCC, 38%). In 19 lesions MVAB detected high-risk pathology, 3 of which were upgraded to malignancy. Older age (Mean 61 vs 54 years, P = .04), washout kinetics (29% vs 13%, P = .01), and indication for extent of disease evaluation (53% vs 32%, P = .06) were the strongest predictors of malignancy. Lesion size and morphology were not significantly associated with outcome. Conclusions: Given the considerable cancer rate, T2 hyperintensity should be used with caution as a benign indicator and not as a sole criterion for ruling out malignancy. Additional factors such as patient age, kinetic features, and MRI indication should be considered to improve diagnostic accuracy.}, } @article {pmid40535424, year = {2025}, author = {Carvalhais França, D and da Silva, AL and Chami, AM and Braga, LDC}, title = {Epidemiological profile of breast cancer in a reference center in the north region of Brazil.}, journal = {Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia}, volume = {47}, number = {}, pages = {}, pmid = {40535424}, issn = {1806-9339}, mesh = {Humans ; Female ; Brazil/epidemiology ; Retrospective Studies ; *Breast Neoplasms/epidemiology/pathology ; Middle Aged ; Adult ; Aged ; Cohort Studies ; *Carcinoma, Lobular/epidemiology/pathology ; }, abstract = {OBJECTIVE: To describe the epidemiological data of women with breast cancer at a referral center in oncology in the northern region of Brazil.

METHODS: This is a retrospective cohort study. The study population consists of patients who were diagnosed with in situ or invasive BC (invasive carcinoma of no special type (ICNST) and invasive lobular carcinoma (ILC)) at the Hospital de Amor da Amazônia, in Porto Velho - Rondônia, between January 2012 and December 2021. The sampling plan adopted was of the convenience type. All patients who received the anatomopathological diagnosis of in situ or invasive BC at the Hospital de Amor da Amazônia from 2012 to 2021 and came from the North region were included. Exclusion criteria were non-origin from the North region and absence of diagnosis established by anatomopathological examination of breast cancer. Analysis of the database and medical records of the Hospital de Amor da Amazônia was carried out to collect information.

RESULTS: 420 patients were included, 99.5% female, with complete elementary school (32,6%) and brown skin (68,1%). The mean age at diagnosis was 49 years. Forty-five percent were born in the northern region and 55% in other regions of Brazil. Eighty percent of tumors were invasive ductal carcinoma; 32.7% were luminal A-like, 25.1% luminal B-like, 19.4% HER2 enriched and 12.8% triple negative. When patients were subdivided by age ≤40 years and > 40 years, there was a statistically significant difference in the association with staging (p=0.000), histological type (p= 0.035), immunohistochemistry subtype (p=0.000), neoadjuvant chemotherapy (p=.000) and genetic counseling (p=0.001). The median survival was 7.99 years. The 5-year overall survival was 81%. The higher the stage, the lower the survival rate. Twenty-four distinct variants were described in patients undergoing genetic testing, 16 of uncertain significance and 8 pathogenic. Three new variants were described: ATM (c.8726G>C), BRCA2 (c.2232A>C) and ERCC5 (c.2164G>Ap).

CONCLUSION: In this study, the age at diagnosis of breast cancer was lower, the tumor subtype was more aggressive, and patients were admitted in more advanced stages. Overall survival is lower compared to national and international data. Despite the small number of patients referred to genetic testing, it is important to search for germline mutations to improve patients' diagnosis and treatment.}, } @article {pmid40530022, year = {2025}, author = {Paripooranan, N and Nirasha, WB and Perera, HRP and Vijithananda, SM and Hewavithana, PB and Sherminie, LPG and Jayatilake, ML}, title = {Machine learning-based classification model to differentiate subtypes of invasive breast cancer using MRI.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1588787}, pmid = {40530022}, issn = {2234-943X}, abstract = {INTRODUCTION: Breast cancer is considered one of the most lethal diseases among women worldwide. Invasive Ductal Carcinoma (IDC) and Invasive Lobular Carcinoma (ILC) are the two most prominent subtypes of breast cancer. They differ in epidemiology, molecular alterations, and clinicopathological features. Patient treatment and management also differ due to these variations.

AIM: The study aimed to develop a predictive model to differentiate IDC and ILC using machine learning techniques based on the morphological features of the contralateral breast. Methods- 143 magnetic resonance imaging (MRI) images were sourced from the "DUKE Breast-Cancer" collection on the Cancer Imaging Archive website. Regions of interest were drawn on each slice to compute the morphological features of the contralateral breast using the 3D Slicer application. Supervised learning methods were applied to the morphological features to build a predictive model incorporating a Random Forest Classifier to differentiate IDC and ILC. Hyperparameters were tuned to optimize the model.

RESULTS: The model was able to differentiate IDC and ILC with an accuracy of 79% and an Area Under the Curve of 0.851 on the Receiver Operating Characteristic Curve. Among the morphological features, the total volume of the contralateral breast, surface area of the contralateral breast, breast density, and the ratio of the total volume of the contralateral breast to its surface area had higher F-scores, indicating that the dimensions of the contralateral breast could be an important factor in differentiating IDC and ILC.

CONCLUSION: This study successfully developed and optimized a predictive model based on breast morphological features to differentiate IDC and ILC using machine learning methods.}, } @article {pmid40521724, year = {2025}, author = {Sill, S and Zivehe, F and Heitmann, C and Bahn, D and Busch, J and Eigenfeldt, L and Fleming, T and Szendrödi, J and Granata, C and Ziegler, D and Bönhof, G and Roden, M and Al-Hasani, H and Strom, A and Chadt, A}, title = {Magnesium and thiamine supplementation increases renal mitochondrial respiration in lean C57BL/6J but not in obese ob/ob mice.}, journal = {Diabetes, obesity & metabolism}, volume = {27}, number = {9}, pages = {5327-5331}, doi = {10.1111/dom.16507}, pmid = {40521724}, issn = {1463-1326}, support = {CH 1659/2-1//Deutsche Forschungsgemeinschaft/ ; DFG-RTG 2576 vivid//Deutsche Forschungsgemeinschaft/ ; STR 1032/3-1//Deutsche Forschungsgemeinschaft/ ; //German Federal Ministry of Education and Research (BMBF)/ ; //German Federal Ministry of Health (BMG)/ ; //German Center for Diabetes Research (DZD)/ ; //The Ministry of Innovation, Science, Research and Technology of the state North Rhine-Westphalia/ ; //Deutsche Diabetes Gesellschaft/ ; }, } @article {pmid40519297, year = {2025}, author = {Li, J and Jiang, F and Wang, C and Sun, P and Song, L and Liu, J}, title = {PLCH1 overexpression promotes breast cancer progression and predicts poor prognosis through the ERK1/2-EGR1 axis.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1577114}, pmid = {40519297}, issn = {2234-943X}, abstract = {BACKGROUND: Phospholipase C η1 (PLCH1), a member of the phospholipase C superfamily, has been implicated in the development of multiple cancers. However, its specific role in breast cancer progression, its association with clinicopathological features, and its prognostic significance remain unclear.

METHODS: PLCH1 expression was analyzed across multiple tumor types using the TNMplot database, which integrates RNA-seq, microarray, and normalized data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO), encompassing 40,442 tumor and 15,648 normal samples. Differential expression analysis was performed using boxplots and statistical tests to assess significance. DNA methylation and survival analyses were conducted using TCGA data, with Kaplan-Meier curves and Cox regression to evaluate prognostic value. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, were performed on differentially expressed genes using the clusterProfiler package. Mutation analyses were conducted using mutation annotation format (MAF) files, and pathway activities were correlated with PLCH1 expression via single-sample GSEA (ssGSEA). Experimental validation included immunohistochemistry (IHC) on 100 breast invasive ductal carcinoma samples, real-time quantitative PCR (RT-qPCR), and Western blotting. PLCH1 knockdown functional studies assessed cell proliferation and signaling pathways.

RESULTS: PLCH1 was significantly overexpressed in various cancers, including breast cancer, compared to normal tissues. PLCH1 expression was strongly correlated with the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in breast cancer tissues, further linking PLCH1 to poor prognosis and adverse patient outcomes. Functional studies revealed that PLCH1 was highly expressed in breast cancer cell lines, and PLCH1 knockdown significantly inhibited cell proliferation, induced cell cycle arrest, and reduced cyclin-dependent kinase 1 (CDK1) expression in BT-474 cells. Mechanistically, PLCH1 silencing downregulated early growth response 1 (EGR1) expression by suppressing the extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathway, impairing tumor cell proliferation.

CONCLUSIONS: PLCH1 was overexpressed in breast cancer and was associated with worse patient outcomes. Its role in promoting cell proliferation via the ERK1/2-EGR1 axis highlighted PLCH1 as a potential therapeutic target for breast cancer. These findings offer new insights into the molecular mechanisms underlying breast cancer progression and suggest promising avenues for targeted therapy development.}, } @article {pmid40516663, year = {2025}, author = {Göransson, S and Olofsson, H and Johansson, HJ and Yan, F and Vogiatzakis, C and Liang, S and Bellato, HM and Masvidal, L and Aksoylu, I and Hartman, J and Hajj, GN and Larsson, O and Lehtiö, J and Strömblad, S}, title = {Mechanical control of breast cancer malignancy by promotion of mevalonate pathway enzyme synthesis.}, journal = {Matrix biology : journal of the International Society for Matrix Biology}, volume = {140}, number = {}, pages = {1-15}, doi = {10.1016/j.matbio.2025.05.005}, pmid = {40516663}, issn = {1569-1802}, mesh = {Humans ; *Mevalonic Acid/metabolism ; *Breast Neoplasms/pathology/metabolism/genetics ; Female ; *Mechanotransduction, Cellular ; Extracellular Matrix/metabolism/pathology ; *Hydroxymethylglutaryl-CoA Synthase/genetics/metabolism ; Gene Expression Regulation, Neoplastic ; rac1 GTP-Binding Protein/metabolism/genetics ; Cell Line, Tumor ; Cell Proliferation ; }, abstract = {In breast cancer, mechanotransduction from stiffened extracellular matrix (ECM) drives proliferation and invasion. Here, we use a model of matrix stiffening mimicking progression of breast ductal carcinoma in situ to invasive ductal carcinoma. Quantitative mass spectrometry identified enrichment of ECM-stiffness upregulated mevalonate pathway enzymes, indicating sterol/isoprenoid metabolism reprogramming. Consistently, the first committed mevalonate pathway enzyme, Hydroxymethylglutaryl-CoA Synthase (HMGCS1), was upregulated in human breast cancer specimens and spatially correlated with cross-linked ECM. ECM-stiffness promoted HMGCS1 protein synthesis without corresponding mRNA level alterations, indicating post-transcriptional regulation of mevalonate biosynthesis via microenvironmental mechanical cues to impose rapid metabolic alterations. Moreover, HMGCS1-RNAi blocked the stiffness-driven breast cancer proliferative and invasive phenotype. Mechanistically, mechanotransduction signaling, through integrin and Rac1 to promote HMGCS1 protein expression, drives the breast cancer malignant phenotype. Intriguingly, the Rac1-P29S cancer mutant promoted a malignant phenotype without stiff ECM in a mevalonate-dependent manner. In summary, we define a mechano-responsive pathway controlling mevalonate pathway enzyme synthesis that drives breast cancer malignant behaviors.}, } @article {pmid40516578, year = {2025}, author = {Lin, R and Li, H and Baraban, E and Lotan, T and DeMarzo, A and Argani, P and Baras, A and Matoso, A}, title = {Atypical intraductal proliferation (AIP) of the prostate: Findings in repeat biopsy or radical prostatectomy in patients who met pathologic criteria for active surveillance.}, journal = {Human pathology}, volume = {160}, number = {}, pages = {105841}, doi = {10.1016/j.humpath.2025.105841}, pmid = {40516578}, issn = {1532-8392}, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/surgery ; *Prostatectomy ; Retrospective Studies ; Aged ; Middle Aged ; Neoplasm Grading ; *Watchful Waiting ; *Cell Proliferation ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Biopsy, Needle ; *Prostate/pathology/surgery ; }, abstract = {The clinical significance of 'atypical intraductal proliferation' (AIP) is uncertain when found in prostate needle biopsy without intraductal carcinoma (IDC-P) or intermediate/high-grade prostate carcinoma (PCa). A retrospective review identified 168 patients diagnosed with AIP. Twenty-five (15 %) were AIP alone, the rest with PCa. Follow-up biopsy or RP within 12 months was collected on patients with AIP-only, AIP and grade-group (GG)1, and AIP and GG2 PCa [<20 % Gleason pattern 4 (GP4) without cribriform glands] who met pathologic criteria for active surveillance (AS). From 110 patients who met pathologic AS criteria, 66 did not have follow-up tissue. The findings among 28 patients with repeat biopsy were as follows: 14 (50 %) were reclassified as a higher GG, including 3/6 (50 %) from AIP-only [1 to GG1 and 2 to GG2 (60 % and 20 % GP4)], 8/16 from AIP/GG1 [50 %, all to GG2 (1 with 30 %, all others with <20 % GP4)], 3/6 (50 %) from AIP/GG2 (<20 % GP4) [1 to GG3, and 2 to AIP/GG2 but with ≥20 % GP4]. Five (18 %) patients no longer met pathologic criteria for AS. Among patients with RP, 4 (33 %) showed IDC-P. Quantitative and morphologic evaluation showed that higher number of cores, foci, and lumina in AIP with cribriform glands were more frequent in patients who were reclassified into higher grade-groups. In conclusion, AIP should be considered a potential marker for aggressive disease, warranting further evaluation. Although similar to IDC-P, it should remain a separate entity, as repeat biopsy does not show higher-than-expected AS exit rate.}, } @article {pmid40513789, year = {2025}, author = {Kavazis, C and Ekmektzoglou, A and Kokolakis, A and Liappis, T and Douganiotis, G and Natsiopoulos, I}, title = {The role of PIK3CA mutation in lobular breast cancer in the era of precision oncology - A systematic review.}, journal = {Critical reviews in oncology/hematology}, volume = {214}, number = {}, pages = {104805}, doi = {10.1016/j.critrevonc.2025.104805}, pmid = {40513789}, issn = {1879-0461}, mesh = {Humans ; *Class I Phosphatidylinositol 3-Kinases/genetics ; *Breast Neoplasms/genetics/diagnosis ; *Mutation ; Female ; *Carcinoma, Lobular/genetics/diagnosis ; Prognosis ; Precision Medicine/methods ; }, abstract = {BACKGROUND: Ιnvasive lobular carcinoma (ILC) is a distinct subtype of breast cancer with unique clinical and molecular features. Although ILC generally responds to endocrine therapy, it tends to exhibit lower chemotherapy sensitivity, underscoring the need for tailored therapeutic approaches. PIK3CA mutations are frequently observed in ILC. This systematic review evaluates the prevalence of PIK3CA mutations in ILC and examines their prognostic and predictive significance.

METHODS: We searched PubMed and Scopus for studies reporting PIK3CA mutations in lobular breast cancer. Inclusion criteria encompassed studies on stage I-III ILC examining mutation frequency, prognosis, or predictive value. Data on mutation prevalence in ILC (and comparisons to invasive ductal carcinoma, IDC) and associated outcomes were extracted. Meta-analyses were performed with assessment of heterogeneity and publication bias.

RESULTS: Ten relevant studies (nine cohorts) were included. The prevalence of PIK3CA mutations in ILC ranged from ∼30 % to ∼50 %. Statistic analysis showed that nearly half of ILCs harbor PIK3CA mutations. Mutation rates in ILC were generally higher than in IDC. No significant association between PIK3CA mutation status and patient prognosis was observed in the available studies. There were limited data ontreatment response.

CONCLUSIONS: PIK3CA is a commonly mutated gene in ILC, but current evidence does not demonstrate a clear impact on prognosis or definite predictive value for therapy response in this subtype. Nonetheless, the high mutation frequency provides a rationale for targeted therapeutic approaches. PIK3CA testing may be considered in advanced ILC to identify candidates for PI3K inhibitor therapy, although further research is needed.}, } @article {pmid40507963, year = {2025}, author = {Zeiringer, S and Derler, M and Mussbacher, M and Kolesnik, T and Fröhlich, E and Leitinger, G and Kolb, D and Tutz, S and Vargas, C and Keller, S and Roblegg, E}, title = {Immune Modulation with Nanodiscs: Surface Charge Dictates Cellular Interactions and Activation of Macrophages and Dendritic-like Cells.}, journal = {International journal of molecular sciences}, volume = {26}, number = {11}, pages = {}, pmid = {40507963}, issn = {1422-0067}, mesh = {Humans ; *Dendritic Cells/immunology/drug effects/metabolism/cytology ; *Macrophages/immunology/drug effects/metabolism/cytology ; *Cell Communication/drug effects/immunology ; *Nanostructures/chemistry ; Cytokines/metabolism ; Lipid Bilayers/chemistry ; Reactive Oxygen Species/metabolism ; Cell Survival/drug effects ; }, abstract = {The immunological barrier is among the most significant barriers in vivo. Macrophages and dendritic cells play a crucial role in immune responses, involving phagocytosis, antigen presentation, and triggering adaptive responses. Nanoscale drug-delivery vehicles, such as polymer-encapsulated lipid-bilayer nanodiscs, are of particular interest in the development of new therapeutic approaches, but require well-characterized human in vitro cell models. To this end, the present study differentiated human monocytes into two distinct states, resting macrophages and immature dendritic-like cells (iDCs). These cells served as model systems to assess the efficacy of lipid-bilayer nanodiscs encapsulated by anionic glyco-DIBMA (diisobutylene-maleic acid) or electroneutral sulfo-DIBMA polymers. Nanodisc-cell interaction studies-including cell viability, reactive oxygen species production, cytokine release, particle uptake, and activation marker expression-demonstrated that immune responses depend sensitively on the cell type and polymer and thus on the surface charge of the nanodiscs. Sulfo-DIBMA nanodiscs induced minimal immune cell activation, accompanied by cytokine release and reduced uptake of the nanodiscs by immune cells. In contrast, glyco-DIBMA nanodiscs exhibited increased interactions with cells, elicited pro-inflammatory immune responses, and promoted iDC maturation. This involved co-stimulatory and antigen-presenting molecules, potentially leading to T-cell activation. These findings underscore the potential of glyco-DIBMA nanodiscs to modulate immune responses through receptor-specific interactions, paving the way for immunotherapeutic strategies.}, } @article {pmid40503404, year = {2025}, author = {Luo, M and Liu, RN and He, ZM and Liang, QF and Huang, FL}, title = {Diagnosis and treatment of metachronous multiple primary carcinoma: A case report and review of literature.}, journal = {World journal of clinical oncology}, volume = {16}, number = {5}, pages = {105444}, pmid = {40503404}, issn = {2218-4333}, abstract = {BACKGROUND: Multiple primary carcinoma (MPC) refers to two or more types of primary malignant tumors occurring simultaneously or sequentially in the same patient. Breast cancer is one of the most common malignant tumors affecting women. On the other hand, diffuse large B-cell lymphoma (DLBCL) is the most frequent form of non-Hodgkin's lymphoma (NHL). In clinical practice, the simultaneous existence of metachronous primary breast cancer and lymphoma is rare. In this case, we highlight the significance of multidisciplinary management and advanced imaging techniques in the early identification and treatment of MPC cases.

CASE SUMMARY: In this study, we report a case of a 40-year-old female who was diagnosed with invasive ductal carcinoma of the breast (T3N1M0 stage IIIA LuminalB type) as the first primary cancer and DLBCL (stage IIIA) as the second primary cancer. The patient underwent the modified radical mastectomy for left breast cancer and received Rituximab, cyclophospha-mide, hydroxydaunorubicin, Oncovin (vincristine) and prednisolone regimen chemotherapy treatment for DLBCL. As of now, the patient is in stable condition. The successful diagnosis of the present patient highlights the need for multidisciplinary management and adoption of advanced imaging techniques to identify the second primary cancer, especially NHL.

CONCLUSION: Accurate diagnosis and management of metachronous MPC requires an interdisciplinary team and selection of an appropriate treatment plan.}, } @article {pmid40496029, year = {2025}, author = {Imran, M and Majeed, MA and Sameen-Bin-Naeem, and Yasmeen, T and Siddiqui, N}, title = {Beyond the Tumor: Invasive Fungal Infection Unveiled in HER2-Positive Breast Cancer Patient Mimicking Disease Relapse.}, journal = {Journal of cancer & allied specialties}, volume = {11}, number = {1}, pages = {8-11}, pmid = {40496029}, issn = {2411-989X}, abstract = {INTRODUCTION: Breast cancer is a major global health concern among all malignancies, with HER2-positive breast cancer representing a particularly aggressive subtype. It affects approximately 20% of patients and is associated with a high risk of relapse. The management of HER2-positive breast cancer has been significantly improved by targeted therapies, though challenges remain, especially in resource-limited settings. Invasive fungal infections are also common and can manifest as metastatic lesions in immunocompromised cancer patients undergoing intensive treatments making the diagnosis challenging for the oncologists.

CASE DESCRIPTION: We report a case of a 39-year-old premenopausal female with relapsed HER2-positive breast cancer complicated by an invasive fungal infection. The patient initially presented with a 5 × 5 cm right breast lump, which was diagnosed as invasive ductal carcinoma, HER2-positive estrogen and progesterone receptor negative. Despite receiving chemotherapy with doxorubicin, cyclophosphamide, paclitaxel in the neoadjuvant setting and breast conservation surgery, the patient experienced disease recurrence. She was then treated with modified radical mastectomy followed by adjuvant chemotherapy TCH (trastuzumab, carboplatin, and docetaxel) six cycles. After three cycles, she developed high-grade fevers, renal impairment, and altered mental status. Imaging initially suggested ongoing infective vs metastatic process in bilateral renal and CNS parenchyma, so biopsy was performed from brain that revealed Aspergillus flavus infection. Treatment was adjusted to include antifungal therapy with voriconazole, and the patient's condition improved.

PRACTICAL IMPLICATIONS: This case underscores the critical need for biopsy of new or evolving lesions in cancer patients, particularly when imaging is not convincing enough for a relapse. Accurate diagnosis is essential to differentiate between disease progression and complications such as opportunistic infections. The occurrence of a fungal brain abscess in this patient highlights the importance of considering such invasive opportunistic infections in immunocompromised individuals, especially those undergoing intensive chemotherapy. Furthermore, the challenges faced due to the unavailability of targeted therapies in resource-limited settings emphasize the need for better access to advanced treatments and comprehensive management strategies. This case also calls for heightened vigilance and prompt diagnostic evaluation to address both cancer progression and potential opportunistic infections effectively.}, } @article {pmid40492227, year = {2025}, author = {Kivuyo, NE and Kitua, DW and Chikelea, ME and Misidai, MA and Mwanga, AH and Nyongole, OV and Akoko, LO}, title = {Treatment outcomes and the associated factors among breast cancer patients in Tanzania: a retrospective cohort study.}, journal = {Ecancermedicalscience}, volume = {19}, number = {}, pages = {1874}, pmid = {40492227}, issn = {1754-6605}, abstract = {BACKGROUND: Breast cancer (BC) is the second most prevalent cancer among women in sub-Saharan Africa. Despite dedicated efforts to enhance BC care in the region through improving diagnostic and treatment services, little is known about the treatment outcomes of BC patients and the predictors of outcomes in our local settings have not been enumerated. This study aimed to investigate the treatment outcomes and the associated factors among BC patients in Tanzania.

MATERIALS AND METHODS: This was a retrospective cohort study at Muhimbili National Hospital and Ocean Road Cancer Institute in 2022. It involved female patients 18 years and above who were confirmed to have BC by histology. A sample size of 240 was determined to be adequate to detect a survival difference between the stages. Using Research Electronic Data Capture, clinical characteristics were collected from patients' treatment records and survival status was ascertained both by case notes or phone calls to patients or next of kin. Data were transferred into Statistical Package for the Social Sciences version 27 for subsequent analysis where continuous variables were summarised as proportions. We used chi-square and Fisher's exact tests to determine the association between various patients' characteristics and treatment outcomes. Kaplan-Meyer analysis was used to determine survival and a p-value less than 0.05 is considered statistically significant.

RESULTS: In total, 298 BC patients were studied with a mean age of 53.2 ± 13.6 (27-89). Invasive ductal carcinoma, parity and late stage at presentation were predominant features in these patients. A triple negative subtype was identified in 35.2% of the women. Only 27.9% and 33.6% of the patients received neoadjuvant and adjuvant chemotherapy respectively, while 8.1% of the patients were palliated. The overall 5 years survival was 29.7%, while being significantly poor in patients with advanced stages of the disease. Luminal subtypes, parity, menopausal status and age had some influence on BC survival among our patients but not in a significant manner.

CONCLUSION: Mastectomy is predominantly offered to BC patients in Tanzania with no standardisation of use of chemo/radiation both in neo/adjuvant settings. Some important prognostic factors were missing including a lack of standardised work up of patients. With the predominance of advanced stage at presentation, BC carries unacceptable high mortality in Tanzania. Efforts to detect BC early, understand patients' perception of their disease and standardisation of care are needed to successfully implement treatment guidelines.}, } @article {pmid40484435, year = {2025}, author = {Iurillo, AM and Abraham, O and McQuillan, J and Newton, E}, title = {Treatment of breast cancer in a patient with sickle cell disease.}, journal = {BMJ case reports}, volume = {18}, number = {6}, pages = {}, doi = {10.1136/bcr-2024-263661}, pmid = {40484435}, issn = {1757-790X}, mesh = {Humans ; Female ; *Breast Neoplasms/therapy/complications/pathology ; *Anemia, Sickle Cell/complications/therapy ; *Carcinoma, Ductal, Breast/therapy/complications/pathology ; Adult ; Trastuzumab/therapeutic use ; Neoadjuvant Therapy/methods ; Chemotherapy, Adjuvant ; Mastectomy, Modified Radical ; Aromatase Inhibitors/therapeutic use ; }, abstract = {We present a woman in her 30s with sickle cell disease (SCD) treated with monthly exchange transfusions who had suffered cerebrovascular complications, presented with a 4-cm left breast mass and was ultimately diagnosed with Estrogen receptor-positive, human epidermal growth factor receptor 2 positive (ER+HER2/Neu+) invasive ductal carcinoma with axillary metastasis. She was treated with neoadjuvant trastuzumab-based chemotherapy, followed by a left-modified radical mastectomy and had residual invasive disease. She received postmastectomy radiation followed by adjuvant trastuzumab emtansine. Given the ER positivity, she also began adjuvant ovarian suppression (OS) and an aromatase inhibitor (AI). Throughout treatment, her SCD remained well-controlled, highlighting the potential for effective and tolerable cancer therapy in patients with SCD and the importance of interdisciplinary collaboration. This case underscores the importance of tailored oncological management and the need for further research on chemotherapy safety in this population.}, } @article {pmid40482189, year = {2025}, author = {Gunes, A and Colapkulu-Akgul, N and Akgul, C and Unlu, I and Cinar, S}, title = {Axillary staging with 18F-FDG PET/CT in early breast cancer: impact of tumor subtypes.}, journal = {Annals of Saudi medicine}, volume = {45}, number = {3}, pages = {145-153}, pmid = {40482189}, issn = {0975-4466}, mesh = {Humans ; Female ; *Positron Emission Tomography Computed Tomography/methods ; Fluorodeoxyglucose F18 ; Retrospective Studies ; Middle Aged ; *Breast Neoplasms/pathology/diagnostic imaging ; Axilla ; Adult ; Lymphatic Metastasis/diagnostic imaging ; Neoplasm Staging ; Aged ; Radiopharmaceuticals ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Sentinel Lymph Node Biopsy ; Reproducibility of Results ; *Carcinoma, Ductal, Breast/pathology/diagnostic imaging ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Breast cancer is one of the most common cancers in women globally. Axillary lymph node metastasis remains one of the most independent prognostic factors in breast cancer.

OBJECTIVE: Evaluate the diagnostic accuracy of 18F-FDG-PET/CT in detecting axillary lymph node metastasis based on immunohistochemical subtypes and its correlation with sentinel lymph node biopsy (SLNB) results.

DESIGN: A retrospective cohort.

SETTING: Tertiary oncology center in Turkiye.

PATIENTS AND METHODS: Patients diagnosed with early-stage invasive ductal breast cancer and who underwent preoperative F-18 fluorodeoxyglucose positron emission computed tomography (18F-FDG PET/CT) evaluation were included in the study. Patients were divided into five immunohistochemical subtypes: Luminal A, Luminal B HER2 (-) (human epidermal growth factor receptor 2), Luminal B HER2 (+), HER2 (+), and triple negative. SLNB and SUVmax (Maximum Standard Unit Value) results were compared.

MAIN OUTCOME MEASURES: Diagnostic accuracy of 18F-FDG PET/CT for detecting axillary metastasis was the primary outcome. Interrater reliability testing in determining the agreement between 18F-FDG PET/CT and SLNB was the secondary outcome.

SAMPLE SIZE: 248.

RESULTS: The sensitivity, specificity, PPV, NPV and accuracy of 18F-FDG-PET/CT for detecting axillary metastasis were 62%, 92%, 88%, 71% and 77%, respectively. Cohen's Kappa coefficient (0.54) showed moderate agreement with SLNB (P<.001). Tumors with positive HER2 gene amplification [HER2 (+) and Luminal B HER2 (+) have higher sensitivity than other subtypes (Luminal A, Luminal B HER2 (-) and triple negative). HER2 gene amplification also increases the agreement between 18F-FDG-PET/CT and SLNB results.

CONCLUSION: 18F-FDG-PET/CT has a high specificity but low sensitivity for ipsilateral axillary metastasis in invasive ductal carcinoma. The presence of HER2 gene amplification can increase sensitivity and concordance with SLNB.

LIMITATIONS: Retrospective design and limited number of patients for each subtype.}, } @article {pmid40478792, year = {2025}, author = {Li, H and Luo, M and Luo, W and Li, H and Cong, S}, title = {Integrated decision-control for social robot autonomous navigation considering nonlinear dynamics model.}, journal = {PloS one}, volume = {20}, number = {6}, pages = {e0324341}, pmid = {40478792}, issn = {1932-6203}, mesh = {*Robotics/methods ; *Nonlinear Dynamics ; Humans ; Algorithms ; Reward ; Decision Making ; Reinforcement, Psychology ; Walking ; }, abstract = {Reinforcement learning (RL) has demonstrated significant potential in social robot autonomous navigation, yet existing research lacks in-depth discussion on the feasibility of navigation strategies. Therefore, this paper proposes an Integrated Decision-Control Framework for Social Robot Autonomous Navigation (IDC-SRAN), which accounts for the nonlinearity of social robot model and ensures the feasibility of decision-control strategy. Initially, inverse reinforcement learning (IRL) is employed to tackle the challenge of designing pedestrian walking reward. Subsequently, the Four-Mecanum-Wheel Robot dynamic model is constructed to develop IDC-SRAN, resolving the issue of dynamics mismatch of RL system. The actions of IDC-SRAN are defined as additional torque, with actual torque and lateral/longitudinal velocities integrated into the state space. The feasibility of the decision-control strategy is ensured by constraining the range of actions. Furthermore, a critical challenge arises from the state delay caused by model transient characteristics, which complicates the articulation of nonlinear relationships between states and actions through IRL-based rewards. To mitigate this, a driving-force-guided reward is proposed. This reward guides the robot to explore more appropriate decision-control strategies by expected direction of driving force, thereby reducing non-optimal behaviors during transient phases. Experimental results demonstrate that IDC-SRAN achieves peak accelerations approximately 8.3% of baseline methods, significantly enhancing the feasibility of decision-control strategies. Simultaneously, the framework enables goal-oriented autonomous navigation through active torque modulation, attaining a task completion rate exceeding 90%. These outcomes further validate the intelligence and robustness of the proposed IDC-SRAN.}, } @article {pmid40478342, year = {2025}, author = {Thill, M and Ghilli, M and Roncella, M and Kelling, K and Fansa, H and Golatta, M and Heil, J and Haasteren, V and Freitag, A and Togawa, R and Sagona, A and Rooney, TB and Fox, MJ and Barth, RJ}, title = {A Multi-institutional Study to Evaluate the Effectiveness and Safety of a Supine MRI-Based Guidance System, the Breast Cancer Locator[TM], for Breast Conserving Surgery in Patients with Nonpalpable Breast Cancer.}, journal = {Annals of surgical oncology}, volume = {}, number = {}, pages = {}, pmid = {40478342}, issn = {1534-4681}, abstract = {BACKGROUND: The Breast Cancer Locator[TM] (BCL) has been demonstrated to be a safe and effective guidance system for breast-conserving surgery (BCS) in patients with palpable breast cancer, but its effectiveness in patients with nonpalpable breast cancer has not been evaluated.

PATIENTS AND METHODS: Supine magnetic resonance imaging (MRI) images were used to generate (1) an interactive three-dimensional (3D) virtual image of the tumor in the breast and (2) a plastic bra-like form (BCL) that enabled the surgeon to place wires that bracketed the tumor volume. The primary objective was to determine the proportion of patients undergoing margin negative resections.

RESULTS: A total of 35 subjects were enrolled at 5 sites by 9 surgeons. In the 33 patients treated per protocol, 31 had margin negative resections (94%). All 31 patients with negative margins had negative margins on the primary lumpectomy specimen resected with BCL guidance. Additional shave margins were taken in 4 of the 31 patients; no cancer was present in the shaves. A total of 25 patients had invasive ductal carcinoma, 7 invasive lobular carcinoma, and 3 ductal carcinoma en situ (DCIS). The mean tumor diameter was 3.1 cm and specimen volume was 56 ml. The median actual/targeted specimen volume ratio was 1.18. There was no significant difference in preop versus postop Breast-Q scores: 66.5 versus 64.0, p = 0.58. Surgeons judged the BCL guidance system to be easy to use in 91% of cases.

CONCLUSIONS: The BCL guidance system enabled surgeons to do precise BCS: margin negative resections were obtained in a high proportion of cases, resected specimen volumes were relatively low, and patients' satisfaction with their breasts was not adversely effected by surgery.}, } @article {pmid40474937, year = {2025}, author = {Miranda-Pinzon, M and Gomez-Caturla, J and Ivorra-Martinez, J and Guijarro, N and Marset, X and Balart, R}, title = {Sustainable Approach to Overcome Polylactide Brittleness with Biobased Esters of Isosorbide and Fatty Acids.}, journal = {ACS sustainable chemistry & engineering}, volume = {13}, number = {21}, pages = {7962-7974}, pmid = {40474937}, issn = {2168-0485}, abstract = {This work reports on the design and synthesis of sustainable plasticizers from plant-based isosorbide to enhance the intrinsic brittleness of polylactide (PLA). To keep fully biobased carbon, isosorbide was esterified with fatty acids of varying chain length, leading to isosorbide dibutyrate (IDB), dicaprylate (IDC), and dipalmitate (IDP). These esters were incorporated into PLA at different concentrations. An approach to assess PLA-plasticizer miscibility was conducted by calculating solubility parameters (δ) and the Flory-Huggins interaction parameter, χ. The effect of plasticizer type and concentration on mechanical, thermal, and thermomechanical properties, as well as on microstructure and biodegradation, was also addressed. The results indicated that IDB and IDC notably enhanced PLA toughness, reducing the PLA's glass transition temperature (T g) from 60.3 to 27.7 °C with 20 wt % IDC. Consequently, strain at break dramatically increased from 12.8% (PLA) to over 300% with 20 wt % IDB or IDC. In contrast, IDP exhibited limited miscibility, resulting in phase separation, though it still improved the impact strength and ductility. All formulations demonstrated exceptional disintegration in compost soil, underscoring their potential as "double green" plasticizers suitable for PLA. Since both PLA and isosorbide can be industrially derived from starch, this work places starch as a key platform for sustainable polymers.}, } @article {pmid40470417, year = {2025}, author = {Matsuo, T and Tanaka, T and Shien, T and Muraoka, A and Doihara, H}, title = {Detailed Ophthalmic and Pathological Features of Choroidal Metastasis From Breast Cancer: A Case Series of Five Patients.}, journal = {Cureus}, volume = {17}, number = {5}, pages = {e83484}, pmid = {40470417}, issn = {2168-8184}, abstract = {Breast cancer causes choroidal metastases on rare occasions. This study presented the eye manifestations of choroidal metastases from breast cancer and their response to treatments in detail as well as their pathological correlation in five patients. The patients' age at the diagnosis of breast cancer ranged from 24 to 69 years (median: 37 years). The time from the diagnosis of breast cancer to the detection of metastases was concurrent in one patient, two years later in three patients, and six years later in the other patient. The time from the detection of systemic metastases to the detection of choroidal metastases was the same in one patient, while it ranged from one to seven years later in four patients. Choroidal metastases were in the unilateral eye of four patients, whereas they were in both eyes of one patient. Choroidal metastases manifested as one or a few nodular or flat choroidal lesions with serous retinal detachment. As for the treatment of choroidal metastases, enucleation of the right eye was chosen based on the patient's wish as well as the family's wish in the earliest patient when cancer notification was not the norm in Japan. In the other four patients, whole-eye radiation was performed to reduce the choroidal metastatic lesions. As regards the prognosis, which was available in four patients, three patients died within one year from the diagnosis of choroidal metastases, while one patient died one year and eight months later. Regarding the pathology of breast cancer, which was available in four patients, immunostaining of the preserved enucleated eye in the earliest patient revealed that breast cancer cells in the choroidal metastatic lesion were positive for estrogen receptor and negative for progesterone receptor and human epidermal growth factor receptor 2 (HER2). Invasive ductal carcinoma in two patients was positive for estrogen receptor and negative for HER2, while invasive ductal carcinoma in the other patient was triple-negative for estrogen receptor, progesterone receptor, and HER2 with a high Ki-67 index. In conclusion, the prognosis for life was poor in patients with breast cancer who developed choroidal metastases. Choroidal metastatic lesions showed a response to whole-eye radiation to improve the quality of vision at the end of life. Vision-related symptoms should be monitored in the course of chemotherapy for systemic metastases.}, } @article {pmid40470186, year = {2025}, author = {Dahms, PA and Hinckley, B and Prekeris, R and Behbod, F and Lyons, TR}, title = {Semaphorin-7A promotes macrophage-mediated mammary epithelial and ductal carcinoma in situ invasion.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {40470186}, issn = {2693-5015}, support = {R01 CA211696/CA/NCI NIH HHS/United States ; R21 CA185226/CA/NCI NIH HHS/United States ; P30 CA046934/CA/NCI NIH HHS/United States ; R01 HD108335/HD/NICHD NIH HHS/United States ; R01 GM122768/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) accounts for 20-30% of all breast cancer diagnoses. Considered stage 0, DCIS is contained in the ducts by the myoepithelium that surround the luminal cells in the mammary gland. DCIS can progress to invasive ductal carcinoma (IDC) if the tumor cells break through the myoepithelium and invade the surrounding breast tissue. While 30-50% of DCIS tumors will progress to IDC, a majority will remain in a DCIS-like state. The mechanisms that drive this progression are not completely understood. There is currently no clinically recognized biomarker for predicting risk of DCIS progression. Therefore, all DCIS tumors are treated with standard of care, resulting in overtreatment. We have previously identified independent roles for semaphorin-7A (SEMA7A) and collagen in promoting DCIS progression to IDC.

METHODS: To investigate the relationship between SEMA7A and collagen remodeling in the mammary gland, we utilized patient tissues and mouse models of normal development and DCIS progression as well as a novel SEMA7A-blocking antibody.

RESULTS: We show that SEMA7A increases in patient samples of DCIS compared to matched normal tissues and in IDC compared to matched DCIS and normal tissues. This increase was correlated with the presence of CD68 + macrophages. Using puberty in the mammary gland as a model for normal epithelial invasion facilitated by macrophages, we show SEMA7A knockout mice exhibit delayed ductal elongation as well as decreased macrophages. Additionally, our SEMA7A-blocking antibody in a mouse model of DCIS decreased invasive tumor phenotypes and decreased organized collagen around the tumor. The invasive tumors had increased collagen and macrophage influx in the tumor. Finally, we show that SEMA7A activates an AKT/GSK3β/β-catenin signaling pathway within macrophages to promote expression of pro-inflammatory cytokines and the matrix remodeling enzyme MMP9 to facilitate invasion.

CONCLUSIONS: Our results demonstrate that SEMA7A regulates normal and transformed epithelial cell invasion through regulation of pro-invasive matrix remodeling via macrophages. Our studies also suggest that SEMA7A expression, macrophage phenotype, and collagen structure may be a predictor of risk for DCIS invasion. Thus, blocking SEMA7A may be a novel therapeutic strategy for high-risk DCIS patients to slow or prevent progression of disease.}, } @article {pmid40469556, year = {2025}, author = {Suzuki, A and Komiya, T and Fujita, H and Shimada, K and Nonaka, M and Hanano, M and Takeishi, M and Ishikawa, T and Matsumura, H}, title = {Surgical Site Infection Owing to Mycobacterium mageritense After Immediate Breast Reconstruction Using a Deep Inferior Epigastric Perforator Flap.}, journal = {Plastic and reconstructive surgery. Global open}, volume = {13}, number = {6}, pages = {e6823}, pmid = {40469556}, issn = {2169-7574}, abstract = {Mycobacterium mageritense is a rare, rapidly growing, nontuberculosis mycobacterium that belongs to type IV of the rapidly growing mycobacteria. These bacteria are found in soil and water, and cause localized skin and soft tissue infections; however, they are challenging to culture, leading to diagnostic delays. To our knowledge, there have been 12 reported cases of surgical site infections (SSIs) caused by M. mageritense, with only 2 cases following breast reconstruction. A 51-year-old woman underwent nipple-sparing mastectomy and immediate breast reconstruction using a deep inferior epigastric perforator flap for invasive ductal carcinoma of the left breast. One month after surgery, she developed an SSI caused by M. mageritense. Despite initial outpatient treatment, the infection persisted, requiring multiple hospitalizations, administration of intravenous antibiotics, and several debridements under general anesthesia. Negative pressure wound therapy and a coordinated approach among various medical specialties are essential for managing infections. The patient experienced side effects from prolonged antibiotic use but eventually exhibited no signs of infection recurrence. This case highlights the challenges in diagnosing and treating M. mageritense SSIs, emphasizing the need for comprehensive surgical and medical management, together with patient-centered care, to effectively manage long-term treatment.}, } @article {pmid40469550, year = {2025}, author = {Mattia, A and Alomari, M and Hyjazie, T and Devisetti, N and Shen, Y and Haykal, S}, title = {Breast Reconstruction in De Novo Metastatic Breast Cancer: A Systematic Review.}, journal = {Plastic and reconstructive surgery. Global open}, volume = {13}, number = {6}, pages = {e6810}, pmid = {40469550}, issn = {2169-7574}, abstract = {BACKGROUND: Breast reconstruction in de novo metastatic breast cancer (dnMBC) patients is a viable option. There remains no consensus on recommendations. We summarize postreconstruction clinical outcomes in dnMBC patients to identify surgical candidates.

METHODS: A systematic review was conducted across PubMed/MEDLINE, Scopus, and Web of Science from January 1, 1990, to November 1, 2024. The study methods were in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data on patient demographics, disease characteristics, oncological treatment, surgical details, and clinical outcomes were collected.

RESULTS: A total of 7 studies (2635 breast cancer survivors) were identified. The average (SD) age was 47.5 (2.35) years, and most participants were White (n = 2080, 79.3%). Across studies, 39.0% (n = 761) of patients underwent implant-based reconstruction, 38.8% (n = 757) autologous reconstruction, 5.99% (n = 117) combined reconstruction, and 16.4% (n = 320) were not specified. Most cancers were invasive ductal carcinoma (81.3%) with estrogen-positive (73.1%) or progesterone-positive (48.4%) receptors and human epidermal growth factor receptor 2-positive (33.7%) status. Primary tumors most often metastasized to bone (44.4%) or lymph nodes (38.5%). Overall survival and breast cancer-specific survival rates were prolonged among reconstructed patients without increased predilection for complications or delay in tumor treatment.

CONCLUSIONS: Reconstruction in dnMBC patients is an appropriate option, especially among younger patients with oligometastatic disease. Future studies are encouraged to investigate the impact on well-being and prolonged survival rates, which primarily seem to be limited to those with low disease burden and hormone receptor-positive tumor subtypes.}, } @article {pmid40468339, year = {2025}, author = {Irandoust, K and Alipour, V and Arabloo, J and Nahvijou, A and Akbari, A}, title = {Economic burden of five common cancers in Iran: a systematic review of cost-of-illness with a focus on healthcare resource utilization.}, journal = {BMC health services research}, volume = {25}, number = {1}, pages = {800}, pmid = {40468339}, issn = {1472-6963}, mesh = {Humans ; Iran/epidemiology ; *Cost of Illness ; *Breast Neoplasms/economics ; Male ; *Stomach Neoplasms/economics ; *Prostatic Neoplasms/economics ; *Colorectal Neoplasms/economics ; *Lung Neoplasms/economics ; Female ; *Neoplasms/economics ; *Health Care Costs/statistics & numerical data ; *Patient Acceptance of Health Care/statistics & numerical data ; }, abstract = {BACKGROUND: According to the latest World Health Organization report, approximately half of the new cancer cases in Iran are attributed to five common cancers: gastric, breast, colorectal, lung, and prostate cancer. These cancers impose a heavy economic burden on healthcare systems and society, including direct medical costs (DMC), direct non-medical costs (DNMC), and indirect costs (IDC). This systematic review aimed to investigate the economic burden of these cancers in Iran.

METHODS: This systematic review was conducted according to PRISMA guidelines. The search strategy was developed using MeSH terms, Emtree, and previous literature. To identify relevant studies published up until December 27, 2023, searches were conducted in both international databases (PubMed, Scopus, Web of Science, Embase, Cochrane, and the NHS Economic Evaluation Database) and national databases (SID, Magiran, and IranMedex). After removing duplicates and screening studies using Endnote software, eligible studies were selected for inclusion in the review. The costs were converted to USD 2021 using the CCEMG-EPPI-Centre cost converter.

RESULTS: A total of 22 studies were included in this review. Breast and colorectal cancer each had 4 studies, while prostate, gastric, and lung cancer each had 3 studies. The remaining 5 studies covered a combination of multiple cancers. Converting the costs from different studies to USD 2021 showed that the average annual DMC per patient with breast cancer varied from $13,954 to $34,772. These costs ranged from $14,671 to $28,656 for colorectal cancer, $7,970 to $16,821 for prostate cancer, $12,206 to $17,681 for gastric cancer, and $9,369 to $40,682 for lung cancer. Part of these variations may be related to differences in healthcare resource utilization, while another part may be due to differences in cost calculation methodology, study perspective, and study location. Additional cost conversion findings showed that in 85% of the studies, the average annual DNMC per patient for all cancers were estimated to be less than $4,000. Furthermore, the average annual IDC per patient for breast and lung cancer were estimated to be as high as $100,000 due to high mortality, compared to less than $30,000 for other cancers.

CONCLUSIONS: Given the high prevalence of these five cancers in Iran, their economic burden is significant. Policymakers should focus not only on reducing the disease burden but also on minimizing the economic burden of cancer. Strategies such as improving early detection, optimizing treatment pathways, and implementing cost-effective interventions could help reduce both healthcare costs and the overall financial strain on patients and the healthcare system.}, } @article {pmid40464172, year = {2025}, author = {Choi, S and Choi, EJ and Kim, BR and Kim, KM}, title = {An Unusual Occurrence of Synchronous Squamous Cell Carcinoma and Invasive Ductal Carcinoma in the Ipsilateral Breast: A Case Report.}, journal = {Current medical imaging}, volume = {21}, number = {}, pages = {10.2174/0115734056373786250527105407}, doi = {10.2174/0115734056373786250527105407}, pmid = {40464172}, issn = {1573-4056}, mesh = {Humans ; Female ; Middle Aged ; *Carcinoma, Squamous Cell/diagnostic imaging/pathology/surgery ; *Neoplasms, Multiple Primary/diagnostic imaging/pathology/surgery ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology/surgery ; *Breast Neoplasms/diagnostic imaging/pathology/surgery ; Magnetic Resonance Imaging/methods ; Tomography, X-Ray Computed ; Contrast Media ; Breast/diagnostic imaging/surgery/pathology ; Ultrasonography, Mammary ; }, abstract = {BACKGROUND: The synchronous occurrence of primary pure squamous cell carcinoma (SCC) and invasive ductal carcinoma (IDC) of the breast is rare. Accurate identification of synchronous primary malignancies is crucial because their prognosis and treatment differ significantly from recurrent diseases. Herein, we present an unusual case highlighting the synchronous development of primary SCC and IDC in the ipsilateral breast.

CASE REPORT: A 48-year-old woman presented with a palpable mass in her right breast. Preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) demonstrated an irregularly shaped mass with internal rim enhancement. Surgical resection confirmed IDC of nuclear grade 3 with a high proliferation index (Ki-67: 70%), and the patient underwent adjuvant chemotherapy without radiation. Five months postoperation, a chest computed tomography (CT) revealed a new round-shaped lesion with rim enhancement and relatively circumscribed margins near the previous operation site. Breast ultrasound additionally identified a complex cystic and solid mass with an echogenic rind and increased vascularity. Following total resection, a pure squamous cell carcinoma with prominent keratinization was confirmed.

CONCLUSION: Accurate and early diagnosis of synchronous multiple primary malignancies from recurrence of the primary tumor is critical for improving prognosis by establishing an appropriate treatment and follow-up plan. Recognizing complex cystic and solid masses with relatively circumscribed margins on radiological imaging can assist clinicians in identifying and managing rare cases where IDC and SCC coexist or appear sequentially within a short period.}, } @article {pmid40460639, year = {2025}, author = {Shekhar Das, H and Borah, K and Bora, K}, title = {Ensemble learning approach for detecting breast invasive ductal carcinoma from histopathological images.}, journal = {Pathology, research and practice}, volume = {272}, number = {}, pages = {156041}, doi = {10.1016/j.prp.2025.156041}, pmid = {40460639}, issn = {1618-0631}, mesh = {Humans ; *Breast Neoplasms/pathology/diagnosis ; Female ; *Carcinoma, Ductal, Breast/pathology/diagnosis ; *Deep Learning ; Neural Networks, Computer ; *Image Interpretation, Computer-Assisted/methods ; Algorithms ; Ensemble Learning ; }, abstract = {Invasive ductal carcinoma is a type of breast cancer that is one of the most frequent and aggressive forms of breast malignancy, necessitating accurate and timely diagnosis for effective treatment. Though considered the gold standard, traditional histopathological diagnosis is subject to inter-observer and intra-observer variability, potentially impacting patient outcomes. This study proposed an ensemble learning approach for classifying invasive ductal carcinoma to address these challenges. The proposed method combines the strengths of multiple deep-learning models to enhance diagnostic accuracy and robustness. We employed a diverse set of pre-trained convolutional neural networks, viz, ResNet50, Xception, MobileNetV2, VGG16, and VGG19, each trained on histopathological images of breast histology slides. These five different deep learning models were compared in this work, and the resulting inference results are also shown. Ensemble and a fine-tuning approach to transfer learning were also used to extract the best results. These models were evaluated using evaluation metrics like accuracy to see which one does the job best. The proposed weighted average ensemble algorithm achieved 97.27 % accuracy. Among all models, the ResNet50 model outperforms the other models in identifying invasive ductal carcinoma. Therefore, ResNet50 is the preferred model when accuracy is the top concern for a particular resolution image, and the weighted average ensemble approach enhances the performance of the proposed work. Our results indicate that the proposed ensemble approach decreases variability in diagnoses and advancements in accuracy. This method holds promise for enhancing the precision of breast cancer diagnostics, potentially leading to better patient management and outcomes.}, } @article {pmid40455366, year = {2025}, author = {Qiu, X and Tian, B and Gu, Y and Yin, K and Zhao, J and Wang, J}, title = {Novel nomograms for predicting overall survival and cancer-specific survival in invasive lobular carcinoma of the breast.}, journal = {Discover oncology}, volume = {16}, number = {1}, pages = {984}, pmid = {40455366}, issn = {2730-6011}, support = {TRYJ2021JC18//Screening and preliminary functional analysis of specific metabolites of breast malignant tumors/ ; }, abstract = {PURPOSE: Currently, the clinical diagnosis and treatment for invasive lobular carcinoma of the breast (ILC) often draw on the treatment approaches used for invasive ductal carcinoma (IDC), despite significant differences between the two. Studies evaluating the risk and prognosis of ILC are limited; thus, our goal was to construct a predictive model for the prognosis of ILC.

METHODS: Clinical data of patients diagnosed with unilateral primary ILC from 2010 to 2015 were acquired from the SEER database. Independent prognostic factors affecting patients' overall survival (OS) and cancer-specific survival (CSS) were determined through univariate and multivariate analyses based on COX proportional hazards model and Fine-Gray competing risks model. Nomograms were constructed to forecast the 1-year, 3-year, and 5-year OS and CSS of the patients.

RESULTS: A total of 6,616 patients with ILC were included, with 1,083 deaths, of which 541 were attributed to ILC, and 542 to other causes. The univariate and multivariate analyses indicated that age, N stage, stage, surgery, PR status, radiotherapy, and brain metastasis are independent risk factors for OS of ILC patients, while age, N stage, stage, surgery, PR status, and brain metastasis are independent risk factors for CSS of ILC patients. The C-index, area under the ROC curve, and calibration curve of the 1-, 3-, and 5-year OS and CSS prediction models confirmed that it had good predictive capability.

CONCLUSIONS: This study has developed subtype-specific predictive models for OS and CSS of patients with ILC, offering clinicians a regimen. Reference for assessing patient prognosis and formulating individualized treatment.}, } @article {pmid40452670, year = {2025}, author = {Nishiyori, R and Goto-Umeki, M and Fujinaga-Tada, M and Takumi, Y and Osoegawa, A and Furukawa, R and Oyama, Y and Sakai, T and Hatano, Y}, title = {A Rare Case of Male Breast Cancer Presenting as a Superficial Pigmented Nipple Tumor: The Importance of a Deep Excisional Biopsy and Immunohistochemical Analysis in Diagnosis.}, journal = {Cureus}, volume = {17}, number = {5}, pages = {e83353}, pmid = {40452670}, issn = {2168-8184}, abstract = {Nipple lesions present diagnostic challenges due to overlapping clinical and histopathological features. A 65-year-old male presented with a black skin lesion on his right nipple, initially suspected to be malignant melanoma. Dermoscopy suggested basal cell carcinoma, while punch biopsy findings indicated sweat gland carcinoma with negative mammaglobin staining. However, total resection revealed cord-like invasion into the deep dermis near the mammary gland, and immunohistochemistry showed mammaglobin positivity, leading to a final diagnosis of solid-type invasive ductal carcinoma of the breast. This case highlights the diagnostic challenges of male nipple tumors and underscores the need for thorough histopathological and deep-layer assessment to distinguish breast cancer from cutaneous malignancies.}, } @article {pmid40452312, year = {2025}, author = {Grypari, IM and Pomoni, A and Tzelepi, V}, title = {Intraductal carcinoma of the prostate: A comprehensive literature review focused on grading challenges and controversies.}, journal = {Histology and histopathology}, volume = {40}, number = {12}, pages = {1869-1888}, pmid = {40452312}, issn = {1699-5848}, mesh = {Humans ; Male ; Neoplasm Grading ; *Prostatic Neoplasms/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is characterized by neoplastic cell proliferation within pre-existing ducts or acini, exhibiting architectural and cytological atypia exceeding that of high-grade prostatic intraepithelial neoplasia. Its presence in needle biopsies and prostatectomies is associated with adverse clinical and pathological features, including large tumor volume, high grade, advanced stage, early biochemical recurrence, and intrinsic resistance to systemic therapy. Although rare, IDC-P can occasionally occur without concurrent invasive cancer or be associated with low-grade prostate cancer. Molecularly, IDC-P resembles its associated invasive carcinoma, sharing alterations typical of high-grade aggressive tumors. These findings support the hypothesis that IDC-P arises from the retrograde spread of invasive carcinoma, with ducts providing a protective niche against the tumor microenvironment. In contrast, isolated IDC-P and IDC-P associated with low-grade invasive carcinoma may represent precursor lesions. IDC-P must be distinguished from other intraductal lesions, both benign and malignant, particularly in needle biopsies, as its detection impacts therapeutic decisions. While grading does not apply to isolated IDC-P, there is an ongoing debate regarding IDC-P with synchronous invasive cancer. The International Society of Urological Pathology (2019) recommends incorporating IDC-P into Gleason score calculations, whereas the Genitourinary Pathology Society advises against grading it at all. Both approaches have merit, but further validation studies focusing on cases where IDC-P inclusion alters the final grade, though uncommon, are warranted.}, } @article {pmid40449850, year = {2025}, author = {Dubois, C and Chesnel, C and Teng, M and Vivier, M and Noël, C and Amarenco, G and Hentzen, C}, title = {Effect on sensory and motor parameters of a first intradetrusor botulinum neurotoxin A injection in patients with neurogenic bladder: A retrospective study.}, journal = {The French journal of urology}, volume = {35}, number = {8}, pages = {102914}, doi = {10.1016/j.fjurol.2025.102914}, pmid = {40449850}, issn = {2950-3930}, mesh = {Humans ; Retrospective Studies ; *Botulinum Toxins, Type A/administration & dosage/therapeutic use ; Female ; Male ; Middle Aged ; *Urinary Bladder, Neurogenic/drug therapy/physiopathology/etiology ; Adult ; *Neuromuscular Agents/administration & dosage ; *Urinary Bladder, Overactive/drug therapy/etiology/physiopathology ; Urodynamics/drug effects ; Aged ; Urinary Bladder/drug effects/innervation/physiopathology ; Injections, Intramuscular ; Administration, Intravesical ; Treatment Outcome ; }, abstract = {BACKGROUND: Overactive bladder (OAB) is common in suprasacral neurological disorders and often associated with detrusor overactivity (DO). Botulinum neurotoxin A (BoNT-A) is a second-line treatment inducing reversible chemical denervation. While its motor effects are well documented, its impact on sensory parameters in neurogenic bladder dysfunction remains poorly understood.

AIM: To evaluate sensory and motor bladder changes following BoNT-A injection in neurogenic DO (NDO).

METHOD: This retrospective single-center study included patients with NDO who received a first BoNT-A injection (from 2015 to 2024). Urodynamic assessments were performed pre- and 2-6months post-injection. Changes in OAB symptoms and urodynamic parameters were analyzed, including sensory (first desire to void [FDV], strong desire to void [SDV]), and motor parameters (DO occurrence, volume at first involuntary detrusor contraction (IDC)).

RESULTS: Among 90 patients (mean age 50.4±15.6years, 61% female, 53 with multiple sclerosis, 35 with spinal cord injury), urgency and urgency urinary incontinence significantly decreased (from 84% to 52% and from 80% to 42%, respectively; P<0.001). DO occurrence declined from 97% to 42% (P<0.001). Bladder sensations (FDV and SDV) persisted in 84% of patients but were significantly delayed.

CONCLUSION: BoNT-A is an effective treatment for neurogenic overactive bladder in multiple sclerosis and spinal cord injury, improving both urgency and urinary incontinence. Its clinical efficacy is associated with resolution of detrusor overactivity, alongside with sensory changes. Preserved but delayed filling sensations after treatment suggests that BoNT-A may modulate afferent signaling. However, whether its clinical benefits are primarily driven by sensory modulation or motor inhibition remains uncertain.}, } @article {pmid40441223, year = {2025}, author = {Ma, X and Shi, W and Ren, N and Zhang, Y and Tian, X}, title = {Invasive ductal breast cancer with focal mucinous differentiation in a 38-year-old woman: Case report and literature review.}, journal = {Medicine}, volume = {104}, number = {22}, pages = {e42465}, pmid = {40441223}, issn = {1536-5964}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/surgery/diagnostic imaging ; Adult ; *Carcinoma, Ductal, Breast/pathology/surgery/diagnostic imaging ; Tomography, X-Ray Computed ; *Adenocarcinoma, Mucinous/pathology/surgery ; }, abstract = {RATIONALE: Breast cancer (BC) is a common malignant tumor with a poor prognosis that requires early treatment. Invasive ductal BC with focal mucinous differentiation in a 38-year-old woman is rarely reported.

PATIENT CONCERNS: A 38-year-old woman presented to our clinic 3 months after discovering a breast mass that had increased in size during this period. Enhanced computed tomography showed an irregular mass with lobulated edges and burrs at the 9 o'clock position on the patient's right breast. An early enhanced scan showed significant heterogeneous enhancement with continuous enhancement.

DIAGNOSES: The patient's postoperative pathology suggested that the patient had an infiltrating ductal BC with focal mucinous differentiation.

INTERVENTIONS: The patient underwent right breast mass resection first. After the pathological diagnosis was confirmed, the patient underwent right breast resection and right axillary lymph node dissection.

OUTCOMES: The patient's postoperative recovery was good. To date, the patient has not experienced any symptoms of recurrence.

LESSONS: Owing to the poor prognosis of BC, patients with abnormal breast masses should be diagnosed and treated as soon as possible. Further prognosis research on the invasive ductal carcinoma with focal mucinous differentiation occurring in young individuals is warranted.}, } @article {pmid40439394, year = {2025}, author = {Khan, L and Khan, M and Shakeel, F and Ali, T and Hina, M and Arif, A and Rahim Sarfaraz, F and Tariq, M and Hafiz, A and Qureshi, BM and Abbasi, AN and Ali, N}, title = {Effect of DIBH Coaching on Dosimetric Parameters of Heart and Lung Doses in Patients Undergoing Adjuvant Breast Radiotherapy.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {26}, number = {5}, pages = {1809-1813}, pmid = {40439394}, issn = {2476-762X}, mesh = {Humans ; Female ; Middle Aged ; *Heart/radiation effects ; Radiotherapy, Adjuvant/adverse effects/methods ; *Lung/radiation effects ; *Unilateral Breast Neoplasms/radiotherapy ; Radiotherapy Planning, Computer-Assisted/methods ; Radiotherapy Dosage ; *Organs at Risk/radiation effects ; *Breath Holding ; Follow-Up Studies ; *Mentoring/methods ; Adult ; *Breast Neoplasms/radiotherapy ; *Radiation Injuries/prevention & control/etiology ; Prognosis ; }, abstract = {INTRODUCTION: Radiation exposure to the heart in women with left-sided breast cancer can lead to cardiac disease and increased mortality. Several techniques, including deep inspiration breath hold (DIBH), have been used to reduce cardiac exposure during radiotherapy. DIBH coaching prior to radiation planning can further reduce cardiac doses. This study aims to compare heart and lung dosimetric parameters between coached and non-coached patients using the DIBH technique for left-sided breast cancer treatment.

METHODS: All patients with left-sided breast cancer who received adjuvant radiotherapy (RT) using the DIBH were included. The first cohort, designated as the non-coached group, received verbal guidance on the breath hold technique but did not undergo formal coaching. The second cohort involved a comprehensive coaching protocol, which began in January 2022. This protocol, led by a physician, included demonstrations and instructions for performing the DIBH technique in the clinic and encouraged patients to practice at home before and during RT to optimize cardiac protection.

RESULTS: A total of 40 patients met the inclusion criteria for the study, with a mean age of 45.7 ± 8.38 years. Most patients had IDC and Stage II disease, and radiation was primarily delivered using 3DCRT with 4256 cGy in 16 fractions regimes. In terms of cardiac dose exposure, coached patients had slightly lower mean and maximum point cardiac doses, but these differences were not statistically significant. Coached patients also had a significantly lower mean V17 for left lung volume exposure compared to non-coached patients (18.3 vs. 21.6, p < 0.05).

CONCLUSION: DIBH coaching and home practice prior to RT planning can further reduce cardiac and lung doses, offering a cost-effective intervention, particularly in resource-limited settings, though further controlled studies with larger sample sizes and longer follow-up are needed to assess its clinical impact.}, } @article {pmid40437613, year = {2025}, author = {Zheng, Y and Tang, H and Liu, Q and Zhang, Y and Zhao, P and Zhang, S and Wang, C}, title = {Mutational analysis and protein expression of PI3K/AKT pathway in four mucinous cystadenocarcinoma of the breast.}, journal = {Diagnostic pathology}, volume = {20}, number = {1}, pages = {68}, pmid = {40437613}, issn = {1746-1596}, support = {81672606//National Natural Science Foundation of China/ ; ZR2022MH206//Natural Science Foundation of Shandong Province/ ; }, mesh = {Humans ; Female ; *Proto-Oncogene Proteins c-akt/metabolism/genetics ; Middle Aged ; *Cystadenocarcinoma, Mucinous/genetics/pathology ; *Breast Neoplasms/genetics/pathology ; DNA Mutational Analysis ; Mutation ; *Biomarkers, Tumor/genetics/analysis ; Aged ; Adult ; *Phosphatidylinositol 3-Kinases/metabolism/genetics ; Signal Transduction ; Immunohistochemistry ; High-Throughput Nucleotide Sequencing ; }, abstract = {INTRODUCTION: Primary mucinous cystadenocarcinoma of the breast (BMCA) is a rare neoplasm with few reports in the literature. Its molecular characteristics, prognosis, and treatment protocols are not well understood, and there is a lack of consensus concerning the optimal management of this condition.

METHODS: Four cases of clinical and pathological data were collected from 2018 to 2024. Next generation sequencing with a 654 cancer-associated gene panel was utilized to detect gene mutations. Immunohistochemistry was carried out to evaluate protein expression levels.

RESULTS: Firstly, we combined clinical imaging examinations and IHC to exclude the possibility of metastasis from ovarian or pancreatic origins. BMCA was composed of cystically dilated ducts lined by tall columnar mucin-containing epithelium. The morphological spectrum of MCA varied from MCA alone to MCA combined with carcinoma in situ (CIS) to MCA associated with invasive ductal carcinoma (IDC). ER/PR/HER2 and CK20 were all negative, while CK7 and GATA3 were positive by IHC in four cases. Although the prognosis of the other three patients was favorable during the follow-up periods of 13, 10, and 3 months, respectively, case 2# experienced a recurrence of the primary focus after 42 months. No lymphatic metastasis was identified in cases 1-4#. In addition, next-generation sequencing (NGS) identified 17 mutated genes and 25 mutation sites in four cases. TP53, PIK3CA, AKT, PTEN, and RB1 were the highest frequency mutated genes. Given that AKT mutations typically refer to AKT1(E17K) rather than AKT2 or AKT3, AKT protein expression was detected only in Case 2# (AKT1, E17K). PTEN protein was expressed in case 4# (corresponded to missense mutation), loss of PTEN expression were corresponding with splicing mutation in case1#. In brief, AKT and PTEN protein expression could be corresponded to gene mutation in a certain extent. However, PIK3CA protein expression was positive in Case 2# but negative in Case 1#, which did not fully accordance with the NGS-detected missense mutations. No associated germline variations were detected. Additionally, neither PDL-1 expression nor microsatellite instability-high (MSI-H) status was identified.

CONCLUSION: The tumorigenesis and development of BMCA may be regulated to the PI3K/AKT pathway. Consequently, a comprehensive genetic analysis of more cases could elucidate the molecular mechanisms underlying this rare tumor.}, } @article {pmid40433185, year = {2025}, author = {Rezaianzadeh, A and Hosseini-Bensenjan, M and Sephidbakht, S and Haghpanah, S and Khosravizadegan, Z and Asmarian, N and Ramzi, M}, title = {Bayesian Spatial Analysis of the Incidence Rate of Patients with Breast Cancer in Southern Iran.}, journal = {Iranian journal of medical sciences}, volume = {50}, number = {5}, pages = {316-323}, pmid = {40433185}, issn = {1735-3688}, mesh = {Humans ; *Breast Neoplasms/epidemiology ; Female ; Iran/epidemiology ; Incidence ; Bayes Theorem ; Adult ; Spatial Analysis ; Middle Aged ; Registries/statistics & numerical data ; Cohort Studies ; Risk Factors ; Aged ; }, abstract = {BACKGROUND: In the female population, breast cancer is the most common cancer and a leading cause of cancer death. This study was designed to investigate the geographical pattern of breast cancer risk in different counties of Fars province in the south of Iran from 2001 to 2018.

METHODS: In this historical cohort study, data of Shiraz Population-Based Cancer Registry between 2001 and 2018 was used. The geographical variations of breast cancer incidence rate in 36 counties of Fars province were analyzed using the Bayesian spatiotemporal model.

RESULTS: Overall, the averages of relative risk (RR), temporal trend (TT), and δi for breast cancer were 1.59, 1.025, and 0.00 in the total female population; 1.21, 1.002, and 0.00 in the young female population (under 40 years of age); and 1.54, 1.02, and 0.00 in the female population with invasive ductal carcinoma (IDC), respectively. The steady increase in RR of breast cancer and IDC during 2001-2018 was observed in most counties located in the non-central part of the Fars geographic map. Moreover, a steady increase of young breast cancer RR was observed mainly in southern regions and some northern cities of Fars province.

CONCLUSION: Between 2001 and 2018 in Fars province, a steady annual increase of approximately 2% was observed in the total female population for all types of breast cancer, including IDC. High-risk areas, TTs, and changing patterns of breast cancer incidence were determined in this region. Furthermore, areas with a high risk of young breast cancer were identified, which requires special attention.}, } @article {pmid40427132, year = {2025}, author = {Alloush, F and Bahmad, HF and Deb, A and Ocejo, S and Valencia, AK and Abulaban, A and Krishnamurthy, K and Alghamdi, S and Poppiti, R}, title = {Influence of Cancerization of Lobules in Ductal Carcinoma In Situ of the Breast on the Pathological Outcomes in Mastectomy Specimens.}, journal = {Cancers}, volume = {17}, number = {10}, pages = {}, pmid = {40427132}, issn = {2072-6694}, abstract = {Cancerization of lobules (COL) is defined as the involvement of lobular acini by ductal carcinoma in situ (DCIS). Whether it represents a morphological variation in DCIS or a secondary extension of DCIS into lobules is debatable. The relation between COL and the probability of invasion is conflicting among different studies. We assessed if COL is a predictor of adverse pathological outcomes in mastectomy specimens. We reviewed the clinicopathological data of patients who underwent partial or total mastectomy for DCIS during a 3-year period (January 2015 until December 2017). Pathological parameters and follow-up data were collected. Whole-tissue hematoxylin and eosin (H&E) slides were reviewed and re-evaluated for COL. Cases with COL were stained immunohistochemically for E-cadherin and p120 to confirm the ductal phenotype of the neoplasms. In total, 171 mastectomies were identified including 65 specimens with pure DCIS and 106 specimens with DCIS with invasive carcinoma. COL was identified in 73 specimens. COL was significantly associated with adverse pathological outcomes including higher DCIS nuclear grade (p-value = 0.006), central (expansive "comedo") necrosis (p-value = 0.008), presence of DCIS within or less than 2 mm from the surgical resection margin(s) (p-value = 0.004), higher percentage of blocks/slides with DCIS (p-value < 0.001), and extensive intraductal component (EIC) (applicable in cases with invasion) (p-value < 0.001). Invasion was seen in approximately two-thirds of the cases regardless of the presence of COL, with no statistical significance. Ninety-eight patients achieved 60 months of follow-up, of which only one patient developed local DCIS recurrence and had COL and EIC. Four other patients developed metastatic disease related to the invasive component. While other studies have previously hypothesized that COL may be associated with a worse pathological outcome at mastectomy, our results show that it may indeed be a measure of a higher disease burden representing EIC; however, it is not associated with an increased risk of detecting invasive carcinoma.}, } @article {pmid40419691, year = {2025}, author = {Shallah, AB and Zubir, F and Rahim, MKA and Jizat, NM and Basit, A and Yusof, KH and Majid, HA}, title = {Compact dual band crossover for 5G low and mid band applications using a metamaterial branch line coupler.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {18425}, pmid = {40419691}, issn = {2045-2322}, support = {R.J090301.7823.4J610//Higher Institution Centre of Excellence, Ministry of Higher Education Malaysia, Wireless Communication Centre, Universiti Teknologi Malaysia/ ; R.J090301.7823.4J610//Higher Institution Centre of Excellence, Ministry of Higher Education Malaysia, Wireless Communication Centre, Universiti Teknologi Malaysia/ ; R.J090301.7823.4J610//Higher Institution Centre of Excellence, Ministry of Higher Education Malaysia, Wireless Communication Centre, Universiti Teknologi Malaysia/ ; Q.J130000.3823.23H92//UTM Fundamental Research/ ; Q.J130000.3823.23H92//UTM Fundamental Research/ ; Q.J130000.3823.23H92//UTM Fundamental Research/ ; Q.J130000.3823.23H92//UTM Fundamental Research/ ; Q.J130000.3823.23H92//UTM Fundamental Research/ ; }, abstract = {This research paper introduces a compact dual-band crossover designed for the low and mid-band 5G frequencies at 0.7 GHz and 3.5 GHz. The innovative design is achieved by cascading two dual band branch-line couplers (BLCs), which utilize T-shaped transmission lines (TLs) with folded arms and stubs to reduce their overall footprint significantly. Additionally, the integration of metamaterial (MTM) structures, incorporating interdigital capacitor (IDC) unit cells, contributes to an impressive 90% size reduction compared to conventional components. The BLC's and crossover's performances were rigorously evaluated using CST Microwave Studio (CST MWS) simulations. Following successful simulations, the BLC and crossover were fabricated on a Rogers Duroid/RT5880 substrate, characterized by a dielectric constant of 2.2 and a thickness of 0.787 mm. A thorough comparative analysis between the simulated and measured results, alongside similar reported works, signifies the exceptional performance of the proposed BLC and crossover. These findings confirm their suitability for sub-6 GHz 5G frequency spectrum applications.}, } @article {pmid40418704, year = {2025}, author = {Hassan, F and Zhang, H and Idiaquez, DW and Pakasticali, N and Hyjek, E and Hussaini, M}, title = {KRAS may facilitate transformation of chronic lymphocytic leukemia to histiocytic sarcoma with indeterminate dendritic cell features.}, journal = {American journal of clinical pathology}, volume = {164}, number = {2}, pages = {157-162}, doi = {10.1093/ajcp/aqaf041}, pmid = {40418704}, issn = {1943-7722}, mesh = {Humans ; *Leukemia, Lymphocytic, Chronic, B-Cell/pathology/genetics ; *Histiocytic Sarcoma/pathology/genetics ; Male ; Aged ; *Proto-Oncogene Proteins p21(ras)/genetics/metabolism ; *Dendritic Cells/pathology ; *Cell Transformation, Neoplastic/pathology/genetics ; Mutation ; Biomarkers, Tumor/genetics ; }, abstract = {OBJECTIVE: We sought to investigate the molecular mechanism underlying transformation of chronic lymphocytic leukemia (CLL) to histiocytic sarcoma (HS) with indeterminate dendritic cell (IDC) features.

METHODS: Extensive NGS-based genomic profiling was performed on samples of a patient who had CLL, secondary HS with IDC features, and CMML. Clonotypic evaluation of VDJ rearrangement status was performed to confirm clonal relatedness.

RESULTS: HS is a rare proliferation of malignant tissue histiocytes that is usually primary, although secondary HS exists and often demonstrates mutations in the Ras/Raf/MAPK or PI3K/AKT/mTOR pathways, but HS with indeterminate dendritic cell (IDC) features has not been previously reported. A 77-year-old man with chronic lymphocytic leukemia (CLL) presented with an oropharyngeal mass. Biopsy specimen showed large atypical histiocytic cells with oval-to-irregular indented nuclei. They were positive for CD33, CD4, CD68 (subset, weak), CD163 (subset, weak), BCL6, S100 (subset), CD1a, cyclin D1 (subset), and lysozyme (weak) but negative for Langerin, BRAF V600E, CD21, CD23, CD35, CD123, TCF4, TCL1, MPO, CD20, CD79a, CD10, MUM1, and BCL2. The patient was diagnosed with secondary HS with IDC features as well as chronic myelomonocytic leukemia (CMML) in the bone marrow. Careful genomic dissection of all 3 types of malignant cells showed that SF3B1 p.E622D was present in both CLL and HS but not CMML. In addition, the HS acquired KRAS p.G13D, which we hypothesize drove the transdifferentiation of CLL to HS. Moreover, next-generation sequencing (NGS) clonotypic evaluation of variable-diversity-joining (VDJ) rearrangements in both the HS and CLL established relatedness but not the CMML.Conclusion: This is the first report of secondary HS with IDC features arising from CLL. We establish by both IGH NGS analysis and mutational profiling that the CLL and HS are clonally-related and posit that acquisition of KRAS p.G13D drove transdifferentiation. This has therapeutic implications for targeting the RAS-BRAF-MAPK-ERK pathway.}, } @article {pmid40409270, year = {2025}, author = {Trendel, J and Trendel, S and Sha, S and Greulich, F and Goll, S and Wudy, SI and Kleigrewe, K and Kubicek, S and Uhlenhaut, NH and Kuster, B}, title = {The human proteome with direct physical access to DNA.}, journal = {Cell}, volume = {188}, number = {16}, pages = {4424-4440.e17}, doi = {10.1016/j.cell.2025.04.037}, pmid = {40409270}, issn = {1097-4172}, mesh = {Humans ; *Proteome/metabolism ; *DNA/metabolism/chemistry ; Chromatin/metabolism/chemistry ; Cell Line, Tumor ; Transcription Factors/metabolism ; }, abstract = {In a human cell, DNA is packed with histones, RNA, and chromatin-associated proteins, forming a cohesive gel. At any given moment, only a subset of the proteome has physical access to the DNA and organizes its structure, transcription, replication, repair, and other essential molecular functions. We have developed a "zero-distance" photo-crosslinking approach to quantify proteins in direct contact with DNA in living cells. Collecting DNA interactomes from human breast cancer cells, we present an atlas of over one thousand proteins with physical access to DNA and hundreds of peptide-nucleotide crosslinks pinpointing protein-DNA interfaces with single-amino-acid resolution. Quantitative comparisons of DNA interactomes from differentially treated cells recapitulate the recruitment of key transcription factors as well as DNA repair proteins and uncover fast-acting restrictors of chromatin accessibility on a timescale of minutes. This opens a direct way to explore genomic regulation in a hypothesis-free manner, applicable to many organisms and systems.}, } @article {pmid40407816, year = {2025}, author = {Lu, D and Han, Y and Xu, R and Wang, C and Qin, M and Shi, J and Ye, F and Zhang, J and Luo, Z and Wang, Y and Lin, H and Jia, P and Zhu, J and Wang, C}, title = {Respiratory transmission potential of severe fever with thrombocytopenia syndrome bunyavirus: evidence from intranasal exposure in a humanized mouse model.}, journal = {Emerging microbes & infections}, volume = {14}, number = {1}, pages = {2511134}, pmid = {40407816}, issn = {2222-1751}, mesh = {Animals ; Mice ; *Severe Fever with Thrombocytopenia Syndrome/transmission/virology/pathology/immunology ; Disease Models, Animal ; Humans ; *Phlebovirus/physiology/pathogenicity ; Lung/pathology/virology ; Administration, Intranasal ; Female ; }, abstract = {Severe Fever with Thrombocytopenia Syndrome Bunyavirus (SFTSV) is a highly lethal pathogen with expanding endemic regions in Asia. While primarily transmitted by ticks, recent evidence suggests potential airborne transmission, raising significant public health concerns. This study investigates the potential for respiratory transmission and pathogenesis using humanized NCG mice inoculated with SFTSV via subcutaneous injection challenge (SIC) or intranasal drop challenge (IDC). Both groups demonstrated rapid systemic dissemination, marked by viremia, weight loss, and multi-organ injury, with hemorrhagic manifestations observed in high-dose infection groups. Histopathological evaluations revealed lung pathology in the intranasal drop challenge mice, including extensive alveolar disruption and inflammatory cell infiltration. Transcriptomic analyses further confirmed that respiratory route inoculation resulted in heightened expression of inflammatory signalling pathways such as IL-17 and NF-κB, potentially contributing to severe local immunopathology. Subcutaneous infection provoked an earlier systemic immune response, with significant upregulation of antigen-processing genes in peripheral blood mononuclear cells. Nevertheless, both routes ultimately culminated in widespread injury to the liver, spleen, kidney, highlighting the systemic nature of SFTSV pathogenesis. These findings underscore the need for preventive strategies addressing respiratory spread.}, } @article {pmid40406802, year = {2025}, author = {Kumar, SV and Kishore Singh, B and Gopal Madakshira, M and Kumar, V and Kumar Mishra, S and Sati, A and V Kumar, N}, title = {Fluorodeoxyglucose positron emission tomography - computed tomography (FDG PET-CT) negative orbital metastasis secondary to breast carcinoma: a diagnostic pitfall.}, journal = {Orbit (Amsterdam, Netherlands)}, volume = {44}, number = {6}, pages = {815-820}, doi = {10.1080/01676830.2025.2507374}, pmid = {40406802}, issn = {1744-5108}, mesh = {Humans ; Female ; *Fluorodeoxyglucose F18 ; *Breast Neoplasms/pathology/diagnostic imaging ; *Orbital Neoplasms/secondary/diagnostic imaging/radiotherapy ; *Positron Emission Tomography Computed Tomography ; *Radiopharmaceuticals ; Magnetic Resonance Imaging ; Adult ; *Carcinoma, Lobular/diagnostic imaging/secondary/radiotherapy ; *Carcinoma, Ductal, Breast/diagnostic imaging/secondary ; Biopsy ; }, abstract = {Orbital metastases from breast carcinoma are uncommon and often present diagnostic challenges. Fluorodeoxyglucose positron emission tomography - computed tomography (FDG PET-CT) is widely used in oncologic imaging, but may fail to detect small or metabolically inactive orbital lesions. We report a 41 -year-old female with a history of hormone receptor-positive invasive lobular breast carcinoma who presented with a painless progressive swelling of the lower eyelid and proptosis over 3 months. Magnetic resonance imaging (MRI) orbit revealed a lesion in the inferolateral aspect of the left lower eyelid and extraconal compartment of the left orbit. FDG PET-CT did not demonstrate any metabolic activity in the orbit. A biopsy was performed, confirming metastatic breast carcinoma. The patient underwent external beam radiotherapy directed at the eyelid and orbital region, resulting in a favorable clinical response. This case illustrates the limitations of FDG PET-CT in detecting orbital metastasis from breast carcinoma, particularly in lobular subtypes ,and emphasizes the importance of correlating imaging with clinical suspicion and biopsy in such clinical scenarios.Abbreviations: FDG PET-CT= Fluorodeoxyglucose positron emission tomography - computed tomography, MRI= Magnetic resonance imaging,ILC= Invasive lobular carcinoma, IDC= Invasive ductal carcinoma.}, } @article {pmid40404608, year = {2025}, author = {Tanabe, Y and Inoue, K and Takahashi, M and Mukai, H and Yamanaka, T and Egawa, C and Uchida, Y and Higashibeppu, Y and Sakata, Y and Sugawara, M and Tsurutani, J}, title = {Prognosis of Invasive Lobular Carcinoma and Effectiveness of Eribulin in Clinical Practice: A Post Hoc Analysis of a 2-Year Post-Marketing Surveillance.}, journal = {Asia-Pacific journal of clinical oncology}, volume = {21}, number = {6}, pages = {623-630}, pmid = {40404608}, issn = {1743-7563}, support = {//Eisai Co., Ltd/ ; }, mesh = {Humans ; *Ketones/therapeutic use ; *Furans/therapeutic use ; Female ; *Breast Neoplasms/drug therapy/pathology/mortality ; Middle Aged ; *Carcinoma, Lobular/drug therapy/pathology/mortality ; Aged ; Prognosis ; Product Surveillance, Postmarketing ; Prospective Studies ; Adult ; *Antineoplastic Agents/therapeutic use ; Polyether Polyketides ; }, abstract = {AIM: Invasive lobular carcinoma (ILC) is the second most common breast cancer type after invasive ductal carcinoma (IDC). Eribulin mesylate (eribulin) is a non-taxane microtubule dynamics inhibitor approved for advanced or metastatic breast cancer, including ILC and IDC. However, real-world data from eribulin-treated patients with advanced or metastatic ILC are scarce.

METHODS: This post hoc analysis of a Japanese multicenter, prospective, observational post-marketing surveillance (ClinicalTrials.gov: NCT02371174) evaluated data from eribulin-treated patients with ILC or IDC. Overall survival (OS) from the initiation of first-line chemotherapy, OS from the first date of eribulin administration, and time-to-treatment failure (TTF) were evaluated. OS from eribulin initiation was also evaluated by line of eribulin treatment (first-line, second-line, and third-line or later). Adverse drug reactions (ADRs) with ≥ 5% frequency in both groups were evaluated.

RESULTS: Among patients with ILC (n = 33) and IDC (n = 543), median OS from the initiation of first-line chemotherapy was 25.5 and 39.0 months, respectively (hazard ratio 1.94 [95% confidence interval 1.28-2.94]; p < 0.05), median OS from the first date of eribulin administration was 16.0 and 18.0 months, respectively (1.31 [0.87-1.97]), and TTF was 6 and 5 months (0.92 [0.65-1.32]). No significant differences were observed in median OS when stratified by line of eribulin treatment. Type and frequency of ADRs did not differ significantly between the groups.

CONCLUSION: OS and TTF after eribulin initiation were similar between ILC and IDC cases, suggesting that eribulin might be a beneficial treatment option for ILC.}, } @article {pmid40399365, year = {2025}, author = {Kondru, JB and Obulesu, YP}, title = {Comprehensive performance analysis of an electric vehicle using multi-mode Indian drive cycles.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {17699}, pmid = {40399365}, issn = {2045-2322}, abstract = {The constant advancements in the research and development society of vehicle manufacturing made the customer's attention towards EV ownership due to the better economic profile in the view of maintenance and operations. Even though the vehicles have better features the performance of the EV can be estimated with the consideration of the designed drive cycle for the region. According to that the procurement of EVs should be in the approved range of drive cycles with the concern of application. Based on that the article has concentrated on the performance of EV in the view of driving range and energy consumption of the battery for passenger transport applications. To observe the operational attributes of EV the assessment methodology was implemented for three Indian drive cycles (IDC) specifically on IUDC, MIDC, and IHDC. The quantitative assessment has been applied for the specifications of a 106-kW drive powered by the 30.2 kWh battery EV in the operational sequence model of three driving scenarios (aggressive, moderate, and slow) for a distance of 100 km with a four-wheel structure. To provide the vehicle statistics the assessment attempts the execution of performance parameters pictorially with the logistics of software evaluations for a particular average speed range of 21.2-50.02 km/h. From the assessment, it can be realized that the energy consumption of batteries is allowable in the range of 0.129-0.171 kWh/km for EV four-wheelers.}, } @article {pmid40395698, year = {2025}, author = {Hamze, M and Alawa, J and Alahdab, F and Al-Shemali, A and Alhussein, AN and Arab, NMA and Galal, B and Debel, J and Jemo, A and Khalil, M and Chagpar, A and Atassi, B and Khoshnood, K and Abbara, A}, title = {Breast Cancer Diagnosis and Management in an Area of Protracted Conflict: A Case Series from Northwest Syria.}, journal = {Avicenna journal of medicine}, volume = {15}, number = {1}, pages = {9-16}, pmid = {40395698}, issn = {2231-0770}, abstract = {Background Breast cancer remains a significant public health challenge in conflict-affected regions. This study aims to investigate the impact of armed conflict on the burden of breast cancer in female patients in northwest Syria, focusing on clinical presentations, management, diagnosis, access to care, and treatment outcomes. Methods We conducted a retrospective analysis of breast cancer patients diagnosed at the Idlib Oncology Center between March 2017 and January 2022. Data were extracted from clinical files and analyzed in R. The study was conducted at the Idlib Oncology Center, the main referral center for cancer care in northwest Syria, serving a population of 4.6 million. Results A total of 192 patients were included, with a median age of 45.5 years (interquartile range [IQR]: 40-56). Of 108 patients, 56.5% were internally displaced. Most patients were diagnosed with invasive ductal carcinoma (81.3%), and the majority presented at stages II and III (34.8 and 59%, respectively). Among 192 patients, 95.8% underwent surgery, with 96.6% having a mastectomy and 90.7% receiving chemotherapy. The median interval from symptom onset to diagnosis was 100.5 days, that from diagnosis to surgery was 14.5 days, and that from surgery to radiotherapy was 229 days. No significant effect was observed for chemical weapon exposure or family loss on survival. Displacement was associated with significantly lower predicted survival (p = 0.0038; 95% confidence interval [CI]: 0.05064-0.2570). Conclusions This study highlights a high prevalence of late-stage breast cancer, a high rate of mastectomies, delayed access to radiotherapy, and long delays between diagnosis and treatment in northwest Syria. Displacement negatively affects survival rates. Additionally, the substantial lack of radiotherapy in patients needing it and prolonged intervals between treatments contribute to poorer outcomes. Establishing localized oncology services and increasing funding for cancer medications and radiotherapy would improve access to necessary oncology care in this region.}, } @article {pmid40394843, year = {2025}, author = {Raeisi, N and Saber Tanha, A and Jafari Zarrin Ghabaei, F and Barashki, S and Aryana, K}, title = {Favorable Palliative Effect of 177 Lu-FAPI-2286 in Two Breast Cancer Patients With Refractory Bone Pains.}, journal = {Clinical nuclear medicine}, volume = {50}, number = {9}, pages = {e564-e567}, doi = {10.1097/RLU.0000000000005753}, pmid = {40394843}, issn = {1536-0229}, mesh = {Female ; Humans ; *Bone Neoplasms/secondary/complications/radiotherapy ; *Breast Neoplasms/pathology/complications ; *Lutetium/therapeutic use ; *Pain/complications ; *Palliative Care ; Radioisotopes/therapeutic use ; }, abstract = {We present 2 women with advanced invasive ductal carcinoma who developed skeletal metastases despite extensive treatment, including surgery, chemotherapy, and hormonal therapy. Both patients experienced debilitating pain and were evaluated for bone palliation therapy using 177 Lu-FAPI-2286, after 99m Tc-FAPI-46 scintigraphy showed suitable uptake. Remarkably, both patients reported significant pain relief shortly after treatment. The only adverse effect noted was grade III thrombocytopenia in 1 patient. These cases highlight the potential of 177 Lu-FAPI-2286 in providing rapid and effective palliation for breast cancer patients suffering from refractory pain, suggesting further investigation into its role in theranostics and palliative care. In this report, we also conducted a comprehensive literature review on radio-ligand therapy with 177 Lu-FAPI in breast cancer.}, } @article {pmid40392351, year = {2025}, author = {Hu, P and Wu, X and Li, Y and Wei, F and Zeng, S and Xiao, Y and Liu, X and Liu, Z}, title = {Survival outcomes and prognostic factors of breast cancer spinal metastases: a retrospective study.}, journal = {Discover oncology}, volume = {16}, number = {1}, pages = {825}, pmid = {40392351}, issn = {2730-6011}, support = {BYSYZD2022023//Peking University Third Hospital/ ; Y73504-10//Peking University Third Hospital/ ; }, abstract = {PURPOSE: To investigate survival-related factors in patients with breast cancer spinal metastases (BCSM) within the context of multidisciplinary treatment.

METHODS: A retrospective cohort of 78 cases from July 2010 to December 2021 was recruited. These patients underwent surgery-based multidisciplinary treatment. Collected data included demographics, pathologies, symptoms, surgery-related data, adjuvant therapies, postoperative events, and survival data. The primary outcome was overall survival (OS). Kaplan-Meier survival curves were plotted. Univariate analysis employed the log-rank test, and post-hoc multivariate analysis utilized the Cox regression model.

RESULTS: The mean age was 50.9 years. 72 cases (92.3%) reported locoregional pain, and 30 cases (38.5%) presented with neurological dysfunction. The primary pathological subtype was invasive ductal carcinoma (83.3%).

SURGICAL PROCEDURES: total en-bloc spondylectomy (6.4%), debulking surgery (61.5%), palliative surgery (32.1%). Postoperatively, both pain and neurological function significantly improved (P < 0.05). Radiotherapy, endocrine therapy, chemotherapy/targeted therapy were given to 56.4%, 60.3%, 61.5% patients, respectively. The estimated OS was 50.0 months. Tomita's scores (P = 0.355) and Tokuhashi's scores (P = 0.461) showed no significant OS association. Univariate analysis indicated that preoperative neurological dysfunction (P = 0.003), postoperative neurological dysfunction (P = 0.051), adjuvant endocrine therapy (P = 0.025), and hormone receptor expression status (P = 0.009) were associated with patient survival. Multivariate analysis identified endocrine therapy as an independent protective factor for prognosis (aHR = 0.070, 95% CI 0.007-0.727, P = 0.026).

CONCLUSIONS: Patients with BCSM have experienced prolonged survival. Neurological status, adjuvant anti-drugs, and expression of hormone receptors played crucial roles in predicting survival. Conventional prognostic systems may require modification to incorporate these factors. However, this study has limitations inherent to its retrospective design, single-center cohort, and relatively small sample size, which may affect generalizability.}, } @article {pmid40389885, year = {2025}, author = {Ndlovu, AK and Kasvosve, I and Rantshabeng, PS and Sharma, K and Govender, D and Naidoo, R}, title = {Female breast cancer classification using immunohistochemistry biomarkers staining in Botswana.}, journal = {BMC cancer}, volume = {25}, number = {1}, pages = {893}, pmid = {40389885}, issn = {1471-2407}, support = {PhD Scholarship//University of Botswana, Human resources/ ; }, mesh = {Humans ; Female ; Botswana/epidemiology ; *Breast Neoplasms/classification/pathology/metabolism ; *Biomarkers, Tumor/metabolism ; Immunohistochemistry/methods ; Middle Aged ; Retrospective Studies ; Adult ; Aged ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {Breast cancer remains the most diagnosed cancer among women world-wide and a leading cause of cancer-related deaths accounting for 15% of deaths in 2018. Worldwide, the incidence increased from 1.4 million in 2011 to over 2 million in 2018 with a concomitant increase in mortality from 458,400 to 626,679 in the same period. Low- and middle-income countries, such as Botswana, have a disproportionate burden of breast cancer incidence and mortality and there is an urgent need to characterise the unique tumour molecular profiles that may be influencing mortality in these populations. Methods A retrospective study of 125 archived mastectomy specimens (from 2006 to 2009) from women with breast cancer in Botswana was conducted. We determined molecular characteristics of breast cancers by carrying out four immunohistochemistry (IHC)classification (PR, ER, HER2 receptors and Ki 67), cytokeratin 5/6 and EGFR1.Statistical software STATA and SPSS were used to determine the relationship between histology, IHC of biomarkers of interest. Results Out of 125 breast cancer tissues, the distribution of molecular subtypes were as follows: Luminal A (44/125; 35.2%), Luminal B (and TNBC (23/125; 18,4%), HER2 Enriched (17/125; 13.6%), and Luminal B HER2 Enriched (9/125; 7.2%), Basal (9/125; 7.2%), and CK5/6 was expressed by 12.8% (16/125) of tumours. Furthermore 6% of the tumours were basal positive luminal tumours. Morphological 76% of tumours were IDC-NOS and 24% were special type, majority were grade 2 (40%) followed by grade 1(30.4%), grade 3 (23.2%) was and mucinous types were 6.4%. Clinical staging and tumour involvement data were incomplete. Conclusion The discovery of basal positive luminal breast tumours in women from Botswana original not accounted for in the four distinct molecular subtype calls for an expanded antibody panel 6-IHC panel) in order to stratify women of African descent patients into good/poor prognostic groups. Characterising tumour subtypes will better inform optimal therapeutic regimens for women with breast cancer in Botswana.}, } @article {pmid40386043, year = {2025}, author = {Han, Y and Hu, X and Xiong, H and Zeng, L and Peng, Y and Su, T}, title = {CEP55 as a prognostic indicator and a predictive marker in oral squamous cell carcinoma.}, journal = {International journal of medical sciences}, volume = {22}, number = {10}, pages = {2446-2459}, pmid = {40386043}, issn = {1449-1907}, mesh = {Humans ; *Mouth Neoplasms/pathology/immunology/mortality/genetics/diagnosis ; *Biomarkers, Tumor/metabolism/genetics ; *Cell Cycle Proteins/metabolism/genetics ; Prognosis ; Female ; Male ; Middle Aged ; *Carcinoma, Squamous Cell/pathology/immunology/mortality/genetics ; Gene Expression Regulation, Neoplastic ; Aged ; *Squamous Cell Carcinoma of Head and Neck/pathology/immunology/mortality/genetics ; Lymphocytes, Tumor-Infiltrating/immunology ; Immunohistochemistry ; *Nuclear Proteins/metabolism ; }, abstract = {Objective: To investigate the role of CEP55 in the occurrence and development of oral squamous cell carcinoma (OSCC). Materials and Methods: Through the utilization of the online OSCC database and bioinformatic analysis, we examine CEP55 expression and its correlation with prognosis, pathways, and immune infiltration. CEP55 and other biomarkers were stained using immunohistochemical methods in 57 cases of OSCC and 44 cases of adjacent paired tissues, demonstrating the clear involvement of CEP55. Results: The expression levels of CEP55 were significantly higher in OSCC tissues compared to normal tissues. Additionally, higher levels of CEP55 were associated with a worse prognosis. CEP55 expression levels were significantly higher in OSCC tissues compared to normal tissues. Additionally, higher levels of CEP55 were associated with a worse prognosis. GSEA results indicated a correlation between CEP55 and the cell cycle. Immunohistochemical staining revealed a significant positive correlation between CEP55 and cell cycle-related protein markers (PCNA, P16, P21, and P53). Furthermore, CEP55 was found to significantly inhibit tumor immune infiltration. As a result, CEP55 expression decreased infiltration of 9 types of immune cells (iDC, mast cells, pDC, DC, Th17 cells, TFH, Treg, T cells, and neutrophils), while increasing infiltration of only 3 types of immune cells (Tcm, T Helper cells, and Th2 cells). Conclusion: The results suggest that CEP55 plays a crucial role in the progression of OSCC promoting cell cycle progression and suppressing immune infiltration.}, } @article {pmid40385773, year = {2025}, author = {Mokhtar, J and Almarzooqi, S and Tahlak, S and Grassi, V}, title = {Lateral Intercostal Artery Perforator Flap for Enhanced Aesthetic Outcomes in Breast-Conserving Surgery.}, journal = {Cureus}, volume = {17}, number = {4}, pages = {e82354}, pmid = {40385773}, issn = {2168-8184}, abstract = {Oncoplastic breast-conserving surgery (O-BCS) combines oncological safety with superior aesthetic outcomes, enabling women to maintain their breast contour following partial mastectomy and other procedures. The lateral intercostal artery perforator (LICAP) flap, a muscle-sparing technique, is a procedure that utilizes excess soft tissue below the armpit to fill the cavity remaining after a lumpectomy for tumors located in the outer quadrant of the breast. We present an exemplary case of a 45-year-old female who underwent O-BCS for multifocal invasive ductal carcinoma, followed by reconstruction with the LICAP flap. The patient exhibited exceptional aesthetic outcomes following the LICAP flap procedure, preserving a natural breast contour while achieving clear surgical margins and eliminating residual cancer tissue. The efficacy and versatility of the LICAP flap technique qualify it as an effective approach that addresses the reconstructive aspects of oncoplastic breast surgery, while also achieving a successful oncological response.}, } @article {pmid40379596, year = {2025}, author = {Soran, A and Gultekin, MB and Venkatesulu, BP and Barry, PN and King, C and Bhargava, R and Karanlik, H and Yildiz, F and Soyder, A and Goktepe, B and Senol, K and Guzel, C and Sen, E and Yeniay, L and Dag, A and Trabulus, DC and Coskun, A and Veliyeva, H and Utkan, Z and Demirors, B and Sezgin, E and Vargo, JA}, title = {Biologically Informed Decision-Making for PMRT in pT3N0M0 Luminal Breast Cancers (Protocol MF22-02): International Multicenter Real-World Data.}, journal = {Clinical breast cancer}, volume = {25}, number = {7}, pages = {e887-e896}, doi = {10.1016/j.clbc.2025.04.012}, pmid = {40379596}, issn = {1938-0666}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/radiotherapy/mortality/therapy/surgery ; Middle Aged ; Retrospective Studies ; Mastectomy ; Aged ; Adult ; *Neoplasm Recurrence, Local/epidemiology/pathology ; Neoplasm Staging ; Radiotherapy, Adjuvant/methods ; *Clinical Decision-Making ; Receptors, Estrogen/metabolism ; Follow-Up Studies ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; *Carcinoma, Ductal, Breast/pathology ; Chemotherapy, Adjuvant ; Prognosis ; Receptors, Progesterone/metabolism ; }, abstract = {BACKGROUND: Current guidelines do not list definitive recommendations for postmastectomy radiation therapy (PMRT) in patients with luminal pT3N0M0 breast cancer (BC). Increased data suggests de-escalation of radiation therapy (RT) in genomically defined biologically favorable luminal BCs. The goal of this study is to determine whether PMRT can be safely omitted for this specific subgroup of patients.

METHODS AND MATERIALS: Two hundred and 2 women from 16 centers with pT3N0M0 hormone receptor (HR) positive, HER2 negative BC who underwent mastectomy were retrospectively analyzed. No patients received neoadjuvant chemotherapy. Three patients were excluded because of positive surgical margins. Patients were divided into 2 groups: PMRT (n = 130) and no PMRT (n = 69). Groups were compared in terms of overall survival (OS), loco-regional recurrence (LRR) rate, and distant metastases (DM) in light of the Magee Equations Score (MS), menopausal status/age, axillary surgery, pathology, lymphovascular invasion (LVI), adjuvant chemotherapy, and adjuvant endocrine therapy.

RESULTS: The majority of the patients had invasive ductal carcinoma (49%, n = 98). There was no significant difference regarding tumor size, axillary surgery, and adjuvant endocrine therapy between the 2 groups (P = .82, P = .28, P = .12, respectively). LVI was 19% (n = 39), and it was greater in the PMRT group (25% vs. 10%; P = .01). Patients in the PMRT group received more chemotherapy (66% vs. 30%; P < .001), had more grade 3 tumors (28% vs. 9%, P = .005), and were more premenopausal (49% vs. 22%; P = .0001). At a median follow-up of 51.3 months for the no PMRT group and 65.9 months for the PMRT group (P = .041), 9% (n = 6) of patients from the no PMRT group and 2% (n = 3) from the PMRT group developed LRR (P = .047). There was no difference in local recurrence (1% in no PMRT group vs. 2% in PMRT group; P = .7) and distant recurrence (7% in no PMRT group vs. 3% in PMRT group; P = .16) in patients who received PMRT and no PMRT. Further comparison of the LRR in the no PMRT and PMRT groups in patients with an MS < 18 did not show a significant difference (3% vs. 4%; P = .64). However, among patients with an MS ≥ 18, no PMRT group had a higher LRR rate compared to the PMRT group (11% vs. 2%; P = .01). In patients with an MS ≥ 18, the administration of PMRT correlates with statistically significantly better LRR-free survival (HR 0.19; 95% CI 0.05-0.79; P = .02).

CONCLUSIONS: Our findings imply that when considering PMRT for patients with pT3N0M0, HR-positive, and HER2-negative BC, clinicians can benefit from a combination of pathological risk factors and recurrence prediction models. Patients with MS < 18 experience a comparable rate of recurrence irrespective of PMRT, while those with MS ≥ 18 have higher rates of LRR and thus should not omit PMRT.}, } @article {pmid40376199, year = {2025}, author = {Bian, Y and Song, C and Nie, Y and Shen, X and Hui, F and Yu, G}, title = {Breast cancer metastasis to the nasopharynx: A case report.}, journal = {Oncology letters}, volume = {30}, number = {1}, pages = {331}, pmid = {40376199}, issn = {1792-1082}, abstract = {Breast cancer is a leading cause of cancer-related mortality in women, with metastasis posing a significant clinical challenge. However, spread to the nasopharynx and nasal cavity is exceptionally rare. The current study presents the case of a 53-year-old woman diagnosed with invasive ductal carcinoma of the right breast, which later metastasized to the nasopharynx. Despite undergoing modified radical mastectomy, chemotherapy and endocrine therapy, the patient developed symptoms indicative of distant metastasis. The present study reviews the diagnostic and therapeutic approaches for such rare occurrences, offering insights into effective management. The study analyzes this case alongside previously reported instances with the aim of enhancing awareness and facilitating early detection and intervention.}, } @article {pmid40367329, year = {2025}, author = {Úbeda, B and Mensión, E and Ganau, S and Sitges, C and Macedo, M and Gasior, DM and Cebrecos, I and Sanfeliu, E and Bargalló, X}, title = {Second-Look Ultrasound: When Things Are Not Always as They Seem.}, journal = {Ultrasound quarterly}, volume = {41}, number = {2}, pages = {}, pmid = {40367329}, issn = {1536-0253}, mesh = {Humans ; Female ; Middle Aged ; Aged ; Retrospective Studies ; Adult ; *Ultrasonography, Mammary/methods ; *Breast Neoplasms/diagnostic imaging/pathology ; Aged, 80 and over ; Magnetic Resonance Imaging/methods ; Breast/diagnostic imaging/pathology ; Image-Guided Biopsy ; }, abstract = {The purpose of this study was to compare size, morphologic features, and degree of suspicion between findings at second-look ultrasound (SL-US) and additional lesions with histological confirmation detected on breast magnetic resonance imaging (MRI). We performed an observational retrospective study including women who underwent SL-US between January 2021 and August 2022. Size, morphology according to Breast Imaging Reporting and Data System (BI-RADS) lexicon, and BI-RADS categories were analyzed for MRI and US findings. Two hundred twenty-four consecutive patients (aged 29-88 years; mean, 59.2 years) underwent SL-US to identify 235 additional lesions detected on MRI. US identified 173 (73.6%) findings. US- guided biopsy was performed in 148 (85.5%) of the detected lesions, proving 56 (37.8%) malignant and 92 (62.2%) benign. Mean size was 15.2 mm on MRI and 9.4 mm on US. Foci and masses showed good correlation, whereas nonmass enhancements tended to appear larger on MRI, and this difference was statistically significant (P = 0.0001). Morphology showed a higher agreement in the case of foci and masses than with nonmass enhancements. BI-RADS categories agreed in 66 cases (44.6%), whereas in 61 cases (41.2%), the degree of suspicion was higher for MRI, and in only 21 cases (14.2%) were lesions more suspicious on US than on MRI. In conclusion, lesions detected at SL-US show a higher agreement in size and morphologic features for foci and masses than with nonmass enhancements and similar or lower degree of suspicion than on MRI; therefore, decision to perform a biopsy should be based primarily on MRI findings.}, } @article {pmid40364451, year = {2025}, author = {Nourbakshs, M and Du, L and Acosta, AM and Alaghehbandan, R and Amin, A and Amin, MB and Aron, M and Berney, D and Brimo, F and Chan, E and Cheng, L and Colecchia, M and Dhillon, J and Downes, MR and Evans, AJ and Harik, LR and Hassan, O and Haider, A and Humphrey, PA and Jha, S and Kandukuri, S and Kao, CS and Kaushal, S and Khani, F and Kryvenko, ON and Kweldam, C and Lal, P and Lobo, A and Maclean, F and Magi-Galluzzi, C and Mehra, R and Miyamoto, H and Mohanty, SK and Montironi, R and Nesi, G and Netto, GJ and Nguyen, JK and Nourieh, M and Osunkoya, AO and Paner, GP and Sangoi, AR and Shah, RB and Srigley, JR and Tretiakova, M and Troncoso, P and Trpkov, K and Van Der Kwast, TH and Zhang, M and Zynger, DL and Williamson, SR and Giannico, GA}, title = {Current practices in prostate pathology reporting: results from a survey of genitourinary and general pathologists.}, journal = {Histopathology}, volume = {87}, number = {2}, pages = {206-222}, pmid = {40364451}, issn = {1365-2559}, mesh = {Humans ; Male ; Pathologists/statistics & numerical data ; *Prostatic Neoplasms/pathology ; *Pathology, Clinical/standards ; Surveys and Questionnaires ; Neoplasm Grading ; *Practice Patterns, Physicians'/statistics & numerical data ; *Prostate/pathology ; }, abstract = {AIMS: Standardizing pathology reporting protocols through peer consensus review is critical for the best quality of care metrics. Reporting heterogeneity due to discrepancies among professional societies and practice patterns may lead to heterogeneous management and treatment approaches. This issue prompted a multi-institutional survey of pathologists to address potential similarities or differences in trends and practice patterns in prostate pathology reporting worldwide.

METHODS AND RESULTS: A REDCap survey was distributed among 175 pathologists worldwide, recruited through invitations and social media. The response rate among invited pathologists was 83%. The practice locations were as follows: North America (USA, Canada, and Mexico, 62%), Europe (17%), Australia/New Zealand (3%), Central/South America (2%), Asia (13%), and Africa (2%). Most pathologists practiced for <5 years (28%). A genitourinary (GU) pathology fellowship was completed by 37%, 58% practiced in a subspecialized setting, and 43% in academia. Reporting includes (63%) or subtracts (37%) intervening benign tissue. Both Gleason score and Grade Groups (GG)s were reported by 96% of responders, whereas 94% report percent pattern 4 (%4). Aggregate grading and volume estimation in undesignated cores with different grades in the same jar are reported by 73% and 54% for systematic biopsies, and 83% and 62% for targeted biopsies, respectively. Cribriform morphology was reported by 81%. For presumed intraductal carcinoma (IDC), 89% use basal cell markers when isolated (iIDC), 82% with GG1 cancer, and 37% with ≥GG2. iIDC or IDC associated with GG1 or with ≥GG2 was not graded by 90%, 78%, and 70%, respectively. In radical prostatectomies, 90% report %4, but only 53% report it if the overall grade is ≥7. A tumour with Gleason 3 + 3 = 6 and <5% pattern 4 was graded as GG2 by 64%. A <5% cutoff for defining tertiary pattern was used by 74%, and 80% report >5% pattern 4 or 5 as a secondary pattern. Grading was assigned based on the dominant nodule by 59%. Finally, reporting practices were significantly associated with demographic characteristics.

CONCLUSIONS: Although most issues are agreed upon, significant discordance is identified among societies and pathologists in different practice settings. We hope this survey will serve as the basis for future studies and new collaborative approaches to more standardized reporting practices.}, } @article {pmid40360413, year = {2025}, author = {Sakurai, K and Suzuki, S and Adachi, K and Hirano, T and Kubota, H and Sakamoto, A and Osakaya, A and Fujisaki, S and Ono, T and Tsuji, T}, title = {[A Case of Thyroid Cancer Discovered Incidentally after Breast Cancer Surgery].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {52}, number = {4}, pages = {339-341}, pmid = {40360413}, issn = {0385-0684}, mesh = {Humans ; Female ; Middle Aged ; *Thyroid Neoplasms/surgery/pathology/diagnosis ; *Breast Neoplasms/surgery/pathology ; Incidental Findings ; Carcinoma, Papillary/surgery ; Thyroid Cancer, Papillary ; Thyroidectomy ; Mastectomy ; *Carcinoma/surgery ; }, abstract = {The patient was a 51-year-old woman. A left breast tumor was detected during a health checkup and the patient was referred to our hospital. Upon arrival, a mobile mass measuring 17 mm in diameter was palpable in the CD region of the left breast. The mammogram showed a sawtooth mass. Ultrasonography revealed a hypoechoic mass with abundant blood flow. Needle biopsy revealed invasive ductal carcinoma. Systemic examination revealed masses in both thyroid lobes, and a fine-needle aspiration cytology diagnosis showed it to be benign. A left circular mastectomy and sentinel lymph node biopsy were performed. Pathological examination revealed a resection margin negative, ER negative, PgR negative, HER2 negative invasive ductal carcinoma, with a tumor diameter of 20 mm and 17.2% Ki-67 positivity. Thirty months after surgery, the left thyroid tumor showed a tendency to grow, and fine-needle aspiration cytology was performed again, which revealed a papillary carcinoma. A left thyroid lobectomy and lymph node dissection were performed. Pathological examination revealed that the patient had papillary thyroid cancer, T1aN0M0=Stage Ⅰ(<55y). Currently, 3 years after surgery, there is no evidence of metastasis or recurrence of either cancer.}, } @article {pmid40352795, year = {2025}, author = {Lee, SR and Lee, JH and Kang, HJ}, title = {Tumors arising from an axillary accessory breast: a 10-year retrospective cohort study at a single center.}, journal = {Annals of surgical treatment and research}, volume = {108}, number = {5}, pages = {302-309}, pmid = {40352795}, issn = {2288-6575}, abstract = {PURPOSE: Pathologic lesions may occur in an axillary accessory breast (AAB). This study aimed to evaluate the characteristics of tumors arising from AABs and to recommend appropriate treatment.

METHODS: This retrospective study involved 3,544 women (18-65 years old) with AAB at Damsoyu Hospital in Korea from 2014 to 2023. The patients were divided into an AAB with benign tumors (TAAB) group and an AAB without tumors (AAB) group, and the tumors' pathologies were reviewed. A core biopsy was performed on tumors with possible malignancy identified by preoperative ultrasonography. All patients underwent complete excision of accessory mammary gland (AMG) tissue, including tumors. The postoperative results were checked 6 months after surgery.

RESULTS: Fifty-two out of 3,554 patients had tumors confirmed by preoperative ultrasonography. Preoperative core biopsies were performed on 11 patients. Two patients had malignant tumors (invasive ductal carcinoma) identified by core biopsy. Fifty patients had benign tumors identified by postoperative pathological analysis (46 fibroadenomas, 2 fibrocystic changes, and 2 sclerosing adenoses). Carcinoma in situ was confirmed in 2 patients using postoperative pathological analysis. No patients in either group developed tumors in the axilla during the follow-up period. All patients were satisfied with the axillary pain relief and the disappearance of bulging lesions.

CONCLUSION: We recommend a core biopsy if preoperative ultrasonography indicates a possibly malignant tumor. AAB patients may experience tumors, pain, and bulging appearance of an AMG; thus, complete AMG excision is necessary.}, } @article {pmid40350661, year = {2025}, author = {Farzan, JJ and Guart, JA and Kulkarni, N and Roberts, S and De la Cruz-Ku, G and Czerniach, DR and Dinh, KH}, title = {Managing Necrotizing Soft-Tissue Infection in Breast Cancer: A Case of Emergency Toilet Mastectomy.}, journal = {The American journal of case reports}, volume = {26}, number = {}, pages = {e946669}, pmid = {40350661}, issn = {1941-5923}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery/complications/pathology ; Aged ; *Mastectomy/methods ; *Carcinoma, Ductal, Breast/surgery/complications ; *Soft Tissue Infections/surgery/etiology ; Debridement ; Necrosis ; }, abstract = {BACKGROUND This case report presents a rare instance of advanced breast cancer presenting with superimposed necrotizing soft-tissue infection (NSTI) and sepsis, uniquely managed with an emergency toilet mastectomy. Toilet mastectomies have become increasingly rare and controversial in modern surgical oncology and are generally limited to palliative indications. This report contributes to the limited literature on NSTI of the breast in the setting of malignancy and highlights the potential utility of toilet mastectomy as a palliative option for carefully selected patients with advanced breast cancer complicated by infection. CASE REPORT A 71-year-old woman presented with a large fungating right breast mass after 50 years of receiving no health care. She was septic, with clinical signs of NSTI. Emergency surgical intervention involved a toilet mastectomy with extensive debridement. Histopathological analysis confirmed high-grade invasive ductal carcinoma of the breast with skin involvement, ER/PR-positive, HER2-negative, pT4bN0Mx. Cultures were consistent with type 1 NSTI. The postoperative course was complicated, requiring prolonged ICU care, multiple debridements, and advanced wound management. Significant complications included septic shock, acute kidney injury, and wound dehiscence. CONCLUSIONS This case is notable for 3 key aspects: (1) NSTI and sepsis are rare but serious complications of advanced breast cancer, underscoring the need for clinicians to maintain a high index of suspicion for this condition; (2) timely and aggressive management of NSTI, regardless of its association with underlying malignancy, is critical for reducing morbidity and mortality; and (3) toilet mastectomy, although less commonly performed today, remains an appropriate palliative intervention in select cases.}, } @article {pmid40341568, year = {2025}, author = {Lossos, C and Sanchez, S and Nonogaki, H and Gabrielson, E and Cimino-Mathews, A and Maleki, Z}, title = {Assessment of Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 on Cell Blocks and Core Needle Biopsies in Metastatic Breast Cancer: A Real-World Experience.}, journal = {Acta cytologica}, volume = {69}, number = {4}, pages = {367-376}, doi = {10.1159/000546274}, pmid = {40341568}, issn = {1938-2650}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/metabolism ; *Receptors, Progesterone/analysis/metabolism ; *Erb-b2 Receptor Tyrosine Kinases/analysis/metabolism ; *Receptors, Estrogen/analysis/metabolism ; Biopsy, Large-Core Needle ; Middle Aged ; Adult ; Aged ; Aged, 80 and over ; *Biomarkers, Tumor/analysis ; Immunohistochemistry ; Young Adult ; Biopsy, Fine-Needle ; Retrospective Studies ; }, abstract = {INTRODUCTION: The status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) plays a crucial role in the management of patients with metastatic breast cancer. Herein we report our experience on ER, PR, and HER2 immunostains on cell block and core needle biopsy (CNB) specimens of metastatic breast cancers.

METHODS: Cytological samples of metastatic breast cancer with associated cell blocks or core needle biopsies were identified, on which ER, PR, or HER2 were ordered from 2019 to 2021. Both fine needle aspiration specimens and body effusion fluids were included. Patients' demographics, cancer histological subtype, biopsy site, specimen type (cell block or CNB) for immunohistochemistry and ER, PR, and HER2 expression were recorded.

RESULTS: 192 specimens from 177 patients were identified. Patients' mean age was 58.5 years (range 24-96). The majority of samples were obtained from patients with invasive ductal carcinoma. Staining was performed on core biopsies (n = 74/192, 38.5%) and on cell blocks (n = 118/192, 61.5%). Pleural fluid (n = 75) was the most commonly sampled site, followed by the liver (n = 48) and lymph nodes (n = 44). ER, PR, and HER2 were positive in 76.3%, 79.3%, and 13.2% of samples, respectively. Concordantly, ER+PR+HER2- was the most common sample phenotype. Seven samples had insufficient tissue to evaluate ER, PR, or HER2 status.

CONCLUSION: ER, PR, and HER2 immunohistochemical staining can be performed on cell block or CNB specimens of metastatic breast cancer and can provide reliable information to clinicians for optimal patient care.}, } @article {pmid40340873, year = {2025}, author = {Gao, Y and Ali, H and Hu, Z and Sun, H}, title = {Sarcoid-like Reaction in Breast Cancer Tumor Bed and Axillary Lymph Nodes Following Neoadjuvant Chemotherapy: A Case Report.}, journal = {Annals of clinical and laboratory science}, volume = {55}, number = {2}, pages = {281-285}, pmid = {40340873}, issn = {1550-8080}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/drug therapy/surgery ; *Neoadjuvant Therapy/adverse effects ; *Lymph Nodes/pathology ; Axilla/pathology ; Middle Aged ; Lymphatic Metastasis ; *Sarcoidosis/pathology ; *Carcinoma, Ductal, Breast/drug therapy/pathology ; }, abstract = {Although granulomatous change is not commonly seen in breast cancer tumor bed and/or lymph node after neoadjuvant chemotherapy (NCT), they may mimic lymph node metastasis or tumor progression or recurrence. We present a case of diffuse sarcoid-like reaction (SLR) developed in both the breast tumor bed and axillary lymph nodes after NCT. A postmenopausal Hispanic woman presented with a 11.4 cm left breast mass with swollen lymph nodes in her left axilla. A core biopsy of the breast mass was performed, leading to the diagnosis of grade 3 invasive ductal carcinoma. The tumor is negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receoptor-2 overexpression. The patient received NCT with three cycles of doxorubicin and cyclophosphamide, followed by weekly paclitaxel for 12 weeks. After NCT, the tumor in her left breast significantly reduced in size, but the lymph nodes remained swollen. She subsequently underwent left modified radical mastectomy. Histological examination of the treated tumor bed revealed residual invasive tumor with frequent non-caseating granulomatous change. The granulomatous reaction was also seen in several axillary lymph nodes, of which only one had residual metastatic tumor cells. Idiopathic granulomatous mastitis, sarcoidosis, and infective etiologies were excluded based on the patient's medical history, imaging, and histological findings. We report a case of localized SLR in response to NCT in breast cancer tumor bed and axillary lymph nodes. Recognizing this feature is important to avoid misdiagnosis and overtreatment of SLR as residual cancer.}, } @article {pmid40337425, year = {2025}, author = {Mohamed, NMI and Yousif, AME}, title = {The yield of axillary clearance in breast cancer in Khartoum locality -Sudan: a cross-sectional study.}, journal = {Annals of medicine and surgery (2012)}, volume = {87}, number = {5}, pages = {2589-2601}, pmid = {40337425}, issn = {2049-0801}, abstract = {OBJECTIVES: Axillary clearance is an established part of the management of breast cancer. The aim of this study was to determine the number of retrieved lymph nodes (LNs) after axillary clearance surgery.

METHODS: Over a 2-year period (January 2020-December 2022), data from 96 patients, who underwent axillary clearance surgery in Khartoum locality, were collected. Multivariate analysis was used to assess the yield of axillary clearance.

RESULTS: The mean of total number of retrieved LNs was 12.8, the mean of positive LNs was 2.6. There was statistical correlation between the total number of retrieved LNs and total number of positive LNs (P = 0.000). 53.1% of patients had stage II breast cancer, with 91% of them having invasive ductal carcinoma. Neoadjuvant chemotherapy decreased the total number of retrieved LNs (P = 0.001). No statistically significant correlation was found between previous axillary surgery and the number of the retrieved LNs (P > 0.05).

CONCLUSIONS: There were enough axillary LNs for histological studies; the total number of positive LNs increased with the increase in total number of retrieved LNs. Neoadjuvant chemotherapy reduced the yield of axillary clearance.}, } @article {pmid40337059, year = {2025}, author = {Kumar, N and Gera, K and Patel, P and Lakhera, KK and Singh, S and Gurjar, B and Kumar, A and Singhal, P and Gora, B and Sharma, RG}, title = {From Statistics to Stories: Unveiling the Epidemiology of Breast Carcinoma in Northwestern India.}, journal = {Indian journal of surgical oncology}, volume = {16}, number = {2}, pages = {543-549}, pmid = {40337059}, issn = {0975-7651}, abstract = {After receiving the pathology report for breast cancer, the first question most patients ask their doctor is about their journey ahead. The type of cancer and how it spreads can give us an idea of what to expect during follow-up. Unfortunately, there is a lack of reporting, management, and documentation of breast cancer cases in India, resulting in a shortage of information on the different types of breast cancer. To address this issue, a study was conducted to gain a better understanding of the pattern of breast carcinoma in Northwestern India. A total of 2619 breast cancer pathology reports were gathered from four major diagnostic centres in Northwest India. Out of all breast cancer patients, 97.74% (2560) were women, while men accounted for only 2.25% (59) of the sample. At the time of diagnosis, 72% of patients were in stages III and IV, while only 28% of patients were in the early stages of cancer (stages I and II). The most common type of breast cancer was infiltrating duct carcinoma (IDC), which constituted 80.71% (2114/2619) of all malignant lesions. infiltrating lobular carcinoma was the second most common pathology, accounting for 5.38% (141/2619) of all cases. The rarer pathologies had a presentation rate below 10%. Our study revealed the most common symptom as a painless lump. Significant majority presented in advanced stages. An alarming 20% presented with foul-smelling ulceration or fungation of the skin. Varied presentations of breast cancer subtypes were evident. As the age-old saying goes-the 'most common' is often ignored as a large portion of the researcher's attention is focused on 'rarer stuff'. Similarly, IDC being the commonest deserves most of our attention. Not just the histology but its grades too. The lack of awareness regarding the risk factors and early detection methods of breast cancer is unfortunately even prevalent in 49% of healthcare workers. What India needs are more data reporting, timely diagnostic strategies, standardized reporting for pathology, and guideline-based management strategies. Increasing data collection electronically in the coming years will help India in displaying more data.}, } @article {pmid40337051, year = {2025}, author = {Pai, S and Murthy, SV}, title = {Molecular Subtypes and Ki-67 index in Breast Carcinoma with Special Emphasis on Triple Negative Breast Cancer. A 3-year Study in a Tertiary Care Center.}, journal = {Indian journal of surgical oncology}, volume = {16}, number = {2}, pages = {478-490}, pmid = {40337051}, issn = {0975-7651}, abstract = {PURPOSE: Molecular subtyping of breast carcinoma and Ki-67 index has gained prominence in the recent past, as conventional factors such as surgical margins, tumor size, grade and lymph node involvement, are not sufficient to assess prognosis and make better therapeutic decisions. These subtypes include Luminal A, Luminal B, Triple Negative breast cancer (TNBC), and HER2-enriched subtypes. This study aimed to analyze the molecular subtypes and Ki-67 index in prognosis of breast carcinoma.

METHOD: This retrospective study was conducted in the department of Pathology in a tertiary care center over a period of 3 years. All invasive breast carcinomas (IDC) which were molecularly subtyped and Ki-67 indexed were included in the study. Statistical analysis was done using SPSS software.

RESULTS AND DISCUSSION: Out of 253 cases, 231 cases (91.3%) were IDC-NST and 22 cases (8.7%) were special types. Metaplastic and papillary tumors were associated with higher grade and high Ki-67 value. TNBC (35.2%) showing a majority of high-grade tumors, was the most prevalent subtype followed by Luminal A (32%) showing low grade, unlike other studies which showed luminal A to be most common subtype. The rare PR positive subtype was also observed in our study.

CONCLUSION: TNBC and HER 2-positive subtypes exhibited bad prognosis with higher histological grade, high Ki-67 index and higher age at presentation whereas Luminal A subtype, with lower grade and low Ki-67 index showed better prognosis. Thus, this vast array of predictive and prognostic information obtained by molecular subtyping will help clinicians in not only distinguishing between low-risk and high-risk subtypes but also in customization of the treatment and follow-up of the patients.}, } @article {pmid40332918, year = {2025}, author = {Basik, M and Cecchini, RS and De Los Santos, JF and Umphrey, HR and Julian, TB and Mamounas, EP and White, JR and Lucas, PC and Balanoff, CR and Tan, AR and Weber, JJ and Edmonson, DA and Brown-Glaberman, UA and Diego, EJ and Teshome, M and Matsen, CB and Seaward, SA and Wapnir, IL and Wagner, JL and Tjoe, JA and Thompson, AM and Wolmark, N}, title = {Breast Tumor-Bed Biopsy for Pathological Complete Response Prediction: The NRG-BR005 Nonrandomized Clinical Trial.}, journal = {JAMA surgery}, volume = {160}, number = {7}, pages = {723-731}, pmid = {40332918}, issn = {2168-6262}, support = {U10 CA180822/CA/NCI NIH HHS/United States ; U10 CA180868/CA/NCI NIH HHS/United States ; U24 CA196067/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; Biopsy, Large-Core Needle ; *Breast/pathology ; *Breast Neoplasms/pathology/therapy/diagnostic imaging ; *Carcinoma, Ductal, Breast/pathology/therapy ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Chemotherapy, Adjuvant ; Mammography ; Neoadjuvant Therapy ; Prospective Studies ; Pathologic Complete Response ; }, abstract = {IMPORTANCE: Use of modern neoadjuvant chemotherapy (NAC) regimens has markedly increased rates of pathologic complete response (pCR) in breast cancer, raising the question of whether surgical removal of the primary tumor is required for patients with pCR. For surgery to be omitted, one must be able to accurately predict pCR before surgery.

OBJECTIVE: To investigate if adding post-NAC core needle biopsy of the tumor bed to trimodality imaging in patients who have clinical complete response (cCR) will predict pCR (resolution of both invasive disease and ductal carcinoma in situ) in 90% or more cases.

This was a phase 2, prospective, nonrandomized clinical trial. Patients were enrolled from August 2017 to June 2019. This is the final analysis, which was completed in December 2023. The setting included academic and community hospital center members of NRG (ie, the National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group, and the Gynecologic Oncology Group) in the US and Canada. Patients with operable (T1-T3, stage I-III) invasive ductal carcinoma who completed NAC and achieved cCR and radiological complete response (rCR) or near rCR by mammography (mass ≤1 cm and no malignant microcalcifications), ultrasound (mass ≤2 cm), and magnetic resonance imaging (no mass with rapid rise or washout kinetics).

INTERVENTIONS: Patients underwent marker-directed stereotactic multiple-core needle biopsy of the tumor bed with marker placement before breast-conservation surgery.

MAIN OUTCOMES AND MEASURES: End points were negative predictive value (NPV) and sensitivity of the biopsy.

RESULTS: A total of 105 patients were enrolled with 101 evaluable (mean [SD] age, 52.8 [10.5] years); 77 patients (76.2%) were younger than 60 years, and all breast cancer subtypes were represented with 32 (31.7%) triple-negative breast cancer, 21 (20.8%) hormone receptor-positive/epidermal growth factor receptor 2 (ERBB2; formerly HER2)-negative (ERBB2-) breast cancer, and 46 (45.5%) ERBB2-positive (ERBB2+) breast cancer. In 101 evaluable patients, 36 had residual disease at surgery (pCR = 64%). With imaging criteria, NPV of the biopsy was 78.3% (95% CI, 67.9%-86.6%), and the sensitivity of the biopsy was 50% (95% CI, 32.9%-67.1%). In an exploratory subset analysis, the NPV in patients with ERBB2+ breast cancer was 90% (95% CI, 76.3%-97.2%). On retrospective central review, 62 of 101 enrolled patients met imaging eligibility criteria. In this exploratory post hoc analysis, NPV in these patients was 86.8% (95% CI, 74.7%-94.5%).

CONCLUSIONS AND RELEVANCE: These findings do not support breast conservation treatment without surgery based on the study criteria for cCR and rCR/near rCR by trimodality imaging and negative tumor-bed biopsy. Strict adherence to imaging criteria may be required to achieve acceptable predictive values.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03188393.}, } @article {pmid40332647, year = {2025}, author = {Azizi, A and Mansouri, N and Faridi, B and Ramezani, M}, title = {Male breast cancer: common biomarkers, clinicopathology, and outcomes in the west of Iran.}, journal = {Journal of the Egyptian National Cancer Institute}, volume = {37}, number = {1}, pages = {35}, pmid = {40332647}, issn = {2589-0409}, mesh = {Humans ; *Breast Neoplasms, Male/pathology/therapy/mortality/epidemiology/diagnosis/metabolism ; Male ; Middle Aged ; Iran/epidemiology ; *Biomarkers, Tumor/metabolism ; Cross-Sectional Studies ; Adult ; Retrospective Studies ; Aged ; Neoplasm Staging ; Prognosis ; *Carcinoma, Ductal, Breast/pathology/therapy/epidemiology/mortality ; Survival Rate ; }, abstract = {BACKGROUND: Male breast cancer is a rare disease that accounts for less than 1% of all cancers in men and less than 1% of all diagnosed breast cancers. We retrospectively evaluated clinicopathologic features, treatment options, and overall survival in male breast cancer cases over 10 years (2012-2021).

METHODS: In this descriptive-cross-sectional study, the men with a breast cancer patient information based on demographic characteristics, type of surgery performed, pathological characteristics of samples (including the type of tumor involving lymph nodes and its grade), distant metastasis, immunohistochemical markers as well as family history of cancer, number of chemotherapy and radiotherapy sessions, use of anabolic drugs, and patient survival after surgery were recorded in the designed checklist.

RESULTS: The results showed that the mean age of men with breast cancer was 56.14 ± 14.59. Invasive ductal carcinoma was diagnosed in 86.3% of patients. In addition, metastasis occurred in 23.5% of patients, and most metastases occurred in the liver and then in the bone marrow, respectively. The highest frequency was related to stage IIB, with a frequency of 29.4%. The overall survival rate of 1, 3, and 5 years for 51 cases was 96%, 91%, and 65%, respectively, with an average survival period of 96 months. There was a significant relationship between age, metastasis, and disease stage with the survival status of patients (P = 0.03).

CONCLUSIONS: In the present study, old age, higher stage, and metastasis in male breast cancer were associated with unfavorable survival.}, } @article {pmid40325205, year = {2025}, author = {Bhagwat, A and Dutta, S and Saha, D and Reddy, MJB}, title = {An online 11 kv distribution system insulator defect detection approach with modified YOLOv11 and mobileNetV3.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {15691}, pmid = {40325205}, issn = {2045-2322}, abstract = {With the advent of smart distribution grids, detection of defects in insulators with unmanned aerial vehicles as a part of distribution automation system (DAS) has attained a widespread attention. The defects are essential to detect to avoid damaging the service life of distribution lines, serious power loss and cascading power outages in extreme conditions. The intricate background, limited image dataset and small-scale object makes the problem of detection more complex. Owing to the exponential advancement in deep learning, deep learning-based insulator defect detection is gradually attaining a foothold in the research domain. This paper presents a novel approach for detecting insulator defects in an 11 kV distribution system using a modified version of You Only Look Once (YOLO V11) and the MobileNetV3 model. Data augmentation was applied as part of the preprocessing phase to train the proposed model. The model's performance was compared with earlier versions of YOLO and other existing methods to demonstrate its effectiveness. Additionally, multiple case studies were conducted to validate the method's robustness and reliability for insulator defect detection. This paper incorporates a modified version of YOLOv11 architecture using the constituent C3K2, SPFF and C2PSA algorithmic blocks, mounted with a MobileNetV3 classifier to allow lightweight framework in DAS based devices. Studies involving various real-life scenarios show the efficacy and applicability of the proposed algorithmic pipeline.}, } @article {pmid40314919, year = {2025}, author = {Takano, Y and Mizuno, K and Iwase, M and Morita, S and Torii, N and Kikumori, T and Ando, Y}, title = {Tumor mutational burden status and clinical characteristics of invasive lobular carcinoma of the breast.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {32}, number = {4}, pages = {816-825}, pmid = {40314919}, issn = {1880-4233}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/mortality ; Middle Aged ; *Carcinoma, Lobular/genetics/pathology ; *Biomarkers, Tumor/genetics ; Mutation ; *Carcinoma, Ductal, Breast/genetics/pathology ; Aged ; Adult ; Tumor Burden/genetics ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: High tumor mutational burden (TMB-H) is an established biomarker for a favorable response to immune checkpoint inhibitors. However, tumor mutational burden (TMB) in invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) has not been sufficiently investigated.

METHODS: We collected data of patients with ILC or IDC from the Center for Cancer Genomics and Advanced Therapeutics database between June 2019 and August 2023. Furthermore, we examined the clinicopathological factors and TMB status.

RESULTS: Patients with ILC (n = 170) had a median TMB score of 4.00 mut/Mb (interquartile range, 2.00-7.14 mut/Mb), whereas those with IDC (n = 2598) had a score of 3.90 mut/Mb (2.00-6.00 mut/Mb). TMB-H was more common in patients with ILC than in those with IDC (18.2% vs. 10.1%, P < 0.001), particularly in the ER+ /HER2- subtype. Multivariate analysis revealed that the pathological diagnosis of ILC (P = 0.006), tissue samples collected from metastatic sites (P < 0.001), and older age (50 years, P < 0.001) were independent factors for TMB-H.

CONCLUSIONS: Patients with ILC were more likely to have TMB-H than those with IDC. The findings of this study would be invaluable in selecting treatment strategies for patients with ILC.}, } @article {pmid40314623, year = {2025}, author = {Poppe, MM and Boucher, K and Gaffney, DK and Brownson, KE and Smith, G and Howell, JN and Ticona, FF and Kim, J and Burt, L and Cannon, D and Kokeny, K}, title = {NOVEMBER, A Phase 2 Trial of a 9-Day Course of Whole Breast Radiation Therapy With a Simultaneous Lumpectomy Boost for Early-Stage Breast Cancer.}, journal = {International journal of radiation oncology, biology, physics}, volume = {123}, number = {1}, pages = {141-149}, doi = {10.1016/j.ijrobp.2025.03.078}, pmid = {40314623}, issn = {1879-355X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Middle Aged ; *Breast Neoplasms/radiotherapy/pathology/surgery ; *Carcinoma, Ductal, Breast/radiotherapy/pathology/surgery ; Dose Fractionation, Radiation ; *Mastectomy, Segmental/methods ; Neoplasm Staging ; Patient Satisfaction ; Prospective Studies ; }, abstract = {PURPOSE/OBJECTIVES: A phase 2 prospective noninferiority trial evaluating a novel 9 fraction course of whole breast radiation and simultaneous lumpectomy boost.

MATERIALS AND METHODS: Tis and T1-3N0 patients enrolled to receive 3420 cGy radiation to the breast with 3960 cGy to the lumpectomy cavity. The primary endpoint was averaged photographic cosmetic scores at 24 months with a hypothesis of >70% good to excellent cosmetic breast scoring 24 months after completing radiation, assuming a baseline excellent/good cosmetic scoring of 80% with an 80% power, α = 0.1.

RESULTS: From 2018 to 2020, with institutional review board approval, 103 patients were enrolled. Patients had mostly invasive ductal carcinoma (75%), tumor size ≤ 2cm (88%), negative margins (92%), no lympho-vascular invasion (80%), and estrogen receptor positive (85%). Patients had a mean age of 59.5 years (33-82). With a mean follow-up of 51 months, there were no local recurrences and 1 patient with both regional (axilla) and distant (brain) recurrence. Twenty-four-month post-radiation therapy (RT) cosmetic photos were 68% excellent/good, and 32% fair/poor. The null hypothesis was not rejected with one-sided 95% exact binomial confidence interval of 59.1% (59.1%-100%). There were no reported late ≥grade 3 radiation toxicity events and only 4 patients with late grade 2 events. Patient-reported outcomes utilizing the Breast-Q survey revealed breast satisfaction in 85% of women.

CONCLUSIONS: We demonstrate an effective novel 9 fraction whole breast + lumpectomy boost radiation schedule. This trial uses one of the shortest published radiation schedules for a lumpectomy boost. Although we did not meet our prespecified cosmetic endpoint, no significant cosmetic change from baseline was seen in 80% of patients. We demonstrate excellent local control, and patient-reported satisfaction with low RT-related toxicity. We hope to move this concept forward in a randomized trial against the 5-day United Kingdom (UK) Fast Forward regimen, inclusive of a simultaneous lumpectomy cavity boost.}, } @article {pmid40313479, year = {2025}, author = {Fukada, R and Murakami, A and Wada, T and Inari, H and Yoshida, T}, title = {Epithelioid Malignant Peripheral Nerve Sheath Tumor of the Breast with Breast Cancer in the Contralateral Breast: A Case Report.}, journal = {Case reports in oncology}, volume = {18}, number = {1}, pages = {531-538}, pmid = {40313479}, issn = {1662-6575}, abstract = {INTRODUCTION: Malignant peripheral nerve sheath tumors (MPNSTs) are common in the peripheral nerves of the head, neck, and limbs, with few reports of their occurrence in the breasts, and the epithelioid type is rare. Here, we aimed to report a case of an epithelioid MPNST of the breast.

CASE PRESENTATION: A 76-year-old woman presented with bilateral breast masses. Pathological findings showed a 60-mm invasive ductal carcinoma (T3N0M0 stage IIB) on the right breast and an epithelioid MPNST on the left breast. After surgical resection, the patient was treated with endocrine therapy alone for right breast cancer, and no recurrence was observed 4 years after surgery.

CONCLUSION: Reports of MPNSTs in the breasts are rare. The pathological analysis showed atypia of spindle cells, positive staining for vimentin, S100, SOX10, and epithelial-like cells, and positive staining for cytokeratin AE1/AE3. H3K27me3 is reportedly absent in typical MPNSTs; however, it is expressed in epithelioid types. It sometimes occurs in patients with a germline mutation in SMARCB1/INI1, where INI1 is absent in tumor cells. In this case, the tumor cells expressed H3K27me3 and also maintained INI1.}, } @article {pmid40308712, year = {2025}, author = {Canzani, F and Alquati, S and Bordin, F and Barillaro, C and De Angelis, M and Di Silvestre, G and Dispenza, S and Gobber, G and Magnani, C and Manno, P and Cosci, F and Tanzi, S}, title = {Translation and Cross-Cultural Adaptation of the Instrument for the Diagnosis of the Complexity of Palliative Care Needs.}, journal = {Palliative medicine reports}, volume = {6}, number = {1}, pages = {187-195}, pmid = {40308712}, issn = {2689-2820}, abstract = {BACKGROUND: In recent years, the palliative care (PC) paradigm is evolving from a prognosis-based approach to one centered on complexity, also in response to the aging population and the increase in chronic diseases. It is therefore necessary to strengthen PC networks with effective management of the specialist resources available. The use of tools such as the spanish Diagnostic Instrument for Complexity in Palliative Care (IDC-Pal) can help evaluate the complexity of PC needs, thus guiding the clinical care response. The aims of this study were the translation and the cultural adaptation of the IDC-Pal tool to the Italian language.

METHODS: The methodology proposed by Beaton et al. and Sousa et al. was used for the translation and cultural adaptation of the IDC-Pal tool. Phase 1: a forward-backward translation with linguistic and cultural adaptation of the tool by two native Spanish translators and two native Italian translators, including two PC professionals and two nonprofessionals, was performed. Phase 2: the translation was evaluated by a panel of 12 Italian PC experts, who assessed the comprehensibility of the translated instrument, and proposed changes to the text, which was found to be incomprehensible to at least 20% of them. Phase 3: this version of the tool was proposed to a sample of the Italian target population (93 professionals including general practitioners, nurses, and hospital doctors at 9 Italian PC networks tested it on 168 patients in home and hospital settings), to evaluate its comprehensibility and usability. At the end of the experimental phase, a semi-structured interview was organized with the main researcher of each network, with the aim of receiving information about the comprehensibility of the tool. Finally, a definitive version was developed.

RESULTS: The translation and adaptation were achieved without major problems.

CONCLUSIONS: A conceptually, culturally, and linguistically equivalent italian version of the original IDC-Pal was obtained.}, } @article {pmid40307530, year = {2026}, author = {Carletti, F and Maggi, M and Fazekas, T and Rajwa, P and Nicoletti, R and Olivier, J and Preisser, F and Soeterik, TFW and Giganti, F and Martini, A and Heidegger, I and Kasivisvanathan, V and Pradère, B and Ploussard, G and Hadaschik, B and Moro, FD and van den Bergh, RCN and Marra, G and Gandaglia, G and Zattoni, F and Kesch, C and , }, title = {Diagnostic accuracy of multiparametric MRI for detecting unconventional prostate cancer histology: a systematic review and meta-analysis.}, journal = {European radiology}, volume = {36}, number = {1}, pages = {17-29}, pmid = {40307530}, issn = {1432-1084}, mesh = {Humans ; *Prostatic Neoplasms/pathology/diagnostic imaging ; Male ; *Multiparametric Magnetic Resonance Imaging/methods ; Sensitivity and Specificity ; }, abstract = {BACKGROUND AND OBJECTIVE: Accurate detection of unconventional histologies (UH) in prostate cancer (PCa) is crucial for treatment planning and prognosis. This systematic review and meta-analysis aimed to evaluate the accuracy of multiparametric magnetic resonance imaging (mpMRI) in detecting UH on prostatectomy, particularly cribriform architecture (CA) and intraductal carcinoma (IDC-P), in patients with localized PCa.

METHODS: A literature search was conducted in major databases for studies published after 2000. Seventeen articles fulfilled the inclusion criteria and were eligible for qualitative analysis. Five studies met the inclusion criteria for meta-analysis.

RESULTS: The pooled sensitivity and specificity of mpMRI (Prostate Imaging Reporting and Data System (PI-RADS) cutoff 3) to detect cribriform architecture were 0.91 and 0.29. The proportion of cribriform lesions increased with higher PI-RADS scores (23.2% for PI-RADS 1-2 to 66.7% for PI-RADS 5). For intraductal carcinoma (IDC-P), two studies found that IDC-P lesions were visible on mpMRI and had lower apparent diffusion coefficient (ADC) values compared to acinar prostate cancer. Four studies evaluating combined CA/IDC-P found sensitivities ranging from 33 to 100%. Lower ADC values were associated with CA/IDC-P in some studies, but not in others. Overall, mpMRI demonstrated promising sensitivity but moderate specificity in detecting these aggressive histological variants, with continued challenges in accurate sampling and characterization of mpMRI.

CONCLUSIONS: mpMRI shows high sensitivity but moderate specificity in detecting cribriform architecture in PCa, especially for high PI-RADS scores. These findings support the use of mpMRI for UH detection, but caution is advised in clinical interpretation. Larger prospective studies are needed to validate these results before routine clinical application. We studied how effective MRI is at identifying different UH of PCa, such as cribriform architecture and intraductal carcinoma. MRI is accurate at detecting these cancers when they are present, but it also produces a significant number of false positives. More research is needed to standardize imaging protocols and histological definition and ensure an accurate diagnosis.

KEY POINTS: Question The accurate detection of unconventional histologies in prostate cancer, particularly cribriform architecture and intraductal carcinoma, is challenging but crucial for treatment planning and prognosis. Findings mpMRI shows high sensitivity (91%) but low specificity (29%) for detecting cribriform architecture, with detection rates increasing proportionally with higher PI-RADS scores. Clinical relevance mpMRI can effectively detect aggressive unconventional histologies in prostate cancer, though its moderate specificity suggests the need for careful interpretation. This aids in risk stratification and treatment planning, potentially improving patient outcomes.}, } @article {pmid40302091, year = {2025}, author = {Al-Naqqash, M and Kareem, TF and Al-Bairmany, Y and Al-Serarati, W and Alshewered, A}, title = {Survival Values of Iraqi Male Breast Cancer.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {26}, number = {4}, pages = {1379-1384}, pmid = {40302091}, issn = {2476-762X}, mesh = {Humans ; *Breast Neoplasms, Male/mortality/pathology/therapy ; Male ; Middle Aged ; Iraq/epidemiology ; Retrospective Studies ; Survival Rate ; Follow-Up Studies ; Adult ; Prognosis ; Aged ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; *Neoplasm Recurrence, Local/pathology/mortality ; }, abstract = {BACKGROUND: Male breast cancer (mBC) is a rare disease, accounting for approximately 1% of all breast cancers. In Iraq, the mBC rate was 0.39% for all cancer types by 2022. This study aimed to estimate the survival rates and features of mBC in Iraq.

METHODS: This was a retrospective survival study. Males with BC were treated between March 2020 and March 2024 at the Department of Radiation Oncology and Department of Medical Oncology. The following data were collected from the records: age, marital status, family history, body mass index, surgery type, chemotherapy, radiotherapy, hormonal therapy, recurrence and/or metastasis, period of follow-up, histological type, tumor size, tumor grade, tumor stage, estrogen and/or progesterone receptor expression, HER2 neu status, metastasis site, BC side, and lymph node positivity.

RESULTS: The mean age of the patients was (54.75 ±12.25). The majority (95.7%) of the patients were married, and only (17.4%) of patients presented with a positive family history. Most patients underwent surgery (21, 91.3%), chemotherapy (19, 86.4%), radiotherapy (13, 59.1%), and hormonal therapy (15, 68.2%). The mean follow-up was (30.73 ± 24.55) months. The majority (16, 88.9%) of the patients presented with positive PR and ER, and most (11, 64.7%) presented with negative HER-2. The lungs, bones, surgical beds, and multiple sites represented metastasis.

CONCLUSION: The mean age of Iraqi male breast cancer patients was in the upper middle age. Most patients presented with T2 N0 stage, ER/PR positivity, and Her2neu negative. Grade II right invasive ductal carcinoma was reported in half of the men. The median follow-up period was 30 months. Disease free survival (DFS) after full treatment was 75 months.}, } @article {pmid40299211, year = {2025}, author = {Shan, Y and Hou, F and Wang, Y and Han, Y and Cui, Z and Yin, G}, title = {Cervical metastasis of breast cancer: a case report and review of the literature.}, journal = {Discover oncology}, volume = {16}, number = {1}, pages = {633}, pmid = {40299211}, issn = {2730-6011}, abstract = {Metastatic breast cancer (BC) to the cervix is relatively rare among women with BC. Although the most common histopathological type of BC is invasive ductal carcinoma, invasive lobular carcinoma is more likely to metastasize to the female reproductive system due to its characteristic of the loss of E-cadherin. BC patients with metastasis to the cervix often exhibit no obvious clinical symptoms or may present with cervical-related symptoms, making early diagnosis challenging. CDK4/6 inhibitors, when combined with either aromatase inhibitors or fulvestrant, can enhance the prognosis for both premenopausal and postmenopausal women with recurrent ER-positive BC. We reported a patient with cervical metastasis of BC, who was ER-positive and HER2-negative. The patient received treatment with fulvestrant and abemaciclib after surgery for metastatic cervical cancer, achieving a progression-free survival of 31 months. We hope this case report will encourage more clinicians to prioritize gynecological examinations for patients with BC, particularly cervical cancer screening, in order to enhance the quality of life and prognosis for these individuals.}, } @article {pmid40298601, year = {2025}, author = {Kim, HJ and Choi, WJ and Eom, HJ and Chae, EY and Shin, HJ and Cha, JH and Kim, HH}, title = {Impact of Preoperative MRI on Survival Outcomes in Patients with HER2-positive and Hormone Receptor-negative Breast Cancer.}, journal = {Radiology}, volume = {315}, number = {1}, pages = {e242712}, doi = {10.1148/radiol.242712}, pmid = {40298601}, issn = {1527-1315}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/mortality/surgery/metabolism ; *Magnetic Resonance Imaging/methods ; Middle Aged ; Retrospective Studies ; Aged ; *Erb-b2 Receptor Tyrosine Kinases/metabolism ; Adult ; Aged, 80 and over ; Preoperative Care/methods ; Young Adult ; Breast/diagnostic imaging ; }, abstract = {Background Little is known regarding the impact of preoperative breast MRI on the long-term outcomes of patients with breast cancer that is human epidermal growth factor receptor 2 (HER2) positive and hormone receptor negative. Purpose To evaluate the impact of preoperative breast MRI on recurrence-free survival (RFS) and overall survival (OS) in patients with HER2-positive and hormone receptor-negative breast cancer by using propensity score matching. Materials and Methods This retrospective study included women diagnosed with HER2-positive and hormone receptor-negative invasive ductal carcinoma between January 2007 and December 2016. Patients who underwent preoperative MRI (the MRI group) were matched with those who did not (the no-MRI group) using propensity score matching based on 19 clinical-pathologic covariates. RFS and OS were compared using Kaplan-Meier estimates, Cox proportional hazards models, and inverse probability weighting. Results Among 1094 women (median age, 52 years; age range, 24-91 years), 47.81% (523 of 1094) underwent preoperative MRI. The rates of total recurrence and death were 14.3% (75 of 523) and 7.07% (37 of 523) in the MRI group, respectively, compared with 16.5% (94 of 571) and 13.1% (75 of 571) in the no-MRI group. In the propensity score-matched set, preoperative MRI was not associated with total recurrence (hazard ratio [HR], 0.69; 95% CI: 0.47, 1.02; P = .06), local-regional recurrence (HR, 0.94; 95% CI: 0.52, 1.70; P = .84), contralateral breast recurrence (HR, 0.55; 95% CI: 0.24, 1.25; P = .15), or distant recurrence (HR, 0.56; 95% CI: 0.31, 1.03; P = .06). OS was not higher with preoperative MRI (HR, 0.63; 95% CI: 0.39, 1.00; P = .05). At multivariable analysis, preoperative MRI was not associated with improved RFS (HR, 0.89; 95% CI: 0.67, 1.19; P = .44) or OS (HR, 0.73; 95% CI: 0.48, 1.10; P = .14). Conclusion Preoperative MRI did not improve RFS or OS in patients with HER2-positive and hormone receptor-negative breast cancer. © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Imbriaco and Ponsiglione in this issue.}, } @article {pmid40293750, year = {2025}, author = {Raghavendra, AS and Bassett, R and Damodaran, S and Barcenas, CH and Mouabbi, JA and Layman, R and Tripathy, D}, title = {Clinical Characteristics and Survival Outcomes of Metastatic Invasive Lobular and Ductal Carcinoma.}, journal = {JAMA network open}, volume = {8}, number = {4}, pages = {e251888}, pmid = {40293750}, issn = {2574-3805}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/mortality/pathology ; *Carcinoma, Lobular/mortality/pathology ; Adult ; *Carcinoma, Ductal, Breast/mortality/pathology ; Aged ; Cohort Studies ; Neoplasm Metastasis ; Retrospective Studies ; }, abstract = {IMPORTANCE: Comparing the clinical and molecular features of metastatic invasive lobular carcinoma (mILC) and metastatic invasive ductal carcinoma (mIDC) is essential to enhance understanding of breast cancer biology and improve personalized treatment approaches.

OBJECTIVE: To compare mILC and mIDC in terms of survival outcomes and to investigate the association of clinicopathologic characteristics with those outcomes.

This cohort study included adult patients at the University of Texas MD Anderson Cancer Center with their first metastatic diagnosis occurring between January 1997 and December 2020. Patient records were obtained from an institutional database. The study follow-up concluded in July 2023, and data were analyzed from July to December 2024.

EXPOSURE: Diagnosis of mIDC and mILC.

MAIN OUTCOMES AND MEASURES: Progression-free survival (PFS), overall survival (OS), and disease-free interval (DFI) were estimated using the Kaplan-Meier method. Survival distributions were compared using the log-rank test. Multivariable Cox proportional hazards regression was used to assess the association of metastasis onset, estrogen receptor (ER) expression level, and tumor grade with OS and PFS.

RESULTS: The analysis included a total of 9714 patients (9628 women [99%]), 8535 with mIDC and 1179 with mILC. The median age at metastasis was 53.3 years (range, 17.6-62.0 years). Generally, patients with mILC were older and had lower nuclear grade tumors and fewer metastasis sites than patients with mIDC. Patients with mILC had longer PFS (median, 0.65 years; 95% CI, 0.58-0.74) than patients with mIDC (median, 0.46 years; 95% CI, 0.45-0.48) (hazard ratio [HR], 0.78; 95% CI, 0.73-0.84; P < .001). For OS, patients with mILC had longer OS (median, 3.06 years; 95% CI, 2.87-3.29) than patients with mIDC (median, 2.60 years; 95% CI, 2.52-2.67 years) (HR, 0.91; 95% CI, 0.84-0.98; P = .01). Overall, patients with mILC had longer DFI than patients with mIDC (HR, 0.69; 95% CI, 0.64-0.75; P < .001). At initial diagnosis, patients with mILC were less likely to present with visceral metastasis (522 patients [44.3%]) than patients with mIDC (4909 patients [57.5%]). A higher proportion of patients with mILC (931 patients [79.0%]) than patients with mIDC (5431 patients [63.6%]) had bone-only metastasis.

CONCLUSIONS AND RELEVANCE: In this cohort study, patients with mILC had longer OS and PFS than those with mIDC. Metastasis onset, ER positivity, and tumor grade were associated with survival outcomes, and distinct metastatic patterns of mIDC and mILC were also associated with survival for mIDC and mILC, which may help guide more personalized treatment strategies for each subtype.}, } @article {pmid40292978, year = {2025}, author = {Wang, H and Shi, J and Wang, Q and Dong, L and Liu, H}, title = {Surface Crack Detection of Aluminum Alloy Using Injected Direct Current-Magnetic Field Measurement Method.}, journal = {Sensors (Basel, Switzerland)}, volume = {25}, number = {6}, pages = {}, pmid = {40292978}, issn = {1424-8220}, support = {52065026//National Natural Science Foundation of China/ ; 809B032101//Young Talent Fund Project of Joint Fund of the Ministry of Education for Equipment Pre-research/ ; }, abstract = {Injected Direct Current-Magnetic Field Measurement (IDC-MFM) is a promising nondestructive technique for crack evaluation of aluminum alloy due to its high sensitivity to defect states. Finite element simulation and experiment were introduced in this research to reveal the relationship between the magnetic field and the crack size. The finite element simulation showed that the magnetic field at the defect increased with the currents, and the peak-to-peak value of the tangential component magnetic field Bx (ΔBxpp) correlated with both the width and depth of the crack very well. The high-sensitivity tunnel magnetoresistance probe was used for crack detection of aluminum alloy specimens with different crack widths and depths, and the results show that the relationship between the ΔBxpp and the crack was consistent with the simulation results, and ΔBxpp has a nonlinear positive correlation with crack width and a linear positive correlation with crack depth. The results of the present work show that IDC-MFM has high sensitivity in crack size detection and is a feasible solution for the quantitative evaluation of cracks in aluminum alloy.}, } @article {pmid40291355, year = {2024}, author = {Singh, P and Khandelwal, Y and Bharti, K and Singh, S}, title = {An Uncommon Breast Odyssey: A Rare Case of Carcinoma Breast with Mesenteric Metastasis.}, journal = {Indian journal of nuclear medicine : IJNM : the official journal of the Society of Nuclear Medicine, India}, volume = {39}, number = {6}, pages = {463-465}, pmid = {40291355}, issn = {0972-3919}, abstract = {We present an unusual case of invasive ductal breast carcinoma in a postmenopausal female with a clinically node-negative disease that was incidentally found to have mesenteric metastatic deposits on [18]F-fluorodeoxyglucose positron emission tomography/computed tomography scan. Mesenteric metastasis from invasive breast carcinoma is rare, with <1% cases reported worldwide and limited availability of diagnostic and therapeutic protocols for carcinoma breast with mesenteric metastasis, this proved to be a challenging and intriguing case. To further accentuate the complexity, the primary tumor of this mesenteric metastasis was found to be invasive ductal carcinoma, which is even more infrequent, and <0.5% of cases have been reported till date.}, } @article {pmid40277687, year = {2025}, author = {Otake, H and Ogata, F and Nakazawa, Y and Misra, M and Tsubaki, M and Kawasaki, N and Nagai, N}, title = {Pharmacological Behavior of Propylene Glycol/Polyvinyl Alcohol Hydrogel Incorporating Indomethacin Nanocrystals in the Skin.}, journal = {Gels (Basel, Switzerland)}, volume = {11}, number = {4}, pages = {}, pmid = {40277687}, issn = {2310-2861}, support = {2024068087//Takeda Science Foundation Pharmaceutical Research Grants/ ; }, abstract = {BACKGROUND: We previously reported that carbopol hydrogels incorporating indomethacin nanoparticles (IMC NPs) improved the low permeability and bioavailability of skin formulations in transdermal drug delivery systems. However, the combination of NPs with other types of hydrogels has not been sufficiently explored to date. Therefore, this study investigated propylene glycol (PG)/polyvinyl alcohol (PVA) hydrogel as an alternative base to carbopol hydrogel for incorporating IMC NPs.

METHODS: IMC NPs were prepared using bead milling treatment, and these NPs were incorporated into PG/PVA hydrogel (IMC-NP@PG/PVA hydrogel). The IMC concentration was measured using the HPLC method, and seven-week-old Wistar rats were used to evaluate skin absorption.

RESULTS: Bead milling reduced the IMC particle size in the PG/PVA hydrogels to the nanoscale (30-200 nm) without altering its crystalline form. The IMC-NP@PG/PVA hydrogel exhibited enhanced uniformity, solubility, and drug release compared to the IMC microparticle-loaded PG/PVA hydrogel (IMC-MP@PG/PVA hydrogel), with a 1.44-fold greater area under the concentration-time curve. Transdermal permeability studies revealed that IMC-NP@PG/PVA had 2.36-fold higher absorption than the IMC-MP@PG/PVA hydrogel, with dissolved IMC permeating the skin. Pharmacokinetics in the rats showed significantly increased plasma levels, absorption rates, and bioavailability for IMC-NP@PG/PVA, demonstrating its superior delivery efficiency. Moreover, the skin absorption of IMC-NP@PG/PVA was higher than that of carbopol hydrogel.

CONCLUSIONS: These findings highlight the potential of PG/PVA hydrogels as an effective base for transdermal drug delivery systems based on NPs.}, } @article {pmid40272667, year = {2025}, author = {Switalla, KM and Falade, IO and Quirarte, A and Baxter, M and Kaur, M and Sakr, RA and Corso, G and Mukhtar, RA}, title = {Positive Margin Rates After Breast-Conserving Surgery by Histologic Subtype: A Systematic Review and Meta-analysis Evaluating the Impact of Oncoplastic Surgery.}, journal = {Annals of surgical oncology}, volume = {32}, number = {7}, pages = {4899-4909}, pmid = {40272667}, issn = {1534-4681}, support = {K08 CA256047/CA/NCI NIH HHS/United States ; K08CA256047/RC/CCR NIH HHS/United States ; }, mesh = {Female ; Humans ; *Breast Neoplasms/surgery/pathology ; *Carcinoma, Ductal, Breast/surgery/pathology ; *Carcinoma, Lobular/surgery/pathology ; *Mammaplasty ; *Margins of Excision ; *Mastectomy, Segmental ; Prognosis ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC), the second most common histologic subtype of breast cancer, has a higher risk of positive surgical margins than invasive ductal carcinoma (IDC). Whether this risk persists for patients undergoing breast-conserving surgery (BCS) with oncoplastic approaches remains unclear. We conducted a systematic review and meta-analysis to assess positive margins following oncoplastic BCS by histologic subtype and evaluate the impact of oncoplastic surgery on positive margins in ILC.

METHODS: We systematically searched the literature for articles reporting positive margin rates after oncoplastic BCS in ILC patients. Relative risks (RR) were log transformed and displayed with forest plots.

RESULTS: Eight studies, encompassing 754 ILC patients undergoing BCS (338 with oncoplastic surgery), were included. The pooled positive margin rate for ILC patients undergoing oncoplastic surgery was 31% (95% confidence interval [CI] 21-40%). Patients with ILC had a significantly higher RR for positive margins after oncoplastic BCS compared with IDC (RR 3.4, 95% CI 1.5-7.4). However, for ILC patients with larger tumors, oncoplastic BCS was associated with a significantly lower RR for positive margins compared with standard BCS (RR 0.5, 95% CI 0.3-0.9).

CONCLUSIONS: Invasive lobular carcinoma patients undergoing oncoplastic BCS have higher positive margin risks than IDC patients, underscoring the need for improved preoperative imaging and systemic therapies. However, the addition of oncoplastic surgery to BCS reduces positive margin rates compared with standard BCS in ILC patients, particularly for larger tumors. These findings highlight the role of oncoplastic surgery as an important technique to optimize outcomes for those at high risk of positive margins.}, } @article {pmid40272491, year = {2025}, author = {Cozzi, A and Di Leo, G and Houssami, N and Gilbert, FJ and Helbich, TH and Álvarez Benito, M and Balleyguier, C and Bazzocchi, M and Bult, P and Calabrese, M and Camps Herrero, J and Cartia, F and Cassano, E and Clauser, P and de Lima Docema, MF and Depretto, C and Dominelli, V and Forrai, G and Girometti, R and Harms, SE and Hilborne, S and Ienzi, R and Lobbes, MBI and Losio, C and Mann, RM and Montemezzi, S and Obdeijn, IM and Aksoy Ozcan, U and Pediconi, F and Pinker, K and Preibsch, H and Raya Povedano, JL and Rossi Saccarelli, C and Sacchetto, D and Scaperrotta, GP and Schlooz, M and Szabó, BK and Taylor, DB and Ulus, SÖ and Van Goethem, M and Veltman, J and Weigel, S and Wenkel, E and Zuiani, C and Sardanelli, F}, title = {Preoperative breast MRI for invasive ductal carcinoma with or without a DCIS component at needle biopsy: influence on surgical outcomes in the MIPA study.}, journal = {European radiology}, volume = {35}, number = {10}, pages = {6433-6443}, pmid = {40272491}, issn = {1432-1084}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Middle Aged ; Young Adult ; Biopsy, Needle ; *Breast Neoplasms/surgery/pathology/diagnostic imaging ; *Carcinoma, Ductal, Breast/surgery/pathology/diagnostic imaging ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery/diagnostic imaging ; *Magnetic Resonance Imaging/methods ; Mastectomy/statistics & numerical data ; Preoperative Care/methods ; Prospective Studies ; Treatment Outcome ; }, abstract = {OBJECTIVES: To analyse the impact of preoperative breast MRI on surgical outcomes of patients diagnosed with pure invasive ductal carcinoma (IDC) or IDC with an associated in situ component (IDC + ductal carcinoma in situ [DCIS]) at needle biopsy.

METHODS: Patients aged 18-80 years referred for upfront surgery after a diagnosis of pure IDC or IDC + DCIS at needle biopsy were retrieved from the Multicenter International Prospective Analysis (MIPA) database. In each subgroup, patients who underwent preoperative MRI (MRI groups) were matched 1:1 to those who did not (noMRI groups) according to eight confounding covariates. Surgical outcomes were compared with non-parametric statistics after calculating odds ratios (ORs).

RESULTS: Among 1051 patients with IDC + DCIS, 510 were retained after matching (255 in each group): in comparison to the noMRI group, the MRI group had significantly higher rates of first-line mastectomy (13.3% vs 6.3%; OR 2.30, p = 0.011) and of overall mastectomy (14.5% vs 7.5%; OR 2.11, p = 0.016), without significantly lowering the reoperation rate (9.4% vs 10.6%, OR 0.88, p = 0.768). Among 2459 patients with pure IDC, 1638 were retained after matching (819 in each group): the first-line mastectomy rate was not significantly higher in the MRI group (12.9% vs 12.1% in the noMRI group; OR 1.08, p = 0.654). Instead, the reoperation rate was significantly lower (2.6% vs 7.9%; OR 3.28 for avoiding reoperation, p < 0.001) with no increase in overall mastectomies (13.6% vs 13.7%: OR 0.99, p = 1.000).

CONCLUSIONS: In patients with IDC + DCIS, preoperative MRI did not reduce reoperations and increased mastectomies. Conversely, in patients with pure IDC, preoperative MRI reduced reoperations without increasing mastectomies.

KEY POINTS: Question The impact of preoperative breast MRI on surgical outcomes of patients with IDC at needle biopsy is controversial and lacks large-scale investigations. Findings For pure IDC at needle biopsy, MRI reduced reoperations without increasing mastectomies; for IDC + DCIS, MRI did not reduce reoperations and increased mastectomies. Clinical relevance In patients with IDC at needle biopsy, the decision to perform preoperative breast MRI should take into account the presence of associated DCIS, as the benefits of MRI on surgical outcomes were observed only in patients with pure IDC.}, } @article {pmid40272489, year = {2025}, author = {Goto, M and Le Bihan, D and Sakai, K and Yamada, K}, title = {Reduction of biopsy rate in BI-RADS4 breast lesions: potential of an abbreviated advanced DWI protocol.}, journal = {European radiology}, volume = {35}, number = {10}, pages = {6421-6432}, pmid = {40272489}, issn = {1432-1084}, support = {JP23K07211//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology ; Middle Aged ; Retrospective Studies ; *Diffusion Magnetic Resonance Imaging/methods ; Biopsy/statistics & numerical data ; Contrast Media ; Aged ; Adult ; Breast/diagnostic imaging/pathology ; Unnecessary Procedures/statistics & numerical data ; }, abstract = {OBJECTIVES: This study compared the diagnostic performance of diffusion biomarkers estimated from an abbreviated diffusion-weighted imaging (DWI) protocol and assessed their potential to reduce unnecessary biopsies of benign BI-RADS 4 lesions identified on dynamic contrast-enhanced (DCE) MRI.

METHODS: A retrospective study was conducted from 2019 to 2023. All patients underwent abbreviated DWI at 3 T with four b-values (0 s/mm[2], 200 s/mm[2], 800 s/mm[2], and 1500 s/mm[2]). Regions of interest were manually placed on DWI, and biomarkers, including the apparent diffusion coefficient (ADC0-800), perfusion fraction intravoxel incoherent motion, non-Gaussian diffusion (ADC0 and kurtosis [K]), signature index (S-index), and shifted ADC (sADC), were estimated. Diagnostic performance and the potential to reduce unnecessary biopsies were evaluated for each parameter.

RESULTS: In total, 168 female patients (mean age ± standard deviation, 56.2 ± 13.5 years) with 178 BI-RADS 4 lesions on DCE MRI were analyzed. The median ADC0-800, sADC, and ADC0 were significantly lower in malignant lesions, while S-index and K were significantly higher (all p ≤ 0.001). The diagnostic performance to reclassify lesions as benign or malignant was identical for ADC0-800 (area under the curve = 0.67), sADC (0.69), S-index (0.69), ADC0 (0.68), and K (0.66). Applying an ad-hoc threshold cutoff, all parameters reduced unnecessary biopsies (around 16%), while K resulted in a slightly higher reduction rate than ADC0-800 (20.5% vs 15.9%, p = 0.317) without reducing sensitivity.

CONCLUSION: Diffusion MRI biomarkers obtained using an abbreviated DWI protocol reduced unnecessary biopsies in BI-RADS 4 lesions, with K performing slightly better than ADC.

KEY POINTS: Question MRI BI-RADS category 4 includes a substantial number of benign lesions, and reducing unnecessary biopsies remains a critical clinical concern. Findings The parameters from abbreviated DWI show lesion differentiation comparable to ADC and have greater potential to reduce unnecessary biopsies. Clinical relevance This study underscores the potential of imaging biomarkers from abbreviated DWI for assessing breast MRI BI-RADS 4 lesions. These biomarkers may be comparable or superior to standard ADC in reducing unnecessary biopsies and could aid in improving patient management decisions.}, } @article {pmid40270907, year = {2025}, author = {Šantrůček, J and Kubásek, J and Janová, J and ŠantrůčKOvá, H and Altman, J and Tumajer, J and Hrádková, M and Cienciala, E}, title = {Response of leaf internal CO2 concentration and intrinsic water-use efficiency in Norway spruce to century-long gradual CO2 elevation.}, journal = {Photosynthetica}, volume = {63}, number = {1}, pages = {51-63}, pmid = {40270907}, issn = {1573-9058}, mesh = {*Picea/metabolism/physiology ; *Carbon Dioxide/metabolism ; *Plant Leaves/metabolism/physiology ; *Water/metabolism ; Photosynthesis ; }, abstract = {The strategies of Norway spruce [Picea abies (L.) Karst.] to increasing atmospheric CO2 concentration (C a) are not entirely clear. Here, we reconstructed centennial trajectories of leaf internal CO2 concentration (C i) and intrinsic water-use efficiency (WUEi) from the amount of [13]C in tree-ring cellulose. We collected 57 cores across elevations, soil, and atmospheric conditions in central Europe. Generally, WUEi and C i increased over the last 100 years and the C i/C a ratio remained almost constant. However, two groups were distinguished. The first group showed a quasi-linear response to C a and the sensitivity of C i to C a (s = dC i/dC a) ranged from 0 to 1. Trees in the second group showed nonmonotonic responses with extremes during the peak of industrial air pollution in the 1980s and s increase from -1 to +1.6. Our study shows a marked attenuation of the rise in WUEi during the 20[th] century leading to invariant WUEi in recent decades.}, } @article {pmid40269494, year = {2025}, author = {Nakamura, S and Fujii, K and Sakai, M and Sakai, K and Hanazawa, H and Nishimura, K and Notohara, K and Yamaguchi, K and Itasaka, S}, title = {Arm-Behind-the-Back Position for Breast Cancer Radiotherapy in Patients with Lupus Erythematosus and Shoulder Arthropathy: A Case Report.}, journal = {The American journal of case reports}, volume = {26}, number = {}, pages = {e946674}, pmid = {40269494}, issn = {1941-5923}, mesh = {Humans ; Female ; *Breast Neoplasms/radiotherapy/complications/surgery ; Adult ; *Lupus Erythematosus, Systemic/complications ; *Carcinoma, Ductal, Breast/radiotherapy/complications/surgery ; *Shoulder Joint ; *Patient Positioning/methods ; *Radiotherapy, Conformal/methods ; }, abstract = {BACKGROUND When 3-dimensional conformal radiation therapy (3DCRT) for postoperative breast cancer is performed in the supine position, patients are required to raise their arms to spare the arms from the irradiation field. However, patients with collagen vascular disease can experience severe joint symptoms. CASE REPORT A 43-year-old woman with a history of systemic lupus erythematosus (SLE) 10 years ago received a diagnosis of invasive ductal carcinoma of the left breast. Breast-conserving surgery and sentinel lymph node biopsy were performed. The pathological stage was IA. Physical and immunological examinations indicated that SLE disease activity was stable preoperatively and postoperatively. She had difficulty holding her left arm in a raised position because of arthritis related to SLE and steroid therapy. For postoperative radiation therapy, we developed an arm-behind-the-back position, in which a platform was placed between the patient's body and couch. In this position, the patient's arm was lowered behind the back, such that the arm did not interfere with the irradiation field of 3DCRT. The treatment plan achieved an acceptable homogeneity index, low dose to the lungs and heart, and no problematic hotspots. Although the time required for position matching and irradiation tended to be longer than that in the regular supine position, scheduled irradiation was safely completed. Grade 2 radiation dermatitis was observed. The patient showed no signs of local recurrence or distant metastases after 15 months. No radiation pneumonitis was observed. CONCLUSIONS The ingenuity of positioning can achieve radiotherapy in patients with collagen vascular disease and shoulder joint symptoms.}, } @article {pmid40263095, year = {2025}, author = {Li, Y and Ye, Y and Tao, X and Liang, X and Qiu, X and Zhao, J}, title = {Prognostic Features and Predictive Model for Mixed Invasive Ductal and Lobular Breast Carcinoma in Early-Stage Patients.}, journal = {Clinical breast cancer}, volume = {25}, number = {6}, pages = {e846-e856.e6}, doi = {10.1016/j.clbc.2025.03.019}, pmid = {40263095}, issn = {1938-0666}, mesh = {Humans ; Female ; *Carcinoma, Lobular/pathology/mortality/therapy ; *Breast Neoplasms/pathology/mortality/therapy ; Prognosis ; *Carcinoma, Ductal, Breast/pathology/mortality/therapy ; Middle Aged ; Neoplasm Staging ; SEER Program/statistics & numerical data ; Aged ; Adult ; Survival Rate ; Kaplan-Meier Estimate ; }, abstract = {INTRODUCTION: Mixed invasive ductal and lobular breast carcinoma (IDLC) is a rare and understudied subtype of breast cancer with unique prognostic characteristics.

METHODS: This study analyzed data from the SEER database and the METABRIC database. Survival outcomes of IDLC were compared with those of IDC and ILC using Kaplan-Meier survival curves and Cox regression analyses. Based on these findings, a prognostic model tailored for IDLC patients was developed using the SEER cohort, which was divided into a training set (70%) and an internal validation set (30%). The model incorporated clinical and molecular features and was externally validated using the METABRIC cohort. Its performance was assessed via C-index, AUC, calibration curves, and decision curve analysis (DCA).

RESULTS: A total of 26,138 early-stage IDLC patients were included, along with 391,888 IDC and 47,571 ILC patients. In unadjusted analyses, IDLC showed better overall survival (OS) and breast cancer-specific survival (BCSS) compared to both IDC and ILC. However, after multivariate adjustment, the differences in survival outcomes varied. IDLC demonstrated better OS than IDC and better BCSS than ILC. Additionally, a prognostic model for early-stage IDLC that incorporates clinical and molecular features was developed.

CONCLUSION: This study found that early-stage IDLC had superior BCSS and OS in unadjusted analyses. However, after multivariate adjustment, there was no difference in BCSS between IDLC and IDC, and no difference in OS between IDLC and ILC. A prognostic model was developed and validated, offering precise predictions of OS and BCSS.}, } @article {pmid40262013, year = {2025}, author = {Young, R and Zaworski, E and Hart, M and Grewe, B and Liang, E and Pierpont, Y}, title = {Sarcoidosis Masquerading as Breast Implant- Associated Anaplastic Large Cell Lymphoma - The Importance of Definitive Pathology to Guide Therapy.}, journal = {WMJ : official publication of the State Medical Society of Wisconsin}, volume = {124}, number = {1}, pages = {71-73}, pmid = {40262013}, issn = {2379-3961}, mesh = {Humans ; Female ; Middle Aged ; Carcinoma, Ductal, Breast/surgery ; Breast Neoplasms/surgery ; *Breast Implants/adverse effects ; Mammaplasty/adverse effects/instrumentation ; *Postoperative Complications/diagnosis/etiology/pathology ; *Lymphoma, Large-Cell, Anaplastic/diagnosis ; *Sarcoidosis/diagnosis/etiology/pathology ; Diagnosis, Differential ; *Seroma/diagnosis/etiology/pathology ; }, abstract = {INTRODUCTION: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare critical outcome of breast implantation that typically presents 8 to 10 years after textured-implant placement with periprosthetic seroma. Treatment consists of implant removal and capsulectomy, which is typically curative. But in rare case, malignant infiltration through the capsule results in disseminated disease, necessitating aggressive treatment with systemic chemotherapy. Sarcoidosis, a chronic systemic granulomatous disease characterized by noncaseating granulomas, is another rare cause of periprosthetic seroma.

CASE PRESENTATION: A 61-year-old female with a history of invasive ductal carcinoma of the breast status post textured implant-based reconstruction presented with late periprosthetic seroma and overlying rash. Cytology of seroma aspirate was suggestive of BIA-ALCL, and positron emission tomography-computed tomography was concerning for invasive disease. Surgical specimen pathology of the implant-capsule complex and skin punch biopsy of the overlying rash revealed only granulomatous inflammation. The patient was diagnosed with sarcoidosis and spared systemic chemotherapy treatment for disseminated BIA-ALCL.

CONCLUSIONS: BIA-ALCL should be ruled out in all cases of late periprosthetic seroma. Definitive surgical pathology is necessary to prevent misdiagnosis and inappropriate treatment of masquerading entities, such as sarcoidosis.}, } @article {pmid40260130, year = {2025}, author = {Tamomh, AG and Ali, MO and Walana, W and Mohammed, NM and Hassan, IM and Hamed, ME and Alkab, MJ and Mohammed, GI and Albashir, EA and Mahmoud, RO and Ahmed, MS}, title = {Intestinal Parasitic Infections and Associated Risk Factors Among Children in an Internally Displaced Center (IDC) in Kosti City of the White Nile State, Sudan.}, journal = {Journal of parasitology research}, volume = {2025}, number = {}, pages = {5542680}, pmid = {40260130}, issn = {2090-0023}, abstract = {Background: Intestinal parasitic infections (IPIs) are considered a global health problem, especially in developing countries such as Sudan. Over three million people have been displaced in Sudan due to civil war, and children are severely affected. However, there is limited data regarding IPIs among children in internally displaced centers (IDCs) in the White Nile State, especially in Kosti City. Therefore, this study aimed to determine the prevalence of IPIs and the associated risk factors among Sudanese children in an IDC in Kosti City, White Nile State, Sudan. Methods: A cross-sectional study was conducted among 508 children at the IDC, and 508 corresponding stool samples were collected. Parents and guardians of children aged 1-10 were contacted randomly to voluntarily enroll their wards in the study. The sample collection period was from June 15th to November 15th, 2023. The stool samples were examined using direct wet mount and formal ether concentration techniques. Results: The overall prevalence of IPIs among children of the IDC was 33.9% (172/508). Specifically, the prevalence of intestinal parasites (IPs) among the children were Entamoeba histolytica (6.7%), Giardia lamblia (25.0%), and Hymenolepis nana (2.2%). Age-wise, the proportion of IPIs among children (1-5 years) was 29.8% (59/198), and those 6-10 years were 40.3% (125/310), p < 0.05. IPIs among males (32.1%) were less than females (34.9%), p > 0.05. Conclusion: The study concluded a relatively high prevalence of IPIs among children in IDC in Kosti City, White Nile State, Sudan. Therefore, a swift public intervention plan is needed, such as improving hygiene and sanitation, health education, and periodic screening and deworming of the affected population, particularly children.}, } @article {pmid40256672, year = {2025}, author = {Yuan, M and Yin, Y and Chu, Z and Yan, J}, title = {Investigation of Risk Factors and Development and Validation of a Nomogram for Predicting Overall Survival in Breast-Invasive Lobular Carcinoma.}, journal = {Breast care (Basel, Switzerland)}, volume = {20}, number = {2}, pages = {118-131}, pmid = {40256672}, issn = {1661-3791}, abstract = {OBJECTIVE: Invasive lobular carcinoma (ILC) of the breast is a common pathological subtype of breast cancer, ranks second in terms of incidence rate following invasive ductal carcinoma. The aims of this study were to construct a nomogram for predicting overall survival (OS) in patients with ILC and to identify risk factors that affect their survival prognosis.

METHODS: The patients diagnosed with ILC between 2010 and 2015 were extracted from Surveillance, Epidemiology, and End Results (SEER) database. They were randomly split into a training set with 18,365 samples for model training and parameter tuning and a validation set with 7,872 samples for independent accuracy verification. The independent risk factors were screened by lasso regression and multivariable Cox regression. A nomogram was constructed for the 3-year, 5-year, and 10-year OS rates based on these independent risk factors. Model efficiency was assessed through Harrell's concordance index (C-index), calibration curves, receiver operating characteristic curves, and decision curve analysis (DCA).

RESULTS: A total of 26,237 patients diagnosed with ILC were included. The following factors were identified as independent risk factors associated with OS: age, marital status, grade, estrogen receptor, progesterone receptor, surgery, radiation therapy, tumor size (T), lymph node (N), and metastasis (M) stages. The C-index was 0.795 in the training set, while in the validation set it was 0.791. The corresponding areas under the curve for 3-year, 5-year, and 10-year OS were 0.837, 0.828, and 0.791 in the training set and 0.832, 0.826, and 0.781 in the validation set, respectively. The calibration curve of the nomogram showed good consistency, and the DCA curves also suggested that it can provide valuable guidance for clinical decision-making.

CONCLUSIONS: The established nomogram predicting 3-year, 5-year, and 10-year OS for patients with ILC showed a good performance and it can help clinicians make more favorable clinical decisions.}, } @article {pmid40255334, year = {2025}, author = {Raj, FA and Ajmal, IT and Thiyagarajan, A and Ajmal, MY and Selvam, P and Muralidhar, V}, title = {Synchronous breast carcinoma with ipsilateral axillary tuberculosis, posing a diagnostic dilemma.}, journal = {Journal of surgical case reports}, volume = {2025}, number = {4}, pages = {rjaf218}, pmid = {40255334}, issn = {2042-8812}, abstract = {This case report describes a 63-year-old postmenopausal diabetic female with synchronous primary invasive ductal carcinoma of the right breast and tuberculosis (TB) of the ipsilateral axillary lymph nodes. Presenting with a palpable right breast lump and axillary lymphadenopathy, the patient underwent imaging, revealing BIRADS V classification and suspicious lymph nodes. Core needle biopsy confirmed invasive carcinoma, while lymph node histology revealed caseating granulomatous inflammation consistent with TB. Managed with modified radical mastectomy, adjuvant chemotherapy, and antitubercular therapy, the patient showed complete disease resolution on follow-up. This rare coexistence underscores the necessity for histopathological confirmation and multidisciplinary management to optimize outcomes.}, } @article {pmid40252206, year = {2025}, author = {Sanli, AN and Kara, H and Tekcan Sanli, DE and Arikan, AE and Cabioglu, N and Uras, C}, title = {Comparison of Clinicopathologic Features and Survival Outcomes of Pleomorphic Lobular, Classical Lobular, and Invasive Ductal Carcinoma.}, journal = {World journal of surgery}, volume = {49}, number = {6}, pages = {1406-1417}, doi = {10.1002/wjs.12589}, pmid = {40252206}, issn = {1432-2323}, mesh = {Humans ; Female ; *Breast Neoplasms/mortality/pathology/therapy ; *Carcinoma, Lobular/mortality/pathology/therapy ; Retrospective Studies ; Middle Aged ; *Carcinoma, Ductal, Breast/mortality/pathology/therapy ; Aged ; SEER Program ; Adult ; Survival Rate ; Neoplasm Staging ; Mastectomy ; }, abstract = {PURPOSE: The objective of this research is to assess the clinical importance of pleomorphic lobular carcinoma (PLC) by contrasting its survival outcomes and clinicopathological characteristics with those of classical invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC).

METHODS: Data from the SEER (Surveillance, Epidemiology, and End Results) database, which covers patients with breast cancer diagnosed between 2010 and 2021, are used in this retrospective analysis. Clinical, pathological, and demographic factors were noted. Kaplan-Meier and Cox regression models were used to conduct survival analyses.

RESULTS: A total of 639,943 patients were included in the study. 182 (0.03%) patients were diagnosed with PLC, 74,565 (11.6%) were with ILC, and 565,196 (88.3%) were with IDC. Compared with ILC and IDC, PLC was associated with higher tumor grade, higher T, N stage, and stage 3-4 AJCC stage, higher hormone negativity, and triple negativity rates. Breast-conserving surgery (BCS) rates were lower in the PLC group, whereas mastectomy, no surgery, and chemotherapy rates were higher. Five-year and 10-year overall survival (OS) and disease-specific survival (DSS) rates were significantly lower in the PLC group than in both ILC and IDC (p < 0.05). However, when survival outcomes were evaluated according to stage, no statistically significant differences in overall survival (OS) or disease-specific survival (DSS) were found between PLC and ILC or between PLC and IDC across all disease stages (p > 0.05).

CONCLUSION: PLC, a very rare type of breast cancer, has worse clinicopathological features and worse survival outcomes than both ILC and IDC. These findings highlight the need for more specialized personalized targeted therapeutic strategies for PLC.}, } @article {pmid40251247, year = {2025}, author = {Shahzad, T and Mazhar, T and Saqib, SM and Ouahada, K}, title = {Transformer-inspired training principles based breast cancer prediction: combining EfficientNetB0 and ResNet50.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {13501}, pmid = {40251247}, issn = {2045-2322}, mesh = {Humans ; *Breast Neoplasms/diagnosis/pathology/diagnostic imaging ; Female ; COVID-19 ; Deep Learning ; Machine Learning ; SARS-CoV-2 ; Algorithms ; }, abstract = {Breast cancer is a leading killer and has been deepened by COVID-19, which affected diagnosis and treatment services. The absence of a rapid, efficient, accurate diagnostic tool remains a pressing issue for this severe disease. Thus, it is still possible to encounter issues concerning diagnostic accuracy and utilization of errors in the sphere of machine learning, deep learning, and transfer learning models. This paper presents a new model combining EfficientNetB0 and ResNet50 to improve the classification of breast histopathology images into IDC and non-IDC classes. The implementation steps, it include resizing all the images to be of a standard size of 128*128 pixels and then performing normalization to enhance the learning model. EfficientNetB0 is selected for its efficient yet effective performance while ResNet50 employs deep residual connections to overcome the vanishing gradient problem. The proposed model that incorporates some of the characteristics from both architectures turns out to be very resilient and accurate in classification. The model demonstrates superior performance with an accuracy of 94%, a Mean Absolute Error (MAE) of 0.0628, and a Matthews Correlation Coefficient (MCC) of 0.8690. These results outperform previous baselines and show that the model performs well in achieving a good trade-off between precision and recall. The comparison with the related works demonstrates the superiority of the proposed ensemble approach in terms of accuracy and complexity, which makes it efficient for practical breast cancer diagnosis and screening.}, } @article {pmid40248551, year = {2025}, author = {Abdallaoui Maane, L and Ismaili, N and Siati, A and Fareh, M and Elghanmi, A and Bouziyane, A and Dehayni, M}, title = {Triple-Negative Breast Cancer: A Retrospective Study of 23 Cases in Morocco.}, journal = {Cureus}, volume = {17}, number = {3}, pages = {e80756}, pmid = {40248551}, issn = {2168-8184}, abstract = {Introduction Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone hormone receptor expression in tumor cells, and the lack of human epidermal growth factor receptor 2 (HER2) growth factor expression on immunohistochemistry. It is considered an aggressive subtype with limited treatment options, based mainly on chemotherapy, surgery, and radiotherapy. Materials and methods This retrospective study examines the epidemiological, clinical, pathological, and therapeutic characteristics of TNBC. It is based on a series of 23 cases collected from the Medical Oncology Department of the Cheikh Khalifa Ibn Zaid Al Nahyan International University Hospital in Casablanca, Morocco, over a period of three years and six months. The study focuses on newly diagnosed patients with TNBC, with data collected from the medical records of patients who were diagnosed and treated during this period. Follow-up data were analyzed to assess disease progression and treatment response, but all cases included were diagnosed during the study period. Results Of the total 242 breast cancer cases, 12.4% (30 cases) were diagnosed with TNBC. Due to missing data, only 23 cases were included in the final analysis. The average age of patients was 51.35 years, and 26.09% (six patients) had a family history of breast cancer. Invasive ductal carcinoma (IDC) was the most common histological type, accounting for 91.30% (21 cases) of cases, with a mean tumor size of 40.69 mm. Histoprognostic grades II and III were predominant, representing 30.43% (seven cases) and 52.17% (12 cases) of cases, respectively. Surgical treatments included conservative lumpectomy in 43.48% (10 patients), radical mastectomy according to the Patey technique in 26.09% (six patients), and no surgery for 30.43% (seven patients). Chemotherapy was administered to 69.6% (16 patients) of patients, with 39.1% (nine patients) receiving adjuvant therapy and 30.4% (seven patients) undergoing neoadjuvant treatment. Lymph node involvement was present in 63.64% (14 patients) of cases, with bone metastasis in 45.45% (10 patients) and lung metastasis in 27.27% (six patients). The disease course was considered unfavorable in 55% (13 patients) of cases, with disease progression observed in these patients. Specifically, 35% developed local recurrence, and 35% experienced metastatic progression. The average recurrence-free survival was 22.74 months post-diagnosis. Conclusion TNBC is a highly aggressive form of breast cancer, associated with a poor prognosis due to its high metastatic potential and frequent recurrence, particularly within the first two years after diagnosis. Current therapeutic options remain limited, highlighting the ongoing need for improved treatment strategies and early detection efforts.}, } @article {pmid40248531, year = {2025}, author = {Altamirano, GA and Romero, C and Moreno Cabrera, CS and Sobalvarro, JI and Aragón Conrado, LE}, title = {From Breast to Eye: A Rare Case of Ocular Metastasis From Luminal Breast Cancer in a Nicaraguan Patient.}, journal = {Cureus}, volume = {17}, number = {3}, pages = {e80748}, pmid = {40248531}, issn = {2168-8184}, abstract = {Ocular metastases from breast cancer are rare but significant, with invasive lobular carcinoma (ILC) showing a higher tendency for ocular involvement than invasive ductal carcinoma (IDC). Radiotherapy is the main treatment, but the prognosis is poor. This case involves a 37-year-old woman with a history of bilateral breast cancer, initially treated with surgery, chemotherapy, and radiotherapy. She later developed pulmonary progression, bone metastases, and other complications. The patient experienced worsening vision loss, headaches, tinnitus, and systemic decline. Imaging showed brain lesions and choroidal metastasis. Extensive metastasis was confirmed, including in the pleura, liver, and bones. Ophthalmologic evaluation revealed increased intraocular pressure, requiring medical management and planned cyclophotocoagulation. Due to the advanced disease, a palliative care approach was initiated, with radiotherapy planned for ocular metastasis. This case highlights the aggressive nature of metastatic luminal B breast cancer with ocular involvement and underscores the importance of early detection and a multidisciplinary approach to patient care.}, } @article {pmid40245679, year = {2025}, author = {Feizi, I and Sedigh-Namin, A and Kani, A and Namin, SS and Toularoud, AB}, title = {A rare case report of triple primary malignancies: synchronous breast ductal invasive carcinoma and lung neuroendocrine tumor, followed by chronic myeloid leukemia.}, journal = {International journal of surgery case reports}, volume = {130}, number = {}, pages = {111305}, pmid = {40245679}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Multiple primary malignancies (MPMTs), the occurrence of two or more different primary cancers in a single person, are rare. These tumors can be synchronous or metachronous, with an incidence ranging from 0.73 % to 11.70 % in cancer patients. While invasive ductal carcinoma (IDC) is the most common form of breast cancer and lung neuroendocrine tumors (NETs) are rare, their co-occurrence as MPMT is extremely rare. In addition, chronic myeloid leukemia (CML) makes such cases even more complex.

CASE PRESENTATION: We report the case of a 59-year-old woman who presented with a lump in the left breast. Diagnostic examinations confirmed breast IDC. Metastatic examination identified a separate primary, well-differentiated NET of the left lung. Both malignancies were treated surgically followed by appropriate adjuvant therapy. A year later, routine follow-up revealed an elevated white blood cell count and a subsequent bone marrow biopsy confirmed the diagnosis of CML.

CLINICAL DISCUSSION: The diagnosis of IDC and pulmonary NET as primary tumors is rare and the subsequent development of CML in this setting has not been reported previously. This case highlights the critical importance of thorough diagnostic evaluations to accurately differentiate between metastatic disease and MPMTs. The occurrence of three different malignancies in a single patient presents significant treatment challenges and highlights the need for personalized treatment approaches.

CONCLUSION: This report emphasizes the need for comprehensive diagnostic protocols in the evaluation of multiple tumors and contributes to the growing body of knowledge about MPMT. The coexistence of IDC, pulmonary NET and subsequent CML represents a rare and complex clinical scenario that requires continuous research into optimal management strategies for such cases.}, } @article {pmid40237857, year = {2025}, author = {Stang, P and Weiss, M and Jaensch, P and Scholz, S}, title = {Exploring stress and recovery among students: examining the role of study modes.}, journal = {Discover mental health}, volume = {5}, number = {1}, pages = {55}, pmid = {40237857}, issn = {2731-4383}, abstract = {Understanding stress and recovery dynamics among students is essential for promoting their well-being and academic success. This study delves into the complex interplay of stressors and coping mechanisms among university students. Drawing upon health psychology and resilience research, we investigate the experiences of stress and recovery among both full-time and part-time students, considering gender and age. Our findings reveal significant differences between full-time and part-time students in various aspects of stress, including emotional stress, conflicts, and lack of energy. Full-time students reported higher levels of stress in these dimensions, which could indicate possible effects on their academic performance and general well-being. Moreover, gender-specific differences in stress experiences were observed, with female students exhibiting higher levels of stress compared to their male counterparts, particularly in terms of emotional stress and lack of energy. Interestingly, while age did not significantly impact stress and recovery experiences, other variables such as workload and coping strategies appeared to play crucial roles. Our study underscores the importance of the diverse needs of students. Overall, this research sheds light on the intricate relationship between stress, recovery, and study program variables among students, offering valuable insights for educators, policymakers, and mental health practitioners seeking to enhance student well-being and academic success in higher education settings.}, } @article {pmid40237521, year = {2025}, author = {Irazoki, A and Frank, E and Pham, TCP and Braun, JL and Ehrlich, AM and Haid, M and Riols, F and Hansen, CHF and Jørgensen, AR and Andersen, NR and Hidalgo-Corbacho, L and Meneses-Valdes, R and Ali, MS and Raun, SH and Modvig, JL and Gallero, S and Larsen, S and Gerhart-Hines, Z and Jensen, TE and Rohm, M and Treebak, JT and Fajardo, VA and Sylow, L}, title = {Housing Temperature Impacts the Systemic and Tissue-Specific Molecular Responses to Cancer in Mice.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {16}, number = {2}, pages = {e13781}, pmid = {40237521}, issn = {2190-6009}, support = {0169-00013B//Independent Research Fund Denmark/ ; 101108282//European Union's Horizon program, Marie Skłodowska-Curie Actions/ ; R449-2023-1468//Lundbeck Foundation/ ; NNF23SA0084103//Novo Nordisk Foundation/ ; /ERC_/European Research Council/International ; 949017//European Union's Horizon 2020 research and innovation program/ ; }, mesh = {Animals ; Mice ; *Cachexia/etiology/metabolism ; *Temperature ; *Housing, Animal ; *Neoplasms/complications/metabolism ; Disease Models, Animal ; Male ; Thermogenesis ; Female ; }, abstract = {BACKGROUND: Cancer cachexia, affecting up to 80% of patients with cancer, is characterized by muscle and fat loss with functional decline. Preclinical research seeks to uncover the molecular mechanisms underlying cachexia to identify potential targets. Housing laboratory mice at ambient temperature induces cold stress, triggering thermogenic activity and metabolic adaptations. Yet, the impact of housing temperature on preclinical cachexia remains unknown.

METHODS: Colon 26 carcinoma (C26)-bearing and PBS-inoculated (Ctrl) mice were housed at standard (ST; 20°C-22°C) or thermoneutral temperature (TN; 28°C-32°C). They were monitored for body weight, composition, food intake and systemic factors. Upon necropsy, tissues were weighed and used for evaluation of ex vivo force and respiration, or snap frozen for biochemical assays.

RESULTS: C26 mice lost 7.5% body weight (p = 0.0001 vs. Ctrls), accounted by decreased fat mass (-35%, p < 0.0001 vs. Ctrls), showing mild cachexia irrespective of housing temperature. All C26 mice exhibited reduced force (-40%, p < 0.0001 vs. Ctrls) and increased atrogene expression (3-fold, p < 0.003 vs. Ctrls). Cancer altered white adipose tissue (WAT)'s functional gene signature (49%, p < 0.05 vs. Ctrls), whereas housing temperature reduced brown adipose tissue (BAT)'s (-78%, p < 0.05 vs. ST Ctrl). Thermogenic capacity measured by Ucp1 expression decreased upon cancer in both WAT and BAT (-93% and -63%, p < 0.0044 vs. Ctrls). Cancer-driven glucose intolerance was noted at ST (26%, p = 0.0192 vs. ST Ctrl), but restored at TN (-23%, p = 0.005 vs. ST C26). Circulating FGF21, GDF-15 and IL-6 increased in all C26 mice (4-fold, p < 0.009 vs. Ctrls), with a greater effect on IL-6 at TN (76%, p = 0.0018 vs. ST C26). Tumour and WAT Il6 mRNA levels remained unchanged, while cancer induced skeletal muscle (SkM) Il6 (2-fold, p = 0.0016 vs. Ctrls) at both temperatures. BAT Il6 was only induced in C26 mice at TN (116%, p = 0.0087 vs. ST C26). At the bioenergetics level, cancer increased SkM SERCA ATPase activity at ST (4-fold, p = 0.0108 vs. ST Ctrl) but not at TN. In BAT, O2 consumption enhanced in C26 mice at ST (119%, p < 0.03 vs. ST Ctrl) but was blunted at TN (-44%, p < 0.0001 vs. ST C26). Cancer increased BAT ATP levels regardless of temperature (2-fold, p = 0.0046 vs. Ctrls), while SERCA ATPase activity remained unchanged at ST and decreased at TN (-59%, p = 0.0213 vs. TN Ctrl).

CONCLUSIONS: In mild cachexia, BAT and SkM bioenergetics are susceptible to different housing temperatures, which influences cancer-induced alterations in glucose metabolism and systemic responses.}, } @article {pmid40234892, year = {2025}, author = {Shang, J and Miao, J and Niu, S and Sun, X and Liu, Y}, title = {Redefining therapeutic landscapes: clinicopathological insights into low and ultra-low HER2 expression in male breast cancer.}, journal = {Diagnostic pathology}, volume = {20}, number = {1}, pages = {43}, pmid = {40234892}, issn = {1746-1596}, mesh = {Humans ; *Breast Neoplasms, Male/pathology/metabolism ; Male ; *Erb-b2 Receptor Tyrosine Kinases/metabolism/analysis ; Middle Aged ; Retrospective Studies ; Aged ; *Biomarkers, Tumor/analysis/metabolism ; Adult ; Prognosis ; *Carcinoma, Ductal, Breast/pathology/metabolism ; Immunohistochemistry ; Aged, 80 and over ; Immunophenotyping ; }, abstract = {OBJECTIVE: With the emergence of new antibody coupled drugs, the treatment decisions of patients with low and ultra-low HER2 expression have been reshaped. However, the epidemiological characteristics of relatively rare male breast cancer are still unclear. This study discusses the clinicopathological and immunophenotypic characteristics of male invasive breast cancer with low and ultra-low HER2 expression.

METHODS: The clinicopathological and immunophenotypic features of 106 cases of male invasive breast cancer were retrospectively analyzed. HER2 was evaluated according to ASCO/CAP guidelines. The cutoff value of HER2 positive cell staining was > 10%. HER2 negative cases were divided into HER2 low expression (IHC = 1+/2 + and ISH without amplification) and HER2-0 (IHC-0, HER2 null and < 10% weak staining of cell membrane). The clinicopathological characteristics and prognosis of the cases were collected.

RESULTS: 106 male patients with invasive breast cancer from 2015 to 2024 were included in this study, and more than 85% of male breast cancer histological types were invasive ductal carcinoma. Immunophenotype: There were 23 cases of HER2-zero (including 13 cases of HER2 ultra-low), 72 cases of HER2 low, 11 cases of HER2 positive, and the HER2 positive rate was 10.38%, and the incidence of low expression was 67.93%; The incidence of HER2 low in male breast cancer was significantly higher than that in female breast cancer, and the difference was statistically significant (P < 0.05). In terms of prognosis, there was no statistical difference between HER2 low male breast cancer and female breast cancer (P > 0.05). There was no statistical difference in survival prognosis between different HER2 status in the male breast cancer cohort.

CONCLUSION: Male invasive breast cancer is rare, and it is more common in the elderly over 60 years old. The positive rate of ER and PR is high, and the incidence of HER2 low is high. The high HER2 low expression rate of male breast cancer can provide a new anti-HER2 treatment decision.}, } @article {pmid40234839, year = {2025}, author = {Kim, JH and Bae, J and Bae, JY and Jun, KI and Kim, CJ and Choi, HJ}, title = {Impact of early infectious diseases consultation on the management of central line-associated bloodstream infection: a propensity score weighting retrospective cohort study.}, journal = {BMC infectious diseases}, volume = {25}, number = {1}, pages = {526}, pmid = {40234839}, issn = {1471-2334}, support = {2022R1A2C1092235//National Research Foundation of Korea/ ; }, mesh = {Humans ; Male ; Female ; *Catheter-Related Infections/drug therapy/therapy/diagnosis ; Retrospective Studies ; Propensity Score ; Middle Aged ; Aged ; Intensive Care Units ; *Referral and Consultation ; Anti-Bacterial Agents/therapeutic use ; *Catheterization, Central Venous/adverse effects ; *Communicable Diseases/diagnosis ; *Bacteremia/drug therapy ; }, abstract = {BACKGROUND: Central line-associated bloodstream infection (CLABSI) is an important healthcare-associated infection, particularly in the intensive care unit (ICU). This study aimed to investigate the impact of early infectious disease consultation (IDC) on the quality of care metrics of CLABSI in patients admitted to the ICU.

METHODS: Patients with CLABSI admitted to the ICU were included and divided into early IDC, and late or never IDC groups. The early IDC group indicated patients whose attending physician received IDC within 72 h of CLABSI onset. The main outcomes were the proportion of patients who received optimal targeted antibiotic treatment and catheter removal within 72 h of CLABSI onset. Propensity score analysis with the inverse probability of the treatment weighting method was used to compare the outcomes.

RESULTS: Among the 197 enrolled patients, 52 (26.4%) underwent early IDC and 145 (63.6%) did not. The early IDC group showed considerably higher proportions of catheter removal (76.9% versus 44.8%; adjusted odds ratio (OR): 3.70, 95% confidence interval (CI): 1.72-7.98; P = 0.001) than the late or never IDC group. The proportions of patients receiving optimal targeted antibiotic treatment were significantly higher in the early IDC group than in the late or never IDC group (67.3% versus 46.9%, adjusted OR: adjusted OR: 2.40, 95% CI: 1.17-4.91, P = 0.016)).

CONCLUSIONS: Early IDC was associated with improvement of the quality of care for patients with CLABSI in the ICU. This findings support the implementation of early IDC should be considered as an integral part of care of CLABSI in ICU patients.}, } @article {pmid40234077, year = {2025}, author = {Ajmani, A and Witheiler, DW and Kivelevitch, D}, title = {Carcinoma erysipeloides secondary to male breast cancer in a patient with BRCA1 and BRCA2 mutations: a clinical presentation and management.}, journal = {BMJ case reports}, volume = {18}, number = {4}, pages = {}, doi = {10.1136/bcr-2024-264429}, pmid = {40234077}, issn = {1757-790X}, mesh = {Humans ; Male ; *Breast Neoplasms, Male/genetics/pathology/drug therapy/complications ; *Carcinoma, Ductal, Breast/genetics/drug therapy/pathology ; Aged, 80 and over ; BRCA1 Protein/genetics ; Germ-Line Mutation ; BRCA2 Protein/genetics ; *Skin Neoplasms/secondary/genetics/drug therapy/pathology ; }, abstract = {We report a rare case of carcinoma erysipeloides (CE) in a man in his 80s. The patient exhibited a 15 year history of progressive nodularity over the right areola, accompanied by violaceous erythema extending from the right chest to both the right and left abdomen. The diagnostic workup confirmed invasive ductal carcinoma beneath the areola, intralymphatic carcinoma consistent with CE involving the regional skin and metastatic involvement of a single lymph node. The tumour tested positive for oestrogen and progesterone receptors but negative for HER2; genetic testing revealed the patient harboured germline mutations for BRCA1 and BRCA2. Oncology initiated anastrozole and palbociclib treatment, resulting in objective improvement in his breast cancer and his CE. This case highlights a unique presentation of male breast cancer with CE in the context of BRCA mutations and underscores the importance of genetic evaluation and tailored treatment in men with familial breast cancer syndromes.}, } @article {pmid40233046, year = {2025}, author = {Zhu, G and Dong, Y and Zhu, R and Tan, Y and Liu, X and Tao, J and Chen, D}, title = {Dynamic contrast-enhanced magnetic resonance imaging parameters combined with diffusion-weighted imaging for discriminating malignant lesions, molecular subtypes, and pathological grades in invasive ductal carcinoma patients.}, journal = {PloS one}, volume = {20}, number = {4}, pages = {e0320240}, pmid = {40233046}, issn = {1932-6203}, mesh = {Humans ; Female ; Middle Aged ; *Diffusion Magnetic Resonance Imaging/methods ; *Breast Neoplasms/pathology/diagnostic imaging/diagnosis ; Adult ; *Contrast Media ; *Carcinoma, Ductal, Breast/pathology/diagnostic imaging ; Aged ; Retrospective Studies ; Neoplasm Grading ; *Magnetic Resonance Imaging/methods ; }, abstract = {Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters or diffusion-weighted imaging (DWI) findings provide prognostic information on breast cancer. However, the accuracy of a single MRI technique is unsatisfactory. This study intended to explore the combination of DWI and DCE-MRI parameters in discriminating molecular subtypes in invasive ductal carcinoma (IDC) patients. Eighty-two IDC patients who underwent breast DWI and DCE-MRI examinations were retrospectively analyzed. Eighty-six patients with benign masses were retrieved as benign controls. The combination of ADC value, Ktrans, Kep, Ve, and iAUC had a good ability to discriminate IDC patients (vs. benign controls) with an area under the curve (AUC) [95% confidence interval (CI)] of 0.961 (0.935-0.987). A nomogram-based prediction model with the above combination showed a good predictive value for IDC probability. The combination of ADC value, Ktrans, Kep, and iAUC also had a certain ability to discriminate pathological grade III (vs. I or II) [AUC (95% CI): 0.698 (0.572-0.825)] in IDC patients. Notably, ADC value (P=0.010) and Kep (P=0.043) differed in IDC patients with different molecular subtypes. Besides, ADC value was increased (P<0.001), but Ktrans (P=0.037) and Kep (P=0.004) were decreased in IDC patients with Lumina A (vs. other molecular subtypes). The combination of ADC value, Ktrans, Kep, had an acceptable ability to discriminate Luminal A (vs. other molecular subtypes) [AUC (95% CI): 0.845 (0.748-0.941)] in IDC patients. DWI combined with DCE-MRI parameters discriminates IDC from benign masses; it also identifies Luminal A and pathological grade III in IDC patients.}, } @article {pmid40231894, year = {2025}, author = {Ahmadi, M and Allen, G and Stanway, J and Traviss, N}, title = {Effect of operating conditions and technology on residential wood stove emissions of criteria, greenhouse gas, and hazardous air pollutants.}, journal = {Journal of the Air & Waste Management Association (1995)}, volume = {75}, number = {6}, pages = {483-502}, doi = {10.1080/10962247.2025.2488807}, pmid = {40231894}, issn = {2162-2906}, mesh = {*Wood ; *Greenhouse Gases/analysis ; *Air Pollutants/analysis ; United States ; Air Pollution, Indoor/analysis ; *Cooking/instrumentation ; Heating ; Particulate Matter/analysis ; }, abstract = {Residential wood heating (RWH) is a known source of particulate matter (PM), hazardous air pollutants (HAPs), and greenhouse gases (GHGs). However, the influence of operating conditions on emissions from certified cordwood stoves in the United States (U.S.) remains poorly understood. This study analyzes emissions data from different operational phases, including start-up, high heat, and low heat, to improve indicators of real-world stove performance. We tested five commercially available U.S. stoves through the four distinct operational conditions or phases of the novel Integrated Duty Cycle (IDC) testing protocol, which simulates typical residential wood-burning patterns by incorporating start-up, high heat, medium (or "maintain") heat, and low heat ("overnight" burn) phases. We determined emissions factors (EFs) by IDC phase for criteria, GHG, and HAP compounds, including volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs). We also developed a multiple linear regression model to assess the effect of dry burn rate (DBR) and IDC phase on each pollutant EF by stove technology type. IDC phase significantly influenced (p < 0.01) pollutant EFs from uncertified stoves and most emissions from catalytic/hybrid stoves, while DBR played a more substantial role in emissions from non-catalytic stoves. Current stove certification methods rely on a single nominal load under steady-state combustion, which does not reflect typical residential use. Additionally, we found DBR to be an inconsistent predictor of emissions in cordwood stoves. These findings underscore the importance of stove technology and operating conditions in determining RWH emissions, with implications for air quality science and regulatory policy.Implications: We report cordwood stove emissions factors by operating condition using the novel Integrated Duty Cycle (IDC) protocol on various U.S. technologies meeting 2020 New Source Performance Standards (NSPS) and one pre-NSPS, circa 1980 stove. We determined significant effects from IDC operating phase on uncertified and catalytic/hybrid stove emissions, but not noncatalytic stoves. This has important implications for use of emissions factors in air quality science, policy, and stove design, as different U.S. climate zones will influence the number of stove start-ups, fuel loading patterns, and frequencies of other "real world" operating conditions such as "high heat" and "overnight burn."}, } @article {pmid40230896, year = {2024}, author = {Waykar, R and Kumarapillai, S}, title = {Breast cancer histopathology, classification and clinical management: Current perspectives.}, journal = {Bioinformation}, volume = {20}, number = {12}, pages = {2069-2079}, pmid = {40230896}, issn = {0973-2063}, abstract = {Breast cancer (BC) manifests as a diverse group of malignancies and presents as a wide array of tumors with distinct morphological, biological and clinical characteristics. Molecular classification of BC serves as the basis for current precision-oriented therapeutic strategies. Upcoming therapeutic strategies will emphasize personalized medicine and tailoring treatments according to each patient's specific needs. These approaches will involve modulating the therapy intensity based on the biological characteristics of tumours and early predictive indicators, allowing for more precise and adaptable care in oncology. Additionally, there remains an unfulfilled requirement for the creation of new medications to treat breast cancer in its early stages, as well as in advanced cases. This review article presents an extensive examination of breast cancer, delving into its prevalence, contributing factors, molecular and cellular features and therapeutic interventions.}, } @article {pmid40229675, year = {2025}, author = {Chen, X and Luo, Y and Xie, Z and Wen, Y and Mou, F and Zeng, W}, title = {Prediction of neoadjuvant chemotherapy efficacy in breast cancer: integrating multimodal imaging and clinical features.}, journal = {BMC medical imaging}, volume = {25}, number = {1}, pages = {118}, pmid = {40229675}, issn = {1471-2342}, support = {zdxk202116//Chongqing Regional Key Disciplines (Medical Imaging)/ ; }, mesh = {Humans ; Female ; *Neoadjuvant Therapy ; *Breast Neoplasms/diagnostic imaging/drug therapy/pathology ; Middle Aged ; Retrospective Studies ; Adult ; *Magnetic Resonance Imaging/methods ; *Multimodal Imaging/methods ; Aged ; *Carcinoma, Ductal, Breast/drug therapy/diagnostic imaging/pathology ; Treatment Outcome ; Contrast Media ; Chemotherapy, Adjuvant ; }, abstract = {OBJECTIVES: To assess the predictive value of combining DCE-MRI, DKI, IVIM parameters, and clinical characteristics for neoadjuvant chemotherapy (NAC) efficacy in invasive ductal carcinoma.

METHODS: We conducted a retrospective study of 77 patients with invasive ductal carcinoma, analyzing MRI data collected before NAC. Parameters extracted included DCE-MRI (Ktrans, Kep, Ve, wash-in, wash-out, TTP, iAUC), DKI (MK, MD), and IVIM (D, D*, f). Differences between NAC responders and non-responders were assessed using t-tests or Mann-Whitney U tests. ROC curves and Spearman correlation analyses evaluated predictive accuracy.

RESULTS: NAC responders had higher DCE-MRI-Kep, DKI-MD, IVIM-D, and IVIM-f values. Non-responders had higher DCE-MRI-Ve, DKI-MK, IVIM-D (kurtosis, skewness, entropy), and IVIM-f (entropy). The mean DKI-MK had the highest AUC (0.724), and IVIM-D interquartile range showed the highest sensitivity (94.12%). Combined parameters had the highest AUC (0.969), sensitivity (94.12%), and specificity (90.70%). HER2 status (OR, 0.187; 95% CI: 0.038, 0.914; P = 0.038) and tumor margin (OR, 20.643; 95% CI: 2.892, 147.365; P = 0.003) were identified as independent factors influencing the lack of significant efficacy of neoadjuvant chemotherapy (NAC) in breast cancer.

CONCLUSIONS: Combining DCE-MRI, DKI, and IVIM parameters effectively predicts NAC efficacy, providing valuable preoperative assessment insights.

CLINICAL TRIAL NUMBER: Not applicable.}, } @article {pmid40226110, year = {2025}, author = {Lv, ZD and Zhang, L and Liu, XP and Jin, LY and Dong, Q and Li, FN and Wang, HB and Kong, B}, title = {Erratum: NKD1 down-regulation is associated with poor prognosis in breast invasive ductal carcinoma.}, journal = {International journal of clinical and experimental pathology}, volume = {18}, number = {3}, pages = {128-129}, doi = {10.62347/BKQJ1119}, pmid = {40226110}, issn = {1936-2625}, abstract = {[This corrects the article on p. 4015 in vol. 8, PMID: 26097589.].}, } @article {pmid40225987, year = {2025}, author = {Zhou, X and Zhang, Y and Huang, B and Shi, X and Bian, M}, title = {Upregulated PXDNL promotes invasive breast carcinoma progression.}, journal = {American journal of translational research}, volume = {17}, number = {3}, pages = {2154-2165}, pmid = {40225987}, issn = {1943-8141}, abstract = {BACKGROUND: Invasive breast carcinoma (BRCA) is a common and serious malignancy in women. Peroxidase-like (PXDNL) is associated with poor prognosis in various cancers but has an unclear role in BRCA progression.

METHODS: Bioinformatic analysis of datasets from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and UALCAN investigated a potential carcinogenic role of PXDNL, focusing on its correlation with prognosis, promoter methylation, immune cell infiltration, immune checkpoint genes, and relevant biologic functions and pathways.

RESULTS: PXDNL demonstrated a significant expression profile in BRCA, with considerable diagnostic and prognostic implications. Its up-regulation correlated with decreased survival rates across various molecular subtypes of BRCA. Patients in the high PXDNL expression group showed reduced presence of multiple infiltrative immune cell types, including CD8+ T cells, cytotoxic cells, T cells, B cells, dendritic cells (DC), immature dendritic cells (iDC), natural killer (NK) cells, NK CD56bright cells, NK CD56dim cells, and follicular helper T cells (TFH). Additionally, a significant correlation was observed between PXDNL expression and immune checkpoint genes. Gene Set Enrichment Analysis (GSEA) further indicated that high PXDNL expression triggers pathways such as epithelial-mesenchymal transition and protein secretion, while suppressing crucial processes including allograft rejection, IL6-JAK-STAT3 signaling, TNFα signaling via NFκB, adipogenesis, oxidative phosphorylation, DNA repair, and the P53 pathway.

CONCLUSION: Overexpression of PXDNL is associated with poor prognosis and is linked to immune cell infiltration in BRCA. Thus, PXDNL may be a biomarker or therapeutic target for BRCA.}, } @article {pmid40225816, year = {2025}, author = {Balde, S and Kengne, UIM and Thiam, JAT and Mekontso, JGK and Niang, SD and Fall, A and Ndiaye, M and Sarr, G and Zoure, ET and Sow, M and Ka, S}, title = {Synchronous Primary Malignancies: Incidental Detection of Ascending Colon Adenocarcinoma During Staging of Invasive Ductal Carcinoma of the Breast.}, journal = {Case reports in oncological medicine}, volume = {2025}, number = {}, pages = {7164628}, pmid = {40225816}, issn = {2090-6706}, abstract = {Multiple primary malignant neoplasms (MPMNs) are defined as two or more distinct tumors in the same individual. Synchronous breast and colon cancers are infrequent and present management challenges due to the lack of standardized guidelines. We report a 73-year-old woman presenting with a right breast mass, subsequently diagnosed as Grade 2 invasive ductal carcinoma. Staging CT incidentally revealed right colon wall thickening, and colonoscopy with biopsy confirmed moderately differentiated invasive adenocarcinoma. Following neoadjuvant chemotherapy, she underwent simultaneous radical mastectomy with axillary lymph node dissection and right hemicolectomy. Postoperative recovery was uneventful. Adjuvant chemoradiation was administered per multidisciplinary team (MDT) recommendation. Synchronous breast and colon cancers pose unique diagnostic and treatment planning challenges. MDT collaboration is crucial for personalized treatment strategies and optimized outcomes in these complex cases.}, } @article {pmid40225110, year = {2024}, author = {Al Harthi, S and Al-Masqari, M}, title = {Concurrent Invasive Ductal Carcinoma and Pancreatic Intraepithelial Neoplasia in Duodenal Heterotopic Pancreas: A Case Report.}, journal = {Oman medical journal}, volume = {39}, number = {6}, pages = {e699}, pmid = {40225110}, issn = {1999-768X}, abstract = {Heterotopic pancreatic (HP) tissue is defined as the presence of pancreatic tissue outside of its usual site with no vascular or anatomic association with the normal pancreas. This is most commonly found in the stomach, duodenum, and proximal jejunum. Most HP findings are incidental. Yet, they can occasionally produce symptoms such as bleeding, abdominal pain, and gastrointestinal obstruction symptoms. HP tissues can also become malignant. The following report details a rare case of a 77-year-old man with concurrent invasive ductal carcinoma and low-grade pancreatic intraepithelial neoplasia involving an HP tissue located at the duodenum.}, } @article {pmid40224367, year = {2025}, author = {Yang, Q and Li, F and Ye, Y and Zhang, X}, title = {Antimicrobial, remineralization, and infiltration: advanced strategies for interrupting dental caries.}, journal = {Medical review (2021)}, volume = {5}, number = {2}, pages = {87-116}, pmid = {40224367}, issn = {2749-9642}, abstract = {Dental caries, driven by plaque biofilm, poses a major oral health challenge due to imbalance in mineralization and demineralization. The primary objective in caries management is to maintain biofilm homeostasis while facilitating the repair and regeneration of dental hard tissues, thus restoring both structural integrity and functionality of affected teeth. Though antimicrobial and remineralization approaches haven shown promise, their standalone utilization without concurrent bacterial control or rebalancing lacks an integrated strategy to effectively arrest caries progression. Furthermore, according to the principles of minimally invasive dentistry, treatment materials should exhibit high permeability to ensure optimal sealing of demineralized tooth surfaces. The concept of interrupting dental caries (IDC) has emerged as a holistic approach, drawing upon extensive research encompassing three pivotal techniques: antibacterial strategies, remineralization therapies, and infiltration mechanisms, all of which are indispensable components in combating the progression of dental caries. In this review, we provide a comprehensive overview of the mechanisms and applications of antibacterial, remineralization, and infiltration technologies within the context of caries management. Additionally, we summarize advanced materials that align with the IDC concept, aiming to offer valuable insights for designing next-generation materials adept at preventing or halting caries progression efficiently.}, } @article {pmid40218035, year = {2025}, author = {Durrani, S and Alamri, S and Zaman, SB and Alobaisi, Y and Hamdan, AB and Alharbi, M and Howaidi, J and Alamri, K and Almarzouq, F and Alyahyawi, A}, title = {Differences in Clinical, Epidemiological, and Pathological Features of Breast Cancer in the Saudi Population: An Analytical Cross-Sectional Single Institution Study.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {7}, pages = {}, pmid = {40218035}, issn = {2227-9032}, support = {NA//Research Center at King Fahad Medical City/ ; }, abstract = {Background: In Saudi Arabia, breast cancer is the most common malignancy among women, significantly impacting cancer-related morbidity and mortality. The country's unique demographics and rapid socioeconomic development contribute to distinct breast cancer patterns. Objective: To analyze demographic and pathological characteristics of breast cancer with an emphasis on associations between the Ki67 proliferation index, tumor stages, and molecular subtypes. Materials and Methods: An analytical cross-sectional study was conducted on 294 breast cancer patients from 2013 to 2019, recruited from the Comprehensive Cancer Center at King Fahad Medical City, Riyadh, Saudi Arabia. A one-way ANOVA and logistic regression were used to identify risk factors associated with elevated Ki67 levels. Significance was set at a 95% confidence level. Results: The mean age of patients was 51.58. Among them, 67% were overweight/obese, 21.1% were diabetic, and 17% were hypertensive. Approximately 28.9% of all tumors were classified as T3, 46.9% as Grade III, and 40% as Stage IV. Invasive ductal carcinomas (83.9%) were the most common. ER, PR, and HER2 expression were positive in 63.4%, 54.3%, and 34.9% of patients, respectively, with a high Ki67 index in 50.7%. As compared to Grade I cancer, grade II cancer increased the likelihood of elevated Ki67 by 41 times (p = 0.001), Grade III cancer by 7.43 times (p = 0.001), and Stage IV cancer by 2.26 times (p = 0.03). Conversely, invasive lobular carcinomas and other cancer types were significantly less likely to have high Ki67 levels (p < 0.05). Conclusions: Elevated Ki67 appeared to predict higher tumor grades and certain molecular subtypes cancer.}, } @article {pmid40214389, year = {2025}, author = {Kumar, W and Lohia, S and Agrawal, A and Yadav, V}, title = {A rare case of synchronous cervical squamous cell carcinoma and invasive ductal carcinoma of breast.}, journal = {Journal of cancer research and therapeutics}, volume = {21}, number = {1}, pages = {281-283}, doi = {10.4103/jcrt.jcrt_2653_23}, pmid = {40214389}, issn = {1998-4138}, mesh = {Humans ; Female ; *Uterine Cervical Neoplasms/pathology/diagnosis/therapy ; Middle Aged ; *Neoplasms, Multiple Primary/pathology/diagnosis ; *Carcinoma, Squamous Cell/pathology/diagnosis/therapy ; *Breast Neoplasms/pathology/diagnosis ; *Carcinoma, Ductal, Breast/pathology/diagnosis/therapy ; }, abstract = {Multiple primary neoplasms in the same patient can be of synchronous and metachronous types and are related to common etiologies and common genetic factors. We present a case report of 56-year-old female with the synchronous primary of breast and cervix and the unique challenges we faced in the management. Breast and cervical malignancies have contrasting risk factors and hence lies the significance of this synchronous presentation. The only identifiable commonality lies in the STK gene. We also present a review of the literature regarding similar presentations and a discussion on the possible source of origin of such a unique scenario.}, } @article {pmid40213483, year = {2024}, author = {Garcia-Peiro, JI and Guerrero-López, P and Hornos, F and Hueso, JL and Garcia-Aznar, JM and Santamaria, J}, title = {The Pattern of Copper Release in Copper-Based Nanoparticles Regulates Tumor Proliferation and Invasiveness in 3D Culture Models.}, journal = {Small science}, volume = {4}, number = {12}, pages = {2400206}, pmid = {40213483}, issn = {2688-4046}, abstract = {Cancer is a leading cause of death worldwide. Glioblastoma (GBM) is a major challenge in oncology due to its highly invasive nature and limited treatment options. GBM's aggressive migration beyond tumor margins and rapid tumor growth hinders success in patient treatment. Localized therapeutic delivery, such as the use of transition metals like copper, is highlighted as a novel therapeutic agent for many potential biomedical applications. Herein, it is aimed to study the effects of Cu release on the proliferation and invasiveness of cancer cells. To this end, novel copper-based nanostructures with different release patterns are designed. Using a complex 3D cell culture model to mimic the tumor microenvironment, it is shown that different patterns of copper ion release have a strong impact on GBM progression and invasiveness. The findings highlight the importance of optimizing localized copper release patterns to tailor different tumor treatment strategies. They also show the potential and suitability of 3D microchips as instruments to study the behavior of tumor spheroids. In spite of their limitations, these 3D microdevices enable a controlled and close monitoring of the influence of environmental factors (such as the presence of Cu ions) on the proliferation and invasiveness of the cells, with a better approach to reality compared to 2D models and with a more controlled environment, compared to an in vivo model.}, } @article {pmid40209948, year = {2025}, author = {Fan, TW and Yan, J and Goncalves, CFL and Islam, JMM and Lin, P and Kaddah, MMY and Higashi, RM and Lane, AN and Wang, X and Zhu, C}, title = {Patient-derived organotypic tissue cultures as a platform to evaluate metabolic reprogramming in breast cancer patients.}, journal = {The Journal of biological chemistry}, volume = {301}, number = {5}, pages = {108495}, pmid = {40209948}, issn = {1083-351X}, support = {P20 GM121327/GM/NIGMS NIH HHS/United States ; P30 CA177558/CA/NCI NIH HHS/United States ; R21 EB032515/EB/NIBIB NIH HHS/United States ; }, mesh = {Humans ; *Breast Neoplasms/metabolism/pathology ; Female ; *Tissue Culture Techniques/methods ; Glycolysis ; *Carcinoma, Ductal, Breast/metabolism/pathology ; Metabolic Reprogramming ; }, abstract = {Patient-derived organotypic tissue cultures (PD-OTC) are unique models for probing cancer metabolism and therapeutic responses. They retain patient tissue architectures/microenvironments that are difficult to recapitulate while affording comparison of cancer (CA) versus matched noncancer (NC) tissue responses to treatments. We have developed a long-term culturing method for fresh and cryopreserved PD-OTC of breast cancer patients bearing invasive ductal carcinoma. Five PD-OTC came from patients with treatment-naïve primary ER[+]/PR[+]/HER2[-] tumors while one came from a patient with neoadjuvant therapy for locally metastatic ER[low]/PR[-]/HER2[-] tumor. They all exhibited tissue outgrowth in 1 month with some CA OTC harboring isolatable organoids and fibroblasts. We interrogated reprogrammed metabolism in CA versus paired NC OTC with dual [2]H7-glucose/[13]C5,[15]N2-Gln tracers coupled with stable isotope-resolved metabolomic analysis. We noted variable activation of glycolysis, cataplerotic/anaplerotic Krebs cycle including reductive carboxylation, the pentose phosphate pathway, riboneogenesis, gluconeogenesis, de novo and salvage synthesis of purine/pyrimidine nucleotides, and ADP-ribosylation in CA PD-OTC. Altered metabolic activities were in part accountable by expression changes in key enzymes measured by reverse phase protein array profiling. Notably, Gln-fueled gluconeogenesis products were preferentially diverted to support purine nucleotide synthesis. When blocking this novel process with an inhibitor of phosphoenolpyruvate carboxykinase (3-mercaptopicolinic acid), metastatic, ER[low]/PR[-]/HER2[-] CA OTC displayed compromised cellularity, reduced outgrowth, and disrupted growth/survival-supporting metabolism but the matched NC OTC did not. Thus, our PD-OTC culturing method not only promoted understanding of actual patient's tumor metabolism to uncover viable metabolic targets but also enabled target testing and elucidation of therapeutic efficacy.}, } @article {pmid40204585, year = {2025}, author = {Sun, S and Wang, S and Tang, Y and Liu, K and Lin, Z and Song, Y and Wu, F and Jin, Y}, title = {T1 Mapping-Derived Parameters in Breast Lesions: Diagnostic Accuracy and Correlation with Pathologic Features.}, journal = {Academic radiology}, volume = {32}, number = {7}, pages = {3870-3882}, doi = {10.1016/j.acra.2025.03.029}, pmid = {40204585}, issn = {1878-4046}, mesh = {Humans ; *Breast Neoplasms/diagnostic imaging/pathology ; Female ; Middle Aged ; Adult ; Aged ; *Magnetic Resonance Imaging/methods ; Prospective Studies ; Contrast Media ; Diagnosis, Differential ; Breast/diagnostic imaging/pathology ; Reproducibility of Results ; Sensitivity and Specificity ; Diffusion Magnetic Resonance Imaging ; }, abstract = {RATIONALE AND OBJECTIVES: To evaluate the diagnostic potential of T1 mapping-derived parameters for distinguishing between benign and malignant breast tumors and their associations with pathologic prognostic indicators in invasive breast cancer.

MATERIALS AND METHODS: Patients who underwent breast surgery and quantitative magnetic resonance imaging (MRI), including apparent diffusion coefficient (ADC) and T1 mapping, between August 2023 and March 2024 were prospectively included. T1 parameters, including lesion T1 values before and after contrast agent injection (T10, T1c), reduction in T1 value (ΔT1), ratio of reduction (ΔT1%), extracellular volume fractions (ECVs), and ADC values were compared between benign and malignant breast lesions. The classification effect was evaluated via receiver operating characteristic (ROC) curves, and the correlation between MRI parameters and each prognostic indicator in invasive ductal carcinoma (IDC) was analyzed via Spearman correlation.

RESULTS: The ROC curves revealed that the area under the curve (AUC) of the ECV was slightly larger than that of the ADC (0.90 [95% CI: 0.84-0.95] vs 0.89 [95% CI: 0.83-0.94]). The combined diagnostic model of all parameters had the highest AUC (0.95 [95% CI: 0.90-0.98]). In IDC, ECV was positively correlated with the expression of estrogen receptor (r = 0.449, P < .001) and progesterone receptor (r = 0.433, P < .001) and negatively correlated with Ki-67 protein expression (r = -0.407, P < .001). No correlation was found between the ADC values and prognostic indicators.

CONCLUSION: T1 parameters can effectively differentiate benign and malignant breast lesions and have potential utility in predicting tumor invasiveness.}, } @article {pmid40203054, year = {2025}, author = {Trombley, J and Rakozy, AI and McClear, CA and Jash, E and Csankovszki, G}, title = {Condensin IDC, DPY-21, and CEC-4 maintain X chromosome repression in C. elegans.}, journal = {PLoS genetics}, volume = {21}, number = {4}, pages = {e1011247}, pmid = {40203054}, issn = {1553-7404}, support = {P40 OD010440/OD/NIH HHS/United States ; R01 GM133858/GM/NIGMS NIH HHS/United States ; R35 GM149543/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Caenorhabditis elegans/genetics ; *X Chromosome/genetics ; *Caenorhabditis elegans Proteins/genetics/metabolism ; Dosage Compensation, Genetic/genetics ; *Adenosine Triphosphatases/genetics/metabolism ; *Multiprotein Complexes/genetics/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; Male ; Histones/metabolism/genetics ; Genes, X-Linked ; Gene Expression Regulation, Developmental ; Female ; }, abstract = {Dosage compensation in Caenorhabditis elegans equalizes X-linked gene expression between XX hermaphrodites and XO males. The process depends on a condensin-containing dosage compensation complex (DCC), which binds the X chromosomes in hermaphrodites to repress gene expression by a factor of 2. Condensin IDC and an additional five DCC components must be present on the X during early embryogenesis in hermaphrodites to establish dosage compensation. However, whether the DCC's continued presence is required to maintain the repressed state once established is unknown. Beyond the role of condensin IDC in X chromosome compaction, additional mechanisms contribute to X-linked gene repression. DPY-21, a non-condensin IDC DCC component, is an H4K20me2/3 demethylase whose activity enriches the repressive histone mark, H4 lysine 20 monomethylation, on the X chromosomes. In addition, CEC-4, a protein that tethers H3K9me3-rich chromosomal regions to the nuclear lamina, also contributes to X-linked gene repression. To investigate the necessity of condensin IDC during the larval and adult stages of hermaphrodites, we used the auxin-inducible degradation system to deplete the condensin IDC subunit DPY-27. While DPY-27 depletion in the embryonic stages resulted in lethality, DPY-27 depleted larvae and adults survive. In these DPY-27 depleted strains, condensin IDC was no longer associated with the X chromosome, the X became decondensed, and the H4K20me1 mark was gradually lost, leading to X-linked gene derepression (about 1.4-fold). These results suggest that the stable maintenance of dosage compensation requires the continued presence of condensin IDC. A loss-of-function mutation in cec-4, in addition to the depletion of DPY-27 or the genetic mutation of dpy-21, led to even more significant increases in X-linked gene expression (about 1.7-fold), suggesting that CEC-4 helps stabilize repression mediated by condensin IDC and H4K20me1.}, } @article {pmid40201601, year = {2025}, author = {Lee, KJ and Choi, YY and Choi, SJ and Bae, MS}, title = {Primary Mucosa-Associated Lymphoid Tissue Lymphoma of the Breast with Synchronous Contralateral Invasive Breast Cancer: A Case Report.}, journal = {Journal of the Korean Society of Radiology}, volume = {86}, number = {2}, pages = {272-278}, pmid = {40201601}, issn = {2951-0805}, abstract = {Primary breast lymphoma is a rare malignant breast tumor, accounting for <1% of all breast cancers. Among them, diffuse large B-cell lymphoma is the most common histologic subtype. However, primary mucosa-associated lymphoid tissue (MALT) lymphoma is less common and more indolent than diffuse large B-cell lymphoma, and primary MALT lymphoma of the breast is extremely rare. We report a case of bilateral breast cancer in a 62-year-old woman with primary MALT lymphoma in right braest and contralateral invasive breast cancer in left breast. The patient presented with a palpable right breast lump, which appeared as a noncalcified mass on mammography and an indistinct irregular hypoechoic mass with internal vascularity on breast ultrasonography. The mass was pathologically confirmed by excisional biopsy as primary MALT lymphoma. The patient underwent dynamic contrast-enhanced breast MRI, which additionally detected a small suspicious mass in the left breast. This was a clinically and mammographically occult breast cancer diagnosed as invasive ductal carcinoma.}, } @article {pmid40201022, year = {2025}, author = {Zafar, M and Krishnakumar, M and Reddy, A}, title = {Impact of Early Testing and Analysis of Germline Genetic Mutation in Patients with Breast Cancer: A Single Institution Experience.}, journal = {Journal of cancer prevention}, volume = {30}, number = {1}, pages = {41-46}, pmid = {40201022}, issn = {2288-3649}, abstract = {Breast cancer is the most common cancer among women worldwide, with germline mutations in high-penetrance genes like BRCA1 and BRCA2, and moderate-penetrance genes such as CHEK2 and ATM contributing majorly to the onset of the same. Universal germline genetic testing offers an avenue to improve early identification and develop appropriate management guidelines. Our retrospective cohort study analyzed data from 525 newly diagnosed breast cancer patients at Mercy Hospital Fort Smith from January 2020 to December 2023. Patients underwent germline genetic testing using next-generation sequencing panels irrespective of family history of cancer. Details on patient demographics, clinical characteristics, and genetic test results were collected and analyzed. The median age at diagnosis of patients was 66, with invasive ductal carcinoma (IDC) being the major subtype (66%). CHEK2 mutations were the most common pathogenic mutations (9 patients), followed by BRCA1 and MUTYH (6 each). Pathogenic mutations were more prevalent in patients over 60 years (63%). Germline mutations were identified more frequently in IDC than in ductal carcinoma in situ. Among patients with germline mutations, there was a significant drift toward mastectomy over breast-conserving surgery. Universal germline genetic testing identified pathogenic mutations in a significant proportion of breast cancer patients, especially among the older patient population. The findings further emphasize the importance of integrating universal genetic testing into routine care to guide surgical and risk-reduction management protocols effectively. Further research is needed to regularize genetic testing in similar patients.}, } @article {pmid40198909, year = {2025}, author = {Jin, Y and Zhao, M and Su, T and Fan, Y and Ouyang, Z and Lv, F}, title = {Comparing Random Survival Forests and Cox Regression for Nonresponders to Neoadjuvant Chemotherapy Among Patients With Breast Cancer: Multicenter Retrospective Cohort Study.}, journal = {Journal of medical Internet research}, volume = {27}, number = {}, pages = {e69864}, pmid = {40198909}, issn = {1438-8871}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/mortality/pathology ; Middle Aged ; Adult ; Retrospective Studies ; *Neoadjuvant Therapy ; Proportional Hazards Models ; Aged ; }, abstract = {BACKGROUND: Breast cancer is one of the most common malignancies among women worldwide. Patients who do not achieve a pathological complete response (pCR) or a clinical complete response (cCR) post-neoadjuvant chemotherapy (NAC) typically have a worse prognosis compared to those who do achieve these responses.

OBJECTIVE: This study aimed to develop and validate a random survival forest (RSF) model to predict survival risk in patients with breast cancer who do not achieve a pCR or cCR post-NAC.

METHODS: We analyzed patients with no pCR/cCR post-NAC treated at the First Affiliated Hospital of Chongqing Medical University from January 2019 to 2023, with external validation in Duke University and Surveillance, Epidemiology, and End Results (SEER) cohorts. RSF and Cox regression models were compared using the time-dependent area under the curve (AUC), the concordance index (C-index), and risk stratification.

RESULTS: The study cohort included 306 patients with breast cancer, with most aged 40-60 years (204/306, 66.7%). The majority had invasive ductal carcinoma (290/306, 94.8%), with estrogen receptor (ER)+ (182/306, 59.5%), progesterone receptor (PR)- (179/306, 58.5%), and human epidermal growth factor receptor 2 (HER2)+ (94/306, 30.7%) profiles. Most patients presented with T2 (185/306, 60.5%), N1 (142/306, 46.4%), and M0 (295/306, 96.4%) staging (TNM meaning "tumor, node, metastasis"), with 17.6% (54/306) experiencing disease progression during a median follow-up of 25.9 months (IQR 17.2-36.3). External validation using Duke (N=94) and SEER (N=2760) cohorts confirmed consistent patterns in age (40-60 years: 59/94, 63%, vs 1480/2760, 53.6%), HER2+ rates (26/94, 28%, vs 935/2760, 33.9%), and invasive ductal carcinoma prevalence (89/94, 95%, vs 2506/2760, 90.8%). In the internal cohort, the RSF achieved significantly higher time-dependent AUCs compared to Cox regression at 1-year (0.811 vs 0.763), 3-year (0.834 vs 0.783), and 5-year (0.810 vs 0.771) intervals (overall C-index: 0.803, 95% CI 0.747-0.859, vs 0.736, 95% CI 0.673-0.799). External validation confirmed robust generalizability: the Duke cohort showed 1-, 3-, and 5-year AUCs of 0.912, 0.803, and 0.776, respectively, while the SEER cohort maintained consistent performance with AUCs of 0.771, 0.729, and 0.702, respectively. Risk stratification using the RSF identified 25.8% (79/306) high-risk patients and a significantly reduced survival time (P<.001). Notably, the RSF maintained improved net benefits across decision thresholds in decision curve analysis (DCA); similar results were observed in external studies. The RSF model also showed promising performance across different molecular subtypes in all datasets. Based on the RSF predicted scores, patients were stratified into high- and low-risk groups, with notably poorer survival outcomes observed in the high-risk group compared to the low-risk group.

CONCLUSIONS: The RSF model, based solely on clinicopathological variables, provides a promising tool for identifying high-risk patients with breast cancer post-NAC. This approach may facilitate personalized treatment strategies and improve patient management in clinical practice.}, } @article {pmid40190863, year = {2025}, author = {Sharma, S and Vulasala, SS and Elsherif, S and Sharma, S}, title = {Unusual Presentations of Cancer in the Male Breast.}, journal = {Cureus}, volume = {17}, number = {3}, pages = {e80052}, pmid = {40190863}, issn = {2168-8184}, abstract = {Breast cancer is a frequently diagnosed cancer in women, but the incidence of male breast cancer has also shown an increasing trend. Male and female breast cancers have some similarities, including risk factors and breast symptoms. Invasive ductal carcinoma is the most common type of breast cancer in both males and females. Even though fewer men than women are affected by breast cancer, male breast cancers are diagnosed at a more advanced stage and frequently have worse prognosis than their female counterparts. Through this case series, we are sharing a few unusual presentations of cancers in the male breast. In this case series of three patients, we will discuss the similarities and differences in male and female breast cancer. We aim to highlight the need to identify men at high risk and the importance of investigating any breast symptoms in men promptly.}, } @article {pmid40189767, year = {2025}, author = {Kawata, C and Terakawa, H and Kurokawa, Y and Ohe, Y and Mohri, R and Hirata, M and Kitahara, T and Moriyama, H and Kinoshita, J and Kawashima, H and Inaki, N}, title = {[A Case of Advanced Breast Cancer with Axillary Lymph Node Metastasis Complicated by Neurofibromatosis Type 1].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {52}, number = {3}, pages = {255-257}, pmid = {40189767}, issn = {0385-0684}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/surgery/complications/drug therapy ; Middle Aged ; *Neurofibromatosis 1/complications ; Axilla ; Lymphatic Metastasis ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Lymph Node Excision ; }, abstract = {The patient was a 55-year-old woman who had been diagnosed with neurofibromatosis type 1(NF1)since she was young. A 50 mm mass with skin changes was palpated on the outside of the left breast. As a result of a detailed examination of the whole body, invasive ductal carcinoma of Luminal B like was observed, and cT4N1M0, Stage ⅢB left breast cancer was diagnosed. After preoperative chemotherapy, total left mastectomy and axillary lymph node dissection were performed. NF1 is an autosomal overt inherited disease characterized by multiple neurofibromas and pigment spots. It is called von Recklinghausen disease, and it is said that there are many complications of malignant tumors such as breast cancer, mainly nervous system tumors. In breast cancer complicated by NF1, there is a high rate of diagnosis as advanced cancer due to delayed awareness of breast masses due to unique skin lesions and a tendency to refrain from visiting medical institutions or medical examinations due to latent shame about appearance. In this study, we report 1 case of advanced breast cancer complicated by NF1.}, } @article {pmid40189766, year = {2025}, author = {Mizuyama, Y and Takashima, T}, title = {[A Case of Pulmonary Tuberculosis Developed During Neoadjuvant Chemotherapy for HER2-Enriched Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {52}, number = {3}, pages = {252-254}, pmid = {40189766}, issn = {0385-0684}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/surgery/chemistry ; *Neoadjuvant Therapy/adverse effects ; Aged ; *Tuberculosis, Pulmonary/drug therapy/etiology ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; *Erb-b2 Receptor Tyrosine Kinases/analysis ; *Carcinoma, Ductal, Breast/drug therapy/surgery ; Antitubercular Agents/therapeutic use ; }, abstract = {In the 1990s, the number of newly registered tuberculosis patients in Japan was about 40,000 per year. It has been gradually decreasing and the number of new patients became 10,235 in 2022 with the incidence rate of 8.2 per 100,000 population. However it is still occasionally encountered even in recent years. Herein, we report a case of human epidermal growth factor receptor 2(HER2)-enriched breast cancer patient developed pulmonary tuberculosis just after finishing neoadjuvant chemotherapy and was successfully treated for both disease simultaneously. A 68 years old woman presented due to right breast mass was diagnosed with hormonal receptor-negative, HER2-positive invasive ductal carcinoma. Neoadjuvant chemotherapy with paclitaxel, trastuzumab and pertuzumab was started. After 12 courses of chemotherapy, CT scan revealed disappearance of the right breast tumor and infiltrating shadow in the left lower lung field. Sputum polymerase chain reaction test for tuberculosis was positive. Anti-tuberculosis chemotherapy was started. Four days after starting isoniazid, partial mastectomy was performed under local anesthesia and radiation therapy for the breast was omitted. There are no signs of recurrence of breast cancer and pulmonary tuberculosis for 5 years. Chemotherapy for breast cancer and premedication with corticosteroid may have inhibited cellular immunity, causing endogenous relapse of tuberculosis.}, } @article {pmid40187959, year = {2025}, author = {Moustakas, A and Zemah-Shamir, S and Tase, M and Zotos, S and Demirel, N and Zoumides, C and Christoforidi, I and Dindaroglu, T and Albayrak, T and Ayhan, CK and Fois, M and Manolaki, P and Sandor, AD and Sieber, I and Stamatiadou, V and Tzirkalli, E and Vogiatzakis, IN and Zemah-Shamir, Z and Zittis, G}, title = {Corrigendum to "Climate, land use, and other drivers' impacts on island ecosystem services: A global review" [Sci. Total Environ. Volume 973, 10 April 2025, 179147].}, journal = {The Science of the total environment}, volume = {975}, number = {}, pages = {179244}, doi = {10.1016/j.scitotenv.2025.179244}, pmid = {40187959}, issn = {1879-1026}, } @article {pmid40186732, year = {2025}, author = {Stamey, T and Armel, K and Ju, AW and Chen, S and Navaid, M and Bhatt, A and Larkins, MC}, title = {Treatment outcomes and comparative survival analysis of intraductal carcinoma of the prostate.}, journal = {International urology and nephrology}, volume = {57}, number = {10}, pages = {3143-3149}, pmid = {40186732}, issn = {1573-2584}, mesh = {Humans ; Male ; *Prostatic Neoplasms/mortality/therapy ; Aged ; Treatment Outcome ; Middle Aged ; Survival Rate ; Survival Analysis ; *Carcinoma, Intraductal, Noninfiltrating/mortality/therapy ; SEER Program ; Retrospective Studies ; Prostatectomy ; }, abstract = {PURPOSE: Intraductal carcinoma of the prostate is a rare subset of prostate cancer, for which no consensus treatment guidelines exist. We seek to investigate treatment and survival outcomes for IDC-P in the context of current NCCN guidelines.

METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with intraductal carcinoma of the prostate diagnosed between 2000 and 2020. Cox regression analysis and log-rank comparisons of both overall and cause-specific survival over 5- and 10-year timeframes were conducted.

RESULTS: 945 patients were identified. Cox regression analysis demonstrated treatment with unimodal surgery (hazard ratio (HR) = 3.70, p = 0.005) was associated with decreased 10-year cause-specific survival, while unimodal treatment with radiotherapy was associated with decreased 5- and 10-year overall survival (HR = 2.14, p = 0.025; HR = 2.16, p = 0.005, respectively). Univariate survival subanalysis of treatment regimens demonstrated decreased 5-year cause-specific (p = 0.004) and overall (p = 0.019) survival among patients that received only radiotherapy as treatment. Radical prostatectomy alone was non-inferior to radical prostatectomy with adjuvant radiotherapy in the context of 10-year overall survival (90% vs 80%; p = 0.58).

CONCLUSION: Differences in both 5- and 10-year overall survival and cause-specific survival were present among patients diagnosed with IDC-P. Treatment with unimodal radiotherapy among patients with IDC-P was associated with decreased survival compared to treatment with radical prostatectomy ± adjuvant radiotherapy, while radical prostatectomy alone was non-inferior to radical prostatectomy with adjuvant radiotherapy. Further research into the risk stratification and optimal treatment of these patients is warranted.}, } @article {pmid40186076, year = {2025}, author = {Khani, S and Topel, H and Kardinal, R and Tavanez, AR and Josephrajan, A and Larsen, BDM and Gaudry, MJ and Leyendecker, P and Egedal, NM and Güller, AS and Stanic, N and Ruppert, PMM and Gaziano, I and Hansmeier, NR and Schmidt, E and Klemm, P and Vagliano, LM and Stahl, R and Duthie, F and Krause, JH and Bici, A and Engelhard, CA and Gohlke, S and Frommolt, P and Gnad, T and Rada-Iglesias, A and Pradas-Juni, M and Schulz, TJ and Wunderlich, FT and Pfeifer, A and Bartelt, A and Jastroch, M and Wachten, D and Kornfeld, JW}, title = {Publisher Correction: Cold-induced expression of a truncated adenylyl cyclase 3 acts as rheostat to brown fat function.}, journal = {Nature metabolism}, volume = {7}, number = {4}, pages = {855}, doi = {10.1038/s42255-025-01292-z}, pmid = {40186076}, issn = {2522-5812}, } @article {pmid40177147, year = {2025}, author = {Borges, P and Spencer, HB and Furtado, S and Costa, V and Barbosa, C and Santos, LL}, title = {Breast cancer in Cape Verde: a 24-year retrospective study of clinical presentation, treatment and outcomes at Agostinho Neto University Hospital.}, journal = {Ecancermedicalscience}, volume = {19}, number = {}, pages = {1826}, pmid = {40177147}, issn = {1754-6605}, abstract = {BACKGROUND: Breast cancer is a significant health concern in Cape Verde, but comprehensive data on its presentation, management and outcomes are limited. This study aims to provide insights into breast cancer patterns in this island nation.

METHODS: We conducted a retrospective analysis of 586 breast cancer patients treated at Agostinho Neto University Hospital in Praia, Cape Verde, from January 2000 to May 2024. Data on demographics, clinical presentation, diagnostic methods, treatment modalities and survival outcomes were collected and analysed.

RESULTS: The study population comprised 578 (98.6%) females and 8 (1.4%) males. The mean age at diagnosis was 52.1 years (SD 13.6) for females and 70 years (SD 16.7) for males. Stage III was the most common presentation (39.4%). Invasive ductal carcinoma was the predominant histological type. Immunohistochemical analysis in 307 patients revealed 69.4% luminal, 26.1% triple-negative and 4.6% HER2-positive subtypes. Treatment primarily involved surgery combined with chemotherapy and/or hormone therapy, with 33.4% receiving radiotherapy. The median follow-up was 36.5 months (range: 1-298 months), and the median survival time was 137.1 months.

CONCLUSION: This study reveals breast cancer patterns in Cape Verde that share similarities with other African nations, including younger age at diagnosis and higher rates of late-stage presentation compared to Western countries. However, encouraging trends in survival outcomes and diagnostic capabilities were observed. These findings highlight the need for improved early detection strategies and expanded access to comprehensive treatment modalities, particularly radiotherapy, in Cape Verde.}, } @article {pmid40172395, year = {2025}, author = {Kayalı, Fİ and Habiboğlu, R and Aral, İP and Çevik, V and Tezcan, Y}, title = {Breast cancer radiotherapy: analysis of unintended internal mammary node doses and influencing factors.}, journal = {Revista da Associacao Medica Brasileira (1992)}, volume = {71}, number = {2}, pages = {e20241325}, pmid = {40172395}, issn = {1806-9282}, mesh = {Humans ; Female ; Middle Aged ; Adult ; Aged ; *Lymph Nodes/radiation effects/pathology ; Radiotherapy Dosage ; Retrospective Studies ; *Breast Neoplasms/radiotherapy/pathology ; Radiotherapy, Intensity-Modulated/methods ; Neoplasm Staging ; Radiotherapy, Conformal/methods ; *Carcinoma, Ductal, Breast/radiotherapy/pathology ; *Unilateral Breast Neoplasms/radiotherapy/pathology ; Lymphatic Metastasis ; }, abstract = {OBJECTIVE: Breast cancer is a prevalent malignancy requiring ongoing treatment advancements. Radiotherapy is vital for reducing recurrence and improving survival. This study evaluates unintended doses to internal mammary lymph nodes and influencing factors in patients at Ankara Bilkent City Hospital's Radiation Oncology Clinic.

METHODS: We analyzed 44 right-sided breast cancer patients treated with radiotherapy between November 2019 and April 2023. Data on demographics, treatment, and dose-volume histograms were reviewed using various statistical tests.

RESULTS: Median age was 54 years; 88.6% had invasive ductal carcinoma, and 11.4% had ductal carcinoma in situ. Patients received conventional (54.5%) or hypofractionated radiotherapy (45.5%) using intensity-modulated radiotherapy or three-dimensional conformal radiotherapy. Median internal mammary lymph node volume was 7.3 cc with dose variability. Internal mammary lymph nodes V45 dose showed no correlation with internal mammary lymph nodes volume, radiotherapy field, pT stage, or pN stage. However, the nodal stage significantly impacted the internal mammary lymph nodes D95 dose, with higher doses in N1 patients. Wider radiotherapy fields led to increased D95 doses.

DISCUSSION: The findings highlight the variability in internal mammary lymph nodes doses and the impact of nodal stage and radiotherapy field on dose distribution. Advanced techniques like intensity-modulated radiotherapy can reduce risks, but careful planning is essential.

CONCLUSION: Understanding internal mammary lymph nodes dose factors can enhance treatment planning and outcomes. Future research should focus on refining guidelines and leveraging technology to improve radiotherapy efficacy.}, } @article {pmid40161180, year = {2025}, author = {Asif, H and Ahmad, U and Ahmad, N and Tahir, A and Bokhari, SW and Ahsan, B}, title = {Therapy-Related B-cell Acute Lymphoblastic Leukemia: A Case Series and Literature Review.}, journal = {Cureus}, volume = {17}, number = {2}, pages = {e79664}, pmid = {40161180}, issn = {2168-8184}, abstract = {Therapy-related B-cell acute lymphoblastic leukemia (B-ALL) is a rare disease associated with poor cytogenetics and inferior survival outcomes. In this case series, we present two cases of B-ALL following treatment for invasive ductal carcinoma of the breast and squamous cell carcinoma of the tongue, respectively, along with a third case of B-ALL arising in a patient with chronic lymphocytic leukemia after treatment. The most common cytogenetic abnormalities observed in these patients were t(9;22) and monosomy 7. This case series underscores the importance of recognizing therapy-related B-ALL as a distinct clinical entity, which plays a crucial role in ALL risk classification and the long-term management of both solid and hematologic cancer survivors.}, } @article {pmid40160884, year = {2025}, author = {Sugimura, N and Takao, S and Okamoto, A and Miyashita, M and Chayahara, N and Takahashi, T and Sanada, H and Kanata, N and Katayama, N}, title = {Co-occurrence of breast cancer and malignant peripheral nerve sheath tumor in a patient with neurofibromatosis type 1.}, journal = {International cancer conference journal}, volume = {14}, number = {2}, pages = {177-184}, pmid = {40160884}, issn = {2192-3183}, abstract = {Patients with neurofibromatosis type 1 (NF1) have an increased risk of developing breast cancer and other malignancies. During the search for breast cancer metastases in NF1 patients, there is a substantial probability of detecting malignancies other than breast cancer. We present a case of an 80-year-old woman with NF1 who was diagnosed with both invasive ductal carcinoma of the luminal-HER2 type in the breast and a malignant peripheral nerve sheath tumor (MPNST) of the liver. After noticing a lump in her right breast for 2 months, further examination confirmed breast cancer with metastases to the right axillary lymph nodes. A whole-body contrast-enhanced CT scan revealed large hepatic tumors initially suspected to be metastases from breast cancer. However, given the patient's underlying NF1, an ultrasound-guided liver biopsy was performed, which confirmed the diagnosis of MPNST. The patient had a history of surgical resection for the MPNST in the forearm. Due to the high metastatic potential of MPNST, the liver tumors were diagnosed as metastases of the MPNST. She declined chemotherapy for MPNST and is currently receiving endocrine therapy alone for breast cancer. It is necessary to acknowledge the predisposition of patients with NF1 to develop various tumors throughout the body. When performing a systemic evaluation for breast cancer in NF1 patients, any detected lesions should be thoroughly investigated for potential malignancies other than breast cancer metastasis. Biopsy and pathological examinations are useful to ensure an accurate differential diagnosis.}, } @article {pmid40160864, year = {2025}, author = {Szychta, P}, title = {Breast-Sharing for Post-Mastectomy Reconstruction: Innovations in Aesthetic Symmetry, Surgical Safety, and Oncological Precision.}, journal = {Plastic surgery (Oakville, Ont.)}, volume = {}, number = {}, pages = {22925503251327929}, pmid = {40160864}, issn = {2292-5503}, abstract = {Background: Breast-sharing is an innovative reconstructive approach that combines contralateral reduction mammaplasty with autologous breast reconstruction. This method repurposes tissue typically discarded during reduction mammaplasty to restore post-mastectomy symmetry while minimizing donor site morbidity and preserving oncological safety. Case Presentation: A 46-year-old woman with a significant asymmetry following a left mastectomy for invasive ductal carcinoma (pT2N0M0, ER+, PR+) and adjuvant radiotherapy was treated with a breast-sharing procedure. Preoperative imaging confirmed a robust third intercostal internal mammary artery perforator (IMAP) as the flap's vascular pedicle. The procedure included contralateral reduction mammaplasty, harvest of a glandulocutaneous IMAP flap, and its transposition to the mastectomy site. A subcutaneous tunnel facilitated flap transfer, achieving symmetry and natural contour. In the second case, a 50-year-old female with Stage II invasive ductal carcinoma and significant contralateral breast hypertrophy underwent a breast-sharing procedure utilizing autologous tissue from the contralateral breast, achieving improved symmetry, no disease recurrence, and high patient satisfaction during follow-up. Results: In the first case, postoperative monitoring identified venous congestion at the distal flap tip, successfully managed with medicinal leeches and minor debridement. Over 8 years of follow-up, the patient exhibited no recurrence or contralateral breast cancer. Esthetic outcomes were excellent, with natural projection and texture. In the second case, recovery was uneventful, with no cancer recurrence in the follow-up period of 1 year. Conclusion: Breast-sharing offers a transformative, safe, and effective reconstructive option for select post-mastectomy patients with contralateral hypertrophy, encouraging broader application of this innovative technique.}, } @article {pmid40160190, year = {2025}, author = {Shin, YD and Choi, YJ}, title = {Successful Sentinel Lymph Node Biopsy in Accessory Breast Cancer.}, journal = {Journal of medical cases}, volume = {16}, number = {3}, pages = {107-113}, pmid = {40160190}, issn = {1923-4163}, abstract = {Primary breast cancer occurring in accessory breast tissue is exceptionally rare, with an incidence of 0.2-0.6%. It can aggressively progress, often leading to early metastasis. Treatment is typically delayed due to the rarity, variety of differentials, and lack of clinical awareness of the disease. In axillary surgery, sentinel lymph node mapping in patients with axillary breast cancer is technically challenging and has been poorly described. Here, we present a case of a 53-year-old woman with a 0.5 × 1 cm hard lump in the right axillary region for 2 years, progressive growth for 6 months, and no concomitant breast lesion or axillary lymphadenopathy. Core needle biopsy revealed invasive ductal carcinoma with estrogen receptor and progesterone receptor expression and human epidermal growth factor receptor 2 negativity, whereas mammography and breast magnetic resonance imaging revealed no primary breast lesions. She was diagnosed with invasive cancer arising from an accessory breast and underwent wide total excision of the right accessory breast and sentinel lymph node biopsy. Sentinel lymph node biopsy can be successfully performed using intratumoral dye and subareolar radiocolloid mapping in accessory breast cancer surgery. Axillary accessory breast tissue is outside the scope of the screening breast examination; therefore, oncologists must be aware of this entity and associated pathologies.}, } @article {pmid40158494, year = {2025}, author = {Taji, T and Kumamaru, H and Kataoka, Y and Iijima, K and Suwa, H and Ishiguro, H and Taira, N and Ishida, T and Saji, S}, title = {Comparison of neoadjuvant and adjuvant chemotherapy for operable triple-negative breast cancer before the era of immune checkpoint inhibitors: A retrospective study from the Japanese National Clinical Database-Breast Cancer Registry.}, journal = {Breast (Edinburgh, Scotland)}, volume = {81}, number = {}, pages = {104460}, pmid = {40158494}, issn = {1532-3080}, mesh = {Humans ; *Triple Negative Breast Neoplasms/drug therapy/mortality/pathology ; Female ; Retrospective Studies ; Chemotherapy, Adjuvant/methods ; Middle Aged ; *Neoadjuvant Therapy/methods ; Japan/epidemiology ; Registries ; Aged ; Databases, Factual ; *Immune Checkpoint Inhibitors/therapeutic use ; Adult ; Proportional Hazards Models ; Neoplasm Staging ; East Asian People ; }, abstract = {BACKGROUND: While neoadjuvant chemotherapy (NAC) is recommended for stage II-III triple-negative breast cancer (TNBC), its equivalence to adjuvant chemotherapy (AdjC) has been questioned based on a retrospective study using the National Cancer Database in the United States, which lacked adjustment for important covariates. Given the unlikelihood of new randomized trials being conducted, well-designed, large-scale, retrospective studies are needed.

PATIENTS AND METHODS: We retrospectively analyzed operable TNBC patients from the Japanese National Clinical Database- Breast Cancer Registry (2012-2016). Inclusion criteria were clinical stage I-IIIB, estrogen receptor (ER) < 10 %, progesterone receptor (PgR) < 10 %, and HER2-negative. We excluded patients with carcinoma in situ, cT4a/T4c/T4d, cN3, cM1, bilateral breast cancer, male, non-epithelial tumor, no chemotherapy, no surgery and no follow-up. Primary and secondary outcomes of overall survival (OS) and recurrence-free survival (RFS) were compared between NAC and AdjC using Cox proportional Hazard regression among the exact matched cohort based on age, BMI, cT, cN, histology, ER/PgR positivity, chemotherapy regimen, breast operative technique, radiotherapy, and institution size.

RESULTS: Among 9,000 AdjC and 5,520 NAC patients, 3,256 matched cases were compared. OS and RFS were significantly worse for patients with NAC (Hazard Ratio 1.45 (95 % confidence interval 1.26-1.68) and 1.33 (1.19-1.49), respectively), particularly in patients <65 years, with stage II-IIIB, and with invasive ductal carcinoma.

CONCLUSION: Patients with NAC had worse prognosis, possibly due to unadjusted confounders. Although the availability of immune checkpoint inhibitors (ICIs) limits the clinical impact, the result could provide supplemental insights for treatment decisions in patients who are not candidates for ICIs.}, } @article {pmid40156779, year = {2024}, author = {Arinola, G and Onifade, AA and Adigun, K and Oshingbesan, MB}, title = {Review of immune-metabolic studies and re-purposed treatments of Nigerian COVID-19 patients: A pointer to mild, gender- and age-based status of admitted patients.}, journal = {Nigerian journal of physiological sciences : official publication of the Physiological Society of Nigeria}, volume = {39}, number = {2}, pages = {177-183}, doi = {10.54548/njps.v39i2.2}, pmid = {40156779}, issn = {0794-859X}, mesh = {Humans ; *COVID-19/immunology/metabolism/therapy/epidemiology ; Nigeria/epidemiology ; *COVID-19 Drug Treatment ; SARS-CoV-2 ; Age Factors ; Antiviral Agents/therapeutic use ; Sex Factors ; Female ; Male ; }, abstract = {When Severe Acute Respiratory human Coronavirus 2 (SARS-hCOV 2) infection began in December 2019, detailed knowledge about the virus was lacking. This included non-availability of anti-viral treatment or vaccine, no knowledge of virus-human interaction, and lack of prognostic factors for stages of illness among others. A publication in Nigerian Journal of Physiological Sciences (2020). 35: 20-25 titled "Immune Responses During Human Coronavirus Infection: Suggestions For Future Studies" adduced investigations into immune parameters of COVID-19 patients so as to throw more light on the immunopathogenesis of SAR-CoV-2 infection, in order to create avenue for the development of vaccines or herd immunity. This present publication is a review of studies carried out on COVID-19 patients in one Infectious Diseases Center (I.D.C), Ibadan, Nigeria as a response to the gaps in knowledge raised in above mentioned publication. Cummulatively, immune-metabolic studies from this IDC revealed mild, age- and sex-dependent status of COVID-19 in patients admitted into this center. Thus, explaining the basis for the effectiveness of adopted re-purposed drugs (chloroquine or hydroxychloroquine, zinc, vitamins C and D and or antibiotics), physiotherapy and nutritional support used for the management of admitted COVID-19 patients. Also, this paper vindicated that inflammation was heightened during SARS-CoV 2 infection; therefore therapeutic interventions to control the inflammatory processes, oxidative stress, antibodies against structural and non-structural proteins or blocks receptor sites were proposed. In addition, development of herd immunity and efficacy of COVID-19 vaccines (Astrazeneca and Moderna) were elucidated in general population. However, study to determine host genetic factors in hCoV infection was lacking. This review concluded that interdisciplinary collaborative approach will be useful in the management of future emerging or re-emerging infection.}, } @article {pmid40151274, year = {2025}, author = {Kondo, S and Oura, S and Honda, M}, title = {Breast cancer with medullary features shows a fast and plateau enhancement pattern on magnetic resonance images: A case report.}, journal = {Radiology case reports}, volume = {20}, number = {6}, pages = {2719-2722}, pmid = {40151274}, issn = {1930-0433}, abstract = {An 80-year-old woman with a left breast mass was referred to our department. Mammography showed an oval mass, 2.5cm in size, with circumscribed margins in her left breast. Ultrasound showed an oval tumor with circumscribed margins, heterogenous internal echoes including numerous punctate hyperechoic foci, and posterior echo enhancement. Magnetic resonance imaging (MRI) of the tumor showed low and high signal intensity on T1-weighted images and on fat-suppressed T2-weighted images, respectively. Kinetic curve assessment of the tumor showed a fast and plateau pattern. After the pathological confirmation of malignant cells, the patient underwent mastectomy and sentinel node biopsy. Postoperative pathological study showed that atypical cells formed irregularly arranged papillary nests and grew in a medullary fashion accompanied by massive lymphocyte infiltration, leading to the diagnosis of invasive ductal carcinoma with medullary features (IDCMF). Immunostaining showed that the tumor had a triple negative phenotype and a high Ki-67 labelling index of 52%. In conclusion, breast diagnostic physicians should note that IDCsMF show a fast and plateau enhancement pattern on MRI kinetic curve assessment. Furthermore, the presence of punctate hyperechoic foci in the tumor can be useful in distinguishing IDCsMF from medullary breast carcinomas.}, } @article {pmid40150055, year = {2025}, author = {Verzemnieks, K and Tumelkans, R and Strautmane, S and Kalejs, VR and Valeinis, E and Dolgopolova, J and Tone, T and Balodis, A}, title = {Ruptured Intracranial Dermoid Cyst with Fat Dissemination: A Clinical Case Mimicking an Epidermoid Cyst and Review of the Literature.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {6}, pages = {}, pmid = {40150055}, issn = {2075-4418}, abstract = {Background and Clinical Significance: Intracranial dermoid cysts (IDCs) are rare benign congenital intracranial lesions. In the case of IDC rupture, these lesions may manifest clinically. Cysts may be visualized on non-enhanced computed tomography (NECT) and magnetic resonance imaging (MRI), facilitating discussions between clinicians and radiologists to determine cyst content and potential dissemination in cases of rupture. This case report describes an IDC rupture presenting as fat-containing lesions in the subarachnoid space and ventricular system, resembling a subarachnoid hemorrhage on MRI. Case Presentation: A thirty-two-year-old Caucasian male patient was admitted to the hospital due to recurrent headaches and visual impairment that began at the age of thirty-one. MRI revealed a lesion radiologically consistent with a ruptured dermoid or epidermoid cyst in the anterior fossa with a mass effect on the optic nerve intracranial segments, the chiasma opticum, and proximal optic tracts. The patient underwent a successful neurosurgical resection of the lesion, and histopathological analysis confirmed the diagnosis of a dermoid cyst. The postoperative period was uneventful. MRI follow-up revealed residual tissue of the IDC without any volume increase. Multiple punctate fat-containing lesions were noted, similar to previous MRIs. The patient reported no complaints at discharge. Follow-up MRI imaging demonstrated no recurrence or progression of the dermoid cyst at 4 months, 1 year, and 2 years. Conclusions: IDC rupture is a rare event that may present clinically and appear as a blooming artifact on MRI, mimicking subarachnoid hemorrhage. Fat-containing lesions in the subarachnoid space and ventricular system can demonstrate findings indicative of an IDC rupture. MRI diffusion-weighted imaging (DWI) and decreased apparent diffusion coefficient (ADC) values may mimic an epidermoid cyst, a phenomenon rarely described in the literature, further complicating the diagnostic process.}, } @article {pmid40149589, year = {2025}, author = {Alanazi, F and Alsaleh, AA and Alamoudi, MK and Alasiri, A and Haymond, A and Matou-Nasri, S}, title = {Targeting p70S6K1 Inhibits Glycated Albumin-Induced Triple-Negative Breast Cancer Cell Invasion and Overexpression of Galectin-3, a Potential Prognostic Marker in Diabetic Patients with Invasive Breast Cancer.}, journal = {Biomedicines}, volume = {13}, number = {3}, pages = {}, pmid = {40149589}, issn = {2227-9059}, support = {NRC23R/729/11//King Abdullah International Medical Research Center/ ; }, abstract = {Background: There is an urgent need to identify new biomarkers for early diagnosis and development of therapeutic strategies for diabetes mellitus (DM) patients who have invasive breast cancer (BC). We previously reported the increased activated form of 70 kDa ribosomal protein S6 kinase 1 (phospho-p70S6K1) in a triple-negative BC (TNBC) cell line MDA-MB-231 exposed to glycated albumin (GA) and in invasive ductal carcinoma tissues from T2DM patients, compared to untreated cells and their non-diabetic counterparts, respectively. Objective: We aimed to explore the function of p70S6K1 in GA-promoted TNBC progression. Methods: By employing small interference (si)RNA technology or blocking its kinase activity using its specific pharmacological inhibitor, we monitored cell invasion using Transwell[®] inserts and the expression levels of activated signaling proteins and cancer-related proteins using Western blot. Results: In silico analysis revealed that high mRNA levels of p70S6K1 were associated with an unfavorable prognosis and progression to advanced stages of TNBC in DM patients. The downregulation/blockade of p70S6K1 inhibited GA-promoted MDA-MB-231 cell invasion and the phosphorylation of protein S6 and ERK1/2, the p70S6K1 downstream effector, and the key oncogenic signaling protein, respectively. The suppression of the expression of GA-upregulated cancer proteins, including enolase-2, capping protein CapG, galectin-3, and cathepsin D, was observed after p70S6K1 downregulation/blockade. Further in silico validation analyses revealed increased gene expression of galectin-3 in DM TNBC patients, resulting in poor overall survival and disease-free survival. Conclusions: Targeting p70S6K1 may present a valuable therapeutic strategy, while galectin-3 could serve as a potential prognostic biomarker for invasive BC progression in DM patients.}, } @article {pmid40149336, year = {2025}, author = {Yoon, KH and Ahn, JH and Kim, JY and Park, HS and Kim, SI and Park, S}, title = {Impact of Axillary Burden on Survival: A Comparative Study of Invasive Lobular Carcinoma and Invasive Ductal Carcinoma in Early-Stage Breast Cancer.}, journal = {Cancers}, volume = {17}, number = {6}, pages = {}, pmid = {40149336}, issn = {2072-6694}, support = {2024-04-002//Boryung Pharma (South Korea)/ ; }, abstract = {PURPOSE: Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the most common breast cancer types. While they differ biologically and pathologically, their association with axillary lymph node (ALN) metastasis and survival remains unclear. This study compares the clinical features of ILC and IDC to evaluate ALN surgery considerations for ILC patients.

MATERIALS AND METHODS: We retrospectively analyzed 3543 patients who underwent upfront surgery for early breast cancer at Yonsei University Severance Hospital between January 2015 and December 2019. Multivariate logistic regression assessed factors linked to ALN metastasis, while Cox regression identified predictors of recurrence and survival.

RESULTS: Among the patients, 92.1% had IDC and 7.9% had ILC. T2-stage tumors were more prevalent in ILC (31.4% vs. 18.1%, p < 0.001). The rates of ALN metastasis were similar between the groups (IDC: 21.1%, ILC: 24.6%, p = 0.655); however, the presence of more than two metastatic ALNs was more frequent in ILC (9.6% vs. 5.0%, p = 0.004). Factors associated with having >2 metastatic ALNs included histology, suspicious axillary ultrasound, T stage, and lymphovascular invasion. The median follow-up period was 65 months, with no significant differences observed in 8-year recurrence-free survival (ILC: 95.2%, IDC: 94.1%, p = 0.134) or 5-year overall survival (ILC: 97.1%, IDC: 97.4%, p = 0.289).

CONCLUSIONS: ILC features larger tumors and a higher nodal burden but has similar survival rates to IDC with proper treatment. Caution is essential in axillary surgery to avoid underestimating the nodal burden.}, } @article {pmid40144454, year = {2025}, author = {Arcanjo, AM and de Souza, AF and de Souza Quedas, EP and de Menezes Correia-Deur, JE and Ferreira, DL and de Almeida Toledo, SP and Lourenço, DM}, title = {Primary hypertrophic osteoarthropathy: phenotypic variability and penetrance rate in heterozygotes for SLCO2A1 variants.}, journal = {JBMR plus}, volume = {9}, number = {4}, pages = {ziaf026}, pmid = {40144454}, issn = {2473-4039}, abstract = {Primary hypertrophic osteoarthropathy (PHO) is a rare autosomal recessive disease caused by pathogenic variants (PVs) in HPGD and SLCO2A1 genes whose phenotypes are, respectively, designated as PHOAR1 and PHOAR2. Recently, a dominant inherited form (PHOAD) was identified in SLCO2A1 heterozygotes whose PHO penetrance is widely unknown, and data on phenotype are markedly limited. Our aim was to reveal the penetrance and extend/refine data on phenotype of SLCO2A1 heterozygotes. Both genes were sequenced using Sanger sequencing. The 4 probands had a typical complete form (CF) of PHO. Mean ages at symptom onset and clinical diagnosis were, respectively, 18.5 ± 2.7 (16-22) years and 22 ± 3.4 (18-26) years. They were homozygotes for SLCO2A1 (p.Q188R, p.C420F, p.A176T; p.G104[*]) PVs; 2 were novel variants. We focused on 14 SLCO2A1 heterozygous screened relatives from 3 families: 5 elderly individuals (mean age: 78 ± 6.7 [72-86] years) of the parental generation were affected, 2 by incomplete form (IF) and 3 with isolated digital clubbing (IDC). Combining our 14 carriers and 33 reported so far, the estimated overall PHO penetrance was 70%, being significantly higher in men (83% vs 50%; p = .024) and individuals carrying truncated SLCO2A1 PVs (88% vs 53%; p = .053). In turn, the periostosis penetrance rate in women was 28% (5/18), including our oldest patient (86 years). In the probands, the predominant phenotypes were CF (64%) and IF (36%). Among screened carriers, phenotypes were IDC (41%) followed by IF and fruste form (FF) (28%, each), whereas IDC and FF were the predominant phenotypes in screened men and women, respectively. As a novelty, we uncovered an incomplete penetrance of PHO in SLCO2A1 heterozygotes, with higher rates in elderly individuals, males, and those with truncated PVs. Regarding phenotype, PHO is more pronounced in males, periostosis is likely more frequent in females than previously documented in PHOAR2, and IDC may represent a distinct clinical feature in SLCO2A1 heterozygotes.}, } @article {pmid40137849, year = {2025}, author = {Albrecht, H and Herrmann, HJ and Jaensch, P and Zerth, J and Siebler, J and Neurath, MF and Konturek, PC and Zopf, Y}, title = {A national evaluation of the implementation of guideline recommendations towards antibiotic prophylaxis prior to percutaneous endoscopic gastrostomy and jejunostomy tube placement.}, journal = {Journal of physiology and pharmacology : an official journal of the Polish Physiological Society}, volume = {76}, number = {1}, pages = {}, doi = {10.26402/jpp.2025.1.06}, pmid = {40137849}, issn = {1899-1505}, mesh = {Humans ; *Gastrostomy/methods/adverse effects ; *Antibiotic Prophylaxis/standards/methods ; *Jejunostomy/methods/adverse effects ; Practice Guidelines as Topic ; Germany ; Surveys and Questionnaires ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Percutaneous endoscopic gastrostomy (PEG) and percutaneous endoscopic jejunostomy (PEJ) tube placement are standard procedures for artificially administered nutrition support in malnourished patients. However, minor and major complications can occur. Peristomal infections are most common, potentially leading to severe inflammation, hospitalization, and PEG/PEJ removal. Antibiotic prophylaxis is effective in preventing peristomal infections and recommended by current guidelines but does not seem to be systematically used. The present study evaluated the implementation of prophylactic antibiosis in PEG/PEJ placement in clinical routine in Germany. A web-based survey was conducted among hospitals, ambulatory health care centers, and focus practice. In total, 107 participants have finalized the questionnaire. Most participants were from major regional and maximum care facilities (36.4%), basic and standard care facilities (28.0%), as well as university facilities (23.4%). Routine antibiotic prophylaxis for every PEG/PEJ procedure is performed by 42.6%, whereas 13.9% do not apply antibiotic prophylaxis in general, and 23.8% only use it in patients with risk factors for infectious complications. This decision is based on in-house guidelines in 34.0% of participants or national recommendations 20.2%, whereas international guidelines (8.5%) and other recommendations play a minor role (4.3%). Although prophylactic antibiosis in PEG/PEJ placement is effective and recommended by current guidelines, less than half of the sites reported to routinely apply it. Given that these recommendations are based on outdated evidence, updated data is needed, and guideline recommendations need to be re-evaluated accordingly and fully implemented.}, } @article {pmid40134826, year = {2025}, author = {Zhou, T and Zhang, Y and Cao, J and Tang, Q and Liang, Y and Zhang, S and Hu, M and Feng, B and Jin, J}, title = {Identification of immune infiltration-related ZNF480 for predicting prognosis in breast cancer.}, journal = {American journal of clinical and experimental immunology}, volume = {14}, number = {1}, pages = {1-13}, pmid = {40134826}, issn = {2164-7712}, abstract = {BACKGROUND: Breast cancer is one of the most common cancers in women with high morbidity and mortality. ZNF480, a member of the KRAB-ZNFs family, correlates with cancer progression. However, its role in the development and progression of breast cancer remains unclear.

METHODS: We utilized transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases of breast cancer patients to investigate the potential pro-cancer role of ZNF480, including differential expression of ZNF480 in breast cancer, prognostic value, clinicopathological features, immune cell infiltration relevance and function enrichment analysis.

RESULTS: Our results indicate that ZNF480 is upregulated in breast cancer and is correlations with survival, clinical stage, race and tumor subtype in breast cancer patients. Additionally, immune infiltration analysis revealed significant negative correlations between ZNF480 expression and multiple tumor infiltrating immune cells, including aDC, B cells, CD8 T cells, Cytotoxic cells, DC, iDC, Macrophages, Neutrophils, NK CD56bright cells, NK CD56dim cells, NK cells, pDC, T cells, Tem, TFH and Th1 cells, whereas a significant positive correlation was observed with the infiltration of T helper cells, Tcm, Tgd and Th2 cells. Furthermore, functional enrichment analysis indicated that ZNF480 may be involved in Angiogenesis, Allograft rejection, TNFα signaling via NFκB, Coagulation, IL6 Jak STAT3 signaling, Inflammatory response, Interferon gamma response and other processes.

CONCLUSION: ZNF480 is highly expressed in breast cancer and correlates with immune cell infiltration, and may be a candidate prognostic biomarker, which may assist in breast cancer treatment.}, } @article {pmid40133928, year = {2025}, author = {Zhou, S and Liang, L and Huang, Z and Teng, Y and Xing, W}, title = {Does concomitant ductal carcinoma in situ influence the prognostic outcome after neoadjuvant therapy in triple-negative invasive ductal carcinoma?.}, journal = {World journal of surgical oncology}, volume = {23}, number = {1}, pages = {101}, pmid = {40133928}, issn = {1477-7819}, support = {2024SF57//Peking University First Hospital Research Seed Fund/ ; }, mesh = {Humans ; Female ; Middle Aged ; *Triple Negative Breast Neoplasms/pathology/therapy/mortality ; *Neoadjuvant Therapy/mortality ; Prognosis ; *Carcinoma, Ductal, Breast/pathology/therapy/mortality ; *Carcinoma, Intraductal, Noninfiltrating/pathology/therapy/mortality ; Adult ; Aged ; Follow-Up Studies ; Retrospective Studies ; Survival Rate ; Mastectomy ; }, abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is considered a precursor to invasive ductal carcinoma (IDC), and the coexistence of DCIS with IDC is often observed during the diagnosis of breast cancer. The aim of study is to investigated the clinicopathological features and prognosis of triple-negative IDC with DCIS following neoadjuvant therapy (NAT). Additionally, we explored the risk factors for residual DCIS in these patients post-NAT.

METHODS: This study included patients with stages II-III triple-negative breast cancer with histologically confirmed IDC who underwent radical surgery after NAT between January 2011 and December 2021. Baseline data, clinical features, pathological outcomes, and prognostic information were collected and analyzed.

RESULTS: A total of 315 patients were enrolled and categorized into the IDC + DCIS (n = 67) and IDC groups (n = 248) according to the composition of the pre-NAT biopsy. The proportion of patients with histological grade G3 (78.2% vs. 61.2%, p = 0.004) and a Ki-67 index > 20% (98.4% vs. 86.6%, p < 0.001) was significantly higher in the IDC group than in the IDC + DCIS group. Although no significant difference was observed in the 5-year overall survival (OS) (93.4% vs. 90.8%, p = 0.298) between the two groups, the 5-year disease-free survival (DFS) (90.6% vs. 83.5%, p = 0.041) of the IDC + DCIS group was significantly better than that in the IDC group. Multivariate analysis demonstrated that IDC + DCIS (HR: 0.502; 95% CI, 0.284-0.952; p = 0.048) was an independent prognostic factor for DFS. In addition, the clinical T3-T4 stage (OR = 3.891; 95% CI, 1.320-15.219, p = 0.040) and clinical N1-N3 (OR = 4.500; 95% CI, 1.495-13.564, p = 0.012) were independent preoperative predictors of residual DCIS after NAT in patients with IDC and DCIS components.

CONCLUSION: The presence of DCIS component in patients with triple-negative IDC is associated with lower tumor aggressiveness and improved DFS after NAT compared to patients without DCIS. Additionally, clinical T and N stages are risk factors for residual DCIS after NAT in patients with triple-negative IDC and a DCIS component.}, } @article {pmid40125138, year = {2025}, author = {Debellotte, O and Dookie, RL and Rinkoo, F and Kar, A and Salazar González, JF and Saraf, P and Aflahe Iqbal, M and Ghazaryan, L and Mukunde, AC and Khalid, A and Olumuyiwa, T}, title = {Artificial Intelligence and Early Detection of Breast, Lung, and Colon Cancer: A Narrative Review.}, journal = {Cureus}, volume = {17}, number = {2}, pages = {e79199}, pmid = {40125138}, issn = {2168-8184}, abstract = {Artificial intelligence (AI) is revolutionizing early cancer detection by enhancing the sensitivity, efficiency, and precision of screening programs for breast, colorectal, and lung cancers. Deep learning algorithms, such as convolutional neural networks, are pivotal in improving diagnostic accuracy by identifying patterns in imaging data that may elude human radiologists. AI has shown remarkable advancements in breast cancer detection, including risk stratification and treatment planning, with models achieving high specificity and precision in identifying invasive ductal carcinoma. In colorectal cancer screening, AI-powered systems significantly enhance polyp detection rates during colonoscopies, optimizing the adenoma detection rate and improving diagnostic workflows. Similarly, low-dose CT scans integrated with AI algorithms are transforming lung cancer screening by increasing the sensitivity and specificity of early-stage cancer detection, while aiding in accurate lesion segmentation and classification. This review highlights the potential of AI to streamline cancer diagnosis and treatment by analyzing vast datasets and reducing diagnostic variability. Despite these advancements, challenges such as data standardization, model generalization, and integration into clinical workflows remain. Addressing these issues through collaborative research, enhanced dataset diversity, and improved explainability of AI models will be critical for widespread adoption. The findings underscore AI's potential to significantly impact patient outcomes and reduce cancer-related mortality, emphasizing the need for further validation and optimization in diverse healthcare settings.}, } @article {pmid40124964, year = {2025}, author = {Pan, H and Zhu, L and Xu, J and Ding, M and Lin, H and Chen, Y and Sun, X and He, C and Wei, Q}, title = {Bladder Emptying Strategies, Active Follow-up Adherence and Barriers in Post-Discharge Spinal Cord Injury individuals: A Multiple Center Cross-Sectional Study.}, journal = {Patient preference and adherence}, volume = {19}, number = {}, pages = {623-633}, pmid = {40124964}, issn = {1177-889X}, abstract = {BACKGROUND: Adherence plays a crucial role in the long-term management of chronic conditions, including neurogenic lower urinary tract dysfunction (NLUTD) in individuals with spinal cord injury (SCI). Poor adherence can lead to complications, reduced quality of life, and increased healthcare costs.

PURPOSE: This study aimed to evaluate the post-discharge bladder-emptying practices and adherence to follow-up in SCI individuals with NLUTD, identifying key factors influencing adherence to improve long-term care strategies.

METHODS: A cross-sectional survey was conducted in Southwest China from May 1 to September 30, 2023. Online questionnaires were employed to collect data on sociodemographic characteristics, bladder emptying methods, active follow-up adherence and related barriers.

RESULTS: Out of 412 fully completed questionnaires, as for bladder-emptying method, 70.15% of respondents opted for clean intermittent catheterization (CIC) as their primary or preferred mode. CIC usage was more prevalent among participants with thoracic and lumbar SCI, while those with cervical SCI demonstrated a higher reliance on indwelling catheterization (IDC) and cystostomy. A significant 63.55% did not engage in regular hospital follow-ups participants with thoracic SCI had the lowest adherence rate (49.79%), followed by lumbar (72.62%) and cervical (77.59%) groups. Preferences for medical consultation were highest for rehabilitation physicians at 65.68%, with neurourologists following at 33.83%. Key barriers to follow-up adherence were identified as the more severity of SCI, lack of disease knowledge, increasing age, and reliance on adult children for care. In contrast, positive predictors of follow-up adherence were ample financial support and previous medical consultation experiences.

CONCLUSION: This study revealed insufficient follow-up adherence among SCI individuals with NLUTD, with CIC emerging as the preferred method for bladder emptying strategy. Age and injury level significantly influenced adherence. To improve long-term management of NLUTD, future initiatives should focus on enhancing health education accessibility, optimizing healthcare services, and providing comprehensive financial support to high-risk groups.}, } @article {pmid40124702, year = {2025}, author = {Sahoo, AS and Salman, M and Singh, B and Weston-Petrides, G and Ragad, L and Elayyan, R}, title = {Scout In, Scout out: Savi scout reflector traversing a dilated duct to the nipple in breast cancer localisation-a case report.}, journal = {Oxford medical case reports}, volume = {2025}, number = {3}, pages = {omae196}, pmid = {40124702}, issn = {2053-8855}, abstract = {INTRODUCTION: Savi scout system is being widely used for localising and excising breast tumours. While the migration of scout reflectors has been documented, this is the first case of a Savi Scout reflector migrating through a dilated duct near the lesion and coming out of the nipple.

CASE PRESENTATION: A 56-year-old postmenopausal woman with a history of right breast intraductal papilloma which transformed to Grade II Invasive Ductal Carcinoma (IDC) has a Savi Scout reflector placed in the tumour. However, it migrated through a dilated duct and emerged at the nipple, causing severe pain. The reflector was then surgically removed, and the patient subsequently underwent wide local excision with skin marker localisation.

CONCLUSION: Anatomical variations such as presence of dilated ducts need to be considered before placing scout reflectors. Appropriate positioning would prevent them from migrating through such ducts avoiding patient discomfort and further procedures for localisation.}, } @article {pmid40124148, year = {2025}, author = {Manimaran, P and Shah, A and Gami, A and Gandhi, J and Kakoty, S and Rai, V and Trivedi, PP}, title = {Tumor Budding: A Novel Prognostic Marker in Breast Carcinoma with Correlation of Histopathological and Immunohistochemical Parameters.}, journal = {South Asian journal of cancer}, volume = {14}, number = {1}, pages = {38-44}, pmid = {40124148}, issn = {2278-330X}, abstract = {INTRODUCTION: Breast cancer is a highly heterogenous tumor with different subtypes showing varying prognosis. Tumor budding is an unfavorable histological feature of many epithelial cancers. The purpose of this study is to analyze the association between tumor bud density with various histological and immunohistochemical characteristics and to explore its prognostic role in breast carcinoma.

MATERIALS AND METHODS: A retrospective analysis was performed on 100 patients of breast cancer diagnosed in our institute from January to December 2017. Hematoxylin and eosin (H&E) stained slides from tumors and immunohistochemical slides were reviewed independently by two pathologists, and clinical data were acquired from computerized records. Patients on neoadjuvant chemotherapy were excluded from the study.

RESULTS: The study comprised 100 patients of invasive breast carcinoma. The median age was 52 years, and 96% were invasive ductal carcinoma. The median follow-up was 34 months. High tumor bud density was substantially correlated with primary tumor staging (T3, T4; 73% [11/15] cases) and lymph node staging (N2, N3; 68% [13/19] cases) with p -values of 0.017 and 0.023, respectively. Systemic metastasis (85% [6/7] cases) was significantly associated with high tumor bud density (p =0.025) but lymphovascular invasion (LVI) and perineural invasion (PNI) were not significantly associated with tumor bud density (p  = 0.762 and 0.862, respectively). Patients with N2 nodal stage had low event-free survival rate than N0/N1 nodal stage irrespective of tumor bud status. Grade 3 tumors with high tumor bud density had worse event-free survival than any other grades. There was no association of tumor bud density with tumor staging, necrosis, PNI, LVI, estrogen receptor (ER), progesterone receptor (PR) and Her2/neu , and event-free survival.

CONCLUSION: Strong relationships have been found between tumor bud density and poor prognostic variables such as primary tumor staging and lymph node staging. These results provide credence to the idea that tumor bud density can be an assessable prognostic feature that should be taken into account while reporting breast cancer cases. Tumor bud density evaluation has to be standardized nevertheless if it is to be widely adopted.}, } @article {pmid40124146, year = {2025}, author = {Singh, SP and Thakur, CS and Makhaik, S and Thakur, S and Jhobta, A and Kapila, S and Sharma, N and Aggarwal, N}, title = {Role of Image-Guided Biopsy in Nonpalpable Breast Lesions: A Study in the Sub-Himalayan Region of North India.}, journal = {South Asian journal of cancer}, volume = {14}, number = {1}, pages = {53-61}, pmid = {40124146}, issn = {2278-330X}, abstract = {BACKGROUND: Nonpalpable breast lesions pose a challenge in their early diagnosis. Image-guided biopsy is preferred in these cases so that a pathological diagnosis of breast carcinoma is reached timely for a better prognosis as the disease has an increased chance of successful outcome with early identification and treatment.

OBJECTIVE: The study aims at evaluating the role of stereotactic core needle biopsy (CNB) and percutaneous ultrasound-guided core needle biopsy (US-CNB) in diagnosing suspicious nonpalpable breast lesions.

METHODS: Our study included 35 patients with nonpalpable breast lesions and having a Breast Imaging Reporting and Data System (BI-RADS) risk assessment category IV or V on mammography or sonography. These 35 lesions were subjected to percutaneous image-guided (stereotactic or US) biopsy for histopathological analysis.

RESULTS: Out of a total of 35 cases, 17 were pathologically malignant (48.6%), with the most common subtype being invasive ductal carcinoma (82.3%). Twenty-nine cases underwent US-CNB, 16 (55.1%) of which were malignant and 13 (44.8%) were benign on histopathological evaluation (HPE). The remaining six cases, which on mammography showed no mass but suspicious malignant calcification only, were subjected to stereotactic CNB, out of which one (16.6%) was malignant and five (83.3%) were benign on HPE. Hence, the lesions visible on sonography were more likely to be malignant.

CONCLUSION: Sonography and mammography play a complimentary role in detecting breast carcinoma. Percutaneous biopsy under image guidance can be used as an accurate diagnostic alternative to open surgical excisional biopsy to avoid diagnostic delay.}, } @article {pmid40121795, year = {2025}, author = {Manti, F and Di Carlo, E and Santagata, S and Giovanniello, T and Angeloni, A and Pisani, F and Pascucci, T and Nardecchia, F and Carducci, C and Leuzzi, V}, title = {The clinical value of peripheral biogenic amine metabolites in early-treated phenylketonuria.}, journal = {Molecular genetics and metabolism}, volume = {145}, number = {1}, pages = {109088}, doi = {10.1016/j.ymgme.2025.109088}, pmid = {40121795}, issn = {1096-7206}, mesh = {Humans ; *Phenylketonurias/blood/metabolism/diet therapy ; Female ; Adult ; Male ; *Biogenic Amines/blood/metabolism ; Cross-Sectional Studies ; Serotonin/blood ; Middle Aged ; Phenylalanine/blood ; Tandem Mass Spectrometry ; Young Adult ; 5-Hydroxytryptophan/blood ; Biomarkers/blood ; Case-Control Studies ; Hydroxyindoleacetic Acid/blood ; }, abstract = {BACKGROUND: Brain monoamine depletion is a well-established biochemical consequence of phenylketonuria (PKU). Similar alterations are expected in the peripheral biogenic amines (PBA), which share the same metabolic pathway with the brain. The present cross-sectional study explored the potential prognostic value of PBA by examining their relationship with blood Phe and clinical outcomes in early-treated adult PKU patients (ETPKU).

METHOD: 53 ETPKU (age 27.14 ± 8.22 years; 35 female) and 60 age-matched control subjects (age 43 ± 13 years; 43 female) were enrolled in the study. A UPLC-ESI-MS/MS-based method was developed to assess 5-hydroxytryptophan (5-HTP), serotonin (5-HT), 5-hydroxyhyndolacetic acid (5-HIAA), and 3-O-methyldopa (3-OMD) in different blood-derived matrices. Life-long Index of Dietary Control (IDC), concurrent Phe, and Tyr were other parameters included in the analysis. Clinical outcome measures included IQ, executive functions (BRIEF), and psychiatric morbidity (CBCL/ASR and DSM-5-TR).

RESULTS: 5-HTP, 5-HIAA, and 3-OMD were significantly lower in PKU patients than in controls. 5-HIAA and 3-OMD were negatively correlated with concurrent Phe levels. Concerning outcome measures, IDC influenced IQ and BRIEF-Shift subscale, 5-HIAA BRIEF-Emotional Control, 3-OMD BRIEF-Initiate subscale, and Tyr BRIEF-Control subscale. In contrast, concurrent plasma Phe did not affect any outcome measures.

CONCLUSION: While confirming the negative influence of Phe on PBA in adult ETPKU, mimicking what happens in the brain, we also found an effect of PBA depletion on clinical outcome measures independent of Phe level. This suggests that PBA could serve as new candidate biomarkers for treatment monitoring in adult ETPKU patients.}, } @article {pmid40119428, year = {2025}, author = {Fortunato, A and Mallo, D and Cisneros, L and King, LM and Khan, A and Curtis, C and Ryser, MD and Lo, JY and Hall, A and Marks, JR and Hwang, ES and Maley, CC}, title = {Evolutionary measures show that recurrence of DCIS is distinct from progression to breast cancer.}, journal = {Breast cancer research : BCR}, volume = {27}, number = {1}, pages = {43}, pmid = {40119428}, issn = {1465-542X}, support = {U2C CA233254/CA/NCI NIH HHS/United States ; U54 CA217376/NH/NIH HHS/United States ; U2C CA233254/NH/NIH HHS/United States ; ADHS18-198847//Arizona Biomedical Research Commission/ ; U54 CA217376/CA/NCI NIH HHS/United States ; BC132057//Congressionally Directed Medical Research Programs/ ; R01 CA140657/CA/NCI NIH HHS/United States ; R21 CA257980/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/genetics/therapy ; *Carcinoma, Intraductal, Noninfiltrating/pathology/genetics/therapy ; Disease Progression ; *Neoplasm Recurrence, Local/pathology/genetics ; Middle Aged ; Exome Sequencing ; Biomarkers, Tumor/genetics ; Aged ; Adult ; Cross-Sectional Studies ; Longitudinal Studies ; Prognosis ; }, abstract = {BACKGROUND: Progression from pre-cancers like ductal carcinoma in situ (DCIS) to invasive disease (cancer) is driven by somatic evolution and is altered by clinical interventions. We hypothesized that genetic and/or phenotypic intra-tumor heterogeneity would predict clinical outcomes for DCIS since it serves as the substrate for natural selection among cells.

METHODS: We profiled two samples from two geographically distinct foci from each DCIS in both cross-sectional (n = 119) and longitudinal cohorts (n = 224), with whole exome sequencing, low-pass whole genome sequencing, and a panel of immunohistochemical markers.

RESULTS: In the longitudinal cohorts, the only statistically significant associations with time to non-invasive DCIS recurrence were the combination of treatment (lumpectomy only vs mastectomy or lumpectomy with radiation, HR 12.13, p = 0.003, Wald test with FDR correction), ER status (HR 0.16 for ER+ compared to ER-, p = 0.0045), and divergence in SNVs between the two samples (HR 1.33 per 10% divergence, p = 0.018). SNV divergence also distinguished between pure DCIS and DCIS synchronous with invasive disease in the cross-sectional cohort. In contrast, the only statistically significant associations with time to progression to invasive disease were the combination of the width of the surgical margin (HR 0.67 per mm, p = 0.043) and the number of mutations that were detectable at high allele frequencies (HR 1.30 per 10 SNVs, p = 0.02). No predictors were significantly associated with both DCIS recurrence and progression to invasive disease, suggesting that the evolutionary scenarios that lead to these clinical outcomes are markedly different.

CONCLUSIONS: These results imply that recurrence with DCIS is a clinical and biological process different from invasive progression.}, } @article {pmid40114993, year = {2025}, author = {Salar, H and Anns, KM and Salar, M and Khan, F and Aman, M and Zafar, U and Ahmad, I and Basharat, S and Murad, R and Salar, K and Anwar, SSM}, title = {From Gut to Gray Matter: A Case Report of Posterior Reversible Encephalopathy Syndrome in a Pediatric Patient With Celiac Disease.}, journal = {Clinical case reports}, volume = {13}, number = {3}, pages = {e70260}, pmid = {40114993}, issn = {2050-0904}, abstract = {Posterior reversible encephalopathy syndrome (PRES) is a rare neurological condition characterized by vasogenic edema, primarily affecting the posterior cerebral hemispheres. Although typically reversible with prompt treatment, PRES can lead to severe complications if not recognized early. This report presents an unusual and fatal case of PRES in a pediatric patient with celiac disease, a combination that is rarely documented in medical literature. A 9-year-old child with a history of celiac disease and dermatitis herpetiformis presented to the Emergency Room with a two-month history of vomiting and loose stools, accompanied by a recent 20-min seizure. Initial examination revealed pallor, emaciation, drowsiness, and a generalized rash. The patient was tachycardic, hypertensive (blood pressure 150/100 mmHg), and had an oxygen saturation of 65%. Neurological examination showed a glasgow coma scale (GCS) score of 10/15, increased muscle tone, and heightened reflexes. CT and MRI scans revealed intraparenchymal and subarachnoid hemorrhages. Despite aggressive management including intubation, antihypertensive therapy, anticonvulsants, and broad-spectrum antibiotics, the patient's condition deteriorated rapidly. Complications included pneumoperitoneum and eventual cardiac arrest, leading to the patient's death. This case highlights the potential for severe, life-threatening complications of PRES in pediatric patients with underlying autoimmune conditions such as celiac disease. It underscores the importance of considering PRES in the differential diagnosis for children with celiac disease presenting with neurological symptoms, even in the absence of typical radiological findings. The case also illustrates the need for further research into the relationship between celiac disease and PRES to improve outcomes in similar cases.}, } @article {pmid40114895, year = {2025}, author = {Ahuja, S and Ahluwalia, C}, title = {Comprehensive Analysis of Disease Spectrum in Mastectomy Cases Over a 1-Year Period: An Observational Study.}, journal = {Indian journal of surgical oncology}, volume = {16}, number = {1}, pages = {159-164}, pmid = {40114895}, issn = {0975-7651}, abstract = {Breast cancer is a prevalent malignancy requiring mastectomy for various indications. Understanding the disease spectrum in mastectomy cases is essential for improving patient outcomes and treatment strategies. This retrospective observational study was conducted at a tertiary care hospital from April 2023 to April 2024. We analyzed records of all patients who underwent mastectomy during this period. Data on demographics, clinical indications, and histopathological findings were extracted and analyzed using SPSS software. Descriptive statistics were used for quantitative variables, and qualitative variables were presented as numbers and percentages. A total of 184 mastectomy cases were included, with 182 (98.9%) females and two (1.1%) males. The mean age was 42.5 ± 18.8 years. Among the cases, 107 (58.2%) received neoadjuvant therapy. Pathologies included invasive breast carcinoma (65.8%), ductal carcinoma in situ (7.6%), phyllodes tumor (6.5%), and no residual tumor post-neoadjuvant therapy (20.1%). Most invasive breast carcinomas were grade 2 (69.4%) and T2 stage (47.1%), with 69.4% showing nodal involvement. The predominant histological subtype was invasive ductal carcinoma (92.6%). Molecular classifications were luminal B (42.9%), Her2 enriched (26.5%), and triple-negative (16.5%). Phyllodes tumors were benign (33.3%), borderline (25%), and malignant (41.7%). DCIS cases were mostly high nuclear grade (64.3%). This study highlights the diverse spectrum of breast diseases necessitating mastectomy, emphasizing the need for improved screening, early detection, and personalized treatment. Future research should focus on tracking outcomes and exploring factors contributing to this disease spectrum.}, } @article {pmid40112548, year = {2025}, author = {Moustakas, A and Zemah-Shamir, S and Tase, M and Zotos, S and Demirel, N and Zoumides, C and Christoforidi, I and Dindaroglu, T and Albayrak, T and Ayhan, CK and Fois, M and Manolaki, P and Sandor, AD and Sieber, I and Stamatiadou, V and Tzirkalli, E and Vogiatzakis, IN and Zemah-Shamir, Z and Zittis, G}, title = {Climate land use and other drivers' impacts on island ecosystem services: A global review.}, journal = {The Science of the total environment}, volume = {973}, number = {}, pages = {179147}, doi = {10.1016/j.scitotenv.2025.179147}, pmid = {40112548}, issn = {1879-1026}, abstract = {Islands are diversity hotspots and vulnerable to environmental degradation, climate variations, land use changes and societal crises. These factors can exhibit interactive impacts on ecosystem services. The study reviewed a large number of papers on the climate change-islands-ecosystem services topic worldwide. Potential inclusion of land use changes and other drivers of impacts on ecosystem services were sequentially also recorded. The study sought to investigate the impacts of climate change, land use change, and other non-climatic driver changes on island ecosystem services. Explanatory variables examined were divided into two categories: environmental variables and methodological ones. Environmental variables include sea zone geographic location, ecosystem, ecosystem services, climate, land use, other driver variables, Methodological variables include consideration of policy interventions, uncertainty assessment, cumulative effects of climate change, synergistic effects of climate change with land use change and other anthropogenic and environmental drivers, and the diversity of variables used in the analysis. Machine learning and statistical methods were used to analyze their effects on island ecosystem services. Negative climate change impacts on ecosystem services are better quantified by land use change or other non-climatic driver variables than by climate variables. The synergy of land use together with climate changes is modulating the impact outcome and critical for a better impact assessment. Analyzed together, there is little evidence of more pronounced effects for a specific sea zone, ecosystem, or ecosystem service. Climate change impacts may be underestimated due to the use of a single climate variable deployed in most studies. Policy interventions exhibit low classification accuracy in quantifying impacts indicating insufficient efficacy or integration in the studies.}, } @article {pmid40110252, year = {2025}, author = {Zaiter, M and Naccour, J and Khalil, F and El-Helou, E}, title = {Metaplastic breast carcinoma: a rare and aggressive entity.}, journal = {Annals of medicine and surgery (2012)}, volume = {87}, number = {2}, pages = {985-990}, pmid = {40110252}, issn = {2049-0801}, abstract = {INTRODUCTION: Breast cancer (BC) remains the most prevalent malignancy among women globally, encompassing a variety of tumor subtypes with differing biological behaviors, prognoses, and responses to treatment. Among these, invasive ductal carcinoma (IDC) is the most common, followed by other subtypes such as lobular carcinoma and triple-negative breast cancer. Metaplastic breast carcinoma (MpBC) is a rare and highly aggressive form of BC, representing less than 2% of cases. Characterized by its heterogeneous nature and poorer prognosis compared to other BC subtypes, MpBC often presents significant diagnostic and therapeutic challenges.

CASE DESCRIPTION: We present the case of a 70-year-old woman who presented to our breast care clinic with right mastodynia following a recent trauma. She reported a palpable retro-areolar mass in the right breast that had increased in size over several years and was associated with calcifications. Imaging studies, including mammography and ultrasound, revealed a 3-cm irregular, heavily calcified mass with indistinct borders. Histological analysis of a biopsy confirmed metaplastic carcinoma with chondrosarcoma and osteosarcoma elements, high histological grade, and lymphovascular involvement. The patient underwent successful tumor excision with sentinel lymph node removal. Adjuvant chemotherapy and radiotherapy were planned based on a multidisciplinary team's recommendations.

DISCUSSION: MpBC typically presents as a palpable, irregular mass that may exhibit rapid growth or changes, often complicating its differentiation from other breast malignancies. Standard imaging techniques like mammography and ultrasound may fail to clearly distinguish MpBC from other tumors, leading to potential misdiagnosis. The heterogeneous nature of MpBC, with both epithelial and mesenchymal components, poses additional challenges in diagnosis and treatment. Although MpBC is generally more aggressive and less responsive to conventional therapies compared to IDC, recent analyses suggest that, when adjusted for confounding factors, survival outcomes for MpBC may align more closely with those of aggressive IDC subtypes. Current treatment strategies include surgery, chemotherapy, and radiotherapy, with emerging targeted therapies offering potential for improved outcomes.

CONCLUSION: MpBC remains a rare and challenging BC subtype with a typically poor prognosis. Our case highlights the diagnostic difficulties and the aggressive nature of MpBC. Despite its severe clinical features and histological grades, survival outcomes for MpBC may be comparable to those of aggressive IDC subtypes when appropriate treatment adjustments are made. Continued research into targeted therapies and novel treatment approaches is essential to enhance management strategies and improve outcomes for patients with MpBC.}, } @article {pmid40109539, year = {2025}, author = {Zhang, J and Arroyo, J and Lediju Bell, MA}, title = {Multispectral photoacoustic imaging of breast cancer tissue with histopathology validation.}, journal = {Biomedical optics express}, volume = {16}, number = {3}, pages = {995-1005}, pmid = {40109539}, issn = {2156-7085}, abstract = {Intraoperative multispectral photoacoustic pathology assessment presents a promising approach to guide biopsy resection. In this study, we developed and validated a novel photoacoustic technique to differentiate between healthy and cancerous tissues. Our method consisted of photoacoustic contrast calculations as a function of wavelength, followed by projections of the resulting spectra from training data into a two-dimensional space using principal component analysis to create representative spectra, then calculation of the average cosine similarity between the spectrum of each pixel in test data and the representative spectra. The test healthy tissue region had a 0.967 mean correlation with the representative healthy tissue spectrum and a lower mean correlation (0.801) with the cancer tissue spectrum. The test cancer tissue region had a 0.954 mean correlation with the cancer tissue spectrum and a lower mean correlation (0.762) with the healthy tissue spectrum. Our method was further validated through qualitative comparison with high-resolution hematoxylin and eosin histopathology scans. Healthy tissue was primarily correlated with the optical absorption of blood (i.e., deoxyhemoglobin), while invasive ductal carcinoma breast cancer tissue was primarily correlated with the optical absorption of lipids. Our label-free histopathology approach utilizing multispectral photoacoustic imaging has the potential to enable real-time tumor margin determination during biopsy or surgery.}, } @article {pmid40108012, year = {2025}, author = {Eom, HJ and Choi, WJ and Sun, YJ and Kim, HJ and Chae, EY and Shin, HJ and Cha, JH and Kim, HH}, title = {Preoperative breast MRI in HER2-positive/hormone receptor-negative breast cancer: surgical outcomes using propensity score matching.}, journal = {European radiology}, volume = {35}, number = {9}, pages = {5648-5657}, pmid = {40108012}, issn = {1432-1084}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery/diagnostic imaging/metabolism/pathology ; *Magnetic Resonance Imaging/methods ; Middle Aged ; Propensity Score ; *Erb-b2 Receptor Tyrosine Kinases/metabolism ; Retrospective Studies ; Preoperative Care/methods ; Mastectomy ; Treatment Outcome ; Adult ; *Carcinoma, Ductal, Breast/surgery/diagnostic imaging/metabolism ; Aged ; }, abstract = {OBJECTIVES: To examine the association between preoperative magnetic resonance imaging (MRI) and surgical outcomes in human epidermal growth factor receptor 2 (HER2)-positive/hormone receptor (HR)-negative breast cancer through a propensity score (PS)-matched analysis.

MATERIALS AND METHODS: Patients with HER2-positive/HR-negative invasive ductal carcinoma between 2007 and 2014 were retrospectively assessed and compared according to whether they underwent preoperative MRI. Inverse probability weighting (IPW) analysis and PS matching were used to adjust 17 covariates to control between the MRI and no-MRI groups. Surgical outcomes were compared between two groups and clinicopathologic variables were evaluated to determine who benefited from MRI.

RESULTS: Among 965 women (mean age ± standard deviation, 52 years ± 10), 423 (44%) underwent preoperative MRI and 542 (56%) did not. In the MRI group, a change in surgical management occurred in 48 patients (11%), and the change was appropriate in 31 of those patients (65%). The MRI group had a lower odds of initial mastectomy (odds ratio [OR], 0.63; 95% confidence interval [CI]: 0.47, 0.84; p = 0.002 and OR, 0.67; 95% CI: 0.48, 0.92; p = 0.01 for IPW and PS matching, respectively) and overall mastectomy (OR, 0.60; 95% [CI]: 0.45, 0.80; p = 0.001 and OR, 0.68; 95% CI: 0.49, 0.93; p = 0.02 for IPW and PS matching, respectively). In the subgroup analysis, asymptomatic patients or those with multifocal or multicentric lesions benefited more from MRI (61% vs 36%, p = 0.006 and 52% vs 31%, p = 0.02, respectively).

CONCLUSION: Patients with HER2-positive/HR-negative breast cancer who received preoperative MRI had a lower likelihood of undergoing mastectomy.

KEY POINTS: Question The role of preoperative MRI in predicting surgical outcomes in patients with HER2-positive/HR-negative breast cancer remains uncertain. Findings Preoperative MRI in HER2-positive/HR-negative breast cancer reduces mastectomy rates without increasing the positive resection margin or reoperation rate. Clinical relevance Preoperative MRI is beneficial in reducing mastectomy rates in women with HER2-positive/HR-negative breast cancer.}, } @article {pmid40104919, year = {2025}, author = {Sheikh, F and Fineberg, S and Laurini, J and Lanjewar, S}, title = {Loss of Cytokeratin 7 (CK7) Expression Can be Seen in Significant Proportion of Solid Papillary Carcinoma of Breast and Associated Invasive Component.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {33}, number = {3}, pages = {152-159}, doi = {10.1097/PAI.0000000000001256}, pmid = {40104919}, issn = {1533-4058}, support = {N/A//None/ ; }, mesh = {Humans ; *Keratin-7/metabolism/biosynthesis ; *Breast Neoplasms/pathology/metabolism ; Female ; *Carcinoma, Papillary/metabolism/pathology ; *Biomarkers, Tumor/metabolism ; *Carcinoma, Ductal, Breast/metabolism/pathology ; Immunohistochemistry ; Middle Aged ; Aged ; *Gene Expression Regulation, Neoplastic ; Adult ; Neoplasm Invasiveness ; }, abstract = {ABSTRACT: Cytokeratin 7 (CK7) is a marker of epithelial differentiation and is positive in >90% of breast carcinomas. In the right clinical setting, coexpression of CK7 and GATA3 is considered as strong evidence of breast origin, which can be further confirmed by positive expression of estrogen and progesterone receptors. Pathologists use CK7 in the breast to confirm epithelial differentiation and highlight foci of invasion, and outside the breast it is often used as a marker to support breast origin of metastatic tumors. Few studies have reported loss of CK7 in invasive breast carcinoma, however, association of CK7 loss with any histopathologic subtype has not been well documented in the literature. We stained a series of solid papillary carcinoma of the breast (SPC) and associated invasive ductal carcinoma (IDC) with CK7 to document that CK7 loss can occur in both SPC and associated IDC. Archived breast tumor tissue specimens with a diagnosis of SPC with IDC were identified from our Department of Pathology database from January 2019 to January 2023. Blocks with tumors were initially evaluated on Hematoxylin and Eosin (H&E) slides, and subsequently with CK7, synaptophysin, and chromogranin immunostains. The results of these immunohistochemical markers were tabulated in an Excel sheet. Expression of CK7 was entered as negative, marked loss of CK7 (weak positive staining in <1% of tumor), and positive (diffuse expression >1% to 100% of tumor cells). Out of 26 tumors of SPC, 15 showed negative to a marked loss of expression for CK7 in both in-situ and invasive components (57.7%), while 11 were diffusely positive (42.3%). Neuroendocrine differentiation was present in 57.7% of tumors of which 60% were CK7 negative. However, there was no significant association between neuroendocrine differentiation in SPC and associated IDC with CK7 loss (P =1). In addition, histologic parameters, biomarkers expression, Ki-67 expression, and clinical follow-up were studied in detail.

CONCLUSION: A significant proportion of solid papillary carcinoma of the breast and the associated invasive component can show loss of CK7.}, } @article {pmid40098503, year = {2025}, author = {Jha, A and Regmi, PR and Pradhan, H and Thakur, M and Joshi, BR}, title = {Sonography as an Adjunct to Digital Mammography in Patients with Dense Breasts.}, journal = {Journal of Nepal Health Research Council}, volume = {22}, number = {4}, pages = {670-677}, doi = {10.33314/jnhrc.v22i04.4735}, pmid = {40098503}, issn = {1999-6217}, mesh = {Humans ; Female ; Cross-Sectional Studies ; *Mammography/methods ; Prospective Studies ; Middle Aged ; *Breast Neoplasms/diagnostic imaging/diagnosis ; Adult ; *Breast Density ; Aged ; *Ultrasonography, Mammary ; Sensitivity and Specificity ; Nepal ; Young Adult ; }, abstract = {BACKGROUND: Dense breasts are associated with an increased risk of cancer and also mask lesions on mammograms. In our study, we evaluated the role of sonography as an adjunct to digital mammography in patients with dense breasts.

METHODS: Sonography of 676 female patients with American College of Radiology category C or D mammographic density was done in this prospective cross-sectional analytical study in the Department of Radiology, Tribhuvan University Teaching Hospital. The final imaging diagnosis was classified as per the American College of Radiology Breast Imaging Reporting and Data System categories. Tissue diagnosis was obtained in patients with sonographic category 3 solid lesions larger than 3 cm, category 4 and 5 lesions. The data were tabulated and analyzed using Statistical Package for Social Service (SPSS) for Windows version 22.

RESULTS: Additional sonography confirmed all BIRADS 1 mammograms as normal or benign, 95.7 % (112) of inconclusive, and 82.8% (n=135) of BIRADS 3 ones as benign. It had higher sensitivity and negative predictive value (100%) than mammography with similar accuracy. Most patients (479, 70.9%) had diagnostic indications. There were 540 (79.9%) cases in ACR BIRADS category c. A final diagnosis of benign (316, 46.7%) was most common, followed by normal (293, 43.4%) and malignant (67, 9.9%). The majority of the malignant lesions were Invasive Ductal Carcinoma (59, 88%).

CONCLUSIONS: Additional sonography confirmed mammography findings as normal, benign, or suspicious for malignancy, definitely described morphology and extent of mass, and also guided biopsy. It had higher sensitivity than mammography in dense breasts.}, } @article {pmid40081589, year = {2025}, author = {Podoly, TY and Even-Ezra, H and Doron, G}, title = {A randomized controlled trial evaluating an mHealth intervention for anger-related cognitions in misophonia.}, journal = {Journal of affective disorders}, volume = {379}, number = {}, pages = {350-361}, doi = {10.1016/j.jad.2025.03.060}, pmid = {40081589}, issn = {1573-2517}, mesh = {Humans ; Male ; Female ; *Anger ; Telemedicine ; Adult ; *Mobile Applications ; Young Adult ; *Rage ; Treatment Outcome ; Adolescent ; Hearing Disorders ; }, abstract = {Misophonia is a condition characterized by strong, aversive reactions to specific sounds produced by others, often manifesting as intense negative emotions like anger or rage in response to nearby noises. The present study aimed to evaluate the effectiveness of an mHealth app in reducing misophonia symptoms and related cognitions. In this study, 85 participants were randomly assigned to an immediate app use (iApp) or delayed app use (dApp) group and completed measures at baseline (T0), after 15 days of app use (T1 for iApp, T2 for dApp), and at 1-month follow-up (T3). Intention-to-treat analyses at T1 revealed significant interaction effects; compared with the dApp group, the iApp group exhibited lower misophonia symptoms on select measures (interaction effect sizes ranging from d = 0.06 to 0.52) as well as reductions in anger ruminations and anger-related metacognitions (interaction effect sizes of d = 0.47). Within-group analyses demonstrated substantial reductions in misophonia symptoms from baseline to follow-up (iApp: d = 0.62-1.51; dApp: d = 0.89-1.75) with similar decreases in anger-related outcomes (iApp: d = 0.89-0.92; dApp: d = 0.85-0.90). Mediation analyses, however, did not support an indirect effect of the intervention on misophonia symptoms via changes in rumination or anger-related metacognitions. mHealth applications show promise in alleviating misophonia symptoms and related cognitive processes. Further research is needed to elucidate the roles of anger rumination and metacognitions in misophonia.}, } @article {pmid40079036, year = {2025}, author = {Bui, J and Chalom, T and Nathanson, SD and Schwartz, TL and Hunt, K and Alkhoory, W and Xu, Z}, title = {Invasive ductal carcinoma at the site of a cosmetic nipple piercing.}, journal = {Journal of surgical case reports}, volume = {2025}, number = {3}, pages = {rjaf132}, pmid = {40079036}, issn = {2042-8812}, abstract = {We report a young female patient diagnosed with an invasive ductal carcinoma at the site of a prior cosmetic nipple piercing. She had no significant familial, genetic, or other carcinogenic risk factors to account for her presentation. A review of the literature confirms that trauma can occasionally be associated with invasive breast cancer, but such a connection has not previously been related to nipple piercing procedures.}, } @article {pmid40078045, year = {2025}, author = {Shenkman, G and Ifrah, K and Shaia, Y}, title = {Predictors for desire, intention, and likelihood for more children among LGB parents through assisted reproduction.}, journal = {Journal of reproductive and infant psychology}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/02646838.2025.2478398}, pmid = {40078045}, issn = {1469-672X}, abstract = {BACKGROUND: The global increase in families headed by lesbian, gay, or bisexual (LGB) parents via assisted reproduction was accompanied by increased research on the parenthood aspirations of childfree LGB individuals. However, limited attention has been given to the aspirations of LGB parents for more children. This study explored the multifaceted factors associating with aspirations for additional children among Israeli LGB parents through assisted reproduction, investigating the contribution of sociodemographic variables, parental experiences, as well as social and cultural factors to these aspirations.

METHODS: A survey involving 234 cisgender LGB parents in Israel (aged 24-55; M = 40.23, SD = 6.59) was conducted from November 2022 to February 2024. Participants completed questionnaires assessing their desire, intention, and estimated likelihood to have more children alongside various sociodemographic, parental experience, social, and cultural variables.

RESULTS: Hierarchical regressions revealed that sociodemographic variables, namely younger parent age, fewer current children, higher importance of religious values, and better economic status, were associated with stronger aspirations for additional children. Social (discrimination, enacted stigma, social support) and cultural (pronatalism) factors did not significantly contribute beyond sociodemographic factors.

CONCLUSION: Unlike research on parenthood aspirations among childfree LGB individuals, social and cultural factors played a less significant role in shaping aspirations for more children among LGB individuals who are already parents. The findings offer essential insights for reproductive and family researchers, as well as policymakers, by shedding light on the factors associated with LGB parents' aspiration for additional children through assisted reproduction.}, } @article {pmid40073896, year = {2025}, author = {Kinoshita, M and Takeda, Y and Iwagami, Y and Shinke, G and Ohmura, Y and Yukawa, Y and Arita, A and Yanagisawa, K and Katsuyama, S and Ikeshima, R and Hiraki, M and Sugimura, K and Masuzawa, T and Hata, T and Murata, K}, title = {[A Case of Pancreatic Acinar Cell Carcinoma with Invasive Ductal Carcinoma and Neuroendocrine Tumor].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {52}, number = {2}, pages = {164-166}, pmid = {40073896}, issn = {0385-0684}, mesh = {Humans ; Female ; Middle Aged ; *Pancreatic Neoplasms/pathology/surgery/drug therapy ; *Carcinoma, Acinar Cell/surgery/pathology/drug therapy ; *Carcinoma, Pancreatic Ductal/surgery/pathology ; Lymphatic Metastasis ; Neoplasm Invasiveness ; *Neuroendocrine Tumors/surgery/pathology ; Pancreaticoduodenectomy ; }, abstract = {A 50-year-old female presented with abdominal pain. Upper gastrointestinal endoscopy revealed a 30 mm ulcerative lesion extending from the duodenal bulb to the descending portion, and biopsy confirmed poorly differentiated adenocarcinoma. Abdominal contrast-enhanced CT scan showed an hypovascular tumor in the pancreatic head with suspected invasion into the duodenum, along with enlarged #8 lymph node. PET-CT revealed abnormal uptake in the pancreatic head and #8 lymph node. She underwent robotic pancreaticoduodenectomy for a diagnosis of pancreatic head cancer with lymph node metastasis. Histopathological examination revealed proliferation of atypical cells in acinar, trabecular, ribbon-like anastomosing, and tubular structures. Immunohistochemistry showed positivity for Bcl10(60%), INSM1(20%), Ki-67 index of 45%, and coexistence of invasive ductal adenocarcinoma(20%). Based on these findings, the tumor was diagnosed as predominantly acinar cell carcinoma with invasive ductal adenocarcinoma and neuroendocrine tumor. Lymph node metastasis was positive showing Bcl10-positive acinar cell carcinoma. Four months postoperatively, recurrence was detected in the para-aortic lymph nodes, confirmed by biopsy to be acinar cell carcinoma. Chemotherapy was initiated but discontinued due to tumor progression leading to best supportive care.}, } @article {pmid40068648, year = {2025}, author = {D'Iorio, A and Aiello, EN and Vitale, C and Amboni, M and Verde, F and Silani, V and Ticozzi, N and Ciammola, A and Poletti, B and Santangelo, G}, title = {Diagnostics and Ecological Validity of the Italian Version of the Parkinson's Disease Cognitive Rating Scale.}, journal = {Dementia and geriatric cognitive disorders}, volume = {54}, number = {5}, pages = {347-351}, doi = {10.1159/000545090}, pmid = {40068648}, issn = {1421-9824}, mesh = {Humans ; *Parkinson Disease/psychology/diagnosis/complications ; Male ; Female ; Aged ; Italy ; Middle Aged ; Reproducibility of Results ; *Neuropsychological Tests ; Mental Status and Dementia Tests ; ROC Curve ; *Cognitive Dysfunction/diagnosis ; Sensitivity and Specificity ; Cognition ; }, abstract = {INTRODUCTION: This study aimed to assess the diagnostics and ecological validity of the Parkinson's Disease Cognitive Rating Scale (PD-CRS) within an Italian cohort of non-demented Parkinson's disease (PD) patients.

METHODS: N = 128 non-demented PD patients were administered the PD-CRS, Montreal Cognitive Assessment (MoCA), and Parkinson's Disease Cognitive Functioning Rating Scale (PD-CFRS). Receiver-operating characteristic analyses were performed to explore the diagnostics of both raw and adjusted PD-CRS scores, by operationalizing the positive state as a below-cut-off MoCA score. Correlational analyses were run to test the ecological validity of the PD-CRS against the PD-CFRS.

RESULTS: Both raw and adjusted PD-CRS scores accurately identified patients with a defective MoCA scores (AUC = 0.84-0.85), yielding optimal diagnostics. A cut-off of <73.93, as identified on demographically adjusted PD-CRS scores, yielded the best diagnostics (sensitivity = 0.70; specificity = 0.89; positive and negative predictive values = 0.83 and 0.79; positive and negative likelihood ratios: 6.23 and 0.37: number needed for screening utility: 0.78). The PD-CRS was related to the PD-CFRS (rs = -0.24; p = 0.018).

CONCLUSIONS: The Italian PD-CRS is a diagnostically sound and ecologically valid screener for cognitive impairment in non-demented PD patients.}, } @article {pmid40061778, year = {2024}, author = {Helena, V and Suresh, A and Muninathan, N and Baskaran, K and Khan, SA}, title = {Association of Triglycerides and HbA1c Levels with Stages of Invasive Ductal Breast Cancer: A Prospective Study.}, journal = {Journal of pharmacy & bioallied sciences}, volume = {16}, number = {Suppl 5}, pages = {S4559-S4562}, pmid = {40061778}, issn = {0976-4879}, abstract = {BACKGROUND: This prospective study investigates the association between triglyceride (TG) levels and HbA1c values with different stages of invasive ductal breast cancer (IDC) in female patients. Metabolic alterations, including dyslipidemia and hyperglycemia, are increasingly recognized as potential factors associated with cancer progression.

METHODS: A total of 150 female patients diagnosed with IDC were included in the study, categorized into four stages of the disease. Triglyceride levels were measured using colorimetry, and HbA1c values were determined using the ion exchange resin method. Descriptive statistics and distributions of TG and HbA1c values were analyzed across the cancer stages.

RESULTS: In Stage 1, patients had a mean TG level of 347.5 mg/dL and a mean HbA1c of 10.2%. These values declined in subsequent stages, with Stage 4 patients showing a mean TG level of 208.6 mg/dL and a mean HbA1c of 6.9%. A majority of Stage 1 patients (n = 35) had TG levels between 200 and 499 mg/dL, while Stage 4 had the highest number of patients with TG levels below 150 mg/dL (n = 6). Additionally, a significant proportion of Stage 1 patients had HbA1c values ≥10% (n = 17), indicating poor glycemic control. As the disease progressed, this proportion decreased, with only two patients in Stage 4 having HbA1c levels ≥10%.

CONCLUSION: This study suggests a correlation between lower TG and HbA1c levels and more advanced stages of IDC. These findings highlight the importance of metabolic factors in IDC progression and may inform future research on potential therapeutic targets.}, } @article {pmid40055309, year = {2025}, author = {El Bounkari, O and Zan, C and Yang, B and Ebert, S and Wagner, J and Bugar, E and Kramer, N and Bourilhon, P and Kontos, C and Zarwel, M and Sinitski, D and Milic, J and Jansen, Y and Kempf, WE and Sachs, N and Maegdefessel, L and Ji, H and Gokce, O and Riols, F and Haid, M and Gerra, S and Hoffmann, A and Brandhofer, M and Avdic, M and Bucala, R and Megens, RTA and Willemsen, N and Messerer, D and Schulz, C and Bartelt, A and Harm, T and Rath, D and Döring, Y and Gawaz, M and Weber, C and Kapurniotu, A and Bernhagen, J}, title = {An atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2297}, pmid = {40055309}, issn = {2041-1723}, mesh = {Animals ; *Lipogenesis/genetics ; *Atherosclerosis/metabolism/pathology/genetics ; Mice ; *Liver/metabolism/pathology ; Receptors, CXCR4/metabolism ; Humans ; *Macrophage Migration-Inhibitory Factors/metabolism/genetics ; Male ; *Intramolecular Oxidoreductases/metabolism/genetics ; *Chemokines/metabolism/genetics ; Mice, Inbred C57BL ; Mice, Knockout, ApoE ; Antigens, Differentiation, B-Lymphocyte/metabolism ; Signal Transduction ; Hepatocytes/metabolism ; Mice, Knockout ; Apolipoproteins E/genetics ; Histocompatibility Antigens Class II ; }, abstract = {Atherosclerosis is the underlying cause of myocardial infarction and ischemic stroke. It is a lipid-triggered and cytokine/chemokine-driven arterial inflammatory condition. We identify D-dopachrome tautomerase/macrophage migration-inhibitory factor-2 (MIF-2), a paralog of the cytokine MIF, as an atypical chemokine promoting both atherosclerosis and hepatic lipid accumulation. In hyperlipidemic Apoe[-/-] mice, Mif-2-deficiency and pharmacological MIF-2-blockade protect against lesion formation and vascular inflammation in early and advanced atherogenesis. MIF-2 promotes leukocyte migration, endothelial arrest, and foam-cell formation, and we identify CXCR4 as a receptor for MIF-2. Mif-2-deficiency in Apoe[-/-] mice leads to decreased plasma lipid levels and suppressed hepatic lipid accumulation, characterized by reductions in lipogenesis-related pathways, tri-/diacylglycerides, and cholesterol-esters, as revealed by hepatic transcriptomics/lipidomics. Hepatocyte cultures and FLIM-FRET-microscopy suggest that MIF-2 activates SREBP-driven lipogenic genes, mechanistically involving MIF-2-inducible CD74/CXCR4 complexes and PI3K/AKT but not AMPK signaling. MIF-2 is upregulated in unstable carotid plaques from atherosclerotic patients and its plasma concentration correlates with disease severity in patients with coronary artery disease. These findings establish MIF-2 as an atypical chemokine linking vascular inflammation to metabolic dysfunction in atherosclerosis.}, } @article {pmid40053423, year = {2025}, author = {Pecora, V and Samynathan, A and Rosenfeld, A and Tariq, Z and Saardi, K}, title = {Cutaneous metastases mimicking hidradenitis suppurativa: a diagnostic challenge.}, journal = {Wounds : a compendium of clinical research and practice}, volume = {37}, number = {2}, pages = {63-67}, doi = {10.25270/wnds/24155}, pmid = {40053423}, issn = {1943-2704}, mesh = {Humans ; *Breast Neoplasms/pathology ; Diagnosis, Differential ; *Hidradenitis Suppurativa/diagnosis/pathology ; *Skin Neoplasms/secondary/diagnosis/pathology ; }, abstract = {BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, recurrent, and debilitating inflammatory condition characterized by abscesses, comedones, and nodules. The heterogeneous presentation of HS often leads to diagnostic challenges, with clinical mimics such as cutaneous metastases (CMs) being of particular importance. CMs can present as initial manifestations of metastatic disease, necessitating accurate identification to guide potentially lifesaving treatment. However, the diagnostic and therapeutic approaches for HS and CMs differ significantly, underscoring the need for prompt and accurate differentiation.

CASE REPORT: This report presents 3 cases of primary malignancies in which CMs mimicked HS. Case 1 had diffuse large B-cell lymphoma; case 2 had a history of right breast atypical ductal hyperplasia and borderline low-grade ductal carcinoma in situ, along with triple-negative invasive ductal carcinoma of the left breast with extensive metastasis to the iliac bone and lung; and case 3 had invasive mammary carcinoma of the right breast with axillary lymph node involvement. All 3 patients presented with nodular lesions resembling HS, but further investigation, including molecular testing, confirmed the diagnosis of CMs.

CONCLUSION: The clinical overlap between HS and CMs, which can present with similar features such as nodules, abscesses, and draining lesions, underscores the critical importance of distinguishing these entities. Despite their similar clinical appearance, HS and CMs have vastly different management protocols. Accurate diagnosis of CMs enables timely and appropriate intervention, which in turn aids in optimizing clinical outcomes and ensuring the use of effective treatment strategies for affected patients.}, } @article {pmid40050715, year = {2025}, author = {Ong, SC and Tay, LX and Ong, HM and Tiong, IK and Ch'ng, ASH and Parumasivam, T}, title = {Annual societal cost of Alzheimer's disease in Malaysia: a micro-costing approach.}, journal = {BMC geriatrics}, volume = {25}, number = {1}, pages = {154}, pmid = {40050715}, issn = {1471-2318}, mesh = {Humans ; Malaysia/epidemiology ; *Alzheimer Disease/economics/epidemiology/therapy/diagnosis ; Male ; Female ; Aged ; *Cost of Illness ; *Caregivers/economics ; Aged, 80 and over ; *Health Care Costs ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) is expected to have a significant impact on resource use and economic consequences along with population aging. This study aims to investigate the annual economic burden of Alzheimer's disease along with underlying cost drivers.

METHODOLOGY: Patients with AD aged 65 and above accompanied with primary caregivers were recruited in 6 tertiary care hospitals. A structured interview was conducted to collect sociodemographic, clinical and resource use information using an adapted questionnaire. Direct medical cost, direct non-medical cost and indirect cost were annualised and categorised by severity level. Generalised linear models were applied to investigate predictors of costs.

RESULTS: Among 135 patient-caregiver dyads, the annual economic burden of AD from a societal perspective was USD 8618.83 ± USD 6740.79 per capita. The societal cost of severe AD patients (USD11943.19 ± USD6954.17) almost doubled those in mild AD (USD6281.10 ± USD6879.83). IDC was the primary cost driver (77.7%) which represented the impact of productivity loss due to informal care. Besides disease severity, time spent in informal care, caregivers' employment and use of special accommodation were predictors of AD cost. This neurodegenerative disorder is estimated to impose a burden of USD1.9 billion in 2022, which represents 0.47% of Malaysia's GDP.

CONCLUSION: This study provided real-world empirical cost estimates of AD burden in Malaysia. Informal care is a significant contributor to the societal cost of AD. Optimal healthcare resource allocation is essential in the decision making of healthcare stakeholders to address rising demands.}, } @article {pmid40046312, year = {2025}, author = {Rotbart, N and Kaminsky, O and Aranovich, D and Shochat, T and Atar, E and Grubstein, A}, title = {Revisiting the Need for Breast Imaging in Young Women with Clinically Significant Breast Pain and a Normal Physical Breast Examination.}, journal = {Breast care (Basel, Switzerland)}, volume = {20}, number = {1}, pages = {8-15}, pmid = {40046312}, issn = {1661-3791}, abstract = {INTRODUCTION: Although breast pain as a sole symptom is very rarely associated with cancer, national guidelines recommend that all women with a complaint of breast pain have to be referred for ultrasound evaluation. This study sought to investigate the necessity of this practice.

METHODS: A retrospective study was conducted in consecutive women aged between 17 and 39 years, at average risk of breast cancer who presented at a major tertiary breast clinic with clinically significant breast pain (unilateral, unifocal, and noncyclic) in 2017-2023. Data on background, physical examination, imaging, and pathology were collected from the electronic medical records and analyzed by outcome.

RESULTS: The cohort included 814 women. Among the 574 women (70%) with a normal physical breast examination, ultrasound revealed normal findings or BI-RADS 1-2 lesions in 499 (87%), BI-RADS 3 lesions in 59 (10%), and BI-RADS 4 lesions in 16 (3%). Biopsies, performed in 30 BI-RADS 3 lesions and all BI-RADS 4 lesions, were benign. Half of the 337 patients with available follow-up data continued to attend the breast clinic (mean 3.5 ± 2.2 years). Among the 240 women (30%) with a palpable abnormality on breast examination, ultrasound revealed normal or benign BI-RADS 2 findings in 112 (47%), BI-RADS 3 lesions in 69 (29%), and BI-RADS 4-5 lesions in 59 (25%). Biopsies performed in BI-RADS 3 lesions (12%) were all benign. Biopsies, performed in all BI-RADS 4-5 lesions, yielded malignant pathology in 16 lesions (7%) (including IDC, DCIS, or angiosarcoma). The overall breast cancer risk was 2%. Ultrasound sensitivity was 94%, specificity 85%, and negative predictive value 99%. The negative predictive value for dedicated physical examination without imaging was 100%. The biopsy-proven positive predictive value was 0 in patients with a normal breast examination compared to 18% in patients with a palpable finding on breast examination (p = 0.0017).

CONCLUSION: A subset of women <40 years old with average breast cancer risk and breast pain, who would normally be referred for imaging, can be triaged by a dedicated physical examination. Limiting ultrasound evaluation to those with palpable findings will spare patients and the healthcare system unnecessary radiology and biopsy studies.}, } @article {pmid40042344, year = {2025}, author = {Raeisi, N and Saber Tanha, A and Aryana, K and Akbari Oryani, M and Barashki, S}, title = {99m Tc-FAPI-46 Uptake in Simultaneous Occurrence of Benign Thyroid Nodule and Mixed-Mucinous-Invasive Ductal Breast Carcinoma.}, journal = {Clinical nuclear medicine}, volume = {50}, number = {5}, pages = {e297-e299}, doi = {10.1097/RLU.0000000000005729}, pmid = {40042344}, issn = {1536-0229}, mesh = {Humans ; Female ; Aged ; *Breast Neoplasms/diagnostic imaging/complications/pathology/metabolism ; *Thyroid Nodule/diagnostic imaging/complications/metabolism ; *Carcinoma, Ductal, Breast/diagnostic imaging/complications ; *Organotechnetium Compounds/metabolism ; Biological Transport ; Positron Emission Tomography Computed Tomography ; Neoplasm Invasiveness ; Radionuclide Imaging ; }, abstract = {We present a case of a 65-year-old woman diagnosed with mixed mucinous-invasive ductal carcinoma, a rare subtype of breast cancer. Utilizing 99m Tc-FAPI-46 scintigraphy, we observed a high target-to-background ratio in the breast mass and metastatic axillary lymph nodes. Notably, a benign follicular nodule was also detected in the thyroid which showed absent 99m Tc-FAPI uptake. Our findings suggest that 99m Tc-FAPI-46 shares similar characteristics with 68 Ga-FAPI and may outperform 18 F-FDG PET/CT in mucinous breast cancer. This case highlights the potential of FAPI as a predictive biomarker for malignancy and its role in benign findings.}, } @article {pmid40042161, year = {2025}, author = {Kayadibi, Y and Kargin, OA and Aladag Kurt, S and Ozturk, T and Yilmaz, MH}, title = {Pilot Study to Evaluate the Association Between Superb Microvascular Imaging (SMI) and Histologic Markers of Angiogenesis in Patients With Invasive Ductal Carcinoma.}, journal = {Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine}, volume = {44}, number = {7}, pages = {1201-1211}, pmid = {40042161}, issn = {1550-9613}, support = {TSA-2021-35724//Scientific Research Coordination Unit of Istanbul University-Cerrahpasa/ ; }, mesh = {Pilot Projects ; *Carcinoma, Ductal, Breast/blood supply/diagnostic imaging/pathology ; *Breast Neoplasms/blood supply/diagnostic imaging/pathology ; *Microvessels/diagnostic imaging ; Prognosis ; Humans ; Female ; Adult ; Middle Aged ; Aged ; Neovascularization, Pathologic/diagnostic imaging ; *Breast/blood supply/diagnostic imaging/pathology ; Vascular Endothelial Growth Factor A/analysis ; Antigens, CD34/analysis ; Biopsy ; Proto-Oncogene Proteins c-ets/analysis ; Prospective Studies ; Ultrasonography ; Biomarkers, Tumor/analysis ; *Ultrasonography, Mammary/methods/statistics & numerical data ; *Ultrasonography, Doppler, Color/methods/statistics & numerical data ; }, abstract = {OBJECTIVES: Increasing microvessel density and angiogenesis are linked to a poor prognosis in patients with invasive ductal carcinoma (IDC) of the breast. This study aims to investigate intratumoral and peritumoral microvascular flow using superb microvascular imaging (SMI) in patients with IDC and explore its association with histologic markers of tumoral angiogenesis.

METHODS: Fifty-four female patients with IDC (mean age 49.5 ± 14.8 years) were evaluated using SMI before biopsy. The quantitative and qualitative vascular parameters on SMI (Adler's classification, vascular index, morphology, distribution, and penetration) were assessed. Histologic markers of angiogenesis (VEGF, ERG, and CD34) were analyzed via immunohistochemical staining in both intratumoral and peritumoral compartments of biopsy specimens. The expression levels were categorized semi-quantitatively as low or high groups based on the Allred scoring system. The association between histological and SMI parameters was analyzed. Subgroup analysis was performed according to lesion size, axillary lymph node metastasis, and histological grade.

RESULTS: IDCs with higher expression of VEGF in the peritumoral region showed a higher vascular index (7 ± 6.4 [95% CI 5.2-8.8] versus 3.7 ± 0.9 [95% CI 2.3-5.2], P = .003) on SMI. Likewise, high peritumoral ERG expression was linked to a higher vascular index (7.2 ± 6.3 [95% CI 5.4-9.0] versus 2.4 ± 1 [95% CI 1.1-3.8], P < .001), complex vessel morphology (66.7% versus 20%, P = .024), penetrating vessels (63% versus 20%, P = .037), and central vascularity (77.6% versus 20%, P = .006). Tumors with higher intratumoral ERG expression demonstrated a more complex vessel morphology on SMI (85.7% versus 60%, P = .047). The presence of axillary lymph node metastasis was associated with a higher vascular index (10 ± 7.6 [95%CI 6.7-13.2] versus 4.2 ± 3 [95%CI 3.1-5.3], < .001), complex morphology (83.3% versus 53.3%, P = .020), and penetrating vessels (63.2% versus 50%, P = .027) on SMI, as well as higher peritumoral ERG expression (100% versus 83.3%, P = .045).

CONCLUSIONS: In this pilot study, tumors with higher neo-angiogenic activity based on histological markers correlate with increased vascular index, complex vessel morphology, penetrating vessels, and central vascularity on SMI. Larger studies are needed to assess the diagnostic accuracy and utility of risk stratification of patients.}, } @article {pmid40039929, year = {2024}, author = {Rukhsana, and Khan, WA and Conway, M and Lee, YJ and Khattak, AM}, title = {BCAT2 Expression in IDC Breast Cancer subtypes: A Weighted Feature-Based Approach to Identify and Rank Associated Genes Across Public Datasets.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2024}, number = {}, pages = {1-4}, doi = {10.1109/EMBC53108.2024.10782766}, pmid = {40039929}, issn = {2694-0604}, mesh = {Humans ; *Breast Neoplasms/genetics/classification ; Female ; *Transaminases/genetics/metabolism ; *Gene Expression Regulation, Neoplastic ; *Carcinoma, Ductal, Breast/genetics ; Gene Expression Profiling/methods ; Databases, Genetic ; }, abstract = {It has been observed that breast cancer is associated with dysregulation of several metabolic pathways that produce metabolite addiction, such as the dependence on glutamine for tumor development. These discoveries might be applied to personalized treatment of this heterogeneous illness by employing specific gene expression or metabolites in cancer therapy. BCAT1 and BCAT2 encode the human branched-chain aminotransferase proteins (hBCAT) involved in cellular metabolism process. Here BCAT2 is exploited through weighted feature-based approach to identify and rank associated genes across public datasets of breast cancer invasive ductal carcinoma patients. BCAT2 lower expression was observed to have the worst prognosis, and BCAT2 gene expression which might be associated with triggering the risk, are ranked, and visualized in different subtypes of breast cancer. These findings give a strong clue to further investigate through experimental approach.}, } @article {pmid40038709, year = {2025}, author = {Reunanen, VLJ and Jokinen, TS and Lilja-Maula, L and Hytönen, MK and Lappalainen, AK}, title = {Allelic frequency of 12-FGF4RG and the association between the genotype with number of calcified intervertebral discs visible on radiographs in Coton de Tuléar and French Bulldog breeds.}, journal = {BMC veterinary research}, volume = {21}, number = {1}, pages = {140}, pmid = {40038709}, issn = {1746-6148}, mesh = {Animals ; Dogs ; *Dog Diseases/genetics/diagnostic imaging ; *Intervertebral Disc Degeneration/genetics/diagnostic imaging/veterinary ; Genotype ; Male ; Female ; *Gene Frequency ; Retrospective Studies ; Radiography/veterinary ; Intervertebral Disc/diagnostic imaging/pathology ; *Calcinosis/diagnostic imaging/genetics/veterinary ; Breeding ; Prospective Studies ; *Fibroblast Growth Factor 4/genetics ; Intervertebral Disc Displacement ; }, abstract = {BACKGROUND: Intervertebral disc disease (IVDD) is a major welfare issue in chondrodystrophic dogs. It is a consequence of chondroid metaplasia of the nucleus pulposus, leading to premature degeneration and calcification of the intervertebral discs (IVDs). Radiographic grading based on the number of calcified discs visible on radiograph (CDVR) between the ages of 24-48 months is an established method for selective breeding against IVDD in dogs. Premature IVD degeneration has a genetic background, and a FGF4 retrogene insertion on chromosome 12 (12-FGF4RG) has been shown to be involved. The aim of this study was to determine the 12-FGF4RG allele frequency and genotype proportions, and the influence of the 12-FGF4RG genotype on number of CDVR in a study population of young adult Coton de Tuléars and French Bulldogs. In this combined prospective and retrospective analytical study, we investigated dogs radiographically screened at 24-48 months of age. The first dataset consisted of 12-FGF4RG genotyping results of 465 Coton de Tuléars and intervertebral disc calcification (IDC) grading results (no, mild, moderate, or severe) for 222 of them. The second dataset included 12-FGF4RG genotypes and IDC grading results (no or severe) of 81 French Bulldogs.

RESULTS: We observed 12-FGF4RG homozygous, heterozygous and wildtype individuals in both studied breeds. The 12-FGF4RG allele frequencies were also lower than previously reported in the studied breeds and Coton de Tuléars had lower allele frequency (0.35) than French Bulldogs (0.85). The distribution of IDC grading results were 59% no, 16% mild, 9% moderate and 16% severe in Coton de Tuléars and 59% no and 41% severe in French Bulldogs. In both breeds, every copy of the 12-FGF4RG allele significantly increased the risk for a higher number of CDVR, indicating incomplete dominance.

CONCLUSIONS: Our results confirm the significant association between the 12-FGF4RG allele and the number of CDVR and IDC grade in two different chondrodystrophic breeds in age-controlled cohorts of young adult dogs. Our results also suggest that radiographic screening of CDVR and genetic testing of 12-FGF4RG could be used to breed against IVD degeneration predisposing to IVDD.}, } @article {pmid40037930, year = {2025}, author = {Shaikh, K and Arif, A and Mooghal, M and Mushtaque Vohra, L}, title = {Promoting Oncological Safety: Extreme Oncoplasty as an Alternative to Mastectomy-Insights From a Single-Center Experience in Low and Middle-Income Country.}, journal = {World journal of surgery}, volume = {49}, number = {4}, pages = {789-796}, doi = {10.1002/wjs.12521}, pmid = {40037930}, issn = {1432-2323}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery/mortality/pathology ; Middle Aged ; *Mastectomy, Segmental/methods ; Adult ; Neoplasm Recurrence, Local/epidemiology ; Margins of Excision ; Treatment Outcome ; Developing Countries ; Aged ; Retrospective Studies ; Mastectomy ; Follow-Up Studies ; }, abstract = {BACKGROUND: Extreme oncoplastic breast-conserving surgery (eOBCS), euphemism for radical conservation, expands the indications of breast conservation for tumor that typically requires a mastectomy. Existing data show no discernible survival differences between mastectomy and breast-conserving surgery; however, limited evidence exists regarding local recurrences between these groups. We report the oncological outcomes of eOBCS in terms of margin safety and disease recurrence at our institute. Median surgical margin was 0.68 (0.2-2) cm away. Two patients (4.3%) required re-excision of positive margins. One locoregional and four distant disease recurrences were encountered with 5-year local recurrence free, distant recurrence free, and overall survivals estimated to be 91%, 73%, and 78%, respectively. Satisfactory cosmesis was attained in all patients without significant perioperative complications.

METHODOLOGY: 47 patients underwent eOBCS between July'17 and June'22. Mean follow-up was 54 (24-84) months. Primary endpoints were the resection margin status and need for reoperation. Secondary endpoints were 5-year local and distant recurrence free and overall survivals. Median surgical margin was 0.68 (0.2-2) cm away. Two patients (4.3%) required re-excision of positive margins. One locoregional and four distant disease recurrences were encountered with 5-year local recurrence free, distant recurrence free, and overall survivals estimated to be 91%, 73%, and 78%, respectively. Satisfactory cosmesis was attained in all patients without significant perioperative complications.

RESULTS: Mean age at diagnosis was 46.8 (±13.2) years. IDC (70.2%) was the commonest histological type. 32% of cancers were >5 cm in size, 30% were multifocal, and 40.4% were node positive. 25% were triple negative whereas, 7% were Her2Neu positive. Therapeutic mammoplasty (44.4%) was the frequently performed surgical procedure followed by local rotational flaps (27.6%). Mean pretreatment mammographic tumor size was 50 mm (±7.5) mm. 40.4% of the patients qualified for neoadjuvant therapies and 91.5% received radiation. Median surgical margin was 0.68 (0.2-2) cm away. Two patients (4.3%) required re-excision of positive margins. One locoregional and four distant disease recurrences were encountered with 5-year local recurrence free, distant recurrence free, and overall survivals estimated to be 91%, 73%, and 78%, respectively. Satisfactory cosmesis was attained in all patients without significant perioperative complications.

CONCLUSION: eOBCS is an innovative and aesthetically promising surgical technique enabling successful breast conservation in patients necessitating mastectomy. Our data substantiate the oncological safety of eOBCS; however, it requires appropriate patient selection and multidisciplinary planning.}, } @article {pmid40037859, year = {2025}, author = {DE Sarkar, S and Banerjee, S and Ismail, A and Mavadia, A and Choi, S and Ghose, A and Boussios, S}, title = {Male Breast Cancer: A Single Institutional Clinicopathological Profiling.}, journal = {Anticancer research}, volume = {45}, number = {3}, pages = {1097-1104}, doi = {10.21873/anticanres.17497}, pmid = {40037859}, issn = {1791-7530}, mesh = {Humans ; *Breast Neoplasms, Male/pathology/therapy/epidemiology/mortality ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Aged ; *Triple Negative Breast Neoplasms/pathology/epidemiology/therapy ; *Carcinoma, Ductal, Breast/pathology/therapy/epidemiology ; Neoplasm Staging ; India/epidemiology ; }, abstract = {BACKGROUND/AIM: Male breast cancer (MBC) is an infrequent occurrence accounting for <1% of overall breast cancers. With limited data, MBC remains a therapeutic challenge, warranting the need for meticulous recording of all cases encountered.

PATIENTS AND METHODS: A retrospective observational study in an Indian tertiary public hospital where 29 MBC cases registered between August 2020 and July 2023 were recorded and their epidemiological data, clinical profile, treatment history and survival data were analyzed.

RESULTS: MBC was 3% of all breast cancer cases reported in three years, and the most common age group affected was between 41 and 60 years. Most cases presented at Stage IIIB, with the majority showing axillary nodal involvement. Invasive ductal carcinoma was the most frequent histology with luminal B and triple-negative variants having the highest incidence. Most patients underwent upfront surgery followed by adjuvant chemotherapy. At the end of one year, 50% of patients were found to survive with no disease progression.

CONCLUSION: Our results corroborate with previously recorded experience with MBC in terms of age distribution, stage of presentation, histology and treatment offered. However, our results demonstrated a higher proportion of triple-negative breast cancer (TNBC) cases, as compared to previous literature. The increment of TNBC cases among males, therefore, reassures the need for breast cancer (BRCA) gene testing among all males afflicted with breast cancer.}, } @article {pmid40037052, year = {2025}, author = {Qayyum, MA and Mahmood, S and Bahadur, A and Iqbal, S and Zidan, A and Saad, M and Mahmood, MH and Farooq, T and Batool, M and Atif, M and Jaber, F and Rahman, KM and Farooq, Z and Asiri, YA and Farouk, AE and Aloufi, S}, title = {Study of toxic and essential elemental imbalances at more advance stage of breast carcinoma patients.}, journal = {Pathology, research and practice}, volume = {269}, number = {}, pages = {155866}, doi = {10.1016/j.prp.2025.155866}, pmid = {40037052}, issn = {1618-0631}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/metabolism ; Middle Aged ; *Trace Elements/analysis/blood ; Adult ; Hair/chemistry ; Nails/chemistry ; Aged ; Neoplasm Staging ; *Carcinoma, Ductal, Breast/pathology ; }, abstract = {Delayed diagnosis and limited access to healthcare resources are leading to advanced stage breast carcinoma posing a formidable health challenge to modern medical science. Avoiding the occurrence of breast carcinoma is only possible by ascertaining the risk factors contributing to the progression of this fatal malignancy. Among other factors, exposure to trace elements plays a decisive role in progression of breast carcinoma development. The purpose of this investigation was to evaluate the harmful traces and vital components (Pb, Ca, Mn, Cd, Na, Cr, Cu, Mg, Sr, K, Fe, Zn, Co, Li, Se, Ag, Hg, As, Al and Ni) contents in the blood (n = 161), scalp hair (n = 149) and nails (n = 135) of stage IV breast carcinoma patients and female controls by atomic absorption spectrometry. The results revealed that mean Cr, Cu, Pb and Cd levels were elevated significantly (p < 0.05) in the nails and blood, while Ni, Co, Cr, Pb and Cd levels (p < 0.05) were elevated in the scalp hair of stage IV breast carcinoma patients than the female controls. Based on pathological breast cancer types, Pb and Cd were elevated in invasive ductal carcinoma, while Cu and Co were higher in invasive lobular carcinoma patients. Multivariate analysis was applied for the source of identification and apportionment of toxic trace elements in both donor groups. Most of the factors showed significant differences between the malignant and control groups' dietary, housing, and tobacco use/nonuse behaviors. The correlation analysis revealed significantly different association patterns for toxic trace elements in patients and controls and has an influential effect on cancer risk. Overall, the current study indicates a potential role of toxic trace elements in the development of breast carcinoma and these findings could be significant in the predicting diagnosis/prognosis of breast malignancy.}, } @article {pmid40035809, year = {2026}, author = {Rammal, R and Seethala, RR and Bilofsky, EJ and Freeman, TJ and Lajara, S}, title = {Intraductal carcinoma of the parotid gland, mixed intercalated duct and oncocytic subtype with mucinous and serous acinar differentiation: cytologic and histologic features of a novel morphology.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {488}, number = {2}, pages = {429-434}, pmid = {40035809}, issn = {1432-2307}, mesh = {Humans ; Female ; Aged ; *Parotid Neoplasms/pathology/genetics ; Biomarkers, Tumor/analysis/genetics ; Cell Differentiation ; Oxyphil Cells/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology/genetics ; *Carcinoma, Ductal/pathology/genetics ; *Acinar Cells/pathology/chemistry ; }, abstract = {Intraductal carcinoma (IDC) of the salivary gland is rare. Histologic subtypes include intercalated duct, oncocytic, apocrine, and hybrid/mixed. Molecular correlates have been described, with intercalated duct IDC typically harboring NCOA4::RET, while TRIM33::RET, or BRAF[V600E] pathogenic variants predominating in oncocytic IDC. We describe the case of a 77-year-old female with a parotid mass. Fine needle aspiration showed a population of low-grade epithelial cells with frequent cytoplasmic vacuolization, which were positive for S-100, SOX-10, and mammaglobin, and was interpreted as compatible with secretory carcinoma. A dual cell population was recognized on surgical resection, predominantly oncocytic, with at least one focus prototypical of intercalated IDC. Luminal secretions were positive for mucicarmine, while PAS after diastase highlighted the latter in addition to zymogen-like cytoplasmic granules. RNA sequencing detected a NCOA4::RET fusion. This is the first report of the cyto-histologic features of the mixed intercalated duct and oncocytic subtype IDC with mucous and serous acinar-like differentiation.}, } @article {pmid40031189, year = {2025}, author = {Requadt, R and Fink, M and Kubica, P and Steinem, C and Munk, A and Li, H}, title = {Robust Inference of Cooperative Behavior of Multiple Ion Channels in Voltage-Clamp Recordings.}, journal = {IEEE transactions on nanobioscience}, volume = {24}, number = {3}, pages = {305-317}, doi = {10.1109/TNB.2025.3532441}, pmid = {40031189}, issn = {1558-2639}, mesh = {*Ion Channels/physiology/chemistry/metabolism ; *Patch-Clamp Techniques/methods ; Computer Simulation ; Markov Chains ; Gramicidin ; *Models, Biological ; }, abstract = {Recent experimental studies have shed light on the intriguing possibility that ion channels exhibit cooperative behaviour. However, a comprehensive understanding of such cooperativity remains elusive, primarily due to limitations in measuring separately the response of each channel. Rather, only the superimposed channel response can be observed, challenging existing data analysis methods. To address this gap, we propose IDC (Idealisation, Discretisation, and Cooperativity inference), a robust statistical data analysis methodology that requires only voltage-clamp current recordings of an ensemble of ion channels. The framework of IDC enables us to integrate recent advancements in idealisation techniques and coupled Markov models. Further, in the cooperativity inference phase of IDC, we introduce a minimum distance estimator and establish its statistical guarantee in the form of asymptotic consistency. We demonstrate the effectiveness and robustness of IDC through extensive simulation studies. As an application, we investigate gramicidin D channels. Our findings reveal that these channels act independently, even at varying applied voltages during voltage-clamp experiments. An implementation of IDC is available from GitLab.}, } @article {pmid40030574, year = {2024}, author = {Shin, J and Yang, W and Seo, J and Chang, WS and Kim, HD and Kim, SH and Chung, JM}, title = {Intracranial Disease Region Composite Interpretation Technology for Enhanced Source Localization in Pediatric Epilepsy Surgery.}, journal = {IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/TNSRE.2024.3514940}, pmid = {40030574}, issn = {1558-0210}, abstract = {Electroencephalography (EEG) based source localization (ESL) is a useful method to localize the epileptogenic zone in epilepsy surgery. However, previous techniques only perform 3-dimensional (3D) reconstruction, and do not conduct delineation on the cortex surface as a resection guidance, and there is very little data on intracranial EEG and pediatric cases. This study proposes an Intracranial Disease-region Composite-interpretation (IDC) EEG-based source localization (ESL) scheme that uses 3D extended reality (XR) edge computing to enhance visualization and comprehensive interpretation of intracranial EEG-based source localization (iESL) for patients with pediatric epilepsy. The proposed IDC-ESL method was effective in predicting the surgical outcome in patients with focal epilepsy, which can be effectively used for epilepsy surgery. Seizure freedom was clearly associated with complete resection of combined EEG features of interictal spike, high-frequency oscillation (HFO), and seizure onset zone (SOZ), and it had the highest significance in localizing the epileptogenic zone. However, for patients with Lennox-Gastaut syndrome (LGS), IDC-ESL was not performed effectively because of a deeply seated lesion and multifocal abnormalities. It could only roughly estimate the affected area, mainly because of insular involvement. Cautious interpretation based on intraoperative electrocorticography (ECoG) is required for accurate insular resection, particularly for LGS cases.}, } @article {pmid40018471, year = {2025}, author = {Verboven, G and Huizing, MT and Weijer, M and Ysebaert, D and Ramadhan, A and Wyngaert, T and Broeckx, G and Tjalma, WA}, title = {Long-Term Survival of Metachronous Isolated Adrenal Metastasis in Luminal Breast Cancer: A Case Report and Literature Review.}, journal = {Cureus}, volume = {17}, number = {1}, pages = {e78142}, pmid = {40018471}, issn = {2168-8184}, abstract = {Metachronous metastasis occurs many years later in cases of hormone-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, with the most common sites being the lymph nodes, bones, liver, lungs, and brain. The late recurrence of estrogen receptor (ER)-positive breast cancer is attributed to prolonged adjuvant therapy and the high expression of dormancy-associated genes, allowing cancer cells to survive for decades without proliferating. It is a form of chronic breast cancer that remains asymptomatic, with no clinical signs of progression or recurrence. Estrogen receptor-negative breast cancers, on the other hand, have no long-term tumor dormancy due to their fast growth and low expression of dormancy-related genes. Adrenal gland metastasis, particularly as an oligometastatic presentation, is exceedingly rare, and optimal treatment strategies remain elusive. In this report, we present a case demonstrating long-term survival after treatment of adrenal gland metastasis, accompanied by a comprehensive literature review. At the age of 48, our patient was diagnosed with invasive ductal carcinoma of the left breast. Treatment included breast-conserving surgery, radiotherapy, and adjuvant hormone therapy. Ten years later, she developed a solitary left adrenal metastasis. Treatment included laparoscopic adrenalectomy and a change in hormonal therapy. Our patient is currently still asymptomatic with no evidence of disease. Her overall survival of over 20 years is exceptional. Resection of the adrenal metastasis combined with systemic hormonal therapy represents the recommended approach for this metachronous metastasis. In the contemporary context, antihormonal therapy in combination with CDK4/6 inhibitors should be considered. The present case underscores the necessity of establishing a lifelong (inter)national cancer registry to document rare recurrences systematically. Such a registry would provide insights into the prevalence of uncommon scenarios and offer invaluable data on proposed treatments, facilitating the development of uniform treatment strategies.}, } @article {pmid40016543, year = {2025}, author = {Botty van den Bruele, A and Ren, Y and Thomas, SM and Ntowe, KW and Rosenberger, LH and Menendez, C and Grimm, LJ and Chiba, A and Plichta, JK}, title = {High risk surveillance MRI may not be necessary in BRCA1/2 mutation carriers over 70 years old.}, journal = {Breast cancer research and treatment}, volume = {211}, number = {2}, pages = {421-429}, pmid = {40016543}, issn = {1573-7217}, support = {K12 AR084231/AR/NIAMS NIH HHS/United States ; P30 CA014236/CA/NCI NIH HHS/United States ; P30CA014236/NH/NIH HHS/United States ; }, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/diagnostic imaging/epidemiology/diagnosis/pathology ; Middle Aged ; Aged ; Adult ; *Magnetic Resonance Imaging/methods ; *Mutation ; *BRCA2 Protein/genetics ; *BRCA1 Protein/genetics ; Heterozygote ; Genetic Predisposition to Disease ; Retrospective Studies ; Mammography ; Genetic Testing ; Early Detection of Cancer ; Age Factors ; Genes, BRCA1 ; Genes, BRCA2 ; }, abstract = {BACKGROUND: The risk of developing breast cancer up to age 80 for women with BRCA1/2 mutations is approximately 69-72%. The risk estimates, however, become labile in the later years of life. Many older BRCA1/2 mutation carriers who have not developed breast cancer continue to undergo high-risk surveillance. We evaluated breast cancers in women age ≥ 70 and identified which modality diagnosed the malignancy.

METHODS: Females with BRCA1/2 mutations identified between 1996 and 2022 were included in this single institution retrospective review. The cohort was divided by age at BRCA1/2 diagnosis (30-59, 60-69 & ≥ 70). The number of malignancies and imaging modality which led to the diagnosis were recorded.

RESULTS: There were 316 patients with BRCA1/2 mutations: 266/316 (84.2%) were 30-59 years old at the time of genetic testing, 35/316 (11.1%) were 60-69, and 15/316 (4.7%) were ≥ 70. Median follow-up was 57 months (IQR 21.6-114.6). There were 178 (56.3%) breast malignancies diagnosed; 161/266 (60.5%) age 30-59, 11/35 (31.4%) ages 60-69, and 6/15 (40%) age ≥ 70 (p = 0.002). Of patients with a malignant diagnosis (n = 178), 140/178 (78.7%) had their cancers discovered on either screening or diagnostic mammogram, 30/178 (16.9%) by MRI, 1 /178 (0.6%) on ultrasound, and 1/178 (0.6%) was discovered on surgical pathology. Of the breast cancers diagnosed in patients age ≥ 70, 66.7% (4/6) were found on mammogram.

CONCLUSIONS: In women ≥ 70 with BRCA1/2 mutations, mammograms may be sufficient surveillance. Given that a number of older BRCA1/2 carriers may never develop breast cancer, our data supports individualized care and consideration for de-escalated surveillance in those ≥ 70.}, } @article {pmid40013144, year = {2025}, author = {Li, X and Wu, N and Wang, C and Pei, B and Ma, X and Xie, J and Yang, W}, title = {NALCN expression is down-regulated and associated with immune infiltration in gastric cancer.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1512107}, pmid = {40013144}, issn = {1664-3224}, mesh = {Humans ; *Stomach Neoplasms/immunology/genetics/pathology/metabolism ; Cell Line, Tumor ; *Gene Expression Regulation, Neoplastic ; *Lymphocytes, Tumor-Infiltrating/immunology/metabolism ; Down-Regulation ; Tumor Microenvironment/immunology ; Female ; Cell Proliferation ; Male ; }, abstract = {BACKGROUND: NALCN has been identified as a tumor suppressor gene, and its role in human cancer progression has garnered significant attention. However, there is a paucity of experimental studies specifically addressing the relationship between NALCN and immune cell infiltration in gastric cancer (GC).

METHODS: The expression levels of NALCN in tumor tissues, peripheral blood and gastric cancer cells lines from patients with GC were assessed using RNA sequencing, immunohistochemistry (IHC) staining and RT-qPCR. Data obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were utilized to investigate the correlation between NALCN expression and immune cell infiltration in GC. Subsequently, the relationship between NALCN expression and infiltrating immune cells in GC tissues was examined through immunofluorescence method. Additionally, in vitro experiments were conducted to evaluate the impact of NALCN knockdown on T cells function in GC cell lines.

RESULTS: RNA sequencing analysis revealed that NALCN expression was significantly downregulated in GC tissues. Specifically, NALCN levels were lower in GC tumor tissues and plasma compared to adjacent non-tumor tissues and healthy controls. Consistent with these findings, the expression trend of NALCN mRNA in the GEO database mirrored the experimental results. Mechanistically, NALCN knockdown markedly enhanced cell proliferation, colony formation and migration while reducing apoptosis rates in AGS and GES-1 cells. Analysis of the TCGA database indicated a positive correlation between NALCN expression and the infiltration of B cells, cytotoxic cells, immature dendritic cells (iDC) cells, CD8[+] T cells, and others in GC tissue. Conversely, Th17 and Th2 cells infiltration exhibited a negative correlation with NALCN expression. Immunofluorescence staining confirmed that B cells and CD8 T cells were more abundant in GC tumor tissues with high NALCN expression, whereas Th17 and Th2 cells were less prevalent. Subsequently, we co-cultured GC cells transfected with NALCN knockdown or control vectors along with their supernatants with T cells. The results demonstrated that NALCN knockdown in GC cells or their supernatants inhibited T cell proliferation compared to control conditions. Moreover, NALCN may play a role in glucose and glutamine uptake.

CONCLUSIONS: NALCN facilitates immune cell aggregation in GC and has potential as a biomarker for immune infiltration.}, } @article {pmid40011966, year = {2025}, author = {Pirooznia, P and Meighani, EM and Ghaffari, F}, title = {Exploring new frontiers in oncofertility preservation: a case of ovarian stimulation during pregnancy.}, journal = {Journal of ovarian research}, volume = {18}, number = {1}, pages = {39}, pmid = {40011966}, issn = {1757-2215}, mesh = {Humans ; Female ; *Ovulation Induction/methods ; Pregnancy ; *Fertility Preservation/methods ; Adult ; *Breast Neoplasms/therapy/complications/drug therapy ; Letrozole ; *Pregnancy Complications, Neoplastic ; }, abstract = {BACKGROUND: The standard treatment for Pregnancy-Associated Breast Cancer (PABC) includes surgery and neoadjuvant chemotherapy, which can impair fertility, emphasizing the critical need for fertility preservation in these patients. This case report discusses a breast cancer patient who was found to be pregnant shortly after starting treatment. Despite the pregnancy and increased levels of βHCG and progesterone, the ovarian stimulation cycle yielded a satisfactory number of mature oocytes and high-quality embryos.

CASE PRESENTATION: A 40-year-old woman, G1Ab1 (Gravida1Abortion1), who was diagnosed with Invasive Ductal Carcinoma with negative receptors (Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2) was referred to the oncofertility unit of the Royan Infertility Center for fertility preservation prior to the commencement of chemotherapy. Following necessary consultations and procedures, and confirming a negative pregnancy test, a random start letrozole-based protocol was initiated for ovarian stimulation. During the cycle, a positive pregnancy test was encountered. Despite the positive test, the cycle continued, and on day 13 of the cycle, triggering was performed with a GnRH agonist. A puncture was performed 36 h later, yielding 12 oocytes and 8 embryos.

CONCLUSION: This case highlights the feasibility of adapting random-start ovarian stimulation protocols during pregnancy, warranting further investigation in similar clinical scenarios.}, } @article {pmid40009584, year = {2025}, author = {Dong, J and Lei, R and Ma, F and Yu, L and Wang, L and Xu, S and Hu, Y and Sun, J and Zhang, W and Wang, H and Zhang, L}, title = {Machine learning-based prediction of distant metastasis risk in invasive ductal carcinoma of the breast.}, journal = {PloS one}, volume = {20}, number = {2}, pages = {e0310410}, pmid = {40009584}, issn = {1932-6203}, mesh = {Humans ; Female ; *Machine Learning ; *Breast Neoplasms/pathology/diagnosis ; *Carcinoma, Ductal, Breast/pathology/diagnosis ; Neoplasm Metastasis ; Algorithms ; Prognosis ; ROC Curve ; }, abstract = {More than 90% of deaths due to breast cancer (BC) are due to metastasis-related complications, with invasive ductal carcinoma (IDC) of the breast being the most common pathologic type of breast cancer and highly susceptible to metastasis to distant organs. BC patients who develop cancer metastases are more likely to have a poor prognosis and poor quality of life, so it is extremely important to recognize and diagnose whether distant metastases have occurred in IDC as early as possible. In this study, we develop a non-invasive breast cancer classification system for detecting cancer metastasis. We used Anaconda-Jupyter notebooks to develop various Python programming modules for text mining, data processing, and machine learning (ML) methods. A risk prediction model was constructed based on four algorithms: Random Forest, XGBoost, Logistic Regression, and SVM. Additionally, we developed a hybrid model based on a voting mechanism using these four algorithms as the base models. The models were compared and evaluated by the following metrics: accuracy, precision, recall, F1-score, and area under the ROC curve (AUC) values. The experimental results show that the hybrid model based on the voting mechanism exhibits the best prediction performance (accuracy: 0.867, precision: 0.929, recall: 0.805, F1-score: 0.856, AUC: 0.94). This stable risk prediction model provides a valuable reference support for doctors in assessing and diagnosing the risk of IDC hematogenous metastasis. It also improves the work efficiency of doctors and strives to provide patients with increased chances of survival.}, } @article {pmid40004850, year = {2025}, author = {Lauder, AP and Nwiloh, A and Eximond, M and LeBlanc, RE and Dagrosa, AT and Barth, R and Chamberlin, M and McVorran, S}, title = {Resolution of Pyoderma Gangrenosum During Adjuvant Breast Cancer Therapy.}, journal = {Journal of clinical medicine}, volume = {14}, number = {4}, pages = {}, pmid = {40004850}, issn = {2077-0383}, support = {P30 CA023108/CA/NCI NIH HHS/United States ; }, abstract = {Background/Objectives: Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by rapidly developing, painful ulcerative lesions. It exhibits pathergy, a phenomenon in which minor trauma or injury to the skin triggers an exaggerated inflammatory response. This leads to the development of new skin lesions or the worsening of existing ones. Treatment typically involves a combination of corticosteroids and immunosuppressive agents. However, even with effective therapy, the overall management of pyoderma gangrenosum remains challenging, and wound healing can be prolonged. The development of pyoderma gangrenosum after breast cancer surgery is rare, and its presence complicates the treatment of patients requiring additional oncologic therapy. In particular, the effect of radiation on these lesions is not well documented. Given the known skin toxicity of radiotherapy and its negative impact on wound healing, the use of adjuvant breast radiation raises significant concerns in this context. Methods: We present the case of a 66-year-old female with Stage IIB invasive ductal carcinoma of the left breast who developed postoperative pyoderma gangrenosum after breast-conserving surgery. The patient was treated with systemic corticosteroids and cyclosporine, and then subsequently underwent standard-of-care adjuvant chemotherapy and radiation. Results: During therapy, she demonstrated rapid resolution of her pyoderma gangrenosum without experiencing excess skin toxicity. Conclusions: While the literature on the direct application of radiation in pyoderma gangrenosum is limited, our case provides evidence supporting the safety of radiation therapy in oncologic cases complicated by this disease. In addition to receiving the benefit of adjuvant therapy for her breast cancer, our patient demonstrated an improvement in her postoperative PG with no adverse skin effects.}, } @article {pmid40002558, year = {2025}, author = {Jang, HM and Bae, K and Lee, TY and Lim, S and Bang, M}, title = {Contrast-Enhanced Chest Computed Tomography for In-Breast Recurrence Detection: Clinical and Imaging Predictors of Visibility.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {4}, pages = {}, pmid = {40002558}, issn = {2075-4418}, abstract = {Purpose: Routine surveillance chest CT is not recommended by current guidelines; however, its use has been increasing with improved accessibility. This study aimed to evaluate the utility of surveillance contrast-enhanced chest computed tomography (CT) in detecting in-breast recurrence among survivors, focusing on imaging and clinicopathological features that enhance tumor visibility. Additionally, this study sought to determine which patient populations may derive benefit from contrast-enhanced chest CT. Materials and Methods: A retrospective analysis was conducted on records of patients diagnosed with in-breast recurrence through biopsy during follow-up after breast cancer surgery between January 2016 and August 2022. Patients who underwent contrast-enhanced chest CT within one month of diagnosis were included. Two radiologists reviewed the chest CT scans for breast cancer lesions by consensus, and their findings were validated by two other radiologists blinded to tumor locations. Statistical analyses were performed to evaluate associations among clinicopathological factors, image features, and visibility. Results: Eighty-nine recurrent tumors in 85 patients were included. Fifty-eight recurrent tumors were identified by radiologists who were not blinded. The blinded radiologists independently identified 50 and 56 recurrences, with substantial inter-observer agreement (κ-value = 0.768, p < 0.001). The visible group had a significantly higher rate of invasive ductal carcinoma (IDC) compared to the non-visible group (81.0% vs. 54.8%, p = 0.002). Additionally, the visible group exhibited larger tumors than the non-visible group (mean ± SD: 1.9 ± 1.5 cm vs. 1.3 ± 0.6 cm, p = 0.018). Tumors located in fatty backgrounds demonstrated significantly greater visibility on chest CT than those in glandular backgrounds (67.2% vs. 16.1%, p < 0.001). Recurrent breast cancer was also more frequently visible on chest CT in patients who had undergone mastectomy compared to those who had received breast-conserving surgery (p < 0.001). Conclusions: Contrast-enhanced chest CT can aid in the detection of in-breast recurrence, particularly in patients who have undergone mastectomy, as a complementary imaging modality. Tumors in fatty backgrounds, large tumors, mass-type tumors, and IDCs are better visible on chest CT.}, } @article {pmid39999730, year = {2025}, author = {Naowaset, P}, title = {The association between surgical margins and local recurrence in women with ductal carcinoma in situ treated with breast conserving therapy: Observational study.}, journal = {Cancer treatment and research communications}, volume = {43}, number = {}, pages = {100885}, doi = {10.1016/j.ctarc.2025.100885}, pmid = {39999730}, issn = {2468-2942}, mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; *Breast Neoplasms/mortality/pathology/radiotherapy/surgery ; *Carcinoma, Intraductal, Noninfiltrating/mortality/pathology/radiotherapy/surgery ; Follow-Up Studies ; *Margins of Excision ; *Mastectomy, Segmental/methods ; *Neoplasm Recurrence, Local/epidemiology/pathology/prevention & control ; Radiotherapy, Adjuvant ; Retrospective Studies ; Disease-Free Survival ; }, abstract = {INTRODUCTION: The incidence of DCIS (DCIS) constitutes 25 % of the newly identified breast cancers. Approximately 35 % of DCIS cases are detected in asymptomatic women during routine mammography screening. The 20-year breast-cancer-specific mortality rate was 3.3 %. Breast-conserving surgery(BCS), followed by radiotherapy, is the treatment of choice. However, an adequate margin for BCS remains unclear. Therefore, we need to investigate the relationship between the margin distance and cancer recurrence.

METHODS: A total of 4,355 patients with DCIS were assessed between January 1, 2010, and January 31, 2020. Of these, 4,123 patients who had invasive ductal carcinoma co-existing DCIS and who were treated with mastectomy were excluded. Thus, 232 patients with pure DCIS treated with BCS were included. All distant radial margins were measured.

RESULTS: A total of 232 patients with DCIS underwent breast-conserving surgery, 169 patients received whole breast radiotherapy, and 63 did not. Most patients received hormone therapy, and as indicated, the median follow-up was 73 months. Recurrence was observed in seven patients. Among them, four had margins <2 mm, while the others had margins > 2 mm. There were no significant differences in disease-free survival (DFS) among the margin statuses.

CONCLUSION: Margins wider than 2 mm did not demonstrate a reduction in local recurrence for women receiving adjuvant whole-breast radiation therapy, supporting the recommendation of a negative margin threshold for surgical management of DCIS.}, } @article {pmid39991119, year = {2025}, author = {Canice Nwagbara, VI and Ashindoitiang, JA and Ugbem, TI and Magam, DN and Meremikwu, CM and Nnalue, VD and Asuquo, ME}, title = {Breast cancer in a patient with neurofibromatosis type 1: A case report and review of literature.}, journal = {Rare tumors}, volume = {17}, number = {}, pages = {20363613251322866}, pmid = {39991119}, issn = {2036-3605}, abstract = {Neurofibromatosis 1 (NF1) represents a cluster of clinical features based on the National Institute of Health(NIH) diagnostic criteria. It is a multi-systemic disease with progressive features characterized by variable expression. NF1 is associated with an increased risk of malignancies including breast cancer. Presented was a 56 year old woman with a painless lump in the right breast in the past 15 months. Clinical evaluation revealed features of NF1 and an advanced right breast cancer. Histologic evaluation revealed an invasive ductal carcinoma and she was offered a right modified radical mastectomy. Due to clinical presentation with discrete lesions, NF1 may be diagnosed at presentation with malignancy. Clinicians are urged to be familiar with the subtle features of NF1 for early diagnosis that is largely clinical. Institution of early breast cancer surveillance in patients with NF1 is recommended for early diagnosis and improved outcomes.}, } @article {pmid39985623, year = {2025}, author = {Randall Armel, S and Malcolmson, J and Volenik, A and Maganti, M and Watkins, N and Charames, GS and McCuaig, J}, title = {Genetic counseling referral rates and genetic testing outcomes in women with young breast cancer: a 20-year Canadian review.}, journal = {Breast cancer research and treatment}, volume = {211}, number = {2}, pages = {321-330}, pmid = {39985623}, issn = {1573-7217}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/epidemiology/diagnosis/pathology ; *Referral and Consultation/statistics & numerical data ; *Genetic Counseling/statistics & numerical data ; *Genetic Testing/statistics & numerical data ; Adult ; Canada/epidemiology ; Retrospective Studies ; Young Adult ; Genetic Predisposition to Disease ; }, abstract = {PURPOSE: Despite guidelines recommending genetic testing for all cases of very young breast cancer (VYBC), poor uptake has been reported. This study aimed to examine genetic testing referral rates and outcomes over a 20-year period within the Canadian context.

METHODS: A retrospective chart review of all incident VYBC cases (at or below 35 years of age) between January 1, 2000 and December 31, 2019 was conducted. Descriptive statistics were used to summarize demographic factors and logistic regression analyses were performed to identify the predictors associated with referral for genetic counseling and positive genetic test results.

RESULTS: 628 women were identified with VYBC. Most women presented with stage 2 (42%), hormone receptor-positive (HR +) and HER2-negative (54%) invasive ductal carcinoma (94%). Over the study period, referral rates increased from 44 to 84%. Of women initially tested for BRCA1/BRCA2, only 21% were referred for updated panel testing. Among those tested, 19% had a pathogenic variant, 21% of whom reported no family history of cancer. Predictors of referral included stage 0-2 disease while predictors of positive test results included a second breast cancer diagnosis and positive family history.

CONCLUSION: Despite guidelines based on age alone, barriers to referral persist. Results of this study suggest the need for new models of care that ensure equitable access to genetic testing for all women diagnosed with VYBC regardless of family history, ethnicity, or disease stage. As genetic testing criteria evolve, protocols must address these barriers to prevent missed opportunities for testing.}, } @article {pmid39985618, year = {2025}, author = {Tang, W and Zhou, M and Lu, C and Qi, L and Zhang, Y and Tang, Y and Gao, X and Hu, S and Cai, Y}, title = {CD13 as a potential theranostic target for prostate-specific membrane antigen-negative prostate cancer and first-in-human study of [[18]F]AlF-CD13-L1 PET/CT imaging.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {52}, number = {8}, pages = {2826-2840}, pmid = {39985618}, issn = {1619-7089}, support = {2024JJ2090//Outstanding Youth Fund Project of Hunan Province/ ; 2024JJ2094//Outstanding Youth Fund Project of Hunan Province/ ; 2023LNJJ13//Clinical Research Foundation of the National Clinical Research Center for Geriatric Diseases (XIANGYA)/ ; 2023LNJJ16//Clinical Research Foundation of the National Clinical Research Center for Geriatric Diseases (XIANGYA)/ ; 2020LNJJ01//Clinical Research Foundation of the National Clinical Research Center for Geriatric Diseases (XIANGYA)/ ; 82272907//National Natural Science Foundation of China/ ; 81974397//National Natural Science Foundation of China/ ; 81572524//National Natural Science Foundation of China/ ; 91859207//National Natural Science Foundation of China/ ; 81771873//National Natural Science Foundation of China/ ; 82272045//National Natural Science Foundation of China/ ; 82273121//National Natural Science Foundation of China/ ; 81801740//National Natural Science Foundation of China/ ; 2023SK2017//Key Research and Development Program of Hunan Province/ ; CEIEC-2022-ZM02-0219//Key Program of Ministry of Industry and Information Technology of China/ ; 2021RC4056//Science and Technology Innovation Program of Hunan Province/ ; 2017YFC0908004//National Key Research and Development Plan/ ; 33020125030//Clinical Big Data System Construction Project Fund of Xiangya Hospital/ ; 33020123007//Xiangya Famous Doctor Fund of Central South University/ ; 2023ZZTS0551//Fundamental Research Funds for the Central Universities of Central South University/ ; 2024ZZTS0870//Fundamental Research Funds for the Central Universities of Central South University/ ; 2022M23561//China Postdoctoral Science Foundation/ ; }, mesh = {Humans ; Male ; *Positron Emission Tomography Computed Tomography ; *Prostatic Neoplasms/diagnostic imaging/metabolism/therapy ; Aged ; Middle Aged ; *Glutamate Carboxypeptidase II/metabolism ; *CD13 Antigens/metabolism ; Antigens, Surface/metabolism ; Fluorine Radioisotopes ; *Theranostic Nanomedicine ; }, abstract = {PURPOSE: Approximately 10% of prostate cancer (PCa) are prostate-specific membrane antigen (PSMA)-negative, leading to blind spots in PSMA-based diagnosis. This study aimed to identify a potential target for PSMA-negative PCa and preliminarily evaluate the feasibility of using radionuclide probe targeting the identified target for PCa diagnosis.

METHODS: Quantitative protein analysis was performed on eight PSMA-negative PCa and eleven controls to identify a potential molecular target, followed by validation with an expanded cohort using immunohistochemistry. Sixteen participants underwent [[18]F]AlF-CD13-L1 PET/CT scanning, with the PCa pathological tissues used as references to interpret the imaging results.

RESULTS: Quantitative protein analysis revealed CD13 as the most significantly upregulated membrane protein in PSMA-negative PCa. Expanded validation results indicated that CD13 positivity rates were 92.9% (13/14), 82.7% (105/127), 91.7% (11/12), and 70% (14/20) in PSMA-negative PCa, PSMA-positive PCa, ductal adenocarcinoma of the prostate (DAC), and intraductal carcinoma of the prostate (IDC-P), respectively. In PCa participants, the median [[18]F]AlF-CD13-L1 PET/CT maximum standardized uptake value (SUVmax) of tumors and tumor-to-muscle ratio were 4.3 (1.5-5.8) and 4.6 (1.7-6.1), respectively. The SUVmax value of the PCa lesions and the tumor-to-muscle ratio showed a positive correlation with the immunohistochemical score of CD13 of the PCa lesions (rspearman = 0.6249, p = 0.025; rspearman = 0.6714, p = 0.015, respectively), with CD13-positive tumors showing significant radiotracer accumulation.

CONCLUSION: CD13 was a potential target for PSMA-negative PCa and also showed high positivity rates in PSMA-positive PCa, DAC, and IDC-P. [[18]F]AlF-CD13-L1 selectively accumulated in CD13-positive PCa, enabling visualization. (Trial registration: ChiCTR2300077817. Registered November 21, 2023).}, } @article {pmid39980805, year = {2025}, author = {Liu, Y}, title = {Recent advances and updated highlights in breast cancer pathologic diagnosis: a narrative review.}, journal = {Translational breast cancer research : a journal focusing on translational research in breast cancer}, volume = {6}, number = {}, pages = {3}, pmid = {39980805}, issn = {2218-6778}, abstract = {BACKGROUND AND OBJECTIVE: With the rapid development of breast cancer treatment, breast cancer pathologic diagnosis has faced many requirements and challenges. This article reviews and summarizes important results that will change the clinical practice of breast cancer in 2023 and 2024.

METHODS: As of April 2024, a comprehensive literature search, compilation, and analysis were conducted across PubMed, Baidu Scholar, ClinicalTrials.gov, and relevant academic conferences.

KEY CONTENT AND FINDINGS: This article focused on invasive lobular carcinoma (ILC), phyllodes tumors, new advances in immunohistochemical (IHC) indexes, updated advances in neoadjuvant therapy for breast cancer, and advances in the study of human epidermal growth factor receptor 2 (HER2)-low breast cancer. ILC has unique molecular distribution and clinical characteristics, distinguishing it from the traditional molecular classification and clinical features of invasive ductal carcinoma. Understanding the accurate diagnosis, immune microenvironment, and genetic changes of phyllodes tumors holds pivotal importance in guiding clinical treatment. Pathologic evaluation after neoadjuvant therapy is essential for the treatment of breast cancer patients, but clear and uniform criteria are lacking. With the breakthrough of new antibody-drug conjugate drugs in the treatment of breast cancer patients with low HER2 expression, the pattern of traditional anti-HER2 treatment has changed, bringing targeted benefit opportunities for more breast cancer patients. At the same time, the dichotomy used for breast cancer HER2 detection and interpretation has also been broken, which puts forward more accurate requirements for pathological diagnosis. IHC results for HER2 low also exhibit variability and are influenced by various factors.

CONCLUSIONS: Breast cancer treatment and pathology have made significant progress in 2023 and 2024. This will help ensure more accurate diagnoses and provide long-term treatment benefits for patients.}, } @article {pmid39980666, year = {2025}, author = {Kuribayashi, M and Isono, T and Satake, Y and Yokochi, Y and Kawamura, T and Kishi, R and Koreyasu, R and Sakyo, K and Watanabe, T and Ueda, T and Nozawa, M and Tachibana, M and Tsukamoto, K and Kamimura, K and Wada, H}, title = {Sebaceous Carcinoma of the Breast in a Japanese Male with a BRCA2 Pathogenic Variant: Report of an Exceedingly Rare Case and Review of the Literature.}, journal = {Surgical case reports}, volume = {11}, number = {1}, pages = {}, pmid = {39980666}, issn = {2198-7793}, abstract = {INTRODUCTION: Sebaceous carcinoma (SC) is a malignant neoplasm differentiated from the mature sebocyte and occurs mainly in the periorbital area. However, SC of the breast is extremely rare. We report a case of sebaceous breast carcinoma in a Japanese man with a BRCA2 pathogenic variant.

CASE PRESENTATION: A 77-year-old Japanese man had been aware of a mass in his right breast for about a year and had visited his previous physician for a follow-up. Over the next year, the mass grew, and the last doctor he visited referred him to our hospital for further examination and treatment. Physical examination revealed a palpable 3-cm-large mass of the right breast. There was no skin invasion, and core needle biopsy revealed invasive ductal carcinoma cT2N1M0 cStage IIB, estrogen receptor (+)/progesterone receptor (+)/HER2/neu (-)/Ki-67 labeling index: 27.8%. His daughter had a history of breast cancer, and he had a BRCA2 pathogenic variant. The patient underwent a total right mastectomy and axillary lymph node dissection. Pathological diagnosis was primary SC of the breast, pT2N0M0, pStage IIA. His postoperative clinical course was good. Postoperatively, the patient received endocrine therapy and S-1 for 1 year and is currently receiving endocrine therapy alone. One year and 5 months have passed since the operation, with no recurrence or metastasis noted.

CONCLUSIONS: The prognosis of SC of the breast has not been elucidated. As cases of SC with a BRCA2 pathogenic variant are exceedingly rare, it will be necessary to continue accumulating cases in the future to understand this disease further. This research is essential to elucidating SC.}, } @article {pmid39980517, year = {2025}, author = {Suwanvecho, S and Kiatikajornthada, N and Phikulsod, P and Suwanrusme, H and Jirawatnotai, S}, title = {Durable and Drastic Response to the Trastuzumab, Letrozole, Abemaciclib, and Goserelin Combination as First-Line Therapy in HER2-Positive and Hormone Receptor-Positive Metastatic Breast Cancer: A Case Report.}, journal = {Case reports in oncology}, volume = {18}, number = {1}, pages = {130-136}, pmid = {39980517}, issn = {1662-6575}, abstract = {INTRODUCTION: Chemotherapy combined with anti-human epidermal growth factor receptor 2 (HER2)-targeted therapy is currently a standard treatment for advanced HER2/HR-positive breast cancer (BC), although evidences showed that HR expression compromised effectiveness of the treatment. While cyclin-dependent kinase (CDK) 4/6 inhibitors combined with endocrine therapy is a key therapy for the BC with HR expression, data on the effectiveness and safety of CDK 4/6 inhibitors combined with trastuzumab and endocrine therapy as a first-line treatment for HER2-positive and HR-positive metastatic BC are limited.

CASE PRESENTATION: Here, we report a case of a 46-year-old premenopausal woman diagnosed with stage 4 HER2/HR-positive invasive ductal carcinoma from both right and left breast with hypermetabolic activities in multiple lymph nodes, adrenal, bone, and skin.

INTERVENTIONS: Due to the patient's refusal to use chemotherapy, she was started on goserelin, abemaciclib, letrozole, and trastuzumab.

OUTCOMES: The patient's symptoms were relieved with near resolution of the primary breast mass and nearly all of the metastatic sites. Metabolic resolution was observed in bone lesions. The disease was under control for 57 weeks. During the treatment, neutropenia (grade 1-2) and anemia (grade 1) occurred, which spontaneously recovered. Additionally, diarrhea improved after symptomatic treatment.

CONCLUSION: We believe that the combination of trastuzumab, hormone suppression, and abemaciclib is a practicable and effective treatment for HER2-positive and HR-positive metastatic BC in premenopausal patients who cannot tolerate the first-line chemotherapy.}, } @article {pmid39979484, year = {2025}, author = {Richter, FGB and Mattar, A and Antonini, M and Teixeira, MD and Amorim, AG and Millen, EC and Brenelli, FP and Cavalcante, FP and Zerwes, F and Frasson, AL and Lopes, RGC and Gebrim, LH and Real, JM}, title = {The relationship between body mass index and pathological complete response in Brazilian breast cancer patients.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {6174}, pmid = {39979484}, issn = {2045-2322}, mesh = {Humans ; Female ; *Body Mass Index ; Brazil/epidemiology ; Middle Aged ; *Breast Neoplasms/pathology/epidemiology/drug therapy/therapy/mortality ; Retrospective Studies ; Adult ; Aged ; Neoadjuvant Therapy ; Obesity/epidemiology ; Neoplasm Staging ; }, abstract = {Body mass index (BMI) is a key factor in the progression of breast cancer (BC), with conflicting evidence on its influence on pathological complete response (pCR) following neoadjuvant chemotherapy (NAC). Despite these global findings, studies focusing on real-world Brazilian data remain scarce. This study aimed to evaluate the impact of BMI on pCR rates, recurrence-free survival (RFS), and overall survival (OS) in Brazilian women with BC treated with NAC. A retrospective cohort of 1,751 patients with stage I-III invasive primary BC treated between January 2011 and December 2020 at two public healthcare centers Hospital Pérola Byington (HPB) and Hospital do Servidor Público Estadual (HSPE) in Brazil was analyzed. Data included BMI categories (normal, overweight, and obese) and their associations with pCR, RFS, and OS outcomes. Obesity was prevalent (35.5%) among the cohort, with most patients being postmenopausal (50.9%). Tumors were predominantly stage III invasive ductal carcinoma, with triple-negative and luminal B subtypes being the most common. Radical surgery was performed in 79.8% of cases, achieving a pCR rate of 22.3%, and 30.9% of patients experienced recurrence, predominantly systemic (27.7%). No significant differences in pCR, RFS, or OS were observed across BMI categories. BMI was not associated with pCR, RFS, or OS in this large Brazilian cohort, highlighting the need for further studies to explore BMI dynamics during treatment and its potential influence on therapeutic outcomes. Future investigations in diverse healthcare settings may provide additional insights into optimizing breast cancer management across BMI strata.}, } @article {pmid39974553, year = {2025}, author = {Maeda, Y and Ikeda, T and Sato, A and Matsumoto, A and Jinno, H}, title = {Breast Cancer with a Newly Diagnosed Variant in the PTEN Gene: A Case Report.}, journal = {Surgical case reports}, volume = {11}, number = {1}, pages = {}, pmid = {39974553}, issn = {2198-7793}, abstract = {INTRODUCTION: The phosphatase and tensin homolog hamartoma tumor syndrome (PHTS) refers to a spectrum of disorders caused by variants of the phosphatase and tensin homolog (PTEN) gene, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome, adult Lhermitte-Duclos disease, and autism spectrum disorders associated with macrocephaly. PHTS is characterized by hamartomas in multiple organs and is associated with an increased risk of developing malignant tumors including, breast, thyroid, endometrial, colorectal, and kidney tumors. Breast cancer is the most common malignancy associated with PHTS.

CASE PRESENTATION: We describe the case of a 44-year-old female patient with invasive ductal carcinoma of the right breast. Cobblestone papillomatosis was present in the gingiva. She had a medical history of bilateral adenomatous goiters for 10 years. Her mother had been diagnosed with breast cancer, thyroid and tongue tumors, gastric polyps, hepatic hemangioma, and collagen disease. Additionally, the patient's maternal grandmother had a history of colon cancer. Based on the patient's family history and physical findings, CS was suspected, and direct DNA sequencing analysis revealed a haplotype c.634del mutation in exon 7 of the PTEN gene. Although there is no clear evidence supporting risk-reducing surgery for PHTS, a right nipple-sparing mastectomy, sentinel lymph node biopsy, and tissue expander reconstruction were performed.

CONCLUSIONS: We report a case of breast cancer with a newly diagnosed c.634del mutation in the PTEN gene. We also reviewed the current literature on PTEN genetic variants and breast cancer subtypes.}, } @article {pmid39973691, year = {2025}, author = {Grinberg, E and Nachoum, R and Kanat-Maymon, Y}, title = {The effect of basic psychological needs on healthcare professionals' work-related psychological outcomes.}, journal = {Work (Reading, Mass.)}, volume = {80}, number = {4}, pages = {1634-1639}, doi = {10.1177/10519815241295906}, pmid = {39973691}, issn = {1875-9270}, mesh = {Humans ; Male ; *Job Satisfaction ; Female ; Adult ; Surveys and Questionnaires ; Middle Aged ; Personal Autonomy ; *Health Personnel/psychology ; Workplace/psychology ; Compassion Fatigue/psychology ; *Occupational Therapists/psychology ; *Physical Therapists/psychology ; }, abstract = {Backgroundself-determination theory (SDT) posits that the satisfaction of the three basic psychological needs of autonomy, competence, and relatedness affects employees' work-related psychological outcomes. Despite the wealth of studies addressing SDT in the workplace domain, little is known of the effect of each basic need to the work-related psychological outcomes of healthcare workers.ObjectiveTo evaluate the relative effect of each basic psychological need to occupational and physical therapists' work-related psychological outcomes.MethodsParticipants were 152 occupational and physical therapists who completed questionnaires tapping basic psychological needs satisfaction, well-being, work meaning, work satisfaction and compassion fatigue. A series of linear regressions were performed.ResultsCompetence, relatedness toward co-workers, and relatedness toward patients were positive predictors of occupational and physical therapists' mental well-being. Autonomy and competence predicted job satisfaction. Autonomy, competence, and relatedness toward patients predicted work meaning. Autonomy and competence were significant negative predictors of compassion fatigue.ConclusionsStudy results demonstrate each basic psychological need makes its own influence to different psychological outcomes, highlighting the importance of supporting all three needs.}, } @article {pmid39971939, year = {2025}, author = {Yanik, S and Venkatesh, V and Gordy, JT and Alameh, MG and Meza, J and Li, Y and Glass, E and Flores-Garcia, Y and Tam, Y and Chaiyawong, N and Sarkar, D and Weissman, D and Markham, R and Srinivasan, P}, title = {iDC-targeting PfCSP mRNA vaccine confers superior protection against Plasmodium compared to conventional mRNA.}, journal = {NPJ vaccines}, volume = {10}, number = {1}, pages = {34}, pmid = {39971939}, issn = {2059-0105}, support = {R01 AI155598/AI/NIAID NIH HHS/United States ; T32 AI138953/AI/NIAID NIH HHS/United States ; R01AI155598//U.S. Department of Health & Human Services | NIH | Center for Scientific Review (NIH Center for Scientific Review)/ ; }, abstract = {Malaria resurgence in 2022 saw 249 million clinical cases and 608,000 deaths, mostly in children under five. The WHO-approved circumsporozoite protein (CSP)-targeting vaccines, RTS,S and R21, remain limited in availability. Strong humoral responses are crucial for sporozoite neutralization before hepatocyte infection, yet first-generation vaccines provide suboptimal protection, necessitating improved strategies. With the success of mRNA-LNP vaccines against COVID-19, there is interest in leveraging this approach to malaria. Here, we developed a novel chemokine fusion mRNA vaccine targeting immature dendritic cells (iDC) to enhance immunity against P. falciparum CSP (PfCSP). Mice immunized with MIP3α-CSP mRNA-LNP exhibited stronger CD4 + T cell responses and higher anti-NANP6 antibody titers than conventional CSP mRNA-LNP. Importantly, upon P. berghei PfCSP transgenic sporozoite challenge, MIP3α-CSP mRNA provided significantly greater protection from liver infection, strongly associated with multifunctional CD4 + T cells and anti-NANP6 titers. This study underscores iDC targeting as a promising strategy to enhance malaria vaccine efficacy.}, } @article {pmid39968442, year = {2025}, author = {K N, S and Devaranavadagi, BB and Hundekari, IA}, title = {Immunohistochemical Expression of Vitamin D Receptors (VDRs) and Estrogen Receptor Beta 1 (ERβ1) in Molecular Subtypes of Triple-Negative Breast Cancer Tumors: A Cross-Sectional Study.}, journal = {Cureus}, volume = {17}, number = {1}, pages = {e77637}, pmid = {39968442}, issn = {2168-8184}, abstract = {Introduction Breast cancer (BC) is still the most common malignancy among women globally, and triple-negative breast cancer (TNBC) presents major therapeutic and management issues due to its aggressive nature. Recent studies suggest that the vitamin D receptor (VDR) and estrogen receptor beta 1 (ERβ1) play crucial roles in regulating TNBC progression. Increased expression of VDR and ERβ1 has been linked to tumor suppression, highlighting their potential to impact cancer progression via various signaling pathways. This study analyzes VDR and ERβ1 expressions in TNBC subtypes to discover potential therapeutic targets and improve treatment outcomes for this challenging BC subtype. Method This cross-sectional study analyzed 30 invasive ductal carcinoma (IDC) cases of TNBC subtypes using formalin-fixed paraffin embedding (FFPE) tissues. Immunohistochemistry assessed cytoplasmic and nuclear VDR and ERβ1 expression, scoring staining intensity and extent, categorized as negative/low, moderate, or high expression. Results High VDR and ERβ1 expressions were analyzed across molecular subtypes of TNBC to explore their therapeutic potential, particularly in TNBC. In TNBC, a high VDR expression was observed in the cytoplasm (n = 10, 33.3%) and the nucleus (n = 2, 6.6%), with statistical significance (p < 0.042). Luminal A cases demonstrated high VDR expression in the cytoplasm (n = 6, 20%) and the nucleus (n = 2, 6.6%) (p < 0.042), while luminal B exhibited high VDR expression exclusively in the cytoplasm (n = 4, 13.3%) (p < 0.042). In HER2-enriched, high VDR expression was confined to the nucleus (n = 3, 10%) (p < 0.042). ERβ1 expression patterns in TNBC showed moderate cytoplasmic expression (n = 9, 50%) and high cytoplasmic expression (n = 1, 5.5%), with statistical significance (p < 0.025). By contrast, luminal A displayed moderate cytoplasmic expression (n = 3, 16.6%) and high cytoplasmic expression (n = 5, 27.7%) (p < 0.025). These findings suggest that VDR and ERβ1 exhibit subtype-specific expression patterns, with significant expression in TNBC, indicating their potential as therapeutic targets. Conclusion VDR and ERβ1 expressions differ between TNBC subtypes, indicating their potential as targeted therapies, particularly in TNBC.}, } @article {pmid39962573, year = {2025}, author = {Deng, J and Wei, L and Chen, Y and Li, X and Zhang, H and Wei, X and Feng, X and Qiu, X and Liang, B and Zhang, J}, title = {Identification of benzo(a)pyrene-related toxicological targets and their role in chronic obstructive pulmonary disease pathogenesis: a comprehensive bioinformatics and machine learning approach.}, journal = {BMC pharmacology & toxicology}, volume = {26}, number = {1}, pages = {33}, pmid = {39962573}, issn = {2050-6511}, mesh = {*Pulmonary Disease, Chronic Obstructive/genetics/chemically induced ; Humans ; *Benzo(a)pyrene/toxicity ; *Machine Learning ; Computational Biology ; Molecular Docking Simulation ; Protein Interaction Maps ; Nomograms ; Oxidative Stress/drug effects ; }, abstract = {BACKGROUND: Chronic obstructive pulmonary disease (COPD) pathogenesis is influenced by environmental factors, including Benzo(a)pyrene (BaP) exposure. This study aims to identify BaP-related toxicological targets and elucidate their roles in COPD development.

METHODS: A comprehensive bioinformatics approach was employed, including the retrieval of BaP-related targets from the Comparative Toxicogenomics Database (CTD) and Super-PRED database, identification of differentially expressed genes (DEGs) from the GSE76925 dataset, and protein-protein interaction (PPI) network analysis. Functional enrichment and immune infiltration analyses were conducted using GO, KEGG, and ssGSEA algorithms. Feature genes related to BaP exposure were identified using SVM-RFE, Lasso, and RF machine learning methods. A nomogram was constructed and validated for COPD risk prediction. Molecular docking was performed to evaluate the binding affinity of BaP with proteins encoded by the feature genes.

RESULTS: We identified 72 differentially expressed BaP-related toxicological targets in COPD. Functional enrichment analysis highlighted pathways related to oxidative stress and inflammation. Immune infiltration analysis revealed significant increases in B cells, DC, iDC, macrophages, T cells, T helper cells, Tcm, and TFH in COPD patients compared to controls. Correlation analysis showed strong links between oxidative stress, inflammation pathway scores, and the infiltration of immune cells, including aDC, macrophages, T cells, Th1 cells, and Th2 cells. Seven feature genes (ACE, APOE, CDK1, CTNNB1, GATA6, IRF1, SLC1A3) were identified across machine learning methods. A nomogram based on these genes showed high diagnostic accuracy and clinical utility. Molecular docking revealed the highest binding affinity of BaP with CDK1, suggestive of its pivotal role in BaP-induced COPD pathogenesis.

CONCLUSIONS: The study elucidates the molecular mechanisms of BaP-induced COPD, specifically highlighting the role of oxidative stress and inflammation pathways in promoting immune cell infiltration. The identified feature genes may serve as potential biomarkers and therapeutic targets. Additionally, the constructed nomogram demonstrates high accuracy in predicting COPD risk, providing a valuable tool for clinical application in BaP-exposed individuals.}, } @article {pmid39962362, year = {2025}, author = {Simoes, E and Uchida, R and Nucci, MP and Duran, FLS and Lima, JDCC and Gama, LR and Costa, NA and Otaduy, MCG and Bin, FC and Otoch, JP and Alcantara, P and Ramos, A and Laviano, A and Diaz, MB and Esiri, MM and DeLuca, GC and Herzig, S and Filho, GB and Seelaender, M}, title = {Cachexia Alters Central Nervous System Morphology and Functionality in Cancer Patients.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {16}, number = {1}, pages = {e13742}, pmid = {39962362}, issn = {2190-6009}, mesh = {Humans ; *Cachexia/etiology/pathology/physiopathology ; Male ; Female ; Middle Aged ; *Neoplasms/complications/pathology/physiopathology ; Aged ; Magnetic Resonance Imaging ; *Central Nervous System/pathology/physiopathology ; Aged, 80 and over ; }, abstract = {BACKGROUND: Cachexia is a clinically challenging multifactorial and multi-organ syndrome, associated with poor outcome in cancer patients, and characterised by inflammation, wasting and loss of appetite. The syndrome leads to central nervous system (CNS) function dysregulation and to neuroinflammation; nevertheless, the mechanisms involved in human cachexia remain unclear.

METHODS: We used in vivo structural and functional magnetic resonance imaging (Cohort 1), as well as postmortem neuropathological analyses (Cohort 2) in cachectic cancer (CC) patients compared to weight stable cancer (WSC) patients. Cohort 1 included treatment-naïve adults diagnosed with colorectal cancer, further divided into WSC (n = 12; 6/6 [male/female], 61.3 ± 3.89 years) and CC (n = 10; 6/4, 63.0 ± 2.74 years). Cohort 2 was composed by human postmortem cases where gastrointestinal carcinoma was the underlying cause of death (WSC n = 6; 3/3, 82.7 ± 3.33 years and CC n = 10; 5/5, 84.2 ± 2.28 years).

RESULTS: Here we demonstrate that the CNS of CC patients presents regional structural differences within the grey matter (GM). Cachectic patients presented an augmented area within the region of the orbitofrontal cortex, olfactory tract and the gyrus rectus (coordinates X, Y, Z = 6, 20,-24; 311 voxels; pFWE = 0.023); increased caudate and putamen volume (-10, 20, -8; 110 voxel; pFWE = 0.005); and reduced GM in superior temporal gyrus and rolandic operculum (56,0,2; 156 voxels; pFWE = 0.010). Disrupted functional connectivity was found in several regions such as the salience network, subcortical and temporal cortical areas of cachectic patients (20 decreased and 5 increased regions connectivity pattern, pFDR < 0.05). Postmortem neuropathological analyses identified abnormal neuronal morphology and density, increased microglia/macrophage burden, astrocyte profile disruption and mTOR pathway related neuroinflammation (p < 0.05).

CONCLUSIONS: Our results indicate that cachexia compromises CNS morphology mostly causing changes in the GM of cachectic patients, leading to alterations in regional volume patterns, functional connectivity, neuronal morphology, neuroglia profile and inducing neuroinflammation, all of which may contribute to the loss of homeostasis control and to deficient information processing, as well as to the metabolic and behavioural derangements commonly observed in human cachexia. This first human mapping of CNS cachexia responses will now pave the way to mechanistically interrogate these pathways in terms of their therapeutic potential.}, } @article {pmid39960111, year = {2025}, author = {Stavrou, S and Paynter, JA and Carins, T and Qin, KR and Brennan, J}, title = {Variation in the Definitions of Urinary Retention in Studies of Intravesical Botulinum Toxin for Idiopathic Overactive Bladder: A Narrative Systematic Review.}, journal = {Neurourology and urodynamics}, volume = {44}, number = {4}, pages = {860-877}, pmid = {39960111}, issn = {1520-6777}, mesh = {Humans ; *Urinary Retention/diagnosis/physiopathology/therapy ; *Urinary Bladder, Overactive/drug therapy/physiopathology ; Administration, Intravesical ; *Botulinum Toxins, Type A/administration & dosage/adverse effects ; *Neuromuscular Agents/administration & dosage/adverse effects ; *Urinary Bladder/physiopathology/drug effects ; *Botulinum Toxins/administration & dosage/adverse effects ; }, abstract = {PURPOSE: To categorise and quantify definitions of urinary retention reported in studies assessing botulinum toxin (BoNT) injections for idiopathic overactive bladder (iOAB) syndrome.

MATERIALS AND METHODS: A narrative systematic review was conducted using three databases: EMBASE (via Ovid), PubMed, and SCOPUS. Inclusion criteria comprised studies published as full-text articles in English involving adults receiving BoNT injections (any formulation) for iOAB syndrome, where urinary retention was reported as an outcome.

RESULTS: From 1986 screened studies, 135 were assessed, and 57 met the eligibility criteria for the narrative systematic review. Reported rates of urinary retention varied widely, ranging from 0% to 42.6%. A definition of urinary retention was provided in 33 studies (57.9%), which were broadly categorised as follows. 1. Post-void residual (PVR) volume threshold: 14 studies (21.5%). 2. Inability to void: 6 studies (9.2%). 3. Initiation of clean intermittent catheterisation (CIC): 6 studies (9.2%). 4. PVR volume threshold and initiation of CIC/indwelling catheterisation (IDC): 6 studies (9.2%). 5. Bladder symptoms and PVR volume threshold and initiation of CIC/IDC: 6 studies (9.2%). 6. Bladder symptoms and PVR volume threshold: 3 studies (4.6%). Notably, 24 studies (42.1%) omitted a definition altogether.

CONCLUSIONS: Urinary retention rates varied significantly between studies, likely due to the heterogeneous definitions used. The omission of definitions in nearly half of studies further complicates efforts to accurately inform and consent patients regarding the risk of urinary retention and the need for CIC/IDC after intravesical BoNT injection. Standardised definitions are urgently needed to enhance research, improve clinical practice, and support informed patient counselling.}, } @article {pmid39955968, year = {2025}, author = {Zhou, S and Shi, Y and Huang, Z and Teng, Y and Xing, W}, title = {Does the Presence of Ductal Carcinoma in situ Affect Prognostic Outcomes After Neoadjuvant Therapy in Invasive Ductal Carcinoma of the Breast?.}, journal = {Clinical oncology (Royal College of Radiologists (Great Britain))}, volume = {40}, number = {}, pages = {103781}, doi = {10.1016/j.clon.2025.103781}, pmid = {39955968}, issn = {1433-2981}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/pathology/therapy/mortality/drug therapy ; *Neoadjuvant Therapy ; Prognosis ; *Carcinoma, Ductal, Breast/pathology/therapy/mortality/drug therapy ; *Carcinoma, Intraductal, Noninfiltrating/pathology/therapy ; Adult ; Aged ; Retrospective Studies ; }, abstract = {AIMS: The presence of ductal carcinoma in situ (DCIS) alongside invasive ductal carcinoma (IDC) of the breast is common in clinical practice and affects clinical outcomes and treatment strategies. This study aimed to compare the clinicopathological characteristics and prognosis of patients with IDC coexisting with DCIS versus pure IDC after neoadjuvant therapy (NAT) and to explore the risk factors for residual DCIS following NAT.

MATERIAL AND METHODS: Patients with Stage II-III IDC who underwent NAT followed by radical surgery between January 2015 and December 2022 were included. Baseline data, clinical characteristics, preoperative treatment, surgical approach, pathological outcomes, and prognostic information were collected and analysed.

RESULTS: A total of 852 patients were enrolled in this study, with 279 and 573 patients in the IDC + DCIS and IDC groups, respectively. Compared with patients in the IDC group, those in the IDC + DCIS group had a lower proportion of triple-negative molecular type (15.1% vs. 33.9%, P < 0.001), better histological grade (52.0% vs. 37.7%, P < 0.001), and higher residual rate of DCIS (71.3% vs. 38.7%, P < 0.001). The 5-year disease-free survival (DFS) (85.2% vs. 82.4%, P = 0.188) and overall survival (OS) (93.2% vs. 93.0%, P = 0.810) rates of patients in the IDC + DCIS group were similar to those in the IDC group. However, in the triple-negative breast cancer population, the DFS (88.6% vs. 75.8%, P = 0.032) of patients with IDC + DCIS was significantly better than that of patients with IDC. For patients with IDC + DCIS, age ≥40 years (odds ratio [OR] = 0.421; 95% confidence interval [CI], 0.163-0.889, P = 0.035) and HR+/HER2-molecular subtype (OR=3.347; 95% CI, 1.237-6.577, P = 0.047) were independent preoperative predictors for residual DCIS after NAT.

CONCLUSION: The presence of DCIS in IDC demonstrated less tumour aggressiveness than pure IDC. However, a survival benefit was only observed in patients with triple-negative IDC combined with DCIS after NAT. Furthermore, patients with IDC + DCIS have a higher risk of residual DCIS after NAT, and age <40 years and the luminal subtype are risk factors for residual DCIS after NAT in patients with IDC + DCIS.}, } @article {pmid39949748, year = {2025}, author = {Nkonde, KA and Cheung, SM and Senn, N and He, J}, title = {Understanding cellular proliferation activity in breast cancer using multi-compartment model of transverse relaxation time mapping on 3T MRI.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1482112}, pmid = {39949748}, issn = {2234-943X}, abstract = {INTRODUCTION: Precise understanding of proliferative activity in breast cancer holds significant value in the monitoring of neoadjuvant treatment, while current immunostaining of Ki-67 from biopsy or resected tumour suffers from partial sampling error. Multi-compartment model of transverse relaxation time has been proposed to differentiate intra- and extra-cellular space and biochemical environment but susceptible to noise, with recent development of Bayesian algorithm suggested to improve robustness. We hence hypothesise that intra- and extra-cellular transverse relaxation times using Bayesian algorithm might be sensitive to proliferative activity.

MATERIALS AND METHODS: Twenty whole tumour specimens freshly excised from patients with invasive ductal carcinoma were scanned on a 3 T clinical scanner. The overall transverse relaxation time was computed using a single-compartment model with the non-linear least squares algorithm, while intra- and extra-cellular transverse relaxation times were computed using a multi-compartment model with the Bayesian algorithm. Immunostaining of Ki-67 was conducted, yielding 9 and 11 cases with high and low proliferating activities respectively.

RESULTS: For single-compartment model, there was a significant higher overall transverse relaxation time (p = 0.031) in high (83.55 ± 7.38 ms) against low (73.30 ± 11.30 ms) proliferating tumours. For multi-compartment model, there was a significant higher intra-cellular transverse relaxation time (p = 0.047) in high (73.52 ± 10.92 ms) against low (61.30 ± 14.01 ms) proliferating tumours. There was no significant difference in extra-cellular transverse relaxation time (p = 0.203) between high and low proliferating tumours.

CONCLUSIONS: Overall and Bayesian intra-cellular transverse relaxation times are associated with proliferative activities in breast tumours, potentially serving as a non-invasive imaging marker for neoadjuvant treatment monitoring.}, } @article {pmid39949015, year = {2024}, author = {Kawai, Y and Shinohara, R and Fukuda, C and Nagamori, M and Kaneko, Y and Wakita, K and Hazama, R and Inaba, M}, title = {[A Case of Surgical and Chemotherapeutic Treatment for Ipsilateral Breast Tumor Recurrence during Pregnancy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {13}, pages = {1833-1835}, pmid = {39949015}, issn = {0385-0684}, mesh = {Humans ; Female ; Pregnancy ; *Breast Neoplasms/surgery/drug therapy/pathology ; Adult ; *Pregnancy Complications, Neoplastic/surgery/drug therapy/pathology ; Recurrence ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; }, abstract = {A 40-year-old woman was diagnosed with ipsilateral breast tumor recurrence in the conserved breast 1.5 years after undergoing partial mastectomy for right breast cancer at another hospital. She was referred to our hospital at 19 weeks of gestation. At 21 weeks, total mastectomy of the conserved breast with sentinel lymph node biopsy was performed. The postoperative pathological diagnosis was invasive ductal carcinoma mixed with squamous cell carcinoma. AC chemotherapy was initiated at 33 weeks, and she gave birth by cesarean section at 39 weeks. Postpartum, EC therapy followed by paclitaxel therapy were administered. Currently, she is on endocrine therapy, with no new recurrence observed for 3 years after surgery. Pregnancy-associated breast cancer is rare, accounting for approximately 1% of all breast cancers, and there are few reports on the treatment of local recurrence or distant metastasis during pregnancy. This case, involving breast-conserving surgery recurrence during pregnancy, highlights the importance of careful decision-making and treatment strategies tailored to individual cases, considering the safety of both mother and fetus through multidisciplinary collaboration.}, } @article {pmid39948973, year = {2024}, author = {Omoto, H}, title = {[A Case of Advanced Breast Cancer Resected after the Combined Therapy of Palbociclib and Letrozole].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {13}, pages = {1704-1706}, pmid = {39948973}, issn = {0385-0684}, mesh = {Humans ; *Breast Neoplasms/drug therapy/pathology/surgery/therapy ; Female ; Letrozole ; Middle Aged ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Pyridines/administration & dosage ; Piperazines/administration & dosage ; Nitriles/administration & dosage ; Triazoles/administration & dosage ; Mastectomy ; Neoplasm Staging ; }, abstract = {A 50's postmenopausal woman, she was diagnosed with breast cancer, cT2N3aM0, Stage ⅢC, invasive ductal carcinoma, estrogen-receptor(ER)-positive, progesterone-receptor(PgR)-negative, human epidermal growth factor 2(HER2)-negative. A combination therapy of palbociclib(PAL)and letrozole(LET)was administered to the patient. A method of administration was 125 mg of PAL per day(14 days of treatment followed by 14 days off, 2 courses and 18 days of treatment followed by 10 days off, 8 courses)and 2.5 mg of LET per day every day. This therapy was effective, and the clinical stage showed down staging, T2N1M0, Stage ⅡB. Left total mastectomy and sentinel lymph node biopsy and swelled axillar lymph node resection was performed. Postoperative pathological histology revealed ypT2N1a(1/9). Subsequently this medication (125 mg of PAL per day, 21 days of treatment followed by 14 days off and 2.5 mg of LET per day every day)was continued as an adjuvant therapy and postmastectomy radiation therapy(PMRT 50 Gy)was underwent for her. This patient has survived without recurrence 12 months after operation. PAL probably has a certain effect even if oral administration method were changed.}, } @article {pmid39948972, year = {2024}, author = {Takeda, S and Terakawa, H and Kawata, C and Kurokawa, Y and Machi, R and Tanaka, H and Nishimura, Y and Mohri, R and Hirata, M and Kitahara, T and Moriyama, H and Kinoshita, J and Kawashima, H and Inaki, N}, title = {[A Case in Which Multiple Biopsies from Breast Cancer Skin Metastases Were Performed and Trastuzumab Deruxtecan Was Used after Low HER2 Expression Was Confirmed].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {13}, pages = {1702-1703}, pmid = {39948972}, issn = {0385-0684}, mesh = {Humans ; Middle Aged ; Female ; *Erb-b2 Receptor Tyrosine Kinases/analysis/metabolism ; *Trastuzumab/therapeutic use ; *Skin Neoplasms/secondary/drug therapy ; *Breast Neoplasms/pathology/drug therapy ; Biopsy ; *Camptothecin/analogs & derivatives/therapeutic use ; *Immunoconjugates/therapeutic use ; }, abstract = {In March 2023, Trastuzumab deruxtecan(T-DXd)was added for the treatment of inoperable or recurrent breast cancer with low HER2 expression who has a history of chemotherapy. The patient was a 61-year-old woman who had undergone surgery for bilateral breast cancer, and was diagnosed with Stage ⅡA triple negative(HER2-IHC score 0)on the right and non-invasive ductal carcinoma of the breast on the left. Biopsy from metastases was triple-negative(HER2-IHC score 0, PD-L1 negative). Exacerbation of skin metastases was observed despite repeated regimen changes 3rd skin biopsy was diagnosed with low expression of HER2 for the first time, and T-DXd was started. The therapeutic effect of T-DXd was temporarily observed, such as a decrease in tumor markers. It is useful to repeatedly collect tissues from primary and metastatic lesions and re-evaluate biomarkers in order to develop an appropriate treatment plan.}, } @article {pmid39948901, year = {2024}, author = {Nakakuma, T and Yamasaki, K and Ueno, S and Tabei, T}, title = {[A Case of Resection for a Late-Stage Solitary Hepatic Metastasis from Very Early Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {13}, pages = {1492-1494}, pmid = {39948901}, issn = {0385-0684}, mesh = {Humans ; Female ; Middle Aged ; *Liver Neoplasms/secondary/surgery/drug therapy ; *Breast Neoplasms/pathology/surgery ; Hepatectomy ; Neoplasm Staging ; *Carcinoma, Ductal, Breast/surgery/secondary ; }, abstract = {A 57-year-old woman underwent left breast conserving surgery(Bp+Ax)for breast cancer at 46 years of age. Histopathological findings were invasive ductal carcinoma(tubule forming type), pN0(0/17), Ly0, V0, NG1, HG1, pT1aN0M0, Stage Ⅰ, ER 100%, HER2 score 0. Postoperatively, only radiotherapy to the preserved breast was performed and no adjuvant drug therapy was administered. This time, a 45 mm liver tumor in segment 4/3 was found by abdominal ultrasound for health checkup. Enhanced ultrasonography showed poor contrast, CT showed a low density tumor with calcification, MRI showed no diffusion reduction, and PET showed no FDG uptake. Although the findings were not typical for suspecting malignancy, but cholangiocellular carcinoma or metastatic liver cancer could not be ruled out. Laparoscopic liver resection was performed. Histopathological findings revealed liver metastasis of breast cancer. We report a rare case, a late-stage solitary hepatic metastasis from very early breast cancer. Although the concept of breast cancer as a systemic disease is well-established, in this case there is a possibility that recurrence would not have occurred if postoperative adjuvant drug therapy had been performed. The importance of postoperative adjuvant drug therapy for breast cancer was suggested. At present, she remains disease-free after hepatectomy.}, } @article {pmid39948885, year = {2024}, author = {Sugimoto, Y and Terada, I and Okamoto, J and Yamazaki, H and Zaimoku, R and Tsukioka, Y}, title = {[A Case of Mastectomy and Axillary Lymph Node Dissection for Breast Cancer on the Side of Pacemaker Implant].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {13}, pages = {1446-1448}, pmid = {39948885}, issn = {0385-0684}, mesh = {Humans ; Female ; Lymph Node Excision ; *Pacemaker, Artificial ; *Breast Neoplasms/surgery/pathology ; Mastectomy ; Axilla ; Aged, 80 and over ; Lymphatic Metastasis ; }, abstract = {The patient was a woman in her 80s with a history of atrial fibrillation at age 80, and catheter ablation and pacemaker implantation for sinus bradycardia. Her chief complaint is a left lateral breast mass. A pacemaker was implanted subcutaneously in the caudal left subclavian region, and palpation revealed a 20 mm-sized elastic hard mass in the left D area. On close examination, she was diagnosed as HER2-enriched invasive ductal carcinoma of the breast, T1cN0M0, cStage Ⅰ. The surrounding fatty tissue was preserved without exposing the pacemaker, and a subtotal left breast resection plus sentinel lymph node biopsy was performed, with additional axillary lymph node dissection due to positive metastasis. Intraoperative pacemaker monitoring was performed and no trouble was observed. The patient was discharged on the 6th postoperative day without complications. Pathology results showed pT2pN2aM0(7/16), pStage ⅢA. Postoperatively, the patient is scheduled to receive radiation to the chest wall without a pacemaker and chemotherapy.}, } @article {pmid39948873, year = {2024}, author = {Satoh, E and Yamazaki, A and Uehira, D and Yonekura, K and Toyofuku, Y and Osanai, T and Sugano, N and Sakoma, T}, title = {[A Case of Locally Advanced Breast Cancer Reconstructed with Rhomboid Flap after Mastectomy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {13}, pages = {1411-1412}, pmid = {39948873}, issn = {0385-0684}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery/pathology/drug therapy ; Mastectomy ; *Surgical Flaps ; Aged, 80 and over ; Mammaplasty ; }, abstract = {We report a case of right locally advanced breast cancer in an 84-year-old woman. Her breast cancer(pathologically invasive ductal carcinoma)was 42 mm in diameter and located at B area(lower-inner quadrant)with marked skin invasion (cT4bN0M0, Stage ⅢB). Mastectomy with about 10×10 cm skin resection plus sentinel lymph node biopsy was performed in August 2022 after neoadjuvant endocrine therapy(anastrozole). The skin defect after mastectomy was reconstructed with the rhomboid flap designed at D area(lower-outer quadrant). Her cutaneous local flap after the operation showed an excellent condition and she was discharged with no wound complications. The rhomboid flap was designed quickly and easily with no special instruments, and resulted in a good cosmetic outcome. Therefore, rhomboid flap reconstruction was a very useful method to cover the skin defect after mastectomy of locally advanced breast cancer.}, } @article {pmid39948851, year = {2024}, author = {Fujimori, T and Kasagawa, T and Ishii, N and Kusashio, K and Yonemori, Y and Ozaki, D}, title = {[A Case of Bladder Metastasis from Invasive Ductal Carcinoma of the Breast-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {13}, pages = {1345-1347}, pmid = {39948851}, issn = {0385-0684}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/surgery/therapy/drug therapy ; Aged ; *Urinary Bladder Neoplasms/secondary/drug therapy ; *Carcinoma, Ductal, Breast/secondary/therapy/surgery/drug therapy/pathology ; Neoplasm Invasiveness ; }, abstract = {We report a patient with left breast cancer who underwent total mastectomy and axillary dissection as primary surgery. The patient, a 78-year-old woman, noticed a tumor about 4 cm in the left breast. She was diagnosed with left breast cancer (cT2N2M0, cStage ⅢA). The pathology revealed invasive lobular carcinoma, 46×31 mm, ly(+), v(0), histological grade: 2, n2, hormone receptor positive, HER2 negative, and pStage ⅢA. We recommended adjuvant chemotherapy, but she did not desire. She started oral administration of an aromatase inhibitor and radiation therapy. When DFI was 3 years, an examination was carried out because the increase in CEA value, CT scan revealed a mass extending from the bladder. We suspected bladder cancer. She underwent a bladder biopsy. The result was bladder metastasis of breast cancer. Later, we introduced chemotherapy. Routine screening of the lower urinary tract is not necessary for all patients, but women with a history of breast cancer presenting with urinary symptoms should undergo a thorough examination of the urinary tract.}, } @article {pmid39948850, year = {2024}, author = {Aoyagi, T and Sakata, H and Namura, M and Tamanuki, T and Iwai, M and Ohira, G and Hayano, K and Matsubara, H and Matsuzaki, H}, title = {[A Case of Locally Advanced Breast Cancer Showing Local Enlargement during Chemotherapy, followed by Surgery and Suppression of Recurrence].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {13}, pages = {1342-1344}, pmid = {39948850}, issn = {0385-0684}, mesh = {Humans ; Female ; Aged ; *Breast Neoplasms/pathology/surgery/drug therapy/therapy ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Recurrence ; Mastectomy ; Antibodies, Monoclonal, Humanized/administration & dosage ; *Carcinoma, Ductal, Breast/surgery/drug therapy ; Trastuzumab/administration & dosage ; Combined Modality Therapy ; }, abstract = {A 71-year-old woman was referred to our hospital for a right breast mass urgency. A CT scan revealed a large right breast tumor with skin involvement. Biopsy results confirmed the diagnosis of Luminal-HER2 type invasive ductal carcinoma. Chemotherapy was initiated with a regimen of paclitaxel, trastuzumab, and pertuzumab. Initially, the tumor flattened and significantly decreased in size. However, after 9 months of treatment, disease progression occurred, leading to sequential changes in the treatment regimen to T-DM1 and T-DXd. Despite these efforts, the tumor continued to grow rapidly. At 13 months after starting chemotherapy, the treatment effect was unsatisfactory, prompting a decision to perform a total mastectomy, including resection of the right breast tumor and the pectoralis major muscle, followed by skin grafting. The histopathological effect of the treatment was judged as Grade 1b, with intermediate tumor margins. Postoperatively, the patient received radiation therapy to the chest wall, followed by continued treatment with trastuzumab and pertuzumab. As of 2 years after surgery, no recurrence has been observed.}, } @article {pmid39945142, year = {2025}, author = {Cremer, A and Rosewick, N and Kelsey, M and Trépo, E and Libert, F and De Vos, M and Baert, F and Moreels, T and Louis, E and Rahier, JF and Demetter, P and Sedivy, JM and Vermeire, S and Franchimont, D}, title = {A transcriptomic score to classify the inflammation-dysplasia-cancer sequence lesions in inflammatory bowel disease.}, journal = {Journal of Crohn's & colitis}, volume = {19}, number = {3}, pages = {}, pmid = {39945142}, issn = {1876-4479}, support = {//Research Foundation against Cancer-Belgium/ ; //Erasme Foundation/ ; R01 AG016694/AG/NIA NIH HHS/United States ; P01 AG051449/AG/NIA NIH HHS/United States ; //Televie/ ; P01 AG051449/NH/NIH HHS/United States ; }, mesh = {Humans ; Female ; Male ; *Inflammatory Bowel Diseases/genetics/pathology/complications ; *Transcriptome ; Middle Aged ; Adult ; *Colorectal Neoplasms/genetics/pathology/etiology ; Gene Expression Profiling ; Inflammation/genetics/pathology ; *Colitis-Associated Neoplasms/genetics/pathology ; Intestinal Mucosa/pathology ; RNA, Long Noncoding/genetics ; }, abstract = {BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is associated with a higher risk of developing colorectal cancer, according to the inflammation-dysplasia-cancer (IDC) sequence from inflammation to colitis-associated colorectal cancer (CAC). The objective of this study was to identify and generate a transcriptomic signature and score, related to the IDC sequence, that could ultimately classify dysplasia and cancer in IBD.

METHODS: Demographics, clinical parameters, histological characteristics, and RNA-sequencing data were evaluated on 134 formalin-fixed paraffin-embedded lesions from 2 independent cohorts of IBD patients with low- or high-grade dysplasia (LGD, HGD) and/or CAC. An ordinal logistic regression screened for significant IDC sequence-associated genes that were computed in a transcriptomic signature score.

RESULTS: Principal component analysis and unsupervised clustering on 1% of the most variable genes showed a good clustering between the 4 lesion groups (Normal Mucosa, Inflamed Mucosa, LGD/HGD, and CAC). A gene signature was identified on 27 genes that correlated with the lesion groups in the exploratory cohort. The most weighted gene in this transcriptomic signature was the long non-coding regulatory RNA KCNQ1OT1, a gatekeeper against genomic instability and transposon activation. Based on the expression of these 27 genes, we built and validated a transcriptomic signature score to classify dysplasia and CAC. The overall accuracy of the transcriptomic signature score was 85.71% in the exploratory cohort and 90.91% in the validation cohort.

CONCLUSION: We identified a tissue-based transcriptomic score to classify IDC lesions in IBD patients and uncovered some of the pivotal genes in carcinogenesis related to inflammation in IBD.}, } @article {pmid39944323, year = {2025}, author = {Dillan, MM and Piktel, J and Perzynski, A and Roach, MJ and Curtis, KK and Tarabichi, Y and Wilson, L and Kelly, ML}, title = {Social determinants and follow-up care after emergency department discharge for traumatic intracranial hemorrhage.}, journal = {Heliyon}, volume = {11}, number = {3}, pages = {e42230}, pmid = {39944323}, issn = {2405-8440}, abstract = {BACKGROUND: Traumatic brain injury (TBI) is a multifaceted condition associated with occupational, social, physical, cognitive, academic, and economic burdens. Mild TBI including traumatic intracranial hemorrhage (tICH), is commonly discharged from the emergency department (ED). Despite the complexity of factors contributing to TBI outcomes, patient education and comprehensive follow-up plans are frequently lacking. We examined health trajectories, recidivism, and follow-up patterns of patients discharged from the ED with tICH to identify opportunities to improve care.

METHODS: We conducted an IRB approved retrospective observational study at a large urban Level 1 trauma center from January 2017 to July 2022. We identified patients (n = 117) discharged from the ED with acute tICH, using IDC 9/10 codes and confirmed by imaging review. Exclusions were hospital admission, chronic ICH, and age under 18. The primary outcome was an ED-revisit within 180 days. Secondary outcomes included any return TBI visit, scheduled specialty TBI provider visit, and post-TBI mental health disorder diagnoses. Age, gender, race, ethnicity, pre-TBI mental health disorders, and socioeconomic status (SES) were analyzed. SES was measured using area deprivation index (ADI). Statistical analysis was performed with logistic regression and Chi-squared tests.

RESULTS: The average age of enrolled patients was 53 ± 20 years with 39 % female, 26 % Black, 69 % White, and 6 % Hispanic. Overall follow-up rates were low, with 49 % of patients having at least one scheduled follow-up visit within 180 days. Only 16 % of Black patients saw a TBI specialty provider visit within 180 days compared to 36 % of White patients (p = .03). ED recidivism rate was 18 %, with 25 % of patients overall having an unscheduled TBI visit. Lower SES was a significant predictor of any TBI revisit (OR 1.39, CI 1.06, 1.82). New mental health diagnoses following tICH occurred in 15 % of patients; depression and anxiety were most common. There was no association between SES, age, gender, race, or ethnicity and new mental health diagnoses.

CONCLUSION: We observed racial and SES differences in follow-up care from the ED for patients with TBI. Individualized discharge planning and formulation of care pathways that account for the mental health and social needs of all patients may improve long-term outcomes. Further understanding of health disparities present in ED TBI care is needed.}, } @article {pmid39943990, year = {2024}, author = {Li, H and Yang, L and Sun, X and Wang, Z and Qin, S and Li, C and Liu, G and Xie, F and Gao, W}, title = {Changes in hormone receptor when breast cancer metastasizes to the colon: case report and literature review.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1391393}, pmid = {39943990}, issn = {2234-943X}, abstract = {The metastasis of breast cancer to the colon is a rare occurrence, especially in the presence of changes in estrogen and progesterone receptors. To date, literature has only reported two cases of invasive ductal carcinoma and two cases of invasive lobular carcinoma metastasizing to the colon with concurrent changes in hormone receptors. This report describes a 65-year-old woman with a history of left breast cancer, who presented with symptoms of bloody stools and abdominal pain. CT and colonoscopy results revealed a malignant tumor in the ascending colon, and the patient underwent surgery. Pathological results post-surgery indicated changes in hormone receptors, differing from the previous breast cancer pathology, ultimately leading to the diagnosis of breast cancer metastasis to the colon. The patient was found to have liver metastasis 14 months after right hemicolectomy, and systemic metastases in various locations were discovered at the 19-month mark.}, } @article {pmid39938227, year = {2025}, author = {Rodriguez, M and Du Thanh, A and Girard, C and Lesage, C and Meunier, L and Bessis, D and Picot, MC and Dereure, O}, title = {Methotrexate in monotherapy or combined with oral steroids for bullous pemphigoid in a real-life setting: A retrospective monocentric cohort.}, journal = {Annales de dermatologie et de venereologie}, volume = {152}, number = {1}, pages = {103329}, doi = {10.1016/j.annder.2024.103329}, pmid = {39938227}, issn = {0151-9638}, mesh = {Humans ; *Methotrexate/administration & dosage/adverse effects/therapeutic use ; Retrospective Studies ; *Pemphigoid, Bullous/drug therapy ; Male ; Female ; Aged ; Drug Therapy, Combination ; Administration, Oral ; Middle Aged ; Aged, 80 and over ; Recurrence ; *Dermatologic Agents/administration & dosage/adverse effects ; Adult ; }, abstract = {BACKGROUND: In bullous pemphigoid (BP), prolonged treatment with low-dose methotrexate (MTX) may represent an effective strategy to maintain an initial clinical remission achieved by short-duration superpotent topical steroids (STS).).

PATIENTS AND METHODS: To evaluate the efficacy and safety of MTX in a real-life setting, a retrospective analysis was conducted in a reference centre for all BP patients treated between 2015 and 2020 with STS and MTX, either in monotherapy (mMTX) or in combination with oral steroids (MTX+OS). The primary endpoints were BP relapse rate and time to relapse during treatment for patients achieving initial disease control (IDC). Secondary endpoints included IDC achievement rate, relapse rate and time to relapse after MTX discontinuation, adverse effect (AE) and mortality rates, number of patients permanently discontinuing MTX owing to AE, number of patients alive and still in complete remission (CR) at the latest updates, and whether they were off treatment (cure rate).

RESULTS: The BP relapse rate during treatment after achievement of IDC was significantly higher in patients treated with mMTX (32.2%) than with MTX+OS (0%) (p = 0.03); mean time to relapse was 10.3 months. The BP relapse rate after MTX discontinuation and the cure rate did not differ significantly between the two groups. One patient (receiving mMTX) died during follow-up and 27.8% of patients experienced at least one AE during the study. The cure rate in patients achieving IDC was 45.2% with mMTX vs. 30% with MTX+OS (p = 0.15).

CONCLUSION: Our study highlights the value of low-dose mMTX for treating BP in a real-life setting, both for achievement of initial response and for long-term control, with a good overall safety profile and no significant additional mortality risk in elderly subjects. However, relapses appear to have been less frequent during treatment when MTX was initially combined with OS.}, } @article {pmid39937534, year = {2025}, author = {Han, M and Chen, T and Ediriwickrema, L}, title = {Intra-operative visualization of the superior ophthalmic vein in carotid-cavernous fistula.}, journal = {Orbit (Amsterdam, Netherlands)}, volume = {}, number = {}, pages = {1}, doi = {10.1080/01676830.2025.2460168}, pmid = {39937534}, issn = {1744-5108}, abstract = {This 55-year-old woman with grade III invasive ductal carcinoma in remission on letrozole and hypertension presented with 4 months of headaches, diplopia, and a left eye with proptosis and circumferential corkscrew vessels extending to the limbus. Computed tomography imaging demonstrated a dilated superior ophthalmic vein consistent with a carotid-cavernous fistula (CCF). Diagnostic direct catheter angiography confirmed a CCF supplied by the left and right meningo-hypophyseal trunks of the internal carotid artery, which is type B by Barrow's classification. Oculoplastic surgery obtained access to the superior ophthalmic vein for direct catheterization on request from the interventional neuroradiology team as demonstrated in the image. Upon catheterization, the fistula had spontaneously thrombosed. Post-procedure, the patient had improved injection and proptosis of the left eye. She was started on apixaban to treat a presumed cavernous sinus thrombosis. She continues to do well at her follow up examinations.}, } @article {pmid39937427, year = {2025}, author = {Kato, M and Sato, H and Naito, Y and Yamamoto, A and Kawanishi, H and Nakano, Y and Nishikimi, T and Kobayashi, M and Kondo, A and Hirabayashi, H and Katsuno, S and Sakamoto, F and Kimura, T and Yamamoto, S and Araki, H and Tochigi, K and Ito, F and Hatsuse, H and Sassa, N and Hirakawa, A and Akamatsu, S and Tsuzuki, T}, title = {Prospective observational study on the relationships between genetic alterations and survival in Japanese patients with metastatic castration-sensitive prostate cancer: the impact of IDC-P.}, journal = {International journal of clinical oncology}, volume = {30}, number = {4}, pages = {789-796}, pmid = {39937427}, issn = {1437-7772}, mesh = {Humans ; Male ; Aged ; Prospective Studies ; Japan/epidemiology ; Middle Aged ; Mutation ; Aged, 80 and over ; *Prostatic Neoplasms, Castration-Resistant/genetics/pathology/mortality ; Prognosis ; *Prostatic Neoplasms/genetics/mortality/pathology ; Tumor Suppressor Protein p53/genetics ; BRCA2 Protein ; Hepatocyte Nuclear Factor 3-alpha ; East Asian People ; }, abstract = {BACKGROUND: Intraductal Carcinoma of the Prostate (IDC-P) is a significant prognostic indicator for prostate cancer, which demonstrates significant associations with homologous recombination repair gene mutations (HRRm) and alterations in tumor suppressor genes. However, no study in Japan has investigated the association between IDC-P and genetic mutations in men with metastatic castration-sensitive prostate cancer (mCSPC).

METHODS: This prospective observational study enrolled 102 de novo mCSPC (LATITUDE high-risk) patients diagnosed between 2018 and 2021, with subsequent monitoring of survival outcomes. A single genitourinary pathologist evaluated all needle biopsy slides. Genetic analyses were performed using the Myriad myChoice HRD plus™. These genetic analyses covered 108 genetic loci, including 15 HRRm genes, with a success rate of 91%.

RESULTS: Genetic alterations were observed in 79 patients (77.5%), with 20 exhibiting HRRm (19.6%). Common genetic alterations included FOXA1 (29.4%) and TP53 (17.6%) mutations; BRCA (9.8%) mutations were the most frequent HRRm (BRCA1:2 cases, BRCA2:8 cases, including 6 biallelic). IDC-P-positive patients demonstrated a significantly higher frequency of genetic aberrations (82.6% vs. 50%, p = 0.0082). Patients with biallelic BRCA2, TP53, and PTEN mutations exhibited significantly poorer cancer-specific survival. Multivariate analysis identified lactate dehydrogenase (LDH) (HR 1.005, p = 0.035), TP53 mutations (HR 5.196, p < 0.001), biallelic BRCA2 mutations (HR 10.686, p = 0.005), and IDC-P as independent predictors of poor cancer-specific survival. No cancer-related deaths occurred in IDC-P-negative cases.

CONCLUSION: Our study emphasizes the significant association between IDC-P and an elevated incidence of genetic alterations in Japanese mCSPC patients, emphasizing the need for early genetic testing to guide therapeutic decision-making.}, } @article {pmid39937011, year = {2025}, author = {Shah, S and Osuala, KO and Brock, EJ and Ji, K and Sloane, BF and Mattingly, RR}, title = {Three-Dimensional Models: Biomimetic Tools That Recapitulate Breast Tissue Architecture and Microenvironment to Study Ductal Carcinoma In Situ Transition to Invasive Ductal Breast Cancer.}, journal = {Cells}, volume = {14}, number = {3}, pages = {}, pmid = {39937011}, issn = {2073-4409}, support = {CA175931//NIH, uncertain of the year./ ; R21 CA175931/CA/NCI NIH HHS/United States ; R01 CA131990/CA/NCI NIH HHS/United States ; U54 CA193489/CA/NCI NIH HHS/United States ; F31 CA213807/CA/NCI NIH HHS/United States ; T32 CA009531/CA/NCI NIH HHS/United States ; P30 CA022453/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Tumor Microenvironment ; Female ; *Breast Neoplasms/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; *Biomimetics/methods ; *Carcinoma, Ductal, Breast/pathology ; Extracellular Matrix/metabolism ; *Models, Biological ; Neoplasm Invasiveness ; Cancer-Associated Fibroblasts/pathology ; Animals ; *Breast/pathology ; }, abstract = {Diagnosis of ductal carcinoma in situ (DCIS) presents a challenge as we cannot yet distinguish between those lesions that remain dormant from cases that may progress to invasive ductal breast cancer (IDC) and require therapeutic intervention. Our overall interest is to develop biomimetic three-dimensional (3D) models that more accurately recapitulate the structure and characteristics of pre-invasive breast cancer in order to study the underlying mechanisms driving malignant progression. These models allow us to mimic the microenvironment to investigate many aspects of mammary cell biology, including the role of the extracellular matrix (ECM), the interaction between carcinoma-associated fibroblasts (CAFs) and epithelial cells, and the dynamics of cytoskeletal reorganization. In this review article, we outline the significance of 3D culture models as reliable pre-clinical tools that mimic the in vivo tumor microenvironment and facilitate the study of DCIS lesions as they progress to invasive breast cancer. We also discuss the role of CAFs and other stromal cells in DCIS transition as well as the clinical significance of emerging technologies like tumor-on-chip and co-culture models.}, } @article {pmid39936988, year = {2025}, author = {González-Martínez, S and Palacios, J and Carretero-Barrio, I and Lanza, VF and García-Cosío Piqueras, M and Caniego-Casas, T and Hardisson, D and Esteban-Rodríguez, I and Cortés, J and Pérez-Mies, B}, title = {Single-Cell RNA Sequencing on Formalin-Fixed and Paraffin-Embedded (FFPE) Tissue Identified Multi-Ciliary Cells in Breast Cancer.}, journal = {Cells}, volume = {14}, number = {3}, pages = {}, pmid = {39936988}, issn = {2073-4409}, support = {PI22/01892, PMP22/00054, PMP21/00107//Instituto de Salud Carlos III/ ; }, mesh = {Humans ; *Breast Neoplasms/genetics/pathology ; *Paraffin Embedding/methods ; Female ; *Single-Cell Analysis/methods ; *Formaldehyde/chemistry ; *Tissue Fixation/methods ; *Sequence Analysis, RNA/methods ; Immunohistochemistry ; }, abstract = {The purpose of this study was to evaluate the suitability of formalin-fixed and paraffin-embedded (FFPE) samples and fixed fresh (FF) samples for single-cell RNA sequencing (scRNAseq). To this end, we compared single-cell profiles from FFPE and matched FF tissue samples of one invasive carcinoma of no special type carcinoma (invasive ductal carcinoma-IDC) and one invasive lobular carcinoma (ILC) to assess consistency in cell type distribution and molecular profiles. The results were validated using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and electron microscopy. Additionally, immune cell proportions identified by IHC were quantified using QuPath and compared to the scRNAseq results. FFPE- and FF-derived libraries demonstrated high-quality sequencing metrics, and cellular heterogeneity was similar. No exclusive cell populations were identified by either approach. The four samples analysis identified six types of epithelial cells, as well as tumoral microenvironment populations. The scRNAseq results from epithelial neoplastic cells were concordant with common IHC markers. The proportion of immune cells identified by IHC in FFPE sections were similar to those obtained by scRNAseq. We identified and validated a previously poorly recognized subpopulation of neoplastic multi-ciliated cells (MCCs) (FOXJ1, ROPN1L). Analysis of FOXJ1 in 214 ER-positive invasive carcinomas demonstrated protein expression in one third of tumors, suggesting frequent focal MCC differentiation. Our results support the suitability of scRNAseq analysis using FFPE tissue, and identified a subpopulation of neoplastic MCC in breast cancer.}, } @article {pmid39928785, year = {2025}, author = {Khanmammadov, N and Doğan, I and Khishigsuren, B and Azizy, A and Saip, P and Aydiner, A}, title = {Rechallenge of trastuzumab-based therapy in HER2-positive breast cancer patients who progressed after lapatinib plus capecitabine.}, journal = {Medicine}, volume = {104}, number = {6}, pages = {e41468}, pmid = {39928785}, issn = {1536-5964}, mesh = {Humans ; Female ; Middle Aged ; *Capecitabine/administration & dosage/therapeutic use ; *Breast Neoplasms/drug therapy/pathology/metabolism/mortality ; Lapatinib/administration & dosage ; *Trastuzumab/administration & dosage/therapeutic use ; Aged ; Adult ; Retrospective Studies ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/administration & dosage ; Disease Progression ; }, abstract = {Data regarding the use of rechallenge trastuzumab (RTmab)-based therapies in the management of heavily pretreated patients with HER2-positive breast cancer (BC) in the literature are limited. This study aimed to evaluate the efficacy of trastuzumab-based therapy in patients who experienced disease progression after receiving lapatinib plus capecitabine (LC). In this retrospective study, the data of thirty three HER2 positive metastatic BC patients who progressed after LC treatment and subsequently received trastuzumab-based treatment were evaluated. Trastuzumab was administered at an initial loading dose of 8 mg/kg followed by a maintenance dose of 6 mg/kg every 21 days. The average age of patients is 47 years (range 25-72 years). The predominant histopathological subtype was invasive ductal carcinoma, which was observed in 23 (70%) patients. Estrogen receptor (ER) positivity was also noted in 16 (48%) patients. All patients had received palliative trastuzumab plus chemotherapy (Cht) before the lapatinib. In conjunction with trastuzumab-based therapy, vinorelbine was administered to 14 (42%) patients, paclitaxel to 12 (36%), and other chemotherapeutic agents to 4 (12%). For all patients, the objective response and disease control rates were 27% and 69%, respectively. Furthermore, the median progression-free survival (PFS) was 8.8 months (95% confidence interval [CI]: 6.6-11), and the median overall survival was 20 months (95% CI: 15.1-25.8). There were no statistically significant differences in PFS rates based on several factors, including age, ER status, denovo metastasis, brain metastasis, perioperative Cht, pre-Rtmab hormone therapy, and which Cht was used along with Rtmab (P > .05). Mild to moderate adverse events were observed in 17 (52%) patients, whereas only 4 (12%) patients had Grade 3 to 4 toxicity. This study demonstrated that RTmab-based therapy is effective in patients who progressed after LC. These findings contribute to the literature by suggesting that RTmab is a viable treatment option for patients with HER2-positive metastatic BC.}, } @article {pmid39926571, year = {2025}, author = {Peshin, S and Iftekher, R and Iqbal, R and Singh, S and Nagaishwarya, M}, title = {The Optimal Treatment of Invasive Ductal and Lobular Carcinoma Occurring at the same time needs to be Established.}, journal = {European journal of case reports in internal medicine}, volume = {12}, number = {2}, pages = {005074}, pmid = {39926571}, issn = {2284-2594}, abstract = {UNLABELLED: Bilateral breast cancer with distinct histological subtypes poses a significant clinical challenge, requiring an individualised approach to management. This case discusses a 61-year-old postmenopausal woman with concurrent invasive ductal carcinoma (IDC) in the right breast and invasive lobular carcinoma (ILC) in the left breast. IDC, the most common breast cancer subtype, is known for its aggressive behaviour, nodal involvement and metastatic potential, while ILC, representing a smaller percentage of breast cancers, often exhibits an indolent course with diffuse growth patterns. Both tumours in this patient were hormone receptor-positive (ER/PR-positive) and HER2-negative, warranting targeted endocrine therapies. The complexity of this case was further heightened by a significant family history of breast and colon cancers, and comorbid conditions including borderline diabetes, hypertension and coronary artery disease (CAD), which required careful therapeutic consideration to balance efficacy and tolerability. Pathological evaluation confirmed stage II, grade 2 IDC in the right breast with one positive sentinel lymph node and stage I, grade 1 ILC in the left breast with no nodal involvement. Given her extensive family history, the patient opted for bilateral mastectomy with sentinel lymph node biopsy. Multidisciplinary tumour board discussions emphasised the integration of genetic testing, including BRCA1/2 evaluation, and Oncotype DX genomic profiling to assess recurrence risk and guide adjuvant chemotherapy decisions. Recommendations included adjuvant radiation therapy for the right breast, endocrine therapy for both tumours and the incorporation of CDK 4/6 inhibitors based on recent evidence from the NATALEE trial, which demonstrated improved outcomes in high-risk, hormone receptor-positive, HER2-negative breast cancers. The case highlights the need for further research into the optimal treatment strategies for synchronous breast cancers, a potential knowledge gap in current oncology practice. A literature review revealed limited reports addressing similar cases, underscoring the lack of consensus guidelines. Our approach integrates the best available evidence with multidisciplinary expertise to inform a personalised treatment plan. The learning points emphasise the need for establishing evidence-based strategies for managing synchronous bilateral breast cancers.

LEARNING POINTS: The optimal treatment of synchronous bilateral breast cancers with differing histological subtypes remains uncertain.This case illustrates the importance of leveraging existing evidence, multidisciplinary collaboration and patient-centred decision-making when addressing knowledge gaps.There is a call for further research to establish guidelines for managing simultaneous, histologically distinct breast cancers.}, } @article {pmid39925473, year = {2025}, author = {Maxey, J and Harvey, D}, title = {Neisseria weaveri: Atypical Infection in Breast Implant-Based Reconstruction.}, journal = {Plastic and reconstructive surgery. Global open}, volume = {13}, number = {2}, pages = {e6505}, pmid = {39925473}, issn = {2169-7574}, abstract = {Surgical site infection (SSI) following breast implant surgery can have devastating complications. Infection is most commonly from coagulase-negative Staphylococcus bacteria. Neisseria weaveri is a gram-negative bacterium that is associated with animal bites. We present the first known case of N. weaveri causing SSI following breast implant reconstruction. We report the case of a 61-year-old woman with invasive ductal carcinoma who underwent bilateral skin-sparing mastectomy with immediate implant-based reconstruction. She presented on postoperative day 24 with malodorous drainage from her Jackson-Pratt drain. The patient explained that she has a shih tzu at home that frequently licked her. Cultures from the drain grew N. weaveri. The patient's antibiotic regimen was transitioned, and she completed her course without complications. Practitioners should counsel their patients on adequate postsurgery hygiene and take into consideration rare causes of SSI and how this may affect patient care.}, } @article {pmid39922236, year = {2025}, author = {de Barros, HA and Downes, MR and Droghetti, M and Bekers, EM and Giunchi, F and Brunocilla, E and Schiavina, R and van der Kwast, TH and van Leeuwen, PJ and van der Poel, HG}, title = {Prognostic Value of Cribriform and Intraductal Carcinoma in Grade Group 2 Prostate Cancer With and Without Synchronous Nodal Metastases at Radical Prostatectomy: Results From a Case-control Matched, Multicenter Study.}, journal = {Urology}, volume = {199}, number = {}, pages = {104-111}, doi = {10.1016/j.urology.2025.01.061}, pmid = {39922236}, issn = {1527-9995}, mesh = {Humans ; Male ; *Prostatic Neoplasms/surgery/pathology/mortality ; *Prostatectomy/methods ; Case-Control Studies ; Aged ; Lymphatic Metastasis ; Prognosis ; Middle Aged ; Neoplasm Grading ; Retrospective Studies ; }, abstract = {OBJECTIVE: To evaluate the occurrence and the oncological predictive value of cribriform growth and/or intraductal carcinoma (CR/IDC) in patients with ISUP grade group (GG) 2 prostate cancer (PCa) at radical prostatectomy (RP) with and without synchronous nodal metastases in a multicenter, international cohort.

METHODS: We identified 1060 patients who underwent RP with ISUP GG2 PCa at histopathology and a pelvic lymph node dissection from 3 tertiary referral centers. Of these, 79 (7.4%) had pN1 disease. Case-control matching was performed using the initial prostate-specific antigen (iPSA) value, pT-stage, age, surgical margin status, and referral center as matching variables to compare histopathological characteristics and oncological outcomes between pN1 and pN0 patients. The predictive value of CR/IDC for biochemical recurrence-free survival (BCRFS), defined as the interval between RP and a PSA of ≥0.2ng/mL, and radiological recurrence-free survival (RRFS), defined as the interval between RP and an RR, was evaluated using Cox regression analysis.

RESULTS: After case-control matching, 106 patients were included (ie, 53 cases and 53 controls). CR/IDC was significantly more common in pN1 than pN0 RP specimens (100% vs 51%, P<.001). In pN0 patients, CR/IDC positivity was not associated with BCRFS (hazard ratio [HR]=0.90, 95% CI 0.32-2.55, P=.842) or RRFS (HR 2.45, 95% CI 0.45-13.34, P=.299). pN1 CR/IDC-positive PCa was associated with adverse BCRFS (HR=2.93, 95% CI 1.26-6.83, P=.013) and RRFS (HR=9.19, 95% CI 2.11-40.04, P=.003) in multivariable Cox regression analysis.

CONCLUSION: In ISUP GG2 PCa, CR/IDC strongly correlates with synchronous nodal metastases, the latter being associated with adverse outcomes.}, } @article {pmid39917195, year = {2025}, author = {Huthwelker, T and Borca, CN and Altamura, D and De Caro, L and Vanna, R and Corsi, F and Morasso, C and Banfi, G and Arpa, G and Bunk, O and Giannini, C}, title = {Microcalcifications in breast cancer tissue studied by X-ray absorption, emission, scattering and diffraction.}, journal = {Journal of applied crystallography}, volume = {58}, number = {Pt 1}, pages = {233-250}, pmid = {39917195}, issn = {0021-8898}, abstract = {Microcalcifications (MC) are observed in various tissues and in relation to several diseases. For breast cancer, recent studies have reported differences in the nature of the MC and correlations to the degree of malignancy of the neoplasm. Here, investigations of benign, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) breast MC using X-ray fluorescence, X-ray absorption spectroscopy and wide-angle X-ray scattering are reported. While Mg has been observed in all MC, only for the benign MC has a rim of crystalline whitlockite been identified as a minor crystalline phase in addition to the major hy-droxy-apatite (HAP) one. MC in DCIS and IDC tissue exhibit a higher abundance of a high-crystallinity HAP phase in comparison with the less well ordered MC in the benign tissue. Moreover, the distribution of other trace elements in the MC, such as Na, S, Cl, Sr and Y, is observed. For the quantitative analysis of the elemental maps, the experimentally determined sample thickness in each pixel has been incorporated as an additional parameter in the fitting process to account for sample roughness.}, } @article {pmid39912231, year = {2025}, author = {Palanjian, R and Welk, B and Myers, JB and Lenherr, SM and Elliott, SP and O'Dell, D and Stoffel, JT}, title = {Impact of Bladder Management Strategies on Autonomic Dysreflexia Severity in People With Spinal Cord Injuries.}, journal = {Neurourology and urodynamics}, volume = {44}, number = {4}, pages = {754-759}, pmid = {39912231}, issn = {1520-6777}, support = {//Patient Centered Outcomes Research Institute Award-CER14092138./ ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Autonomic Dysreflexia/etiology/physiopathology/diagnosis/therapy ; Intermittent Urethral Catheterization ; Neurogenic Bowel/etiology/physiopathology ; Prospective Studies ; Quality of Life ; Registries ; Severity of Illness Index ; *Spinal Cord Injuries/complications/physiopathology ; *Urinary Bladder/physiopathology/innervation ; *Urinary Bladder, Neurogenic/etiology/therapy/physiopathology/diagnosis ; Urinary Catheterization ; }, abstract = {PURPOSE: We investigated whether severity of autonomic dysreflexia (AD) was associated with more patient-reported bladder and bowel symptoms and compared AD severity by bladder management strategy in people with spinal cord injury (SCI).

METHODS: The Neurogenic Bladder Research Group SCI Registry is a prospective study which evaluated quality of life after SCI. Bladder and bowel symptoms were assessed through Neurogenic Bladder Symptom Score and Neurogenic Bowel Dysfunction score, respectively. AD severity was assessed with the Autonomic Dysreflexia Following Spinal Cord Injury (ADFSCI) instrument. Bladder management was classified as volitional voiding, clean intermittent catheterization (CIC), indwelling catheter (IDC), and surgery (augmentation and diversion).

RESULTS: AD scores were identified for 1473 people. The mean age was 45. Bladder management was CIC in 754 (51%), IDC in 271 (18%), surgery in 195 (13%) and voiding in 259 (18%). On univariate analysis, higher ADFSCI scores occurred with complete injuries (3.1 vs 3.4, p = 0.03), cervical/thoracic injuries (3.8 vs 1.5, p < 0.0001), and chronic pain (3.9 vs 2.9, p = 0.0004). IDC (5.2) and surgery (4.5) had higher ADFSCI scores than CIC (3.0) and volitional voiding (2.8) (p < 0.0001). Sub-analysis showed bladder augmentation had significantly higher ADSCI scores than diversion (4.7 vs 3.7, p = 0.03). On multivariate analysis, level of injury, bladder management, and bowel and bladder symptoms remained associated with worse AD.

CONCLUSION: Level of injury, age, worse bowel and bladder symptoms and bladder management type were associated with higher AD scores. Bladder management with surgery, particularly bladder augment, and IDC had associated greater AD symptoms compared to CIC or voiding.

TRIAL REGISTRATION: clinicaltrials.gov NTC06216081 and HSRP20153564, U.S. National Library of Medicine, wwwcf.nlm.nih.gov.}, } @article {pmid39911122, year = {2025}, author = {Lan, HF and Gu, YD and Song, XF and Wang, YJ}, title = {The value of ultrasound (US)-based radiomics in predicting axillary lymph node metastasis in patients with T1 stage breast invasive ductal carcinoma with negative axillary US results.}, journal = {Clinical hemorheology and microcirculation}, volume = {89}, number = {1}, pages = {137-148}, doi = {10.3233/CH-242413}, pmid = {39911122}, issn = {1875-8622}, mesh = {Humans ; Female ; Middle Aged ; *Lymphatic Metastasis/diagnostic imaging ; *Breast Neoplasms/diagnostic imaging/pathology ; Adult ; Axilla/diagnostic imaging ; Ultrasonography/methods ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Aged ; *Lymph Nodes/diagnostic imaging/pathology ; Neoplasm Staging ; Radiomics ; }, abstract = {OBJECTIVES: To evaluate the potential application value of qualitative and quantitative contrast-enhanced ultrasound (CEUS) features for predicting axillary lymph node metastasis in early-stage breast cancer, with special emphasis on area ratio.

METHODS: 146 patients with 146 T1 stage breast cancers were subjected to conventional ultrasound (US) and CEUS before surgeries. Logistic regression analysis was used to identify the associated risk factors and a prediction model was created to predict T1 stage breast IDCs with positive of axillary lymph node metastasis (ALNM). The diagnostic performance of the prediction model was assessed by the analysis of the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. The value of area ratio, a quantitative CEUS feature, was evaluated.

RESULTS: Logistic regression analysis indicated that taller than wide shape on conventional US, coarse or twist penetrating vessels, and area ratio > 1.93 on CEUS were independent risk factors for IDCs with ALNM-positive (all P < 0.05). Among all risk factors, the area ratio > 1.93 showed the highest AUC (i.e. 0.818). The prediction equation was established as follows: P = 1/1 + Exp∑ [-2.665 + 1.750×(if taller than wide shape) + 1.791×(if coarse or twist penetrating vessels) + 4.372×(if area ratio > 1.93)]. In comparison with US BI-RADS alone, the AUCs of the prediction model for both readers increased significantly (AUC: 0. 919 vs. 0.677 in reader 1, 0.919 vs. 0.707 in reader 2, both P < 0.001).

CONCLUSION: Conventional US and CEUS features, especially the area ratio > 1.93 on CEUS, may be useful in the noninvasive prediction of ALNM-positive in breast IDCs.}, } @article {pmid39909175, year = {2025}, author = {Jean, J and Jochelson, MS and Moo, TA and Solomon, SB and Bryce, Y}, title = {Breast Cancer Recurrence after Cryoablation in Patients Who Are Poor Surgical Candidates or Who Refuse Surgery.}, journal = {Journal of vascular and interventional radiology : JVIR}, volume = {36}, number = {6}, pages = {971-978}, pmid = {39909175}, issn = {1535-7732}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA 008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Cryosurgery/adverse effects ; Female ; *Breast Neoplasms/surgery/pathology/diagnostic imaging ; Retrospective Studies ; *Neoplasm Recurrence, Local ; Middle Aged ; Aged ; Treatment Outcome ; Time Factors ; Risk Factors ; *Treatment Refusal ; Adult ; Risk Assessment ; *Carcinoma, Ductal, Breast/surgery/pathology ; Aged, 80 and over ; *Carcinoma, Lobular/surgery/pathology ; Patient Selection ; Tumor Burden ; *Carcinoma, Intraductal, Noninfiltrating/surgery/pathology ; }, abstract = {PURPOSE: To evaluate in-breast recurrence rates after cryoablation in patients with primary breast cancer who were poor surgical candidates or refused surgery.

MATERIALS AND METHODS: Patients with primary breast cancer who were poor surgical candidates or who refused surgery and were treated with cryoablation at a single academic cancer center between October 2018 and June 2023 were retrospectively reviewed. Of the 60 treated patients, 45 had invasive ductal carcinoma, 6 had invasive lobular carcinoma, 2 had multicentric ductal carcinoma in situ, and 7 had other histology. Tumor size ranged from 0.3 to 9 cm, with a mean of 2.7 cm. Recurrence was defined as new tumor or regrowth of residual tumor in the ipsilateral breast.

RESULTS: With a mean follow-up of 21 months and median follow-up of 9.8 months, there was a recurrence rate of 10% (6 of 60 patients). Patients in the recurrence group had more poorly differentiated disease than those in the nonrecurrence group (66.7% vs 22.2%; P = .038). Tumor size did not differ between nonrecurrence and recurrence groups (nonrecurrence group mean, 2.7 cm [SD ± 2.6]; recurrence group mean, 2.5 cm [SD ± 1.0]; P = .506). Patients who were treated with palliative intent rather than curative intent were significantly older (79.7 years [SD ± 12.2] vs 72.5 years [SD ± 11.3]; P = .032).

CONCLUSIONS: Cryoablation can be considered a treatment option in patients who are poor surgical candidates or who refuse surgery, with a 10% recurrence rate at a mean follow-up of 21 months in this retrospective review that included patients with tumors up to 9 cm, unfavorable pathology, and multicentric disease.}, } @article {pmid39908787, year = {2025}, author = {Ciccarelli, S and Eugene, N and Zhang, Z}, title = {Disparities in breast cancer screening and diagnosis: Urban-suburban contrasts in the wake of the COVID-19 pandemic.}, journal = {Clinical imaging}, volume = {120}, number = {}, pages = {110419}, doi = {10.1016/j.clinimag.2025.110419}, pmid = {39908787}, issn = {1873-4499}, mesh = {Humans ; *Breast Neoplasms/diagnostic imaging/diagnosis/epidemiology ; *COVID-19/epidemiology ; Female ; Retrospective Studies ; Mammography/statistics & numerical data ; *Early Detection of Cancer/statistics & numerical data ; *Healthcare Disparities/statistics & numerical data ; Middle Aged ; *Urban Population/statistics & numerical data ; Philadelphia/epidemiology ; *Suburban Population/statistics & numerical data ; Aged ; Pandemics ; }, abstract = {PURPOSE: Compare the reduction and recovery of breast cancer screening and diagnostic services in urban versus suburban communities during the COVID-19 pandemic to identify opportunities for advancing equitable breast cancer detection.

METHODS: This retrospective cohort study used the Montage™ data mining system to analyze percent change in the number of screening and diagnostic mammograms, breast biopsies, and breast cancer diagnoses at a single mid-Atlantic institution with urban and suburban sites centered in and around Philadelphia, Pennsylvania from 1/1/2019 to 12/31/2022, with urban-suburban subset comparison from 1/1/2019 to 12/31/2021.

RESULTS: In 2020, screening mammogram volume dropped 23.9 % at urban sites and 1.6 % at suburban sites while diagnostic mammogram volume decreased 26.4 % at urban and 21.4 % at suburban sites. In 2021, screening volume at urban and suburban sites was 2.6 % and 31.0 % greater than pre-pandemic levels, and diagnostic volume was 28.5 % and 16.9 % below pre-pandemic levels. That same year, the proportion of invasive ductal carcinoma at urban sites increased by 26.2 %. In 2022, screening volume at all sites surpassed pre-pandemic levels by 19.5 % while diagnostic volume remained 21.7 % less than pre-pandemic levels.

CONCLUSION: The COVID-19 pandemic disproportionately reduced breast cancer screening and diagnostic services in urban communities, who experienced slower recovery and increased invasive breast cancer in the subsequent year. Throughout our institution, screening mammograms surpassed pre-pandemic levels in 2021 and 2022 while diagnostic services remained below pre-pandemic levels through 2022. Considering these findings, we must improve access to breast cancer screening and diagnosis to mitigate the long-term consequences of the pandemic.}, } @article {pmid39906646, year = {2025}, author = {Shi, J and Qi, X and Ran, Y and Zhou, Q and Ding, Y and Li, L and Zeng, Y and Qiu, D and Cai, Z and Cai, X and Pan, Y}, title = {Saliva-acquired pellicle inspired multifunctional gargle with wet adhesion, photodynamic antimicrobial, and In situ remineralization properties for dental caries prevention.}, journal = {Bioactive materials}, volume = {47}, number = {}, pages = {212-228}, pmid = {39906646}, issn = {2452-199X}, abstract = {Dental caries is primarily caused by cariogenic bacteria metabolizing carbohydrates to produce acidic substances that erode the dental hard tissues. Traditional remineralization treatments often have limited efficacy due to their lack of antibacterial activity. According to the Interrupting Dental Caries (IDC) theory, ideal caries-preventive materials should possess both antibacterial and remineralizing properties. Furthermore, effective adhesion to dental surfaces is crucial. Inspired by the wet adhesion properties of the salivary acquired pellicle, we developed a multifunctional gargle named Ce6@PDN-SAP (CP-SAP). This formulation employed peptide dendrimer nanogels (PDN) as a carrier for the photosensitizer Ce6, further functionalized with saliva-acquired peptide (SAP) to confer wet adhesion properties. CP-SAP rapidly adhered to the dental surface and remained effective for extended periods. Upon laser irradiation, Ce6 generated reactive oxygen species (ROS), disrupting bacterial outer membrane integrity, causing protein leakage, and reducing ATP levels, thereby achieving potent antibacterial effects. Following this, PDN and SAP acted as nucleation templates to promote in situ remineralization of demineralized dental hard tissues. In vivo studies using rat models demonstrated that CP-SAP provided significantly superior caries-preventive effects compared to chlorhexidine gargle. In conclusion, CP-SAP, as an innovative approach grounded in the IDC theory, holds great promise for the prevention and treatment of dental caries.}, } @article {pmid39906424, year = {2025}, author = {Ferreira de Lemos, P and Fidalgo Maia, R}, title = {Serotonin Syndrome With Concomitant Antidepressant and Tramadol: A Case Report.}, journal = {Cureus}, volume = {17}, number = {1}, pages = {e76968}, pmid = {39906424}, issn = {2168-8184}, abstract = {Serotonin syndrome (SS) is a potentially life-threatening condition that results from the excess of serotonergic activity in the central nervous system. It is classically described as a triad of neuromuscular abnormalities, altered mental status, and autonomic hyperactivity; these are, most often, due to iatrogenic drug interactions or intentional overdose. This case study is about a 58-year-old woman who was being treated with venlafaxine and tramadol due to her past medical history of major depressive disorder and neuropathic pain. These symptoms appeared after a mastectomy, which was performed to treat an invasive ductal carcinoma. The sudden increase of the antidepressant medication and the interaction with another drug that inhibits serotonin reuptake (tramadol) led to tremor, hyperreflexia, diarrhea, tachycardia, hypertension, and fever, meeting Hunter's criteria for diagnosis of serotonergic syndrome. She received supportive care and diazepam, and the offending agents were removed. The signs and symptoms were reverted in less than 24 hours. An increased use of agents affecting the serotonergic system to treat different medical conditions raises the likelihood of a higher prevalence and clinical impact of SS in the future. For this reason, it is crucial to raise awareness of this condition to prevent adverse outcomes.}, } @article {pmid39888049, year = {2025}, author = {Rijstenberg, LL and Harikumar, H and Verhoef, EI and van den Bosch, TPP and Choiniere, R and van Royen, ME and van Leenders, GJLH}, title = {Identification of intraductal-to-invasive spatial transitions in prostate cancer: proposal for a new unifying model on intraductal carcinogenesis.}, journal = {Histopathology}, volume = {86}, number = {7}, pages = {1091-1100}, pmid = {39888049}, issn = {1365-2559}, support = {//Jaap Schouten Foundation/ ; }, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology ; Aged ; Middle Aged ; Immunohistochemistry ; *Carcinoma, Ductal/pathology ; Neoplasm Invasiveness ; *Prostatic Intraepithelial Neoplasia/pathology ; Microscopy, Confocal ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; }, abstract = {AIMS: Intraductal carcinoma (IDC) is an independent pathological parameter for adverse prostate cancer (PCa) outcome. Although most IDC are believed to originate from retrograde spread of established PCa, rare IDC cases may represent precursor lesions. The actual transition areas between intraductal and invasive cancer, however, have not yet been identified. Our objective was to identify intraductal-invasive PCa transitions using 2- and 3-dimensional microscopy.

METHODS AND RESULTS: Seventy-five samples from 46 radical prostatectomies with PCa were immunohistochemically stained for basal cell keratins. In 35 samples, atypical glands that were indistinguishable from invasive adenocarcinoma (IAC) had focal 34BE12-positive basal cells. These IAC-like glands were present adjacent to IDC and prostatic intra-epithelial neoplasia (PIN) in 21 of 45 (46.7%) and 16 of 58 (27.6%) cases, respectively. Whole-mount confocal imaging of immunofluorescent Ker5/18 double-stained and cleared 1-mm-thick intact tissues revealed spatial continuity between IDC, IAC-like glands and IAC with a gradual loss of basal cells. In 24 of 35 (68.6%) samples more than one IAC-like focus (median 3.0) was present.

CONCLUSIONS: We identified areas of spatial transition between PIN, IDC and IAC, characterised by remnant basal cells in IAC-like glands. Based on the coexistence of IDC and PIN, the gradual loss of basal cells in IAC-like glands and IAC-like glands' multifocality, we propose a novel hypothesis on intraductal carcinogenesis, which we term 'repetitive invasion, precursor progression' (RIPP).}, } @article {pmid39880998, year = {2025}, author = {Mooshage, CM and Tsilingiris, D and Schimpfle, L and Fleming, T and Herzig, S and Szendroedi, J and Heiland, S and Bendszus, M and Kopf, S and Kurz, F and Jende, J and Kender, Z}, title = {Intradermal Advanced Glycation End-products Relate to Reduced Sciatic Nerve Structural Integrity in Type 2 Diabetes.}, journal = {Clinical neuroradiology}, volume = {35}, number = {2}, pages = {385-394}, pmid = {39880998}, issn = {1869-1447}, mesh = {Humans ; Female ; Male ; *Diabetes Mellitus, Type 2/complications/metabolism ; *Glycation End Products, Advanced/metabolism ; Middle Aged ; *Sciatic Nerve/diagnostic imaging/pathology/metabolism ; Diffusion Tensor Imaging ; *Diabetic Neuropathies/diagnostic imaging/metabolism/pathology ; Skin/metabolism ; Aged ; Anisotropy ; Adult ; Pulse Wave Analysis ; Vascular Stiffness ; Case-Control Studies ; }, abstract = {BACKGROUND: Cardiovascular risk management is beneficial, but stringent glycemic control does not prevent the progression of distal sensorimotor polyneuropathy (DSPN). Persistent hyperglycemia-induced alterations and cardiovascular factors may contribute to diabetes-associated nerve damage. This study aimed to evaluate the correlation between skin auto-fluorescence (sAF), an indicator of dermal advanced glycation end-product (AGE) accumulations, cardiovascular risk, and changes in peripheral nerve integrity.

METHODS: Sixty-two individuals with type 2 diabetes (T2D) (20 women and 42 men), including 29 diagnosed with DSPN (7 women and 22 men), and 10 healthy controls (HC) underwent diffusion tensor MR imaging of the sciatic nerve to assess fractional anisotropy (FA), an indicator of nerve structural integrity. sAF measurements were combined with clinical, serological, and electrophysiological evaluations. Arterial stiffness was assessed via pulse wave velocity (PWV).

RESULTS: sAF (HC 2.1 ± 0.25 AU, nDSPN 2.3 ± 0.47, DSPN 2.6 ± 0.43; p = 0.005) was higher in individuals with DSPN compared to HC (p = 0.010) and individuals without DSPN (p = 0.035). Within the group of T2D FA correlated negatively with sAF (r = -0.49, p < 0.001), PWV (r = -0.40, p = 0.009) and high-sensitivity troponin T (hsTNT), a marker of microvascular damage (r = -0.39, p < 0.001). In DSPN, sAF correlated positively with hsTNT (r = 0.58, p = 0.005) and with PWV (r = 0.52, p = 0.007), the sciatic nerve's FA correlated negatively with PWV (r = -0.47, p = 0.010).

CONCLUSIONS: This study is the first to show close correlations between reduced peripheral nerve integrity and both intradermal AGE deposition and arterial stiffness in individuals with T2D. These findings highlight a mechanistic link between glycation-related vascular injury and neuronal damage emphasizing the importance of cardiovascular risk management in preventing DSPN.}, } @article {pmid39879501, year = {2025}, author = {Uppal, R and Saeed, U and Khattak, ME and Khan, AA and Uppal, MR and Piracha, ZZ and Khan, MN and Shaikh, D and Tariq, U and Mahmood, AR and Ali, SS and Muhammad, B and Tariq, MN and Gilani, SS and Ozsahin, DU and Uzun, B and Ozsahin, I}, title = {Epidemiological analysis of Leishmaniasis prevalence in Pakistan during 2016-2023.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {84}, number = {}, pages = {e284742}, doi = {10.1590/1519-6984.284742}, pmid = {39879501}, issn = {1678-4375}, mesh = {Pakistan/epidemiology ; Humans ; Prevalence ; Male ; Child ; Female ; Adult ; Retrospective Studies ; Adolescent ; Child, Preschool ; Young Adult ; Middle Aged ; *Leishmaniasis/epidemiology/transmission ; Infant ; Aged ; }, abstract = {Leishmaniasis, caused by the Leishmania parasite, remains a persistent public health challenge in Pakistan. Despite control efforts, the disease prevalence continues to rise, particularly among pediatric populations. Understanding prevalence patterns and transmission dynamics is critical for effective control strategies. This study aims to analyze leishmaniasis prevalence data from January 2016 to July 2023 in Pakistan. Specific objectives include assessing temporal trends, demographic patterns, and geographical hotspots of transmission, while emphasizing the need for enhanced surveillance and research for targeted interventions. Retrospective analysis was conducted on leishmaniasis prevalence data collected from multiple healthcare facilities across Pakistan. Data included results from diagnostic tests on suspected cases, encompassing both pediatric and adult patients. Descriptive statistical analysis was employed to evaluate prevalence rates, demographic characteristics, and geographical distribution of positive cases. Analysis revealed an increasing trend in leishmaniasis prevalence over the study period. Initially, from 2016 to 2020, a positivity rate of 27% was observed exclusively among pediatric patients in Islamabad, with no adult cases. Subsequently, from 2017 to 2022, the positivity rate increased to 42%, affecting both pediatric and adult populations in Islamabad, Rawalpindi, and Swat. Notably, between July 2022 and July 2023, the positivity rate surged to 56%, primarily impacting adult males in the identified hotspots. The study provides evidence of rising leishmaniasis prevalence in Pakistan, particularly among pediatric patients. Identified hotspots suggest localized transmission, warranting targeted interventions. Enhanced surveillance and research efforts are crucial for understanding disease dynamics and implementing effective control measures. Priority should be given to vulnerable populations and high-burden regions to mitigate leishmaniasis impact in Pakistan.}, } @article {pmid39879500, year = {2025}, author = {Piracha, ZZ and Saeed, U and Uppal, R and Uppal, MR and Khan, AA and Abdullah, M and Mari, K and Basra, A and Gilani, SS and Tariq, MN and Ozsahin, DU and Uzun, B and Ozsahin, I}, title = {Prevalence and clinical profile of hepatitis C virus infections in multitransfused thalassemic patients in the capital twin cities of Pakistan.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {84}, number = {}, pages = {e284453}, doi = {10.1590/1519-6984.284453}, pmid = {39879500}, issn = {1678-4375}, mesh = {Humans ; Pakistan/epidemiology ; Male ; Female ; Prevalence ; Adult ; *Hepatitis C/epidemiology ; Young Adult ; Adolescent ; *beta-Thalassemia/therapy/complications/epidemiology ; Middle Aged ; Child ; Alanine Transaminase/blood ; Transfusion Reaction ; }, abstract = {Hepatitis C virus (HCV) presents a significant global health concern, affecting 3.3% of the world's population. The primary mode of HCV transmission is through blood and blood products. Patients with beta thalassemia, who rely on lifelong blood transfusions, are particularly vulnerable to HCV infections. This study aimed to assess the prevalence of hepatitis C virus infections among multitransfused thalassemic patients in the twin cities of Pakistan's capital. The clinical research, involving the enrollment of 262 multitransfused beta thalassemic patients residing in the capital twin cities of Pakistan. The investigation encompassed the evaluation of hepatitis C virus presence, alanine aminotransferase (ALT) levels, serum creatinine, hepatomegaly, splenomegaly, and the occurrence of splenectomy. The overall prevalence of Hepatitis C virus infections was notably high at 55.73%. This was particularly pronounced among patients aged 20 years and older, with a 100% infection rate. In HCV-positive thalassemic patients, the average ALT level was observed to be 98 U/L, while average creatinine values stood at 0.39 mg/dL. Additionally, hepatomegaly was prevalent in 82.20% of HCV-positive thalassemic patients, featuring an average liver size increase of 4.33 cm. Splenomegaly was evident in 67.12% of HCV-positive thalassemic patients, with an average spleen size augmentation of 4.46 cm. Splenectomy was identified in 15.75% of cases. The incidence of HCV infections in the thalassemic population of Pakistan is alarmingly high. Furthermore, the risk of contracting HCV infections escalates with the advancing age of thalassemic patients. Elevated ALT levels and hepatomegaly were pervasive among the majority of HCV-positive thalassemic patients. Consequently, there is a compelling need for rigorous screening of blood products prior to transfusion to mitigate the future burden of HCV in Pakistan.}, } @article {pmid39879499, year = {2025}, author = {Saeed, U and Uppal, R and Najmi, MH and Fazal, I and Khan, AA and Piracha, ZZ and Uppal, MR and Ijaz, HN and Ozsahin, DU and Uzun, B and Ozsahin, I}, title = {Cutting-edge: bionanomaterial solutions in the battle against Severe Acute Respiratory Syndrome Coronavirus 2.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {84}, number = {}, pages = {e279564}, doi = {10.1590/1519-6984.279564}, pmid = {39879499}, issn = {1678-4375}, mesh = {*COVID-19/prevention & control/diagnosis ; Humans ; *SARS-CoV-2 ; *Metal Nanoparticles/therapeutic use ; Pandemics/prevention & control ; Silver ; }, abstract = {Amidst the ongoing COVID-19 pandemic, the imperative of our time resides in crafting stratagems of utmost precision to confront the relentless SARS-CoV-2 and quell its inexorable proliferation. A paradigm-shifting weapon in this battle lies in the realm of nanoparticles, where the amalgamation of cutting-edge nanochemistry begets a cornucopia of inventive techniques and methodologies designed to thwart the advances of this pernicious pathogen. Nanochemistry, an artful fusion of chemistry and nanoscience, provides a fertile landscape for researchers to craft innovative shields against infection. Within this intricate tapestry, nanoparticles emerge as champions, offering multifaceted solutions encompassing detection, treatment, prevention, and the precise targeting of SARS-CoV-2 incursions. Noteworthy among these innovations, the Silver (Ag) Respi-strips command our attention. These strips stand as exemplars of ingenuity, illuminating the path to swift and precise test detection. Moreover, the integration of Ag-based textile materials into the arsenal against viral propagation opens a promising avenue to curtail the virus's insidious reach. The indomitable force of iron nanoparticles, duly sanctioned by the esteemed FDA, shines as a beacon of hope in the treatment of infection. Their interaction with the glycoprotein spikes of the virus unleashes an inhibitory action of profound consequence. Meanwhile, the domain of diagnostics has been revolutionized by the advent of Magnetic Nanoparticles (MNPs). Their role in automating nucleic acid extraction and purification has proven indispensable, particularly in the diagnostic milieu of SARS-CoV-2. These MNPs wield a magnetic allure, streamlining diagnostic processes with unmatched precision. In this realm of nano-wonders, Gold nanoparticles rise as formidable sentinels, poised at the intersection of versatility and innovation. Their functionalization via a kaleidoscope of functional groups or in concert with antiviral drug combinations augments their prowess. These microscopic champions effectively hinder viral ingress into host cells and orchestrate the controlled release of antiviral agents, casting a profound influence on the course of viral infections. The pandemic landscape has borne witness to the ascendancy of nanotechnology, unveiling an arsenal of nanoparticle-based strategies that promise to defy, detect, treat, and ultimately vanquish SARS-CoV-2. The future beckons, and within the infinitesimal realm of nanoparticles, we find the promise of a brighter, healthier tomorrow.}, } @article {pmid39877824, year = {2025}, author = {Pistolese, CA and Giuliano, FD and Cerocchi, M and Volpe, M and Dellanea, MC and Briganti, F and Gigliotti, PE and Goffredo, C and Giudice, L and Caccia, D and Servadei, F and De Majo, A and Materazzo, M and Pistilli, G and Vanni, G and Liberto, V}, title = {Radiological images of an advanced invasive carcinoma with mucinous aspects: A case report.}, journal = {Radiology case reports}, volume = {20}, number = {3}, pages = {1776-1783}, pmid = {39877824}, issn = {1930-0433}, abstract = {Mucinous carcinoma of the breast, also known as colloid carcinoma, is an uncommon type of differentiated adenocarcinoma, representing only 2% of all invasive breast carcinomas. It usually occurs in women ≥ 60 years of age. Mucinous carcinoma is characterized by clusters of epithelial tumour cells suspended in pools of extracellular mucin and is further divided in 2 subgroups, pure and mixed. Compared to invasive ductal carcinoma, mucinous carcinoma has a better prognosis, being characterized by a lower incidence of nodal involvement and a more favorable histological grade, with low proliferative activity and high expression of hormone receptors. Overall 10-year survival is estimated to be more than 90%. We present a case of a 57-year-old female patient who presented a palpable mass in the right breast for at least 2 years. On examination the whole breast appeared swollen, congestive and painless to palpation. Breast ultrasound, breast MRI and tru-cut biopsy were performed and suggested an advanced infiltrated carcinoma with mucinous aspects. Immunohistochemistry study demonstrated ER positivity (95%), PR low (5%), HER-2-Neu negativity (score 0) and proliferative index (Ki67) of 20%, determining a Luminal B-like (HER 2-negative) subtype. The patient was then candidated to mastectomy surgery and breast reconstruction with DIEP flap. Axillary lymp-nodes were sampled surgically.}, } @article {pmid39875793, year = {2025}, author = {Ma, F and Wang, H and Tzachor, A and Hidalgo, CA and Schandl, H and Zhang, Y and Zhang, J and Chen, WQ and Zhao, Y and Zhu, YG and Fu, B}, title = {The disparities and development trajectories of nations in achieving the sustainable development goals.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {1107}, pmid = {39875793}, issn = {2041-1723}, support = {52070034//National Natural Science Foundation of China (National Science Foundation of China)/ ; 52470207//National Natural Science Foundation of China (National Science Foundation of China)/ ; 71961147003//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {The Sustainable Development Goals (SDGs) provide a comprehensive framework for societal progress and planetary health. However, it remains unclear whether universal patterns exist in how nations pursue these goals and whether key development areas are being overlooked. Here, we apply the product space methodology, widely used in development economics, to construct an 'SDG space of nations'. The SDG space models the relative performance and specialization patterns of 166 countries across 96 SDG indicators from 2000 to 2022. Our SDG space reveals a polarized global landscape, characterized by distinct groups of nations, each specializing in specific development indicators. Furthermore, we find that as countries improve their overall SDG scores, they tend to modify their sustainable development trajectories, pursuing different development objectives. Additionally, we identify orphaned SDG indicators - areas where certain country groups remain under-specialized. These patterns, and the SDG space more broadly, provide a high-resolution tool to understand and evaluate the progress and disparities of countries towards achieving the SDGs.}, } @article {pmid39867082, year = {2024}, author = {Truda, G and Howells, S and Berry, M and Al-Shurbasi, N}, title = {Risk Factors for Positive Resection Margins Following Breast-Conserving Surgery.}, journal = {Cureus}, volume = {16}, number = {12}, pages = {e76406}, pmid = {39867082}, issn = {2168-8184}, abstract = {Background The incidence of margin re-excision following breast conserving surgery (BCS) is a quality measure in the National Health Service. The threshold is less than 20% of all BCS procedures. Despite three decades of studies and a wealth of literature identifying multiple factors associated with increased risk for margin involvement, an accepted threshold rate affecting one in five procedures remains high. Aim The aim of the study was to identify adverse features that continue to compromise successful margin clearance despite the recognition of risk factors and the implementation of strategies designed to minimise those risks. Methods All margin re-excisions following BCS for invasive breast carcinoma and ductal carcinoma in situ (DCIS) performed from October 2013 to September 2018 were retrieved from the database of a single institution. A total of 1379 patients underwent BCS during the period considered, 194 of which needed margin re-excision. Radiological investigations and histopathology reports for each patient were retrieved. Lesion size and focality on mammogram, ultrasound (US) scan, and magnetic resonance imaging (MRI), and histopathologic tumour characteristics were recorded and analysed. Results The overall re-excision rate was 14.06% (194/1379 patients). Margin re-excisions cleared 69% (134/194) of wide local excision cavities that had at least one involved margin. 53% (103/194) of patients had no further disease after one attempt at re-excision and 15.9% (31/of 194) had further disease, which was cleared after re-excision. Another 15.9% (31/194) had disease within the shave with involved margins. In this sub-group the presence of DCIS at the new resection margin accounted for 90.3% (28/31) of cases, 3% (1/31) were invasive ductal carcinoma (IDC) and 6% (2/31) were unrecorded. In the sub-group of patients who had an excised margin with pathology and a new clear margin (15.9% of all re-excisions), DCIS was found in 61% (19/31) of cases, IDC in 12.9% (4/31), invasive lobular carcinoma (ILC) in 6% (2/31) of cases, lobular neoplasia (LN) in 12.9% (4/31), mixed IDC and DCIS in 6% (2/31)of cases. The correlation between imaging size and actual histopathological size has shown a statistically significant discrepancy in this cohort. The median size on histology was 22 mm, compared to a median size of 16 mm on mammography, 14 mm on ultrasound, and 17 mm on MRI. Conclusion According to our cohort of patients, the most consistent factor associated with a re-excision was the presence of DCIS at the resection margin, whether pure DCIS or IDC admixed with DCIS. The comparison between tumour size on imaging and final histopathological size revealed the best correlation with mammogram followed by US. The weakest correlation was with MRI.}, } @article {pmid39864363, year = {2025}, author = {Metzger Filho, O and Cardoso, F and Poncet, C and Desmedt, C and Linn, S and Wesseling, J and Hilbers, F and Delaloge, S and Pierga, JY and Brain, E and Vrijaldenhoven, S and Neijenhuis, PA and Rutgers, EJT and Piccart, M and van 't Veer, LJ and Viale, G}, title = {Survival outcomes for patients with invasive lobular cancer by MammaPrint: Results from the MINDACT phase III trial.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {217}, number = {}, pages = {115222}, doi = {10.1016/j.ejca.2025.115222}, pmid = {39864363}, issn = {1879-0852}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/mortality/pathology/therapy ; *Carcinoma, Lobular/genetics/mortality/pathology/therapy ; Middle Aged ; Disease-Free Survival ; Aged ; Adult ; Gene Expression Profiling/methods ; Prognosis ; *Biomarkers, Tumor/genetics ; Neoplasm Invasiveness ; Transcriptome ; }, abstract = {BACKGROUND: Evaluation of the prognostic performance and clinical utility of the MammaPrint 70-gene signature in early-stage invasive lobular carcinoma (ILC) for whom such analyses in a randomized trial is awaited.

PATIENTS AND METHODS: Exploratory subgroup analysis of MINDACT trial patients with centrally assessed histology (n = 5929) with invasive breast cancer of no-special-type (NST), or pure ILC. In the trial patients were categorized based on the 70-gene signature for genomic risk and modified Adjuvant!Online for clinical risk. Survival outcomes at 8.7 years median follow-up by 70-gene signature were compared between NST and ILC for Distant Metastasis-Free Survival (DMFS), Disease-Free Survival (DFS) and Overall Survival (OS).

RESULTS: 5313 patients were ILC (n = 487) or NST (n = 4826). ILC was further classified into classic ILC (n = 255) or ILC variants (n = 232). The 70-gene signature classified 16.2 % of ILC and 39.1 % of NST as genomic high-risk (gH). Survival outcomes for ILC vs. NST revealed similar estimates according to genomic risk overall and across subsets. The 70-gene signature classified 10.2 % of classic ILC and 22.8 % of ILC variants as gH. 5-yr DFS estimates for ILC variants 88.4 % (95 %CI: 83.1-92.1) was inferior to classic ILC 93.0 % (95 %CI: 88.7-95.7).

CONCLUSIONS: Sixteen percent of ILC were classified high genomic risk by the 70-gene signature, with unfavorable survival outcomes. Survival estimates were similar for patients with ILC and NST classified as either low- or high-genomic risk, suggesting that the 70-gene signature also has prognostic value in ILC and may be a clinically useful tool for adjuvant treatment decision-making in ILC.}, } @article {pmid39863461, year = {2025}, author = {Abello Polo, V and Sossa, C and Boquimpani, C and Salazar, LA and Munevar, I and Gómez, R and Cuervo, DM and Varón Jaimes, C and Reyes, J and Idrobo, H and Omaña, P and Daza, J and Pedraza Morales, JE and Agudelo López, C and Quintero-Vega, GE and Correa Correa, M and Herrera, JM and Mantilla, WA and Serrano, JC and Rosales, C and Gálvez Cárdenas, KM and Bermúdez, C and Saavedra Ramírez, D and Alzate, M and Lobatón Ramírez, JF}, title = {Real World Evidence From 2 Decades of First-Line TKI Therapy in Chronic Myeloid Leukemia (CML): Insights From ACHO's RENEHOC Registry.}, journal = {Clinical lymphoma, myeloma & leukemia}, volume = {25}, number = {5}, pages = {e290-e301}, doi = {10.1016/j.clml.2024.12.015}, pmid = {39863461}, issn = {2152-2669}, mesh = {Humans ; *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/mortality ; Female ; Male ; Registries ; Middle Aged ; *Protein Kinase Inhibitors/therapeutic use/pharmacology ; Colombia/epidemiology ; Adult ; Aged ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Chronic myeloid leukemia (CML) treatment has significantly evolved with the introduction of tyrosine kinase inhibitors. However, access to these treatments and outcomes vary globally. This study examines 2 decades of CML management in Colombia using the RENEHOC registry, focusing on TKI efficacy, safety, and healthcare system challenges.

METHODS: We performed a descriptive analysis of the sociodemographic and clinical characteristics of 994 CML patients from the RENEHOC cohort in Colombia, who were treated over the past 20 years. Trends in first-line TKI use were assessed, and Kaplan-Meier survival curves were used to estimate EFS and OS. The log-rank test was used to compare survival curves between different first-line TKIs.

RESULTS: The analysis shows trends in the use of first-line TKIs over a 20-year period in Colombia, where, as in other countries, the use of second-generation TKIs in the first-line setting is gradually increasing. Despite the difficulties of the Colombian healthcare system, the results in terms of OS are excellent regardless of the first-line TKI; however, patients treated with imatinib switched lines significantly more often than those treated with second-generation TKIs (imatinib 58.7%, nilotinib 19.5%, dasatinib 29.3%). The median duration of treatment was significantly shorter with imatinib compared to dasatinib and nilotinib (4.08, 12.75 and not reached, respectively). Intolerance was the most common reason for switching in this cohort of patients. The median observation time for OS was 64.89 months (SD 60.15), with survival rates of 99.4% at 1 year, 97.7% at 3 years and 96.6% at 5 years.

CONCLUSIONS: The results of this analysis show excellent results in terms of OS for patients with CML treated in Colombia over the last 20 years, despite the difficulties inherent in the health system. Patients treated with first-line imatinib had more frequent line changes. In general, intolerance was the most common reason for switching lines. Despite its retrospective nature, this study allows us to outline how treatment patterns in the country have changed over time. Continued efforts to include more centers and patients in prospective studies are essential to better understand the long-term effects of treatment and to improve adherence to guideline recommendations in clinical practice.}, } @article {pmid39863086, year = {2025}, author = {Taylor, H and Spruill, L and Jensen-Smith, H and Rujchanarong, D and Hulahan, T and Ivey, A and Siougiannis, A and Bethard, JR and Ball, LE and Sandusky, GE and Hollingsworth, MA and Barth, JL and Mehta, AS and Drake, RR and Marks, JR and Nakshatri, H and Ford, M and Angel, PM}, title = {Spatial localization of collagen hydroxylated proline site variation as an ancestral trait in the breast cancer microenvironment.}, journal = {Matrix biology : journal of the International Society for Matrix Biology}, volume = {136}, number = {}, pages = {71-86}, doi = {10.1016/j.matbio.2025.01.006}, pmid = {39863086}, issn = {1569-1802}, support = {P30 CA036727/CA/NCI NIH HHS/United States ; R01 CA253460/CA/NCI NIH HHS/United States ; R21 CA286287/CA/NCI NIH HHS/United States ; S10 OD030212/OD/NIH HHS/United States ; }, mesh = {Humans ; *Tumor Microenvironment ; Female ; Hydroxylation ; *Breast Neoplasms/metabolism/pathology/genetics ; *Proline/metabolism ; *Collagen/metabolism/genetics/chemistry ; Proteomics/methods ; Protein Processing, Post-Translational ; Extracellular Matrix/metabolism ; }, abstract = {Collagen stroma interactions within the extracellular microenvironment of breast tissue play a significant role in breast cancer, including risk, progression, and outcomes. Hydroxylation of proline (HYP) is a common post-translational modification directly linked to breast cancer survival and progression. Changes in HYP status lead to alterations in epithelial cell signaling, extracellular matrix remodeling, and immune cell recruitment. In the present study, we test the hypothesis that the breast cancer microenvironment presents unique PTMs of collagen, which form bioactive domains at these sites that are associated with spatial histopathological characteristics and influence breast epithelial cell signaling. Mass spectrometry imaging proteomics targeting collagens were paired with comprehensive proteomic methods to identify novel breast cancer-related collagen domains based on spatial localization and regulation in 260 breast tissue samples. As ancestry plays a significant role in breast cancer outcomes, these methods were performed on ancestry diverse breast cancer tissues. Lumpectomies from the Cancer Genome Atlas (TCGA; n=10) reported increased levels of prolyl 4-hydroxylase subunit alpha-3 (P4HA3) accompanied by spatial regulation of fibrillar collagen protein sequences. A concise set of triple negative breast cancer lumpectomies (n=10) showed spatial regulation of specific domain sites from collagen alpha-1(I) chain. Tissue microarrays identified proteomic alterations around post-translationally modified collagen sites in healthy breast (n=81) and patient matched normal adjacent (NAT; n=76) and invasive ductal carcinoma (n=83). A collagen alpha-1(I) chain domain encompassing amino acids 506-514 with site-specific proline hydroxylation reported significant alteration between patient matched normal adjacent tissue and invasive breast cancer. Functional testing of domain 506-514 on breast cancer epithelial cells showed proliferation, chemotaxis and cell signaling response dependent on site localization of proline hydroxylation within domain 506-514 variants. These findings support site localized collagen HYP forms novel bioactive domains that are spatially distributed within the breast cancer microenvironment and may play a role in ancestral traits of breast cancer.}, } @article {pmid39859945, year = {2024}, author = {Mun, HS and Oh, HY}, title = {Analysis of Clinically Symptomatic Patients to Differentiate Inflammatory Breast Cancer from Mastitis in Asian Women.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, pmid = {39859945}, issn = {2075-1729}, support = {the research grant of Kangwon National University in 2024.//Kangwon National University/ ; }, abstract = {PURPOSE: To differentiate inflammatory breast cancer (IBC) from mastitis in Asian women presenting with symptoms of inflammation.

METHODS: Between January 2012 and June 2024, 101 Asian women with symptoms of inflammation underwent breast ultrasound (US). Clinical and demographic data were extracted from patients' medical records. US analysis assessed lesion bilaterality, location, type, size, internal changes, and lymph node status. Patients with suspicious findings had US-guided biopsies, and pathology reports were reviewed for tumor histology and immunohistochemical markers. Logistic regression was used to determine odds ratios.

RESULTS: Of the 101 participants, 14 (13.9%) were diagnosed with IBC and 87 (86.1%) were diagnosed with mastitis. Patients with IBC were significantly older (46.4 vs. 38.4 years, p = 0.020) and showed a higher prevalence of postmenopausal status (57.1% vs. 12.6%, p < 0.0001). These patients experienced a longer symptom onset duration (37.7 vs. 12.7 days, p = 0.002) and more frequent localized symptoms like swelling (50.0% vs. 13.8%, p = 0.004). US findings showed that 21.4% of IBC lesions involved the entire breast, compared to only 1.1% in patients with mastitis (p = 0.001). Biopsy results revealed that invasive ductal carcinoma was the most common malignancy (78.6%). Logistic regression identified symptom onset duration (adjusted odds ratio (OR) 1.07, p = 0.014) and swelling (adjusted OR 15.24, p = 0.016) as significant predictors of IBC.

CONCLUSION: In Asian women, age, menopausal status, symptom onset duration, and swelling are effective in differentiating IBC from mastitis. Logistic regression confirmed that symptom onset duration and swelling are significant predictors of IBC, with US findings indicating larger lesion sizes and more frequent whole-breast involvement.}, } @article {pmid39850636, year = {2024}, author = {Iannotti, FA}, title = {I. IDC Key-note Lecture: Influence of gut microbiome in Duchenne muscular dystrophy.}, journal = {Journal of stem cells & regenerative medicine}, volume = {20}, number = {2}, pages = {56-57}, pmid = {39850636}, issn = {0973-7154}, } @article {pmid39843553, year = {2025}, author = {Nishida, H and Kato, A and Kaimori, R and Kawamura, K and Daa, T}, title = {Relationship between androgen receptor and androgen receptor-related protein expression in breast cancers focusing on morphologically identified carcinoma with apocrine differentiation.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {2892}, pmid = {39843553}, issn = {2045-2322}, mesh = {Humans ; *Receptors, Androgen/metabolism/genetics ; Female ; *Breast Neoplasms/pathology/metabolism ; Middle Aged ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Adult ; Aged ; Biomarkers, Tumor/metabolism ; Receptors, Estrogen/metabolism ; Cell Differentiation ; Receptors, Progesterone/metabolism ; *Apocrine Glands/pathology/metabolism ; *Carcinoma, Ductal, Breast/pathology/metabolism ; Immunohistochemistry ; Hepatocyte Nuclear Factor 3-alpha/metabolism ; }, abstract = {Breast cancer (BC) is classified based on the expression of histopathological markers, namely, estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). Carcinomas with apocrine differentiation (CAD) are classified based on morphology. Androgen receptor (AR) is highly expressed in CAD; however, no study has comprehensively examined AR-related proteins in CAD. Therefore, we examined the expression of AR-related proteins and AR, compared protein expression patterns between morphologically identified CAD and other BC subtypes, and investigated CAD characteristics. We performed immunohistochemistry for AR and various AR-related proteins in 66 invasive ductal carcinoma (32 ER+/PgR+/HER2-, 8 ER+/PgR+/HER2+, 12 ER-/PgR-/HER2+, and 14 ER-/PgR-/HER2- [triple-negative breast cancer)), 21 invasive lobular carcinoma, and 27 CAD cases. In the CAD group, all cases were AR-positive; some AR-related proteins were highly expressed. Nuclear phosphorylated-mammalian target of rapamycin was highly expressed in CAD cases compared with that in other BC groups, with a 33.3% sensitivity and 97.7% specificity. AR-expressing CAD cases exhibited high expression of other AR-related proteins. Specifically, the combination of AR+, GCDFP15+, and ER - or AR+, FOXA1+, and ER - may be useful for the diagnosis and treatment of AR-positive BC and CAD. These results may assist in androgen-related molecular targeted therapy research.}, } @article {pmid39840900, year = {2025}, author = {Bergqvist, M and Lässer, C and Crescitelli, R and Park, KS and Lötvall, J}, title = {A Non-Centrifugation Method to Concentrate and Purify Extracellular Vesicles Using Superabsorbent Polymer Followed by Size Exclusion Chromatography.}, journal = {Journal of extracellular vesicles}, volume = {14}, number = {1}, pages = {e70037}, pmid = {39840900}, issn = {2001-3078}, support = {2021-03538//Vetenskapsrådet/ ; 20210707//Hjärt-Lungfonden/ ; }, mesh = {Humans ; *Extracellular Vesicles/chemistry/metabolism ; *Chromatography, Gel/methods ; HEK293 Cells ; *Polymers/chemistry ; Ultrafiltration ; }, abstract = {Extracellular vesicles (EVs) can be isolated and purified from cell cultures and biofluids using different methodologies. Here, we explored a novel EV isolation approach by combining superabsorbent polymers (SAP) in a dialysis membrane with size exclusion chromatography (SEC) to achieve high concentration and purity of EVs without the use of ultracentrifugation (UC). Suspension HEK293 cells transfected with CD63 coupled with Thermo Luciferase were used to quantify the EV yield and purity. The 500 mL conditioned medium volume was initially reduced by pressure ultrafiltration, followed by UC, SAP or a centrifugal filter unit (CFU). Using either of these methods, the EVs were concentrated to a final volume of approximately 1 mL, with retained functionality. The yield, quantified by luciferase activity, was highest with UC (70%-80%), followed by SAP (60%-70%) and CFU (50%-60%). Further purification of the EVs was performed by iodixanol density cushion (IDC) or SEC (Sepharose CL-2B or 6B, in either 10 or 20 mL columns). Although the IDC and Sepharose CL-2B (10 mL) achieved the highest yields, the purity was slightly higher (30%) with IDC. In conclusion, combining SAP concentration with CL-2B SEC is an alternative and efficient way to isolate EVs without using UC.}, } @article {pmid39840832, year = {2025}, author = {Giuliano, AR and Palefsky, JM and Goldstone, SE and Bornstein, J and De Coster, I and Guevara, AM and Mogensen, O and Schilling, A and Van Damme, P and Vandermeulen, C and Ellison, MC and , and Kaplan, S and Lin, J and Bonawitz, R and Luxembourg, A}, title = {Immunogenicity of the 9-valent human papillomavirus vaccine: Post hoc analysis from five phase 3 studies.}, journal = {Human vaccines & immunotherapeutics}, volume = {21}, number = {1}, pages = {2425146}, pmid = {39840832}, issn = {2164-554X}, mesh = {Adolescent ; Adult ; Child ; Female ; Humans ; Male ; Young Adult ; *Antibodies, Viral/blood ; Clinical Trials, Phase III as Topic ; *Immunogenicity, Vaccine ; *Papillomavirus Infections/prevention & control/immunology ; *Papillomavirus Vaccines/immunology/administration & dosage ; }, abstract = {Post hoc analyses of 9-valent human papillomavirus (9vHPV) vaccine immunogenicity were conducted in five Phase 3 studies that enrolled males. Month 7 antibody geometric mean titers (GMTs) after three 9vHPV vaccine doses were analyzed in 10,024 males/females aged 16-26 years from studies 001 (NCT00543543), 002 (NCT00943722), 003 (NCT01651949), and 020 (NCT02114385). Covariates considered were age, gender, sexual orientation, region of residence, and race. GMTs among 2599 males/females aged 9-15 years (studies 002 and 010 [NCT01984697]) were assessed 6 months after one, two, and three 9vHPV vaccine doses. 9vHPV vaccine immunogenicity was robust across populations. Month 7 GMTs were generally higher in participants aged 16-21 versus 22-26 years. Region and race minimally impacted immunogenicity. Adjusted integrated analysis showed lower immunogenicity in men who have sex with men (MSM) versus heterosexual men (HM) for nine HPV types, and higher immunogenicity in HM versus females for seven HPV types. Among 9-15-year-olds, trends toward higher GMTs in males versus females post-Dose 3, similar GMTs post-Dose 2, and lower post-Dose 1 were observed. In conclusion, 9vHPV vaccine immunogenicity was robust in males aged 16-26 years across a range of baseline characteristics. GMT ratios for males versus females aged 9-15 years tended to increase with more doses.}, } @article {pmid39840193, year = {2024}, author = {Watanabe, R and Miura, N and Kurata, M and Kitazawa, R and Kikugawa, T and Saika, T}, title = {Genetic Analysis of Intraductal Carcinoma of the Prostate Detected in High-Grade Prostatic Intraepithelial Neoplasia Cases.}, journal = {Cureus}, volume = {16}, number = {12}, pages = {e76165}, pmid = {39840193}, issn = {2168-8184}, abstract = {Background The accurate diagnosis of intraductal carcinoma of the prostate (IDC-P) is occasionally challenging due to the similarity in pathological morphology between IDC-P and high-grade prostatic intraepithelial neoplasia (HGPIN). In this report, we reviewed the pathology of cases previously diagnosed as HGPIN to search for IDC-P cases effectively. In addition, we examined whether those cases had genetic abnormalities. Methods We reviewed 98 patients with HGPIN who underwent prostatectomy at our hospital between 2011 and 2021. They were reviewed by three pathologists to search for IDC-P findings by adding immunostaining for basement membrane markers. Genetic testing of prostatectomy specimens was performed to identify the presence of gene mutations. Results The typical IDC-P was diagnosed in two of the 98 patients. The Gleason score of background prostate cancer (PCa) was 4+5 and 4+4. Genetic testing revealed several mutations in DNA repair-related genes, such as CHEK2, FANCC, TOE1, RECQL, USG2A, and PRPF31. The pathological significance of these mutations has conflicting interpretations, as referenced in the ClinVar. Conclusions IDC-P cases can be identified from past HGPIN cases, and cases with genetic abnormalities of conflicting pathological significance can be efficiently detected. Accurate diagnosis of IDC-P enables early intervention with precision medicine for PCa. It is useful to pay attention to HGPIN cases to avoid missing true IDC-P.}, } @article {pmid39839240, year = {2025}, author = {Zhao, X}, title = {Breast Suspicious Microcalcifications on Contrast-Enhanced Mammograms: Practice and Reflection.}, journal = {International journal of general medicine}, volume = {18}, number = {}, pages = {273-280}, pmid = {39839240}, issn = {1178-7074}, abstract = {PURPOSE: To evaluate the use of contrast enhanced mammography (CEM) in suspicious microcalcifications and to discuss strategies to cope with its diagnostic limitations.

METHODS: We retrospectively evaluated patients with suspicious calcifications who underwent CEM at our institution. We collected and analyzed morphological findings, enhancement patterns and pathological findings of suspicious microcalcifications on CEM. A small proportion of these cases underwent dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The enhancement patterns of CEM in this study were classified into three categories: enhancement, no enhancement, and indeterminate. CEM imaging was independently analyzed by two breast imaging specialists.

RESULTS: A total of 44 patients with 46 lesions were collected from January 2022 to July 2024. Overall, 20 cases (43.5%) microcalcifications showed enhancement on CEM; 23 (50.0%) showed no enhancement; and 3 (6.5%) were indeterminate. Of the 20 enhancement cases, mass enhancement was seen in 9 (45%), and non-mass enhancement (NME) in 11 (55%). DCE-MRI was performed in 13 cases. One case of invasive ductal carcinoma (IDC) showed enhancement on MRI but was indeterminate on CEM due to the masking effect of background parenchymal enhancement (BPE), and one case of ductal carcinoma in situ (DCIS) lacked enhancement on CEM but had significant enhancement on MRI.

CONCLUSION: CEM provides additional information on the enhancement associated with breast suspicious microcalcifications. It is not perfect for diagnosis and strategies are needed to cope with its limitations.}, } @article {pmid39834421, year = {2025}, author = {Prasad, SL and Gudipalli, A}, title = {An effective range estimation and state-of-charge to mitigate range anxiety in electric vehicles.}, journal = {Heliyon}, volume = {11}, number = {1}, pages = {e41494}, pmid = {39834421}, issn = {2405-8440}, abstract = {This article presents a performance investigation of the range and state of electric charge vehicles based on different drive cycles and analyzed. Range anxiety is the major concern in electric vehicles globally. To mitigate the range anxiety issue by reducing the energy consumption in electric vehicles further reduces the range-related problem, and the state of charge reduces the demand for driver's power. The drive cycles predict, optimize, and simulate the performance range of Ev's real-world driving conditions. This research thoroughly focuses on the performance range of electric vehicles incorporated with the state of charge based on various standard drive cycles. A drive cycle plays a vital role in estimating energy consumption (EC) per km. There are many standard drive cycles World Wide Harmonized Light Vehicles Test Procedure (WLTP Class-3), the New European Drive Cycle (NEDC), the Modified Indian Drive Cycle (MIDC), the Indian Drive Cycle (IDC) used to investigate and evaluate Electric vehicle (EVs) performance range and state of charge (SoC). Range obtained from above drive WLTP Class-3, NEDC, MIDC, and IDC drive cycles 135.1123.8115.7 and 101.5 km, respectively. Due to improved road conditions, the WLTP Class-3 drive cycle offers more than the others. Due to road conditions, the IDC drive cycle offers a shorter range of 101.5 km.}, } @article {pmid39833820, year = {2025}, author = {Cao, F and Li, Q and Xiong, T and Zheng, Y and Zhang, T and Jin, M and Song, L and Xing, N and Niu, Y}, title = {Prognostic value of intraductal carcinoma subtypes and postoperative radiotherapy for localized prostate cancer.}, journal = {BMC urology}, volume = {25}, number = {1}, pages = {10}, pmid = {39833820}, issn = {1471-2490}, support = {NSFC 82170783//the National Natural Science Foundation of China/ ; }, mesh = {Humans ; Male ; *Prostatic Neoplasms/radiotherapy/pathology/surgery/classification/mortality ; Retrospective Studies ; Aged ; Prognosis ; Middle Aged ; Prostatectomy ; Radiotherapy, Adjuvant ; *Carcinoma, Intraductal, Noninfiltrating/radiotherapy/pathology/surgery/classification ; }, abstract = {BACKGROUND: Intraductal carcinoma of the prostate cancer (IDC-P), as a specific pathological type in prostate cancer which usually implies a poor prognosis. IDC-P morphology can be divided into two subtypes: Pattern 1, sieve like or loose cribriform structures; Pattern 2, solid or dense cribriform structures. The purpose of the study is to identify the impact of IDC-P and its subtypes on the prognosis of patients undergoing post-operative radiotherapy (PORT) after radical prostatectomy (RP) due to localized prostate cancer(PCa).

METHODS: We performed a retrospective study of patients with localized PCa treated by RP followed by PORT or not. Patients with localized PCa who underwent RP from August 2013 to December 2020 were included in this study.

INCLUSION CRITERIA: post-operative PSA dropped to less than 0.1 ng/ml after RP, had at least 1 poor prognostic risk factor (including high Gleason's grouping; positive surgical margins; seminal vesicle invasion; extraprostatic extension; and lympho-vascular invasion), and were eligible for adjuvant radiotherapy.; In this study, patients who underwent salvage radiotherapy after RP due to biochemical recurrence (two consecutive PSA > 0.2 ng/ml) were also included, but not patients with persistent postoperative PSA > 0.1 ng/ml.

EXCLUSION CRITERIA: patients using other types of therapy prior to biochemical recurrence. Screening cases with pathological results of intraductal carcinoma, subtyping was completed by a pathologist, grouped by intraductal carcinoma (+/-; pattern 1/ 2) and treatment regimen (RP + PORT / RP only), Kaplan-Meier curves were plotted based on the time to biochemical recurrence-free and overall survival of the patients, and Cox regression analyses were performed. Finally, based on the results of Cox regression analysis, we initially predicted the probability of biochemical recurrence and death of the patients by plotting the nomogram.

RESULTS: A total of 139 patients were included in this study with a median follow-up of 61.5 months. K-M curves showed that patients with "IDC-P (+) RP only" had the worst prognosis; patients with IDC-P could have a survival benefit after receiving PORT; whereas patients with non-intraductal carcinoma had a better prognosis than the above patients with or without PORT. In addition, patients with IDC-P(+) pattern 2 were more likely to experience biochemical recurrence and death. Multivariate Cox regression analysis showed that pattern 2 was a risk factor for biochemical recurrence and death. Other BCR-related risk factors in the research: Gleason grading group 5 (HR = 3.343, 95% CI: 1.616-6.916, P = 0.001), PM (HR = 2.124, 95% CI: 1.044-4.320,P = 0.038) and PORT (HR = 0.266, 95%CI: 0.109-0.647, P = 0.004). Other OS-related risk factors in the research: Grading group 5 (HR = 3.642, 95%CI:1.475-8.991, P = 0.005), SVI (HR = 2.522, 95% CI: 1.118-5.691, P = 0.026) and PORT (HR = 0.319, 95%CI: 0.107-0.949, P = 0.040).

CONCLUSION: Patients suffering from localized prostate cancer with IDC-P(+), especially IDC-P pattern 2, are more susceptible to biochemical recurrence and death after radical prostatectomy. While postoperative radiotherapy can alleviate the negative prognostic impact from IDC-P. It is implied that IDC-P can also be an indicator to be considered in PORT decision making to some extent.}, } @article {pmid39829405, year = {2025}, author = {Mansour, A and Ben-David, BM and Sasson, A and Farraj, J and Mansour, A and Roth, Y and Icht, M}, title = {Association between oral feeding versus enteral feeding and cerumen impaction in older hospitalized adults: A retrospective cohort study.}, journal = {JPEN. Journal of parenteral and enteral nutrition}, volume = {49}, number = {3}, pages = {341-348}, doi = {10.1002/jpen.2724}, pmid = {39829405}, issn = {1941-2444}, mesh = {Humans ; Retrospective Studies ; Aged ; Male ; Female ; *Enteral Nutrition/adverse effects ; *Hospitalization ; Aged, 80 and over ; *Cerumen ; Length of Stay ; Deglutition Disorders ; Risk Factors ; *Diet ; }, abstract = {BACKGROUND: Chewing involves jaw movements that propel cerumen along the ear canal. This mechanism may be reduced in dysphagia, especially for older individuals who are enterally fed. Those patients may be at a higher risk for cerumen impaction and may require longer hospital stays. Examining the relationship between diet type, cerumen impaction, and hospital stay duration was the focus of the present study.

METHODS: We performed a retrospective cohort study (not registered) among 114 hospitalized older adults. Data were collected on diet type: (1) oral feeding (individuals fed a solid diet or a pureed diet) or (2) enteral feeding (individuals fed via a feeding tube). The results of an otoscopy that quantified cerumen were recorded, as well as hospital stay duration.

RESULTS: In a mediation analysis, a hospital stay of >1 month was associated with an increased risk of enteral feeding, which in turn, increased the risk of cerumen impaction. Analysis indicated that the link between longer hospitalization and a more severe level of cerumen impaction was fully mediated by diet type (enteral feeding).

CONCLUSIONS: Enteral feeding seems to be a risk factor for cerumen impaction, rather than merely hospitalization length, in our sample of geriatric patients. These results highlight the importance of continuous monitoring by ear, nose, and throat specialists, as well as regular auditory assessments for patients who are enterally fed for early detection and treatment of cerumen impaction. Particular attention should be paid to cases of prolonged hospitalization, which is associated with the severity of dysphagia.}, } @article {pmid39827461, year = {2025}, author = {Matta, L and Weber, P and Erener, S and Walth-Hummel, A and Hass, D and Bühler, LK and Klepac, K and Szendroedi, J and Guerra, J and Rohm, M and Sterr, M and Lickert, H and Bartelt, A and Herzig, S}, title = {Chronic intermittent fasting impairs β cell maturation and function in adolescent mice.}, journal = {Cell reports}, volume = {44}, number = {2}, pages = {115225}, doi = {10.1016/j.celrep.2024.115225}, pmid = {39827461}, issn = {2211-1247}, mesh = {Animals ; *Fasting/physiology ; *Insulin-Secreting Cells/metabolism/pathology ; Mice ; Humans ; Male ; Mice, Inbred C57BL ; Female ; Diabetes Mellitus, Type 2/metabolism/pathology ; Diabetes Mellitus, Type 1/metabolism/pathology ; Intermittent Fasting ; }, abstract = {Intermittent fasting (IF) is a nutritional lifestyle intervention with broad metabolic benefits, but whether the impact of IF depends on the individual's age is unclear. Here, we investigated the effects of IF on systemic metabolism and β cell function in old, middle-aged, and young mice. Short-term IF improves glucose homeostasis across all age groups without altering islet function and morphology. In contrast, while chronic IF is beneficial for adult mice, it results in impaired β cell function in the young. Using single-cell RNA sequencing (scRNA-seq), we delineate that the β cell maturation and function scores are reduced in young mice. In human islets, a similar pattern is observed in type 1 (T1D), but not type 2 (T2D), diabetes, suggesting that the impact of chronic IF in adolescence is linked to the development of β cell dysfunction. Our study suggests considering the duration of IF in younger persons, as it may worsen rather than reduce diabetes outcomes.}, } @article {pmid39822422, year = {2024}, author = {Aleksiev, T and Popov, V and Dobrev, H}, title = {Radiation-Associated Herpes Zoster: A Clinical Case.}, journal = {Cureus}, volume = {16}, number = {12}, pages = {e75857}, pmid = {39822422}, issn = {2168-8184}, abstract = {Herpes zoster (HZ) is a viral infection caused by the reactivation of endogenous and latent varicella-zoster virus that remains dormant in the cranial nerve or dorsal root ganglia. HZ occurs in a portion of the general population, with a higher incidence observed in high-risk individuals. Patients with impaired immunity, including human immunodeficiency virus infection, organ transplantation, old age, and cancer-related treatments such as chemotherapy (CT) and radiotherapy (RT) were found more prone to HZ infection. We present a case of a 50-year-old patient who underwent a surgical excision of an invasive ductal carcinoma of the right breast. Following 15 fractions of RT, the patient presented with HZ appearing in the radiation field. The patient was treated successfully with Acyclovir, and RT was continued while on maintenance therapy with antiviral drugs. This case presents the importance of early diagnosis and the right choice of treatment in cancer patients and HZ due to the higher risk of complications and further development of the primary condition.}, } @article {pmid39821030, year = {2025}, author = {Bullock, E and Brunton, VG}, title = {E-Cadherin-Mediated Cell-Cell Adhesion and Invasive Lobular Breast Cancer.}, journal = {Advances in experimental medicine and biology}, volume = {1464}, number = {}, pages = {259-275}, pmid = {39821030}, issn = {0065-2598}, mesh = {Humans ; *Cadherins/metabolism/genetics ; *Breast Neoplasms/pathology/metabolism/genetics ; Female ; *Carcinoma, Lobular/pathology/metabolism/genetics ; *Cell Adhesion ; Epithelial-Mesenchymal Transition ; Neoplasm Invasiveness ; Adherens Junctions/metabolism/pathology ; Animals ; }, abstract = {E-cadherin is a transmembrane protein and central component of adherens junctions (AJs). The extracellular domain of E-cadherin forms homotypic interactions with E-cadherin on adjacent cells, facilitating the formation of cell-cell adhesions, known as AJs, between neighbouring cells. The intracellular domain of E-cadherin interacts with α-, β- and p120-catenins, linking the AJs to the actin cytoskeleton. Functional AJs maintain epithelial tissue identity and integrity. Transcriptional downregulation of E-cadherin is the first step in epithelial-to-mesenchymal transition (EMT), a process essential in development and tissue repair, which, in breast cancer, can contribute to tumour progression and metastasis. In addition, loss-of-function mutations in E-cadherin are a defining feature of invasive lobular breast cancer (also known as invasive lobular carcinoma (ILC)), the second most common histological subtype of breast cancer. ILC displays a discohesive, single-file invasive growth pattern due to the loss of functional AJs. Despite being so prevalent, until recently there has been limited ILC-focused research and historically ILC patients have often been excluded from clinical trials. Despite displaying a number of good prognostic indicators, such as low grade and high rates of estrogen receptor positivity, ILC patients tend to have similar or poorer outcomes relative to the most common subtype of breast cancer, invasive ductal carcinoma (IDC). In ILC, E-cadherin loss promotes hyperactivation of growth factor receptors, in particular insulin-like growth factor 1 receptor, anoikis resistance and synthetic lethality with ROS1 inhibition. These features introduce clinical vulnerabilities that could potentially be exploited to improve outcomes for ILC patients, for whom there are currently limited tailored treatments available.}, } @article {pmid39821022, year = {2025}, author = {Nair, I and Behbod, F}, title = {Models for Studying Ductal Carcinoma In Situ Progression.}, journal = {Advances in experimental medicine and biology}, volume = {1464}, number = {}, pages = {95-108}, pmid = {39821022}, issn = {0065-2598}, mesh = {Humans ; *Carcinoma, Intraductal, Noninfiltrating/pathology/genetics/metabolism ; Disease Progression ; Female ; *Breast Neoplasms/pathology/genetics/metabolism ; Tumor Microenvironment ; *Models, Biological ; *Carcinoma, Ductal, Breast/pathology ; }, abstract = {An estimated 55,720 new cases of ductal carcinoma in situ (DCIS) will be diagnosed in 2023 in the USA alone because of the increased use of screening mammography. The treatment goal in DCIS is early detection and treatment with the hope of preventing progression into invasive disease. Previous studies show progression into invasive cancer as well as reduction in mortality from treatment is not as high as previously thought. So, are we overdiagnosing and over-treating DCIS? An understanding of the natural progression of DCIS is paramount to address this. The purpose of this chapter is to describe various models that have been developed to simulate the processes involved in DCIS to invasive ductal carcinoma (IDC) transition. While each model possesses a unique set of strengths and weaknesses, they have collectively contributed to the current understanding of the molecular and cellular mechanisms underlying this transition. Even though much has been learned, continued advancement of the current models to best match the composition of DCIS epithelial and stromal microenvironment including the extracellular matrix (ECM), stromal cell types, and immune microenvironment will be essential. These advances will undoubtedly pave the way toward a full understanding of mechanisms associated with progression and in predicting when a DCIS lesion remains indolent and when triggers tip in the balance toward progression to malignancy.}, } @article {pmid39820625, year = {2025}, author = {Klein, C and Anract, J and Pinar, U and Lacroix, X and Mansour, R and Robert, G and Delongchamps, NB}, title = {Comparative study of HoLEP in elderly patients with indwelling catheters: a retrospective dual-center study.}, journal = {World journal of urology}, volume = {43}, number = {1}, pages = {75}, pmid = {39820625}, issn = {1433-8726}, mesh = {Humans ; Retrospective Studies ; Male ; Aged, 80 and over ; *Catheters, Indwelling ; *Prostatic Hyperplasia/surgery ; Aged ; Postoperative Complications/epidemiology ; Treatment Outcome ; }, abstract = {INTRODUCTION: This study aimed to evaluate the safety and efficacy of HoLEP in patients aged > 85 years with indwelling catheter (IDC).

METHODS: We retrospectively analyzed our bicentric HoLEP database to identify consecutive patients with IDC and trial without catheter (TWOC) failure who underwent surgery between June 2012 and April 2020. Our primary focus was on the population over 85 years of age; Patients under 70 years of age were used as controls. We evaluated the rate of postoperative spontaneous micturition, adverse events and mortality, as well as catheterization duration, hospital stay, and rate of urinary incontinence.

RESULTS: In total, 144 patients were included, with 71 (49.3%) and 73 (50.8%) in the ≥ 85 and control group, respectively. The median [IQR] prostatic volume and Charlson score was 90 [70-130] vs. 90 [65-120] mL and 6 [5-7] vs. 3 [2-4] in the ≥ 85 and control groups, respectively. Postoperatively, the rates of major complications (2% vs. 3%) and transfusion (11% vs. 9%) were not significantly different. The median length of stay (2 [1-3] vs. 1 [1-2]; p = 0.03) and rate of TWOC failure during hospitalization (24% vs. 5%, p < 0.001) were significantly higher in the ≥ 85 group. At 3 months and one year follow-up visits, 0 and 10 patients (14.1%) in the ≥ 85 group and 0 and 2 patients (3%) in the control group died, respectively. One year after surgery, 69 (97%) and 73 (100%) (p = 0.2) patients in the ≥ 85 and control groups, respectively, could void spontaneously.

CONCLUSION: HoLEP is a safe and effective procedure for elderly patients with indwelling catheters. At one year, 97% of patients achieved spontaneous voiding, while the urinary incontinence rate was 11%. The 1-year mortality rate was 14%, comparable to that of the general male population of the same age.}, } @article {pmid39815412, year = {2025}, author = {Wankhade, R and Bhake, A and Bankar, N and Tiwade, Y}, title = {Evaluation of Ki67 in pathological prognostic staging of breast cancer: a tertiary care center study.}, journal = {Journal of immunoassay & immunochemistry}, volume = {46}, number = {2}, pages = {186-200}, doi = {10.1080/15321819.2025.2451211}, pmid = {39815412}, issn = {1532-4230}, mesh = {Humans ; *Ki-67 Antigen/analysis ; *Breast Neoplasms/diagnosis/pathology/metabolism ; Female ; Middle Aged ; Prognosis ; Tertiary Care Centers ; Adult ; Neoplasm Staging ; Aged ; Immunohistochemistry ; Biomarkers, Tumor/analysis ; *Carcinoma, Ductal, Breast/diagnosis/pathology ; }, abstract = {BACKGROUND: The rising global burden of breast cancer demands early detection and effective treatment, with a focus on prognostic and predictive markers. The eighth edition of the American Joint Committee on Cancer staging manual introduced a new prognostic staging system to increase the predictive power of the existing anatomical staging system of breast cancer. The current study aimed to establish the correlation between Ki67 expression with molecular subtypes and with the pathological prognostic stage of invasive ductal carcinoma.

MATERIALS AND METHODS: A total of 40 patients were included in the study with samples from 32 modified radical mastectomies and 8 biopsies. Hematoxylin and Eosin staining, histopathological analysis and Ki67 immunostaining were conducted. Descriptive and inferential statistical analyses were performed.

RESULTS: Bloom Richardson Grade II was the predominant histological grade. In Grade II cases, 15 of 24 had a Ki67 labeling index of 26-45%, while 6 exceeded 45% (p = 0.001). Pathological prognostic staging reclassified 27 cases, with 24 (75%) downstaged, 3 (9.38%) upstaged, and 5 (15.63%) retaining their clinical stage.

CONCLUSIONS: Ki67 immunohistochemistry is an effective tool for assessing proliferative activity of invasive ductal carcinoma, aiding in pathological prognostic stage stratification and offering insights into tumor biology.}, } @article {pmid39815122, year = {2025}, author = {Sossa-Melo, C and Abello-Polo, V and Salazar, LA and Peña, AM and Luna-González, M and Cuervo-Lozada, D and Quintero-Vega, GE and Daza, J and Omaña-Orduz, OP and Mantilla, W and Perdomo, I and Galvez, K and Díaz-Correa, LM and Guerrero-Burbano, PA and Herrera, JM and Idrobo, H and Gaviria, LM and Correa-Correa, ME and Lobatón, J and Bermúdez, CD and Pedraza-Morales, JE and Serrano-Casas, JC and Jaramillo, F and Gómez, R and Rosales, C and Solano, MH and Varón, C and Rodríguez-Veiga, R and Martínez-Cuadrón, D and Montesinos, P}, title = {Characteristics, outcomes and treatment patterns in acute myeloid leukemia patients 60 years or older in Colombia: a RENEHOC-PETHEMA study.}, journal = {Annals of hematology}, volume = {104}, number = {1}, pages = {369-381}, pmid = {39815122}, issn = {1432-0584}, mesh = {Humans ; Male ; *Leukemia, Myeloid, Acute/genetics/therapy/mortality/epidemiology/drug therapy/diagnosis ; Female ; Colombia/epidemiology ; Aged ; Middle Aged ; Retrospective Studies ; Aged, 80 and over ; Nucleophosmin ; Treatment Outcome ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Registries ; Survival Rate ; Cytarabine/administration & dosage ; Mutation ; }, abstract = {There is a limited information available on the clinical characteristics, treatment patterns and outcomes on older patients diagnosed with Acute Myeloid Leukemia (AML) in Latin-America. This multicenter retrospective study analyzed 269 patients over 60 years of age diagnosed with AML in Colombia, using data from RENEHOC-PETHEMA registry, from 2009 to 2023. The median age at diagnosis was 70 years (Range:60-98), 55% were men, 61% had an ECOG < 2, and 75.5% had de novo AML. FLT3-ITD or NPM1 mutations were performed in 23.4% and 15.6% patients, and detected in 14.3% and 16.7% of cases, respectively. Treatment included intensive chemotherapy (IC) (36.8%), Low-Intensity Regimen Based on Low-Dose Cytarabine (LDAC-based) (12.6%), hypomethylating agents (HMAs, with/without venetoclax) (35.3%), and supportive care (15.2%). The overall survival (OS) rate was 35.2% at 1 year and 5.6% at 5 years (13.7% for IC, 9.4% for LDAC-based, and 0% for other treatments); with median OS of 8.2 months (10.6 months after IC, 8.8 months after non-IC, 8.9 months after azacitidine/decitabine, 8.2 months after azacitidine-venetoclax, and 1.9 months with supportive care). Only 1.5% of patients underwent a transplant in the first line. The Leukemia-free survival (LFS) rate was 45.8% at 1-year and 13.7% at 5-years (22.4% for IC, 9.4% and 0% for other treatments); with median LFS of 9.5 months (17.3 months after IC, 7.4 months after LDAC-based, and 10.8 months after HMA). This study provides new insights into the management of patients in Colombia, highlighting the need for a highly individualized approach in treating AML in elderly patients.}, } @article {pmid39814814, year = {2025}, author = {Hu, J and Dong, J and Yang, X and Ye, Z and Hu, G}, title = {Erythrocyte modified controlling nutritional status as a biomarker for predicting poor prognosis in post-surgery breast cancer patients.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {2071}, pmid = {39814814}, issn = {2045-2322}, support = {No. LY23H160002//Natural Science Foundation of Zhejiang Province/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/surgery/blood/pathology/mortality ; Middle Aged ; *Nutritional Status ; Prognosis ; Retrospective Studies ; *Erythrocytes/metabolism ; Adult ; *Biomarkers, Tumor/blood ; Aged ; Disease-Free Survival ; Kaplan-Meier Estimate ; Neoplasm Recurrence, Local ; }, abstract = {Nutrition and inflammation are closely related to prognosis in breast cancer patients. However, current nutritional and inflammatory measures predict disease free survival (DFS) of breast cancer are still different, and the most predictive measures remain unknown. This study aimed to compare the predictive effects of commonly used nutritional and inflammatory measures on DFS and to improve existing nutritional or inflammatory measures in order to develop a new model that is more effective for predicting postoperative recurrence and metastasis in breast cancer patients. The clinical data of 536 female breast cancer patients with invasive ductal carcinoma who underwent surgery at Shaoxing People's Hospital from January 2012 to December 2018 were retrospectively evaluated. The predictive effects of nutritional and inflammatory indicators on DFS were evaluated. Machine learning was used to evaluate and rank laboratory indicators, select relatively important variables to modify nutritional or inflammatory indicators with the best predictive power, and evaluate their predictive role in patients' postoperative recurrence and metastasis. Among various metrics predicting DFS, the CONUT score emerged paramount with an area under the curve (AUC) of 0.667. Interestingly, the combination of the erythrocyte levels with the CONUT score (ECONUT) achieved the highest AUC (0.722). The Kaplan-Meier survival analysis showed that the group exhibiting high ECONUT scores experiencing a notably poorer DFS. ECONUT was identified as an independent risk factor for postoperative DFS (P < 0.001). The ECONUT model could provide an effective assessment tool for predicting DFS in breast cancer patients.}, } @article {pmid39812957, year = {2026}, author = {Wei, C and Li, H and Li, J and Liu, Y and Zeng, J and Tian, Q}, title = {Machine learning-based prognostic modeling and surgical value analysis of de novo metastatic invasive ductal carcinoma of the breast.}, journal = {Updates in surgery}, volume = {78}, number = {1}, pages = {415-428}, pmid = {39812957}, issn = {2038-3312}, support = {No.81960441//National Natural Science Foundation of China/ ; No.20232BAB206100//Jiangxi Provincial Natural Science Foundation of China/ ; }, mesh = {Humans ; *Breast Neoplasms/surgery/pathology/mortality ; Female ; *Machine Learning ; Prognosis ; Middle Aged ; *Carcinoma, Ductal, Breast/surgery/mortality/secondary/pathology/diagnosis ; SEER Program ; Aged ; Adult ; *Mastectomy ; }, abstract = {Whether primary lesion surgery improves survival in patients with de novo metastatic breast cancer (dnMBC) is inconclusive. We aimed to establish a prognostic prediction model for patients with de novo metastatic breast invasive ductal carcinoma (dnMBIDC) based on machine learning algorithms and to investigate the value of primary site surgery. The data used in our study were obtained from the Surveillance, Epidemiology, and End Results database (SEER, 2010-2021) and the First Affiliated Hospital of Nanchang University (1st-NCUH, June 2013-June 2023). We used COX regression analysis to identify prognostic factors. We divided patients into training and validation groups and constructed Extreme Gradient Boosting (XGBoost) prognostic prediction model. In addition, we used propensity score matching (PSM), K-M survival analysis, and COX regression analysis to explore the survival benefit of patients undergoing primary lesion surgery. A total of 13,383 patients were enrolled, with 13,326 from SEER and 57 from 1st-NCUH. The results showed that XGboost had good predictive ability (training set C-index = 0.726, 1 year AUC = 0.788, 3 year AUC = 0.774, 5 year AUC = 0.774; validation set C-index = 0.723, 1 year AUC = 0.785.1, 3 year AUC = 0.770, 5 year AUC = 0.764), which has better predictive power than the Coxph model. We used Shiny-Web to make our model easily available. Furthermore, we found that surgery was associated with a better prognosis in dnMBIDC patients. Based on the XGboost, we can accurately predict the survival of dnMBIDC patients, which can provide a reference for clinicians to treat patients. In addition, surgery may bring survival benefits to dnMBIDC patients.}, } @article {pmid39806949, year = {2025}, author = {Gallas, AE and Morenikeji, GO and King, RE and Adegbaju, MS and Ayoola, A and Taiwo, G and Morenikeji, OB}, title = {An Overview of Invasive Ductal Carcinoma (IDC) in Women's Breast Cancer.}, journal = {Current molecular medicine}, volume = {25}, number = {4}, pages = {361-371}, pmid = {39806949}, issn = {1875-5666}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/genetics/therapy/diagnosis/etiology/metabolism ; *Carcinoma, Ductal, Breast/genetics/pathology/therapy/diagnosis/etiology/metabolism ; Biomarkers, Tumor/genetics ; DNA Methylation ; Prognosis ; Mutation ; Gene Expression Regulation, Neoplastic ; }, abstract = {Invasive ductal carcinoma (IDC) is the most common type of breast cancer, primarily affecting women in the United States and across the world. This review summarizes key concepts related to IDC causes, treatment approaches, and the identification of biological markers for specific prognoses. Furthermore, we reviewed many studies, including those involving patients with IDC and ductal carcinoma in situ (DCIS) that progressed to IDC. We reported various studies on the causes of IDC, including mutations on BRCA1 and BRCA2, different levels of expression of specific genes in signaling pathways, menopause status, alcohol consumption, aging, and hormone imbalances that cause IDC while p-SMAD4 expressions, DNA methylation, regulations of hub genes, and underestimation of IDC affecting prognoses. Prompt IDC diagnosis and early intervention have been reported to demonstrate a greater probability of eradicating IDC and preventing further recurrence in the future. It is crucial for physicians and researchers to equip patients with the best information possible to proactively manage their health, whether it be for IDC prevention or treatment. Overall, our review provided a comprehensive understanding of IDC that enables patients to grasp the nature of the disease with the hope of mitigating IDC risk, decrease the anxiety of a cancer diagnosis, and encourage patients to become more involved in making informed decisions for their healthcare.}, } @article {pmid39805165, year = {2025}, author = {Michelon, I and Castro, CER and Madeira, T and Dacoregio, MI and Stecca, C and Soares, LR and Saeed, A and Vilbert, M and Cavalcante, L}, title = {Trastuzumab deruxtecan in human epidermal growth factor receptor 2-positive breast cancer brain metastases: A systematic review and updated meta-analysis.}, journal = {Cancer treatment reviews}, volume = {133}, number = {}, pages = {102882}, doi = {10.1016/j.ctrv.2025.102882}, pmid = {39805165}, issn = {1532-1967}, mesh = {Humans ; *Breast Neoplasms/drug therapy/pathology/metabolism ; *Trastuzumab/therapeutic use/pharmacology ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; *Brain Neoplasms/secondary/drug therapy/metabolism ; Female ; *Immunoconjugates/therapeutic use ; *Antineoplastic Agents, Immunological/therapeutic use ; Camptothecin/analogs & derivatives ; }, abstract = {BACKGROUND: Trastuzumab deruxtecan (T-DXd) has shown promising activity in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and central nervous system (CNS) involvement. In this updated meta-analysis, we explore the effectiveness of T-DXd in a large subset of patients with HER2-positive BC and CNS disease.

METHODS: A systematic search was made on September 16th, 2024, for studies investigating T-DXd in the scenario of HER2-positive BC and brain metastases (BMs) and/or leptomeningeal disease (LMD). We used random effects models for all statistical analyses.

RESULTS: We included 18 studies with 786 HER2-positive BC patients with CNS involvement (16 studies with 750 BMs patients and three studies with 36 LMD patients). We observed high overall antitumor responses (objective response rate [ORR], 60.4 %; disease control rate [DCR], 94.4 %; and clinical benefit rate [CBR], 79.3 %) and a 12-month PFS of 64.7 % and OS of 82.7 %. Intracranial ORR, DCR, and CBR were seen in 62.2 %, 88.6 %, and 68.6 % of patients, respectively, and 67.4 % achieved intracranial PFS at 12 months. Both stable and active BMs subgroups derived similar benefit from T-DXd. Better intracranial responses were seen for 33 patients with untreated BMs compared to 56 patients with previously treated or progressing lesions (odds ratio 3.82, 95 % confidence interval 1.3-10.8, p = 0.01). For the LMD group, T-DXd elicited intracranial ORR and CBR in 59.4 % and 94.1 % of patients, respectively.

CONCLUSIONS: This updated meta-analysis continues to support the overall and intracranial activity of T-DXd in patients with HER2-positive BC and CNS involvement, including those with LMD.}, } @article {pmid39804847, year = {2025}, author = {Wang, K and Fischer, A and Maccio, U and Zitzmann, K and Robledo, M and Lauseker, M and Bauer, J and Bechmann, N and Gahr, S and Maurer, J and Peischer, L and Reul, A and Nieß, H and Zimmermann, P and Ilmer, M and Schilbach, K and Knösel, T and Kroiss, M and Fassnacht, M and Müller, SA and Morand, GB and Huber, A and Vetter, D and Lehmann, K and Kulcsar, Z and Mohr, H and Pellegata, NS and Hantel, C and Reincke, M and Beuschlein, F and Pacak, K and Grossman, AB and Auernhammer, CJ and Nölting, S}, title = {Impact of sex hormones on pheochromocytomas, paragangliomas, and gastroenteropancreatic neuroendocrine tumors.}, journal = {European journal of endocrinology}, volume = {192}, number = {1}, pages = {46-60}, doi = {10.1093/ejendo/lvae163}, pmid = {39804847}, issn = {1479-683X}, support = {314061271 - TRR 205//German Research Foundation/ ; }, mesh = {Humans ; *Neuroendocrine Tumors/pathology/drug therapy/metabolism/genetics ; *Pheochromocytoma/pathology/drug therapy/metabolism/genetics ; *Paraganglioma/pathology/drug therapy/metabolism/genetics ; *Pancreatic Neoplasms/pathology/drug therapy/metabolism/genetics ; Female ; *Intestinal Neoplasms/pathology/drug therapy/metabolism/genetics ; Male ; *Adrenal Gland Neoplasms/pathology/drug therapy/metabolism/genetics ; *Stomach Neoplasms/drug therapy/pathology/metabolism/genetics ; *Gonadal Steroid Hormones/pharmacology ; Middle Aged ; Adult ; Estradiol/pharmacology ; Testosterone/pharmacology ; Estrogen Receptor alpha/metabolism ; Progesterone/pharmacology ; Dehydroepiandrosterone Sulfate/pharmacology ; Aged ; *Gastrointestinal Neoplasms/drug therapy/pathology/metabolism ; Cell Survival/drug effects ; }, abstract = {OBJECTIVE: The effects of sex hormones remain largely unexplored in pheochromocytomas and paragangliomas (PPGLs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

METHODS: We evaluated the effects of estradiol, progesterone, Dehydroepiandrosterone sulfate (DHEAS), and testosterone on human patient-derived PPGL/GEP-NET primary culture cell viability (n = 38/n = 12), performed next-generation sequencing and immunohistochemical hormone receptor analysis in patient-derived PPGL tumor tissues (n = 36).

RESULTS: In PPGLs, estradiol and progesterone (1 µm) demonstrated overall significant antitumor effects with the strongest efficacy in PPGLs with NF1 (cluster 2) pathogenic variants. Estrogen receptor alpha (ERα) positivity was detected in 11/36 PPGLs, including 4/4 head-and-neck paragangliomas (HNPGLs). ERα-positive tumors responded with a significant cell viability decrease to estradiol. DHEAS and testosterone (1 µm) displayed no effects, but higher doses of testosterone (10 µm) demonstrated significant antitumor effects, including a pheochromocytoma lung metastasis with strong androgen receptor positivity (30%). Driven by the antitumor effects of estrogen, we evaluated G-protein-coupled estrogen receptor (GPER) agonist G-1 as a potential therapeutic option for PPGLs and found strong significant antitumor potential, with the strongest efficacy in tumors with NF1 pathogenic variants. Moreover, we detected sex-related differences-tumors from male patients showed significantly stronger responsivity to G-1 compared with tumors from female patients. In GEP-NETs, sex hormones showed overall no effects, especially no tumor growth-promoting effects.

CONCLUSION: We provide novel data on the effects of elevated sex hormone levels, potentially seen during pregnancy or hormone replacement therapy, on PPGL/GEP-NET tumor growth. G-1 might offer a novel therapeutic approach for some PPGLs depending on patient's sex and the individual tumor's genetic/molecular background. All HNPGLs showed ERα positivity.}, } @article {pmid39799921, year = {2025}, author = {Fu, J and Wang, J and Ma, Z and Yuan, D and Zhang, Y and Wang, L and Luo, Y}, title = {CaCO3-coated indoxacarb deep eutectic solvent complexed with diatomaceous earth improves insecticidal activity against the red imported fire ants.}, journal = {Ecotoxicology and environmental safety}, volume = {289}, number = {}, pages = {117709}, doi = {10.1016/j.ecoenv.2025.117709}, pmid = {39799921}, issn = {1090-2414}, mesh = {Animals ; *Ants/drug effects ; *Insecticides/chemistry/toxicity ; *Oxazines/chemistry/toxicity ; *Diatomaceous Earth/chemistry ; *Calcium Carbonate/chemistry ; *Deep Eutectic Solvents/chemistry ; Nanoparticles/chemistry ; Fire Ants ; }, abstract = {The red imported fire ants (RIFAs) are a globally important invasive pest that severely affects the ecosystem and human health, and its current control is primarily through chemical pesticides. However, the extensive use of chemical pesticides causes environmental problems, and alternative strategies for controlling this pest are being explored. In our study, we aimed to design a deep eutectic solvent (DES)-CaCO3 system in which RIFAs were used as target insects to increase the lethal activity and behavioural regulation effects on RIFAs via contact and feeding. Indoxacarb (IDC) was made into DESs with three fatty acids, oleic acid (OA), linoleic acid (LA), and linolenic acid (LNA), which showed a significant increase in lethal activity against worker ants compared with IDC. OA@IDC@CaCO3, LA@IDC@CaCO3, and LNA@IDC@CaCO3 nanoparticles were prepared via interfacial precipitation. Characterization of the structures of the three pesticide-carrying nanoparticles revealed that all three fatty acid eutectic solvents formed spherical CaCO3 nanoparticles, with average particle sizes between 0.59 and 0.90 μm, which increased with increasing degree of fatty acid unsaturation. The pesticide loading ranged from 2.13 %⁓3.43 %, and the surfaces were all positively charged and well dispersed. OA@IDC@CaCO3 was relatively more effective and was able to dramatically inhibit the abandonment and foraging behaviours of RIFAs, prolong the time required for these behaviours, and decrease the number of feeding worker ants and the amount of food consumed. OA@IDC@CaCO3 was subsequently compounded with diatomaceous earth (DA), and spiked into baits, which significantly increased the contact and feeding activity of worker ants, inhibited the feeding, digging, and corpse-discarding behaviours of RIFAs. In the field trial, the combined control effect of the DA + OA@IDC@CaCO3 group was 83.38 %, which was greater than the 69.65 % of the commercial agent control group. In this study, IDC bait was co-prepared by using acid as a comelting solvent, CaCO3 as a coating, and DA as a pesticide adjuvant, which improved the activity against RIFAs, prolonged the holding period of IDC, and improved the prevention and control of RIFAs. Therefore, our research provides a simple and feasible approach for designing and constructing novel nanopesticides for RIFAs control.}, } @article {pmid39795975, year = {2024}, author = {Caca, J and Bartelt, A and Egea, V}, title = {Hypoxia Regulates Brown Adipocyte Differentiation and Stimulates miR-210 by HIF-1α.}, journal = {International journal of molecular sciences}, volume = {26}, number = {1}, pages = {}, pmid = {39795975}, issn = {1422-0067}, mesh = {*MicroRNAs/genetics/metabolism ; Animals ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; *Adipocytes, Brown/metabolism/cytology ; *Cell Differentiation/genetics ; Mice ; Thermogenesis/genetics ; Cell Hypoxia ; }, abstract = {MicroRNAs (miRNAs) are short sequences of single-stranded non-coding RNAs that target messenger RNAs, leading to their repression or decay. Interestingly, miRNAs play a role in the cellular response to low oxygen levels, known as hypoxia, which is associated with reactive oxygen species and oxidative stress. However, the physiological implications of hypoxia-induced miRNAs ("hypoxamiRs") remain largely unclear. Here, we investigate the role of miR-210 in brown adipocyte differentiation and thermogenesis. We treated the cells under sympathetic stimulation with hypoxia, CoCl2, or IOX2. To manipulate miR-210, we performed reverse transfection with antagomiRs. Adipocyte markers expression, lipid accumulation, lipolysis, and oxygen consumption were measured. Hypoxia hindered BAT differentiation and suppressed sympathetic stimulation. Hypoxia-induced HIF-1α stabilization increased miR-210 in brown adipocytes. Interestingly, miR-210-5p enhanced differentiation under normoxic conditions but was insufficient to rescue the inhibition of brown adipocyte differentiation under hypoxic conditions. Although adrenergic stimulation activated HIF-1α signaling and upregulated miR-210 expression, inhibition of miR-210-5p did not significantly influence UCP1 expression or oxygen consumption. In summary, hypoxia and adrenergic stimulation upregulated miR-210, which impacted brown adipocyte differentiation and thermogenesis. These findings offer new insights for the physiological role of hypoxamiRs in brown adipose tissue, which could aid in understanding oxidative stress and treatment of metabolic disorders.}, } @article {pmid39795812, year = {2025}, author = {Cieślik, M and Orlikowski, J and Krakowiak, S and Żakowski, K}, title = {Dynamic Electrochemical Impedance Spectroscopy in Galvanostatic Mode as a Tool for Passive Layer State Monitoring in a Chloride Solution Under a Mechanical Load.}, journal = {Materials (Basel, Switzerland)}, volume = {18}, number = {1}, pages = {}, pmid = {39795812}, issn = {1996-1944}, abstract = {Mechanical stress is one of the factors influencing the initiation of pitting corrosion and deterioration of the protective properties of the passive layer on stainless steel. The tests carried out on AISI 304L stainless steel showed that, in the 3.5% NaCl environment for samples loaded in the elastic and plastic range, no pitting corrosion initiation was observed. Only mechanical damage of the passive layer occurred. Galvanodynamic electrochemical impedance spectroscopy (g-DEIS) was used as the measuring technique. This technique ensures the monitoring of corrosion processes at zero external current (IDC = 0) and no potential perturbation of the system. It also allows one to perform many measurements, so that short-term changes such as cracking of the layer and its repassivation are possible to monitor.}, } @article {pmid39795579, year = {2024}, author = {Khasawneh, AI and Himsawi, N and Alorjani, M and Al-Momani, H and Shahin, U and Sammour, A and Saleh, T and Al-Momani, H and Khasawneh, R and Al Shboul, S}, title = {Triple Viral Infections in Advanced Breast Cancer: Insights from a Three-Case Report and Literature Review.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, pmid = {39795579}, issn = {2075-4418}, support = {745/56/2022//Deanship of Scientific Research, The Hashemite University/ ; }, abstract = {Background and clinical significance: Viral infections are typically considered contributing or secondary factors in the development of breast cancer. Case presentation: This case report presents three instances of advanced breast cancer associated with triple viral infections. Case 1 involves a 78-year-old woman diagnosed with grade 2 invasive ductal carcinoma positive for HPV-18, CMV, and BLV. Case 2 describes a 39-year-old woman with grade 2 invasive ductal carcinoma, positive for HPV-16, CMV, and BLV. Case 3 is a 52-year-old woman with grade 3 invasive ductal carcinoma, positive for HPV-16, BLV, and MMTV. These cases suggest a possible correlation between viral co-infections and breast cancer aggressiveness, posing new questions about the role of viral infections in cancer development and prognosis. Conclusions: The findings contribute to growing evidence that viral infections may influence the progression and therapeutic response of breast cancer, warranting further investigation into targeted preventive measures including vaccinations.}, } @article {pmid39790830, year = {2024}, author = {Rajput, P and Datta, D and Aggarwal, D and Kushwah, R and Kumar, R}, title = {Atypical Presentation of Carcinoma Breast as Paraneoplastic Cerebellar Degeneration on [18F]FDG PET/CT.}, journal = {Indian journal of nuclear medicine : IJNM : the official journal of the Society of Nuclear Medicine, India}, volume = {39}, number = {4}, pages = {325-326}, pmid = {39790830}, issn = {0972-3919}, abstract = {Paraneoplastic neurological syndrome (PNS) represents a rare group of central nervous system disorders that are unrelated to direct tumor invasion or metastasis but may be triggered by an immune system reaction to a neoplasm or malignant tumor. In many patients, PNS is diagnosed before identifying the primary cancer. In such instances, positron emission tomography/computed tomography scan can assess individuals with suspected PNS enabling the detection of hidden malignancies. We share an interesting image of paraneoplastic cerebellar degeneration in a case of invasive ductal carcinoma breast.}, } @article {pmid39788307, year = {2025}, author = {Doan, VTH and Imai, T and Kawazoe, N and Chen, G and Yoshitomi, T}, title = {Regulation of antigen presentation and interleukin 10 production in murine dendritic cells via the oxidative stimulation of cell membrane using a polycation-porphyrin-conjugate-immobilized cell culture dish.}, journal = {Acta biomaterialia}, volume = {193}, number = {}, pages = {231-241}, doi = {10.1016/j.actbio.2025.01.004}, pmid = {39788307}, issn = {1878-7568}, mesh = {Animals ; *Dendritic Cells/cytology/metabolism/immunology/drug effects ; *Porphyrins/chemistry/pharmacology ; *Cell Membrane/metabolism/drug effects ; *Interleukin-10/biosynthesis ; Mice ; *Antigen Presentation/drug effects ; Polyelectrolytes ; Oxidation-Reduction ; *Cells, Immobilized/metabolism/cytology ; *Polyamines/chemistry/pharmacology ; }, abstract = {Tolerogenic dendritic cells with professional antigen presentation via major histocompatibility complex molecules, co-stimulatory molecules (CD80/86), and interleukin 10 production have attracted significant attention as cellular therapies for autoimmune, allergic, and graft-versus-host diseases. In this study, we developed a cell culture dish equipped with polycation-porphyrin-conjugate-immobilized glass (PA-HP-G) to stimulate immature murine dendritic cell (iDCs). Upon irradiation with a red light at 635 nm toward the PA-HP-G surface, singlet oxygen was generated by the immobilized porphyrins on the PA-HP-G surface. When iDCs were cultured on the PA-HP-G surface, moderate light irradiation generated lipid radicals without excessive generation of reactive oxygen species in the cytoplasm and nucleus, which led to the oxidative stimulation of the iDC cell membrane without cell death. Light irradiation changed the morphology of dendritic cells on the PA-HP-G surface to a tree-like structure with dendrites, accelerated their maturation, and enhanced the antigen-presenting ability for the ovalbumin peptide via major histocompatibility complex class I molecules. Additionally, the antigen-presenting dendritic cells on the PA-HP-G surface produced the anti-inflammatory cytokine interleukin 10 upon light irradiation. These results indicated that upon moderate light irradiation, the PA-HP-G surface regulated the maturation of iDCs into tolerogenic dendritic cells. STATEMENT OF SIGNIFICANCE: • Cell culture dish is developed for selective oxidative stimulus of cell membrane. • [1]O2 is generated from polycation/porphyrin-immobilized glass by light irradiation. • Lipid radicals are generated without generation of ROS in cytoplasm and nuclei. • Immature dendritic cells are maturated by oxidative stimulation of cell membrane. • Oxidative membrane stimulus enhances antigen-presentation and IL-10 secretion.}, } @article {pmid39781192, year = {2025}, author = {Liu, C and Xing, H}, title = {Occult breast cancer in an older woman: A case report.}, journal = {Experimental and therapeutic medicine}, volume = {29}, number = {2}, pages = {38}, pmid = {39781192}, issn = {1792-1015}, abstract = {Occult breast cancer (OBC) is a relatively rare clinical condition that can complicate differential diagnosis efforts and delay the administration of specific treatments. The individualized therapy of patients with OBC should be performed based on their clinical symptoms, imaging findings and pathological diagnosis. The present case study describes a 51-year-old woman with a painless left axillary tumor. The axillary lymph nodes of the patient were affected by invasive ductal carcinoma, as determined by histological analysis. However, the primary lesion was missed by numerous testing. The patient underwent surgery and testing for positron emission tomography/computed tomography (PET/CT). The present study comprehensively examined this case and offered a systematic analysis of the relevant scholarly works on the diagnosis, treatment and prognosis of OBC. Ultrasonography revealed the presence of three homogenous hypoechoic masses with irregular margins in the left axilla of the patient. PET/CT scanning identified multiple enlarged left axillary hypermetabolic lymph nodes. After that, the patient underwent a nipple-sparing mastectomy and an axillary lymphadenectomy. With the lymph nodes showing metastatic, infiltrating ductal carcinoma from the breast, ductal carcinoma in situ of the breast diagnosis was supported by a histological examination. Immunohistochemical staining revealed that resected lymph nodes were positive for both estrogen and progesterone receptors, consistent with the status of the breast as the primary tumor site. Following surgery, the patient underwent adjuvant chemotherapy treatment. At 12 months post-surgery, the patient remained well without evidence of disease. OBC cases lack the typical clinical and imaging findings associated with breast cancer, and a combination of axillary lymph node examination and immunohistochemistry is essential for accurately diagnosing affected patients. Ensuring the best patient outcomes necessitates accurate and prompt diagnosis, achieved by thorough physical examination, cautious utilization of diagnostic tools, personalized surgical interventions and histological investigation.}, } @article {pmid39779351, year = {2025}, author = {Gao, Y and Wang, J and Wang, S and Tao, W and Duan, R and Hao, J and Gao, M}, title = {Development and validation of a nomogram to predict survival after neoadjuvant chemotherapy in elderly women with triple-negative invasive ductal breast cancer: A SEER population-based study.}, journal = {Saudi medical journal}, volume = {46}, number = {1}, pages = {43-51}, pmid = {39779351}, issn = {1658-3175}, mesh = {Humans ; Female ; *Nomograms ; Aged ; *Neoadjuvant Therapy ; *SEER Program ; *Triple Negative Breast Neoplasms/drug therapy/mortality/pathology ; Carcinoma, Ductal, Breast/drug therapy/mortality/pathology ; Aged, 80 and over ; Chemotherapy, Adjuvant ; Survival Rate ; }, abstract = {OBJECTIVES: To construct and verify a nomogram for post-neoadjuvant chemotherapy survival predication in elderly women with triple-negative invasive ductal breast cancer.

METHODS: Elderly patients diagnosed as triple-negative invasive ductal breast cancer between 2019-2000 were screened from surveillance, epidemiology, and end results database. Depending on the post-neoadjuvant chemotherapy pathological response, they were assigned to the complete or non-complete response group. Inter-group clinicopathological characteristics and disease-specific and overall survivals were compared. Then, they were allocated randomly into the training or validation cohort. A prediction nomogram was developed in the training cohort and verified in the validation cohort.

RESULTS: A total of 382 patients were included, with 285 patients in non-response group and 97 patients in response group. After propensity score matching, disease-specific survival showed a significant difference between response and non-response groups (88.7% versus 64.6%, p<0.001). The training cohort included 196 patients and the validation cohort included 82 patients. A total of 7 variables (age, race, tumor location, tumor-node-metastasis stage, summary stage, receipt of surgery, and response to neoadjuvant chemotherapy) were integrated to construct a survival prediction nomogram. The C-indexes were 0.756 in the training cohort and 0.791 in the validation cohort. In both cohorts, the predicted survival showed satisfactory coherence with the actual survival in the calibration curve analysis.

CONCLUSION: In elderly women with triple-negative invasive ductal breast cancer, post-neoadjuvant chemotherapy pathological complete response could indicate improved disease-specific survival. A novel survival prediction nomogram was created to have satisfactory performance in these patients.}, } @article {pmid39776839, year = {2024}, author = {Liang, R and Lian, J and Zhang, J and Jing, J and Bian, J and Xu, J and He, X and Yu, S and Zhou, Q and Jiang, J}, title = {The benefits of contrast-enhanced ultrasound in the differential diagnosis of suspicious breast lesions.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1511200}, pmid = {39776839}, issn = {2296-858X}, abstract = {BACKGROUND: Contrast-enhanced ultrasound (CEUS) shows potential for the differential diagnosis of breast lesions in general, but its effectiveness remains unclear for the differential diagnosis of lesions highly suspicious for breast cancers.

OBJECTIVE: This study aimed to evaluate the diagnostic value of CEUS in differentiating pathological subtypes of suspicious breast lesions defined as category 4 of US-BI-RADS.

METHODS: The dataset of 150 breast lesions was prospectively collected from 150 patients who underwent routine ultrasound and CEUS examination and were highly suspected of having breast cancers. All lesions were pathologically confirmed by US-guided needle biopsy and surgery. The qualitative features and the quantitative parameters of CEUS of these breast lesions were analyzed. The CEUS and biopsy examinations were performed after informed consent.

RESULTS: In the qualitative features, crab clam-like enhancement, the presence of more than two enhanced vessels within lesions, and surrounding enriched vessels inserting into lesions were able to differentiate atypical fibroadenomas (FIB) and mass-like non-puerperal mastitis (NPM) from invasive ductal carcinomas (IDC) and ductal carcinomas in situ (DCIS) (p < 0.05). The enlarged scope, irregular shape, and perfusion deficiency were valuable to the differential diagnosis of FIB from the others (p < 0.05). In the four quantitative parameters of CEUS, only the peak intensity (IMAX) contributed to the differential diagnosis between malignant and benign tumors (p < 0.05, ROCAUC: 0.61, sensitivity: 60.4% and specificity: 65.9%, accuracy: 62.1%). However, IMAX did not show any difference in the paired comparison of IDC, DCIS, FIB, and NPM (p > 0.05). The logistic regression analysis results showed that heterogeneous perfusion, crab clam-like enhancement, and partial_ IMAX were independent risk factors for benign and malignant breast lesions (p < 0.05). The area under a receiver operating characteristic of the integrated model was 0.89. In the diagnosis of benign and malignant pathological subtypes of breast lesions, independent risk factors and integrated models had no statistical significance in the diagnosis of IDC and DCISs, FIB, and NPM (p > 0.05).

CONCLUSION: Some qualitative risk features of CEUS can distinguish malignant breast lesions from NPM and atypical FIB with a high score of US-BI-RADS, aiding physicians to reduce the misdiagnosis of suspicious breast lesions in clinical practice.}, } @article {pmid39773413, year = {2025}, author = {Ben-David, BM and Bressler, TE and Ring, L and Shimon-Raz, O and Palgi, Y}, title = {Trauma echoes: factors associated with peritraumatic distress and anxiety five days following Iranian missile attack on Israel.}, journal = {European journal of psychotraumatology}, volume = {16}, number = {1}, pages = {2446070}, pmid = {39773413}, issn = {2000-8066}, mesh = {Humans ; Israel/epidemiology ; Female ; Male ; *Stress Disorders, Post-Traumatic/epidemiology ; Iran ; Middle Aged ; Adult ; *Anxiety Disorders/epidemiology ; Prevalence ; Anxiety/epidemiology/psychology ; Aged, 80 and over ; Aged ; }, abstract = {Introduction: On 13-14 April 2024, Iran launched ∼300 drones and missiles at Israel, in an unprecedented attack. As most studies examine the effects of trauma months or years later, less is known about its effects days later. To fill this gap, this study gauged the population response, five days after the attack. Specifically, we examined the prevalence and factors associated with two precursors for later development of PTSD, peritraumatic distress (PD) and generalized anxiety disorder (GAD).Methods: Five-hundred and fifty-three participants (Mage = 57.51, SD = 13.67 years, range [30-90], 48.3% females) reported their distal and proximal exposure to traumatic events, probable PTSD due to Israel-Hamas-War, sleeping troubles, and media information consumption during the event.Results: Logistic regressions indicated that, after adjusting for demographics, clinical levels of PD and GAD (respectively, using the accepted cutoffs) were significantly linked to probable PTSD due to the Israel-Hamas War (PD:OR = 4.066, 95%CI: 2.236-7.393, p < .001; GAD:OR = 2.397, 95%CI: 1.285-4.471, p = .006), sleeping troubles (PD:OR = 1.248, 95%CI: 1.186-1.314, p < .001; GAD:OR = 1.325, 95%CI: 1.242-1.413, p < .001) and media consumption (PD:OR = 1.442, 95%CI:1.17-1.777, p = .001; GAD:OR = 1.515, 95%CI: 1.144-2.007, p = .004), but not to previous trauma (life-long exposure or Israel-Hamas war).Discussion: Results suggest that previous psychopathology, stress-related reactions (sleeping) and actions (media consumption), rather than previous exposures to traumatic events are the primary indices related to PD and GAD in the first days after exposure to war-related traumatic events. Findings highlight the importance of early detection of reactions and symptoms following trauma exposure. The main limitation of the study is its cross-sectional design. Future longitudinal studies are needed to understand the developmental trajectory of these effects.}, } @article {pmid39750113, year = {2025}, author = {Kim, DHS and Sonni, I and Grogan, T and Sisk, A and Murthy, V and Hsu, W and Sung, K and Lu, DS and Reiter, RE and Raman, SS}, title = {Quantitative 3-T Multiparametric MRI Parameters as Predictors of Aggressive Prostate Cancer.}, journal = {Radiology. Imaging cancer}, volume = {7}, number = {1}, pages = {e240011}, pmid = {39750113}, issn = {2638-616X}, support = {UL1 TR001881/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Prostatic Neoplasms/diagnostic imaging/pathology/surgery ; Male ; *Multiparametric Magnetic Resonance Imaging/methods ; Retrospective Studies ; Middle Aged ; Prostatectomy/methods ; Predictive Value of Tests ; Aged ; Prostate/diagnostic imaging/pathology ; }, abstract = {Purpose To determine which quantitative 3-T multiparametric MRI (mpMRI) parameters correlate with and help predict the presence of aggressive large cribriform pattern (LCP) and intraductal carcinoma (IDC) prostate cancer (PCa) at whole-mount histopathology (WMHP). Materials and Methods This retrospective study included 130 patients (mean age ± SD, 62.6 years ± 7.2; 100% male) with 141 PCa lesions who underwent preoperative prostate 3-T mpMRI, radical prostatectomy, and WMHP between January 2019 and December 2022. Lesions at WMHP were matched to 3-T mpMRI lesions with American College of Radiology Prostate Imaging Reporting and Data System version 2.1 scores of at least 3 or higher, and the following parameters were derived: apparent diffusion coefficient (ADC), volume transfer constant, rate constant, and initial area under the curve (iAUC). Each lesion was categorized into three subcohorts with increasing aggressiveness: LCP negative and IDC negative (subcohort 1), LCP positive and IDC negative (subcohort 2), and LCP positive and IDC negative (subcohort 3). Analysis of variance was performed to assess differences, Jonckheere test was performed to establish trends, and a classification and regression tree (CART) was used to establish a prediction model. Results Of the 141 total lesions, there were 41 (29.1%), 49 (34.8%), and 51 (36.2%) lesions in subcohorts 1, 2, and 3, with mean ADCs of 892 × 10[-6] mm[2]/sec ± 20, 826 × 10[-6] mm[2]/sec ± 209, and 763 × 10[-6] mm[2]/sec ± 163 (P = .007) and mean iAUCs of 5.4 mmol/L/sec ± 2.5, 6.7 mmol/L/sec ± 3.0, and 6.9 mmol/L/sec ± 3.5 (P = .04), respectively. ADC was negatively correlated (P = .004), and rate constant and iAUC were positively correlated (P = .048 and P = .04, respectively) with increasing histologic PCa aggressiveness. The CART model correctly allocated 39.0%, 24.5%, and 84.3% of PCa lesions to subcohorts 1, 2, and 3, respectively. Conclusion Quantitative 3-T mpMRI parameters significantly correlated with and helped predict aggressive LCP and IDC PCa at WMHP. Keywords: Prostate, MRI, Pathology © RSNA, 2025.}, } @article {pmid39749029, year = {2024}, author = {Liu, H and Zhao, G and Fan, Z and Wu, D and Qu, F}, title = {Metaplastic carcinoma of the breast containing three histological components: a case report.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1470986}, pmid = {39749029}, issn = {2234-943X}, abstract = {Malignant breast tumors mainly arise from the ductal and lobular epithelium, whereas sarcomas, which originate from the stromal tissues of the breast, account for less than 5% of cases. Mostly, these tumors consist of a single tissue type, rendering malignant breast tumors with three distinct tissue types exceedingly rare. We report a unique case of a malignant breast tumor comprising three tissue types: squamous cell carcinoma (approximately 25%), invasive ductal carcinoma (approximately 5%), and fibrosarcoma (approximately 70%). Given the case's rarity, pre-operative imaging and tumor biopsy failed to yield definitive diagnostic information, we detail the patient's clinical and therapeutic process, providing insights for physicians on clinical diagnosis and treatment.}, } @article {pmid39741975, year = {2024}, author = {Ayoub, Y and Cheung, SM and Maglan, B and Senn, N and Chan, KS and He, J}, title = {Differentiation of histological calcification classifications in breast cancer using ultrashort echo time and chemical shift-encoded imaging MRI.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1475090}, pmid = {39741975}, issn = {2234-943X}, abstract = {INTRODUCTION: Ductal carcinoma in situ (DCIS) accounts for 25% of newly diagnosed breast cancer cases with only 14%-53% developing into invasive ductal carcinoma (IDC), but currently overtreated due to inadequate accuracy of mammography. Subtypes of calcification, discernible from histology, has been suggested to have prognostic value in DCIS, while the lipid composition of saturated and unsaturated fatty acids may be altered in de novo synthesis with potential sensitivity to the difference between DCIS and IDC. We therefore set out to examine calcification using ultra short echo time (UTE) MRI and lipid composition using chemical shift-encoded imaging (CSEI), as markers for histological calcification classification, in the initial ex vivo step towards in vivo application.

METHODS: Twenty female patients, with mean age (range) of 57 (35-78) years, participated in the study. Intra- and peri-tumoural degree of calcification and peri-tumoural lipid composition were acquired on MRI using UTE and CSEI, respectively. Ex vivo imaging was conducted on the freshly excised breast tumour specimens immediately after surgery. Histopathological analysis was conducted to determine the calcification status, Nottingham Prognostic Index (NPI), and proliferative activity marker Ki-67.

RESULTS: Intra-tumoural degree of calcification in malignant classification (1.05 ± 0.13) was significantly higher (p = 0.012) against no calcification classification (0.84 ± 0.09). Peri-tumoural degree of calcification in malignant classification (1.64 ± 0.10) was significantly higher (p = 0.033) against no calcification classification (1.41 ± 0.18). Peri-tumoural MUFA in malignant classification (0.40 ± 0.01) was significantly higher (p = 0.039) against no calcification classification (0.38 ± 0.02). Ki-67 showed significant negative correlation against peri-tumoural MUFA (p = 0.043, ρ = -0.457), significant positive correlation against SFA (p = 0.008, ρ = 0.577), and significant negative correlation against PUFA (p = 0.002, ρ = -0.653).

CONCLUSION: The intra- and peri-tumoural degree of calcification and peri-tumoural MUFA are sensitive to histological calcification classes supporting future investigation into DCIS prognosis.}, } @article {pmid39734136, year = {2025}, author = {Huws, AM and Davies, GR and Lewis, PD and Morgan, C}, title = {Comparison of Systemic Inflammatory Indices With the Oncotype DX Recurrence Score and the Nottingam Prognostic Index in Early Hormone Receptor Positive Ductal Breast Cancer.}, journal = {Clinical breast cancer}, volume = {25}, number = {4}, pages = {358-367}, doi = {10.1016/j.clbc.2024.11.022}, pmid = {39734136}, issn = {1938-0666}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/genetics/immunology/blood ; Middle Aged ; *Neoplasm Recurrence, Local/pathology/epidemiology/immunology/genetics ; Prognosis ; Retrospective Studies ; *Carcinoma, Ductal, Breast/pathology/genetics/immunology ; Aged ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; *Biomarkers, Tumor ; *Inflammation/blood ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; }, abstract = {BACKGROUND: Adjuvant therapy decisions in hormone receptor positive, HER2 negative breast cancer are evolving. Gene panel testing has reduced the number of patients recommended for chemotherapy by up to two thirds. Identifying low risk genomic cases before testing could represent a significant economic impact. Systemic inflammatory indices have shown promise as prognostic markers in early breast cancer. We investigated the utility of four systemic inflammatory indices with the Nottingham Prognostic Index to predict the Oncotype DX® recurrence scores threshold level (low or high score), in women aged 50 and over with node negative invasive ductal carcinoma of the breast.

METHODS: A retrospective review of 245 patients with Oncotype DX® Recurrence Score testing from 2007 to 2021 were identified. The Nottingham Prognostic Index and systemic inflammatory indices ratios were estimated from histology results and preoperative peripheral blood samples respectively.

RESULTS: 22.4% of the cohort had a Recurrence Score in the higher risk group. This group had a greater percentage of grade 3 tumours, progesterone receptor negativity, higher Nottingham Prognostic Scores, and inflammatory indices ratios than the lower risk group. A decision tree incorporating the Neutrophil Lymphocyte Ratio with clinicopathological features showed potential as an indicator of a high Oncotype DX® RS score, such that further investigation is warranted to assess whether Recurrence Score testing could be triaged in certain cohorts of patients. In this study, 38% of patients might be able to avoid genomic testing based on the decision tree analysis.

CONCLUSION: Utility of inflammatory indices with clinicopathological features may help triage gene panel testing.}, } @article {pmid39733775, year = {2025}, author = {Bistika, M and Marangelo, A and Ascione, F and Valentini, N and Fedeli, F and Schrader, J and Modena, D and Steinkühler, C and Pellegata, NS}, title = {The Novel SSTR3 Full Agonist ITF2984 Shows Antitumor Properties against Pancreatic Neuroendocrine Tumors.}, journal = {Neuroendocrinology}, volume = {115}, number = {5}, pages = {446-459}, doi = {10.1159/000543136}, pmid = {39733775}, issn = {1423-0194}, mesh = {*Receptors, Somatostatin/agonists/metabolism ; Humans ; *Pancreatic Neoplasms/drug therapy/metabolism/pathology ; *Neuroendocrine Tumors/drug therapy/metabolism/pathology ; *Antineoplastic Agents/pharmacology/therapeutic use ; *Somatostatin/analogs & derivatives/pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Apoptosis/drug effects ; }, abstract = {BACKGROUND: Somatostatin analogs (SSAs) binding to and activating somatostatin receptors (SSTRs) have been extensively used for the treatment of neuroendocrine tumors (NETs). The currently approved synthetic SSAs have high affinity for SSTR2 (octreotide/lanreotide) or for SSTR2 and SSTR5 (pasireotide). These agents have shown symptom control and antiproliferative effects in subsets of NET patients and this was associated with the expression of the targeted SSTRs. Pancreatic NETs (Pan-NETs) are uncommon tumors with a propensity to metastasize. For unresectable advanced Pan-NETs expressing SSTRs, SSAs are the first-line medical therapy. Pan-NETs express mainly SSTR1, SSTR2, and SSTR3 and thus should respond to agonists targeting SSTR3.

SUMMARY: We evaluated the efficacy of ITF2984, a novel multireceptor agonist with specificity for SSTR3, against Pan-NET cells representative of well-differentiated, functioning tumors, and expressing high levels of SSTR3. The effect of ITF2984 on cell proliferation/viability and on its ability to promote apoptosis and suppress hormone secretion was evaluated in 2D and 3D organotypic culture systems. Pasireotide was tested in parallel for comparative purposes.

KEY MESSAGE: We found that ITF2984 is as effective as pasireotide at inhibiting both proliferation/viability and hormone secretion, as well as at inducing apoptosis of Pan-NET cells grown as both 2D monolayers and 3D spheroids. High-dose ITF2984 elicits structural alterations in Pan-NET 3D spheroids compatible with cell death more effectively than pasireotide. Altogether, ITF2984 may represent a useful alternative to pasireotide for the medical treatment of Pan-NETs and other tumors with elevated SSTR3 expression.}, } @article {pmid39730784, year = {2025}, author = {Qi, M and Gao, S and Zhang, Z and Lang, R and Huang, Z and Wang, J and Qian, X and Chen, K and Liu, H}, title = {Secretory breast carcinoma: a multicenter clinicopathologic study of 80 cases with emphasis on prognostic analysis and chemotherapy benefit.}, journal = {Breast cancer research and treatment}, volume = {210}, number = {2}, pages = {451-461}, pmid = {39730784}, issn = {1573-7217}, mesh = {Humans ; Female ; Middle Aged ; Prognosis ; Adult ; *Breast Neoplasms/pathology/mortality/drug therapy ; Aged ; Neoplasm Staging ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Triple Negative Breast Neoplasms/pathology/drug therapy/mortality ; Chemotherapy, Adjuvant ; Kaplan-Meier Estimate ; *Carcinoma, Ductal, Breast/pathology/drug therapy/mortality ; Retrospective Studies ; }, abstract = {PURPOSE: To investigate clinicopathologic characteristics and prognosis in secretory breast carcinoma (SBC) and to determine chemotherapy benefits stratified by different subgroups.

METHODS: SBCs and triple-negative invasive ductal carcinoma patients (TN-IDCs) were enrolled from three cancer centers between January 2011 and December 2020. SBCs were further divided into two subgroups: those with triple negativity (TN-SBCs) and those without (non-TN-SBCs). Clinicopathologic characteristics were thoroughly compared among the three subgroups associated with triple negativity. Kaplan-Meier estimates and Cox proportional hazard models were performed for survival analysis.

RESULTS: A total of 80 SBCs and 310 TN-IDCs were included in the study. The TN-SBC subgroup consisted of 35 individuals (43.75%) with mild clinical behaviors and a satisfying prognosis in comparison to non-TN-SBCs and TN-IDCs. In SBCs, N stage (N1 vs. N0: HR = 11.176, 95% CI 0.843-148.132, p = 0.067; N2-3 vs. N0: HR = 30.409, 95% CI 1.378-671.169, p = 0.031), LNR (HR = 23.894, 95% CI 1.614-353.835, p = 0.021), and histological grade (HR = 28.634, 95% CI 2.745-298.703, p = 0.005) were significantly correlated with disease-free survival (DFS). Patients in high LNR group receiving chemotherapy achieved a prolonged DFS (p = 0.025), while chemotherapy did not confer a survival benefit in TN-SBCs of our interest (p = 0.12).

CONCLUSION: TN-SBC is a unique entity with low malignant potential. Advanced N stage, high LNR, and advanced histological grade are adverse determinants of DFS in SBC. Adjuvant chemotherapy provides superior DFS in high LNR SBCs rather than TN-SBCs, hence it is recommended for high LNR SBCs.}, } @article {pmid39724992, year = {2025}, author = {Wang, Y and Zhang, J and Wang, Y and Liu, Y and Shi, B and Li, X and He, J and Zhang, H}, title = {Lower expression of MMP2, FLNA, and CFL1 is correlated with favorable prognosis in invasive micropapillary breast cancer.}, journal = {Gene}, volume = {940}, number = {}, pages = {149192}, doi = {10.1016/j.gene.2024.149192}, pmid = {39724992}, issn = {1879-0038}, mesh = {Humans ; *Breast Neoplasms/genetics/pathology/metabolism/mortality ; Female ; Prognosis ; *Matrix Metalloproteinase 2/genetics/metabolism ; *Filamins/genetics/metabolism ; Middle Aged ; Biomarkers, Tumor/genetics ; Gene Expression Regulation, Neoplastic ; Retrospective Studies ; *Carcinoma, Papillary/genetics/pathology/metabolism/mortality ; *Carcinoma, Ductal, Breast/genetics/pathology ; Nomograms ; Aged ; }, abstract = {PURPOSE: Despite its recognized aggressive clinical manifestations, invasive micropapillary carcinoma has a controversial prognosis in comparison to invasive ductal carcinoma of the breast. This retrospective study aimed to explore the prognosis and underlying molecular mechanisms of invasive micropapillary carcinoma.

METHODS: Through the SEER database, we compared patients survival outcomes with invasive micropapillary carcinoma versus invasive ductal carcinoma, and developed a nomogram to predict the overall survival of the former group. We explored gene profiles of invasive micropapillary carcinoma in the GEO database. Hub genes were identified as the top ten genes in the PPI network with the highest degrees of connectivity, and three of them were selected for validation by immunohistochemistry.

RESULTS: Invasive micropapillary carcinoma patients had better overall survival and breast cancer-specific survival than invasive ductal carcinoma patients did. Multivariate analysis revealed age, marital status, TN stage, ER status, and chemotherapy as independent prognostic factors for invasive micropapillary carcinoma patients, which were used to construct a nomogram with good performance. A total of 294 DEGs were identified, with ten hub genes, including MMP2, FLNA and CFL1, which were expressed at lower levels in invasive micropapillary carcinoma patients than in invasive ductal carcinoma patients, indicating favorable outcomes.

CONCLUSIONS: Patients with invasive micropapillary carcinoma generally have a better prognosis than those with invasive ductal carcinoma does, which could be attributed to the lower expression of pro-oncogenic genes in the former group; however, the underlying mechanism needs further investigation.}, } @article {pmid39724567, year = {2025}, author = {Yang, M and Wang, C and Ouyang, L and Zhang, H and Lin, J}, title = {Establishment of prognostic model for invasive ductal carcinoma with distant metastasis within the triple-negative breast cancer: a SEER population-based study.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {34}, number = {5}, pages = {392-404}, doi = {10.1097/CEJ.0000000000000925}, pmid = {39724567}, issn = {1473-5709}, mesh = {Humans ; *Triple Negative Breast Neoplasms/pathology/mortality/therapy ; Female ; SEER Program/statistics & numerical data ; *Nomograms ; Retrospective Studies ; Prognosis ; Middle Aged ; *Carcinoma, Ductal, Breast/mortality/secondary/therapy/pathology ; Aged ; Adult ; Risk Factors ; Follow-Up Studies ; *Bone Neoplasms/secondary ; *Liver Neoplasms/secondary ; Survival Rate ; }, abstract = {Triple-negative breast cancer (TNBC) is a complex and diverse group of malignancies. Invasive ductal carcinoma (IDC) is the predominant pathological subtype and is closely linked to the ominous potential for distant metastasis, a pivotal factor that significantly influences patient outcomes. In light of these considerations, the present study was conceived with the objective of developing a nomogram model. This model was designed to predict the prognosis observed in IDC with distant metastasis in TNBC. This was a retrospective study based on the SEER database. Data of 9739 IDC-TNBC patients diagnosed from 2010 to 2020 were included in our study. Independent risk factors were screened by univariate and multivariate Cox regression analyses successively, which were used to develop a nomogram model predicting for prognosis. Cox multivariable analysis showed statistical significance in bone metastasis, liver metastasis, surgery, and chemotherapy. Incorporating statistically significant variables, as well as clinically significant age, lung metastasis, and brain metastasis into the construction of the prediction model, the C-indexes of the training group and validation group were 0.702 (0.663-0.741) and 0.667 (0.600-0.734), respectively, while the calibration curves were all close to the eideal 45° reference line, and decision curve analysis curves show excellent net benefit in the predictive model. The prognostic prediction model developed in this study demonstrated enhanced predictive accuracy, enabling a more precise evaluation of mortality risks associated with IDC with distant metastasis in TNBC.}, } @article {pmid39723668, year = {2025}, author = {Mitsa, G and Florianova, L and Lafleur, J and Aguilar-Mahecha, A and Zahedi, RP and Del Rincon, SV and Basik, M and Borchers, CH and Batist, G}, title = {Clinical Proteomics Reveals Vulnerabilities in Noninvasive Breast Ductal Carcinoma and Drives Personalized Treatment Strategies.}, journal = {Cancer research communications}, volume = {5}, number = {1}, pages = {138-149}, pmid = {39723668}, issn = {2767-9764}, mesh = {Humans ; Female ; *Proteomics/methods ; *Breast Neoplasms/metabolism/pathology/therapy/genetics ; *Precision Medicine/methods ; *Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology/therapy/genetics ; *Biomarkers, Tumor/metabolism ; *Proteome ; }, abstract = {ABSTRACT: Ductal carcinoma in situ (DCIS) is the most common type (80%) of noninvasive breast lesions in women. The lack of validated prognostic markers, limited patient numbers, and variable tissue quality have a significant impact on the diagnosis, risk stratification, patient enrollment, and results of clinical studies. In this study, we performed label-free quantitative proteomics on 50 clinical formalin-fixed, paraffin-embedded biopsies, validating 22 putative biomarkers from independent genetic studies. Our comprehensive proteomic phenotyping reveals more than 380 differentially expressed proteins and metabolic vulnerabilities, which can inform new therapeutic strategies for DCIS and invasive ductal carcinoma. Due to the readily druggable nature of proteins and metabolic enzymes or metabolism inhibitors, this study is of high interest for clinical research and the pharmaceutical industry. To further evaluate our findings, and to promote the clinical translation of our study, we developed a highly multiplexed targeted proteomics assay for 90 proteins associated with cancer metabolism, RNA regulation, and signature cancer pathways, such as PI3K/AKT/mTOR and EGFR/RAS/RAF.

SIGNIFICANCE: This study provides real-world evidence for DCIS, a disease for which currently no molecular tools or biomarkers exist, and gives an unbiased, comprehensive, and deep proteomic profile, identifying >380 actionable targets.}, } @article {pmid39721789, year = {2024}, author = {Nagahara, M and Tezuka, K}, title = {[Invasive Ductal Carcinoma with Total Infarction and Necrosis-Case Report and Literature Review].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {12}, pages = {1255-1258}, pmid = {39721789}, issn = {0385-0684}, mesh = {Humans ; Female ; Aged ; *Necrosis ; *Breast Neoplasms/pathology/complications/surgery ; *Infarction/etiology/pathology ; *Carcinoma, Ductal, Breast/complications/pathology/surgery ; Mastectomy ; }, abstract = {A 71-year-old woman visited our hospital with pain and itching in her left breast which had commenced the day before admission. On palpation, we detected a 2.0 cm nodule, indicative of an elastic and hard tumor located centrally in the left breast. Mammography revealed an oval, microlobulated mass in the central quadrant of the left breast. Ultrasonography indicated a 1.5×1.3 cm hypoechoic lesion at the 12 o'clock position near the left nipple. Core needle biopsy revealed an invasive ductal carcinoma. Therefore, we mastectomized the left breast. Histologically, the tumor mass exhibited total necrosis, with viable carcinoma cells detected in a paramammary lymph node at the resected breast edge. Consequently, the tumor was diagnosed as a solid tubular carcinoma with total infarction and necrosis. Here, we present a rare case of breast cancer associated with infarction and necrosis.}, } @article {pmid39715246, year = {2024}, author = {Zhang, W and Huang, Y and Zhou, Y and Xue, J and Gao, S and Kang, L and Shi, J and Zhou, T and Duan, Y and Guo, S and Li, Q}, title = {Delving into female breast cancer: Distinct disease-specific survival outcomes between invasive lobular and ductal carcinomas revealed by propensity score matching.}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0300116}, pmid = {39715246}, issn = {1932-6203}, mesh = {Humans ; Female ; *Breast Neoplasms/mortality/pathology/therapy ; *Propensity Score ; *Carcinoma, Lobular/mortality/pathology/therapy ; Middle Aged ; Retrospective Studies ; *Carcinoma, Ductal, Breast/mortality/pathology ; Prognosis ; Aged ; SEER Program ; Adult ; Survival Analysis ; }, abstract = {PURPOSE: The difference in prognosis between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) is still controversial in the academic community. Resolving this controversy can help to more accurately determine patients' prognosis, provide further personalized treatment, alleviate unnecessary psychological burden for some patients, and provide direction for further fundamental research.

PATIENTS AND METHODS: A retrospective cohort study was conducted using the SEER Research Plus Data 8 Registries, Nov 2021 sub (1978-2019), including female breast cancer patients diagnosed with ILC or IDC between 2010 and 2015. Univariate and multivariate Cox regression analyses were performed, and key covariates affecting prognosis were selected. Propensity score matching (PSM) was employed to match patients, and balance tests were conducted to evaluate covariate distribution. Disease-specific survival (DSS) differences between the matched IDC and ILC groups were compared.

RESULTS: Following PSM, the covariate differences between the IDC and ILC groups were significantly reduced. The survival analysis revealed a significantly better prognosis for the IDC group than the ILC group (Log-rank test p < 0.001), with a 28.0% increased risk observed in the ILC group.

CONCLUSION: This study provides evidence supporting the existence of significant differences in prognosis between IDC and ILC patients after rigorous matching. The IDC group displayed a significantly better prognosis than the ILC group. Notably, these findings have implications for personalized treatment in clinical practice and contribute to the ongoing academic debate on survival differences between IDC and ILC. However, further research is needed to investigate the biological mechanisms, gene expression, and signaling pathway disparities between IDC and ILC, aiming to provide more targeted guidance for clinical decision-making.}, } @article {pmid39712753, year = {2024}, author = {Sandhya, A and Fahim, M and Kulanathan, A and Tansie, A}, title = {Incidence of a Positive Sentinel Lymph Node Biopsy in Screen-Detected Early Breast Cancer.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e74250}, pmid = {39712753}, issn = {2168-8184}, abstract = {Introduction Current guidelines advocate for a sentinel lymph node biopsy (SLNB) in patients with invasive breast cancer with negative axillary ultrasonography. However, emerging evidence has contradicted this, and SLNB omission has been found to be non-inferior in selected low-risk breast cancers. This retrospective study aimed to evaluate the incidence of SLNB in screen-detected invasive breast cancer. The secondary outcome was to identify risk factors in patients with positive SLNB and further axillary disease. Methods All screen-detected histologically confirmed invasive breast cancer and no evidence of spread to ipsilateral axillary lymph nodes (LNs) on ultrasound scans referred from screening between January 2018 and December 2019 were included in the study. All patients underwent surgical excision of the tumor as either breast conservation surgery or mastectomy, along with sentinel node biopsy. SLNB was performed using the dual technique of radioactive dye and blue dye. Results One hundred forty-nine patients were included in the study, all of whom were females. The mean patient age was 61.9 years old, with the majority 65 (43.6%) of the patients being in their 60s. Breast-conserving surgery (BCS) was performed in 138 (92.6%) patients. Eighty (53.7%) patients presented with right breast cancer. The mean size of invasive cancer was 15 mm. The mean total tumor size, including invasive and in situ, was 20.9 mm. One hundred twenty-seven (85.2%) patients had unifocal presentations, 69 (46.3%) of tumor foci were in the upper outer quadrant (UOQ), 122 (81.9%) of all tumors were ductal carcinoma, 81 (54.4%) patients had histologically grade 2 carcinomas, 135 (90.6%) of all patient tumors were ER-positive, HER2-negative, and six (4%) were ER-positive, HER2-positive. Twelve (8.05%) out of 149 included patients had positive sentinel LN biopsy. Of those 12 patients, eight (66.7%) had one to two nodes sampled, three (25%) had three to four nodes, and one (8.3%) had five or more nodes sampled. Out of 12 positive SNB patients, 11 had completed axillary node clearance (ANC) as per the National Institute for Health and Care Excellence (NICE) guidelines: nine (81.8%) had no further disease, and two (18.2%) had four positive nodes. The mean number of nodes taken in ANC was 15.8 ± 11.5. Of the two patients with positive axillary disease, one had BCS, and the other had a mastectomy. Both were grade 3 IDC, and the mean size was 57.5 mm. Nine patients died within four years of diagnosis, with four due to distant breast metastasis. Conclusion Only 8% of patients had positive SLNB in screen-detected breast cancer, which may support the previous studies of omitting SLNB being non-inferior but only in selected postmenopausal small early breast cancers with normal axillary ultrasound in the absence of any other risk factors. However, close follow-up will be required for disease-free survival, overall survival, and locoregional recurrence in this cohort.}, } @article {pmid39710328, year = {2025}, author = {Denimal, L and Klein, C and Capon, G and Alezra, E and Bernhard, JC and Estrade, V and Blanc, P and Bladou, F and Robert, G}, title = {Impact of clean intermittent self-catheterization and indwelling catheterization on perioperative outcomes in patients with urinary retention undergoing BPH surgery: A comparative monocentric retrospective study.}, journal = {The French journal of urology}, volume = {35}, number = {1}, pages = {102851}, doi = {10.1016/j.fjurol.2024.102851}, pmid = {39710328}, issn = {2950-3930}, mesh = {Humans ; Male ; *Urinary Retention/etiology/therapy ; *Prostatic Hyperplasia/surgery/complications ; Retrospective Studies ; Aged ; *Catheters, Indwelling/adverse effects ; Treatment Outcome ; Postoperative Complications/epidemiology/etiology ; Middle Aged ; *Intermittent Urethral Catheterization/methods ; Aged, 80 and over ; *Prostatectomy ; Urinary Catheterization ; Self Care ; }, abstract = {INTRODUCTION AND OBJECTIVES: In case of acute urinary retention (AUR) due to benign prostatic hyperplasia (BPH) first trial without catheter (TWOC) may fail in about 30% of cases. In this situation most of patients have to keep an indwelling catheter (IDC) or to perform clean intermittent self-catheterization (CISC) until surgery. Although CISC has shown several advantages over IDC in neurologic patients, it is barely proposed in case of acute or chronic urinary retention due to BPH and comparative data on the outcomes of BPH surgery are very sparse. The aim of this study was to evaluate peri-operative outcomes of BPH surgery depending on the type of urinary drainage (IDC or CISC) in a population of patients with acute or chronic urinary retention and TWOC failure.

PATIENTS AND METHOD: We retrospectively analyzed a prospectively maintained database on BPH surgery to retrieve the records of all men admitted for surgical treatment of BPH following acute or chronic urinary retention with TWOC failure over a one-year period of time (January to December 2022). Two groups were constituted depending on the type of urinary drainage at the time of surgery (IDC or CISC). Peri-operative outcomes were compared between groups regarding pre-operative urine culture, antibiotic consumption, post-operative complications, length of hospital stay, and spontaneous voiding after catheter removal.

RESULTS: Between January and December 2022, 59 patients underwent BPH surgery after urinary retention and TWOC failure. At the time of surgery, 28 patients were on IDC (47%) and 31 patients were on CISC (53%). Despite a shorter delay between AUR and surgery in the IDC group (42days vs. 80days, P<0.01), patients had a significantly higher rate of pre-operative positive urine culture (100% vs. 51.6%, P<0.01), received antibiotics more frequently (93% vs. 42%, P<0.01), had a higher rate of post-operative complications (50% vs. 13%, P<0.01), stayed longer in the hospital (3days vs. 2days, P=0.02), and had a higher rate of post-operative retention (36% vs. 6.5%, P<0.01).

CONCLUSION: In our experience, the use of CISC before BPH surgery improved peri-operative outcomes as compared to IDC. CISC reduced antibiotic consumption, post-operative complications, length of hospital stay, and improved micturition recovery after catheter removal.}, } @article {pmid39708255, year = {2024}, author = {Salmi, T and Ameur, D and Dali-Sahi, M and Dib, J and Amraoui, N and Kachekouche, Y and Dennouni-Medjati, N}, title = {Exploration of plasma tryptophan levels along with Ki-67 expression binomial investigation for forecasting tumor aggressiveness within invasive ductal breast cancer.}, journal = {Journal of molecular histology}, volume = {56}, number = {1}, pages = {52}, pmid = {39708255}, issn = {1567-2387}, support = {PRFU B00L02UN130120230003//This work was supported by the Algerian Minister of Higher Education and Scientific Research and the training-University Research Project Management Platform/ ; PRFU B00L02UN130120230003//This work was supported by the Algerian Minister of Higher Education and Scientific Research and the training-University Research Project Management Platform/ ; PRFU B00L02UN130120230003//This work was supported by the Algerian Minister of Higher Education and Scientific Research and the training-University Research Project Management Platform/ ; }, mesh = {*Tryptophan/blood/metabolism ; Humans ; *Ki-67 Antigen/blood/metabolism/analysis ; Female ; *Breast Neoplasms/blood/pathology/diagnosis ; Middle Aged ; *Carcinoma, Ductal, Breast/blood/pathology/diagnosis/metabolism ; Aged ; Biomarkers, Tumor/blood ; Adult ; Prognosis ; Mitotic Index ; Aged, 80 and over ; }, abstract = {Ki-67 is a histological marker indicating cancer aggressiveness, while tryptophan (TRP) depletion modulates immune responses, including tumor aggressiveness. The study evaluates Ki-67's predictive value in relation to plasma TRP levels in invasive ductal carcinoma of breast cancer, aiming to improve understanding of tumor characteristics and clinical behavior. A study involving 165 women, measured plasma TRP levels and Ki-67 and analyzed their relationship with tumor aggressiveness markers using statistical analyses and predictive models. Our study highlighted a significant correlation between decreased plasma levels of TRP and a high mitotic index, measured by the Ki-67 marker (Pearson correlation coefficient r = - 0.402; p = 0.011). Tryptophan levels below 40 µmol/L were associated with a Ki-67 level above 15%, suggesting more active tumor growth in patients. Additionally, several risk factors for BC were identified within the studied population. The demographic and clinical characteristics of the participants include an average age of 63 years, plasma glucose levels above 1.2 g/L, and plasma TRP levels below 40 µmol/L, which are associated with an increased risk of BC. Furthermore, various polynomial logistic regression models indicate that TRP levels may be predicted based on Ki-67 expression, providing a promising approach to refine prognostic assessments. The study showed a correlation between low levels of tryptophan (TRP) and a high Ki-67 mitotic index in breast cancer patients, particularly in invasive ductal carcinoma, which is strongly linked to the aggressiveness of the disease. The integration of these markers into routine practice remains a technical and economic challenge.}, } @article {pmid39708123, year = {2024}, author = {Xie, T and Fan, G and Tang, L and Xing, P and Shi, Y}, title = {Artificial neural network systems to predict the response to sintilimab in squamous-cell non-small-cell lung cancer based on data of ORIENT-3 study.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {74}, number = {1}, pages = {29}, pmid = {39708123}, issn = {1432-0851}, mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/drug therapy/immunology ; *Neural Networks, Computer ; *Lung Neoplasms/drug therapy/immunology ; *Antibodies, Monoclonal, Humanized/therapeutic use ; Male ; Female ; Biomarkers, Tumor ; Prognosis ; Middle Aged ; Carcinoma, Squamous Cell/drug therapy/immunology ; Aged ; }, abstract = {BACKGROUND: Existing biomarkers and models for predicting response to programmed cell death protein 1 monoclonal antibody in advanced squamous-cell non-small cell lung cancer (sqNSCLC) did not have enough accuracy. We used data from the ORIENT-3 study to construct artificial neural network (ANN) systems to predict the response to sintilimab for sqNSCLC.

METHODS: Four ANN systems based on bulk RNA data to predict disease control (DC), immune DC (iDC), objective response (OR) and immune OR (iOR) were constructed and tested for patients with sqNSCLC treated with sintilimab. The mechanism exploration on the bulk and the spatial level were performed in patients from the ORIENT-3 study and the real world, respectively.

FINDINGS: sqNSCLC patients with different responses to sintilimab showed each unique transcriptomic spectrum. Four ANN systems showed high accuracy in the test cohort (AUC of DC, iDC, OR and iOR were 0.83, 0.89, 0.93 and 0.94, respectively). The performance of ANN systems was better than that of linear model systems and showed high stability. The mechanism exploration on the bulk level suggested that patients with lower ANN system scores (worse response) had a higher ratio of immune-related pathways enrichment. The mechanism exploration on the spatial level indicated that patients with better response to immunotherapy had fewer clusters of both tumor and cytotoxicity T cell spots.

INTERPRETATION: The four ANN systems showed high accuracy, robustness and stability in predicting the response to sintilimab for patients with sqNSCLC.}, } @article {pmid39701843, year = {2025}, author = {Kayadibi, Y and Karagoz, SH and Kurt, SA and Kargin, OA and Guneren, C and Sahin, OE and Hamid, R and Yilmaz, MH}, title = {Diagnostic Characteristics and Clinical Relevance of Incidental Hypermetabolic Breast Lesions Detected on [18]F-FDG PET-CT: A Retrospective Evaluation.}, journal = {Academic radiology}, volume = {32}, number = {4}, pages = {1806-1815}, doi = {10.1016/j.acra.2024.11.031}, pmid = {39701843}, issn = {1878-4046}, mesh = {Humans ; *Fluorodeoxyglucose F18 ; Female ; *Positron Emission Tomography Computed Tomography/methods ; Retrospective Studies ; Incidental Findings ; Middle Aged ; *Breast Neoplasms/diagnostic imaging/metabolism/pathology ; Radiopharmaceuticals ; Adult ; Aged ; Aged, 80 and over ; Breast/diagnostic imaging ; Clinical Relevance ; }, abstract = {RATIONALE AND OBJECTIVES: The study aimed to evaluate demographic and radiological characteristics of breast incidentalomas found on 18-fluorodeoxyglucose Positron Emission Tomography-Computed Tomography ([18]F-FDG PET-CT) performed for extramammary indications.

MATERIALS AND METHODS: A total of 12633 [18]F-FDG PET-CT scans performed between January 1, 2018 and January 1, 2024, were retrospectively reviewed. Breast incidentalomas that had undergone breast imaging, tissue diagnosis, or at least 2-year radiological follow-up were included. Demographic data and lesion size were recorded. Maximum and average standardized uptake values (SUVmax-SUVavg) and SUV corrected for lean body mass (SUL) were calculated using region of interest (ROI).

RESULTS: The inclusion criteria were met in 101 lesions (81 benign and 20 malignant). The most common benign lesion was fibroadenoma (n = 21), followed by stable lesions during follow-up (n = 18) and benign breast parenchyma (n = 11). The most common malignant lesion was invasive ductal carcinoma (n = 11). The diagnostic characteristics of SUVmax≥ 3, SULmax≥ 2, SUVavg≥ 0.735, SULavg≥ 0.48, and BI-RADS≥ 4 were 75%, 70%, 75%, 70% and 100% for sensitivity, 69%, 69%, 62%, 62% and 67% for specificity, and 69.3%, 68.3%, 62.4%, 61.4% and 73.3% for accuracy, respectively. The highest negative predictive values (NPV) were obtained with BI-RADS and SUVmax (100% and 92%, respectively). No significant difference in malignancy rate was observed for the lesion size and age of the patients (p > 0.05).

CONCLUSION: There is a risk of detecting malignancy in incidental lesions showing [18]F-FDG uptake. Radiological workup must be done, but SUVmax, with a high NPV value, can be used in conjunction with BI-RADS assessment for appropriate patient selection and effective management of resources.}, } @article {pmid39692305, year = {2025}, author = {Cho, SM and Cha, JH and Kim, HH and Shin, HJ and Chae, EY and Choi, WJ and Eom, HJ and Kim, HJ}, title = {Nonmass Lesions on Breast Ultrasound: Interreader Agreement and Associations With Malignancy.}, journal = {AJR. American journal of roentgenology}, volume = {224}, number = {2}, pages = {e2432278}, doi = {10.2214/AJR.24.32278}, pmid = {39692305}, issn = {1546-3141}, mesh = {Humans ; Female ; Retrospective Studies ; Middle Aged ; *Breast Neoplasms/diagnostic imaging/pathology ; *Ultrasonography, Mammary/methods ; Male ; Observer Variation ; Aged ; Adult ; Breast/diagnostic imaging/pathology ; Image-Guided Biopsy ; Reproducibility of Results ; }, abstract = {BACKGROUND. Nonmass lesions (NMLs) on breast ultrasound lack clear definition and encompass a broad range of benign and malignant entities. Given the anticipated inclusion of NMLs in the BI-RADS 6th edition, a thorough understanding of these lesions will be critical for their optimal management. OBJECTIVE. The purpose of the present study was to evaluate interreader agreement for classification of lesions observed on breast ultrasound as NMLs and to identify the imaging features associated with malignancy in these lesions. METHODS. This retrospective study included 2007 patients (2005 women and two men; mean age, 54.0 ± 9.6 [SD] years) who underwent ultrasound-guided biopsy of 2381 breast lesions between January 2020 and December 2020. Two radiologists independently classified the lesions as masses or NMLs, using a definition of NMLs from a presentation at the Radiological Society of North America 2023 annual meeting. The radiologists attempted to reach consensus for discordant cases. Another radiologist recorded the mammographic and ultrasound characteristics of the NMLs. Pathologic outcomes for NMLs were extracted from the EHR. RESULTS. Interreader agreement for lesion classification (mass vs NML) was substantial (κ = 0.73) A total of 216 lesions were classified as NMLs by both readers independently; an additional 101 lesions were classified as NMLs by consensus review after initial discordance. Thus, 317 of 2381 lesions (13.3%) were classified as NMLs; initial reader discordance occurred for 101 of these 317 lesions (31.9%). A total of 133 of 317 NMLs (42.0%) were malignant, including invasive ductal carcinoma (48/133), ductal carcinoma in situ (43/133), and microinvasive ductal carcinoma (micro-IDC) (34/133). A total of 30.8% of malignant NMLs lacked correlative mammographic abnormalities. Ultrasound findings with the highest accuracy for identifying malignancy of NMLs were calcifications (65.6%), posterior shadowing (62.8%), and nonparallel orientation (59.3%). In multivariable analysis, variables showing significant independent associations with malignancy included calcifications (OR = 8.9), asymmetry (OR = 4.7), and mass (OR = 6.4) on mammography and greater size (OR = 1.03), nonparallel orientation (OR = 8.8), and posterior shadowing (OR = 6.3) on ultrasound. CONCLUSION. The analysis provides insights regarding reader variability for classifying ultrasound lesions as NMLs on the basis of an existing definition as well as regarding the potential utility of imaging findings for characterizing such lesions as malignant. CLINICAL IMPACT. These findings indicate the need for further precision and clarification regarding the definition of NMLs and for further investigation to determine which NMLs have the greatest malignancy risk.}, } @article {pmid39690027, year = {2024}, author = {Peng, Y and Xiao, R and Lan, HM and Li, X}, title = {Synchronous bilateral breast carcinoma: Report of a rare case.}, journal = {Asian journal of surgery}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.asjsur.2024.11.226}, pmid = {39690027}, issn = {0219-3108}, } @article {pmid39689129, year = {2024}, author = {Sheehan, KJ and Guerra, S and Ayis, S and Goubar, A and Foster, NE and Martin, FC and Godfrey, E and Cameron, ID and Gregson, CL and Walsh, NE and Ferguson Montague, A and Edwards, R and Adams, J and Jones, GD and Gibson, J and Sackley, C and Whitney, J}, title = {Structured tailored rehabilitation after hip fragility fracture: The 'Stratify' feasibility and pilot randomised controlled trial protocol.}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0306870}, pmid = {39689129}, issn = {1932-6203}, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; Activities of Daily Living ; Cost-Benefit Analysis ; *Feasibility Studies ; *Hip Fractures/rehabilitation/surgery ; Pilot Projects ; *Quality of Life ; Randomized Controlled Trials as Topic ; Pragmatic Clinical Trials as Topic ; }, abstract = {BACKGROUND: Rehabilitation in hospital is effective in reducing mortality after hip fracture. However, there is uncertainty over optimal in-hospital rehabilitation treatment ingredients, and the generalizability of trial findings to subgroups of patients systematically excluded from previous trials. The aim of this study is to determine the feasibility of a randomized controlled trial which aims to assess the clinical- and cost-effectiveness of adding a stratified care intervention to usual care designed to improve outcomes of acute rehabilitation for all older adults after hip fracture.

METHODS: This is a protocol for a single site, feasibility and pilot, pragmatic, parallel group (allocation ratio 1:1) randomised controlled assessor-blind STRATIFY trial (Structured Tailored Rehabilitation AfTer HIp FragilitY Fracture). Adults aged 60 years or more, surgically treated for hip fracture following low energy trauma (fragility fracture), who are willing to provide consent or by consultee declaration (depending on capacity), are eligible. Individuals who experienced in-hospital hip fracture will be excluded. Screening, consent/assent, baseline assessment (demographics, patient reported outcome measures or PROMs [health related quality of life, activities of daily living, pain, falls related self-efficacy], and resource use), and randomization will take place within the first four days post-admission. Participants will then be offered usual care, or usual care plus STRATIFY intervention during their hospital stay. The STRATIFY intervention includes 1) a web-based algorithm to allocate participants to low- medium- or high-risk subgroups; and 2) matched interventions depending on subgroup allocation. The low-risk subgroup will be offered a self-management review, training in advocacy, and a self-managed exercise programme with support for progression, in addition to usual care (1-hour 40 minutes therapist time above usual care). The medium-risk subgroup will be offered education, a goal-orientated mobility programme (with carer training, as available and following carer consent), and early enhanced discharge planning, in addition to usual care (estimated 2-hours 15 minutes therapist time above usual care). The high-risk subgroup will be offered education, enhanced assessment, orientation, and a goal-orientated activities of daily living programme (with carer training, as available and following carer consent), in addition to usual care (estimated 2-hours 45minutes therapist time above usual care). All STRATIFY subgroup treatment interventions are specified using the Rehabilitation Treatment Specification System (RTSS) for treatment theory development and replication. Follow-up PROM data collection, RESOURCE USE alongside readmissions and mortality, will be collected on discharge and 12-weeks post-randomisation. Intervention acceptability will be determined by semi-structured interviews with participants, carers, and therapists at the end of the intervention.

DISSEMINATION: The trial findings will be disseminated to patients and the public, health professionals and researchers through publications, presentations and social media channels.

TRIAL REGISTRATION: The trial has been registered at clinicaltrials.gov (NCT06014554).}, } @article {pmid39685105, year = {2024}, author = {Song, B and Singh, H}, title = {Rare Breast Cancers Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {23}, pages = {}, pmid = {39685105}, issn = {2227-9032}, abstract = {BACKGROUND/OBJECTIVES: Breast cancer is one of the most common malignancies in women, with rare subtypes presenting unique clinical challenges. This review provides a comprehensive analysis of rare breast cancers, including both epithelial and non-epithelial subtypes, and explores their epidemiology, pathology, prognosis, and treatment approaches.

METHODS: A systematic review was conducted focusing on recent advancements in the treatment of rare breast cancer subtypes. Articles were selected based on criteria emphasizing studies from the past five years, with older foundational studies included where necessary. The analysis incorporated molecular profiling, clinical trials, and advancements in targeted and immunotherapies, where possible.

RESULTS: Rare epithelial subtypes, such as tubular, mucinous, and medullary carcinomas, demonstrate distinct clinical and pathological features, with generally favorable prognoses compared to invasive ductal carcinoma (IDC). Non-epithelial cancers, including sarcomas and primary breast lymphomas, require individualized treatment due to aggressive behavior and poor prognosis in certain cases. Recent advancements in targeted therapies (e.g., HER2 inhibitors, PI3K inhibitors, and PARP inhibitors) and immunotherapies (e.g., PD-1 inhibitors) have shown promise in improving outcomes for specific molecularly characterized subtypes.

CONCLUSIONS: While the management of common breast cancers has become increasingly sophisticated, rare subtypes continue to pose challenges due to limited research and small patient populations. Advances in molecular profiling and next-generation sequencing are pivotal in identifying actionable mutations and expanding personalized treatment options. Future research should focus on clinical trials and collaborative efforts to refine treatment strategies and improve outcomes for these rare subtypes.}, } @article {pmid39684874, year = {2024}, author = {Galappaththi, SPL and Smith, KR and Alsatari, ES and Hunter, R and Dyess, DL and Turbat-Herrera, EA and Dasgupta, S}, title = {The Genomic and Biologic Landscapes of Breast Cancer and Racial Differences.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684874}, issn = {1422-0067}, support = {1R21MD019400-01/MD/NIMHD NIH HHS/United States ; }, mesh = {Humans ; *Breast Neoplasms/genetics/pathology/epidemiology ; Female ; *Genomics/methods ; Dysbiosis ; Racial Groups/genetics ; }, abstract = {Breast cancer is a significant health challenge worldwide and is the most frequently diagnosed cancer among women globally. This review provides a comprehensive overview of breast cancer biology, genomics, and microbial dysbiosis, focusing on its various subtypes and racial differences. Breast cancer is primarily classified into carcinomas and sarcomas, with carcinomas constituting most cases. Epidemiology and breast cancer risk factors are important for public health intervention. Staging and grading, based on the TNM and Nottingham grading systems, respectively, are crucial to determining the clinical outcome and treatment decisions. Histopathological subtypes include in situ and invasive carcinomas, such as invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). The review explores molecular subtypes, including Luminal A, Luminal B, Basal-like (Triple Negative), and HER2-enriched, and delves into breast cancer's histological and molecular progression patterns. Recent research findings related to nuclear and mitochondrial genetic alterations, epigenetic reprogramming, and the role of microbiome dysbiosis in breast cancer and racial differences are also reported. The review also provides an update on breast cancer's current diagnostics and treatment modalities.}, } @article {pmid39684409, year = {2024}, author = {Feng, M and Cui, H and Li, S and Li, L and Zhou, C and Chen, L and Cao, Y and Gao, Y and Li, D}, title = {Ubiquitin-Activating Enzyme E1 (UBA1) as a Prognostic Biomarker and Therapeutic Target in Breast Cancer: Insights into Immune Infiltration and Functional Implications.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684409}, issn = {1422-0067}, support = {22YF1407800//Shanghai Municipal Commission of Science and Technology/ ; No.82103429//National Natural Science Foundation of China/ ; No.82303311//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Breast Neoplasms/genetics/immunology/pathology/metabolism ; Female ; *Ubiquitin-Activating Enzymes/genetics/metabolism ; *Biomarkers, Tumor/genetics/metabolism ; Prognosis ; *Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; }, abstract = {Ubiquitin-Activating Enzyme E1 (UBA1), an E1 enzyme involved in the activation of ubiquitin enzymes, has been involved in the onset and progression of different cancers in humans. Nevertheless, the precise contribution of UBA1 in breast cancer (BC) is still poorly characterized. In this study, a thorough investigation was carried out to elucidate the significance of UBA1 and validate its functionality in BC. Through the analysis of mRNA sequencing data of BC patients, the mRNA expression of UBA1 was observed to be notably enhanced in cancer tissues relative to controls, and high UBA1 expression was linked to worse overall survival (OS), disease-specific survival (DSS), and progress-free survival (PFS). Moreover, UBA1 exhibited potential as an independent prognostic and diagnostic biomarker for individuals with BC. Additionally, functional enrichment analysis revealed the involvement of UBA1 in inflammation-linked pathways, like the TNF-α signaling pathway, the IL-6 signaling pathway, and various immune-related biological processes. Notably, single-sample gene set enrichment analysis (ssGSEA) aided in the identification of a negative link between UBA1 expression and the levels of infiltrating mast cells, Th1 cells, iDC cells, B cells, DC cells, Tem cells, Cytotoxic cells, T cells, CD8T cells, and pDC cells. Finally, this study demonstrated that silencing UBA1 significantly impeded the growth and development of BC cell lines. These findings highlight UBA1 as a potential prognostic biomarker linked to immune infiltration in BC, thereby depicting its potential as a new therapeutic target for individuals with BC.}, } @article {pmid39677866, year = {2024}, author = {Konrad, R and Güttler, C and Öhl, N and Heidl, C and Scholz, S and Bauer, C}, title = {Effects of the Tovertafel[®] on apathy, social interaction and social activity of people with dementia in long-term inpatient care: results of a non-controlled within-subject-design study.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1455185}, pmid = {39677866}, issn = {1664-2295}, abstract = {INTRODUCTION: Tovertafel[®] is a VR-based serious game for dementia care (SGDC) that aims to stimulate residents affected by dementia in nursing homes, promote social and cognitive skills and reduce apathy. The aim of this study is to investigate the effects of using Tovertafel[®] on apathy, social interaction and social activity of people with dementia (PWD) in long-term inpatient care in Germany.

METHODS: In this monocentric intervention study, 25 residents of an inpatient long-term care facility with moderate or severe dementia had two weekly applications of Tovertafel[®] over a period of 8 weeks. Effects on the residents' social interaction and activity were recorded before (T1), during (T2) and 1 h after (T3) each intervention using the Engagement of a Person with Dementia Scale (EPWDS). The degree of apathy was assessed using the Apathy Evaluation Scale (AES). Effects of Tovertafel[®] were examined using a simple repeated measures analysis of variance (ANOVA).

RESULTS: Thirteen residents with moderate (52%) and 12 residents with severe dementia (48%) were included. Results showed that residents' apathy changed over the course of the trial and was partially reduced. ANOVA revealed significant changes in the positive expression of social participation in the overall group between individual observation times (p < 0.001; T1: MW = 2.67, SD = 1.352; T2: MW = 3.66, SD = 1.365; T3: MW = 3.10, SD = 1.300) and a significantly lower negative expression of social participation at T2 (MW = 1.09, SD = 0.358) than at T1 (MW = 1.19, SD = 0.579; p = 0.028). There was a significantly higher positive expression of behavioral involvement in the overall group at T3 (MW = 1.17, SD = 0.552) than at T1 (p = 0.003) or T2 (p = 0.045). Analyses did not find any significant interaction between observation times and degree of dementia.

DISCUSSION: Results of the study show that the use of Tovertafel[®] over a period of 2 months had significant effects on apathy, social activity and social interaction in people with moderate or severe dementia. Symptoms of apathy could be reduced and social interaction and activity increased. However, due to limitations of the study design and special circumstances of the COVID-19 pandemic situation, findings might be overestimated and must be interpreted with care. Further research is necessary.}, } @article {pmid39670062, year = {2024}, author = {Liu, Y and Shi, H and He, Q and Fu, Y and Wang, Y and He, Y and Han, A and Guan, T}, title = {Invasive carcinoma segmentation in whole slide images using MS-ResMTUNet.}, journal = {Heliyon}, volume = {10}, number = {4}, pages = {e26413}, pmid = {39670062}, issn = {2405-8440}, abstract = {Identifying the invasive cancer area is a crucial step in the automated diagnosis of digital pathology slices of the breast. When examining the pathological sections of patients with invasive ductal carcinoma, several evaluations are required specifically for the invasive cancer area. However, currently there is little work that can effectively distinguish the invasive cancer area from the ductal carcinoma in situ in whole slide images. To address this issue, we propose a novel architecture named ResMTUnet that combines the strengths of vision transformer and CNN, and uses multi-task learning to achieve accurate invasive carcinoma recognition and segmentation in breast cancer. Furthermore, we introduce a multi-scale input model based on ResMTUnet with conditional random field, named MS-ResMTUNet, to perform segmentation on WSIs. Our systematic experimentation has shown that the proposed network outperforms other competitive methods and effectively segments invasive carcinoma regions in WSIs. This lays a solid foundation for subsequent analysis of breast pathological slides in the future. The code is available at: https://github.com/liuyiqing2018/MS-ResMTUNet.}, } @article {pmid39669383, year = {2024}, author = {Yoon, KH and Kim, EK and Shin, HC}, title = {Prognostic implications of ductal carcinoma in situ components in BRCA1/2-positive breast cancer: a retrospective cohort study.}, journal = {Annals of surgical treatment and research}, volume = {107}, number = {6}, pages = {327-335}, pmid = {39669383}, issn = {2288-6575}, abstract = {PURPOSE: Although the breast cancer susceptibility gene (BRCA)-associated invasive breast cancer is well studied, there are limited reports on ductal carcinoma in situ (DCIS) in patients with BRCA1/2 mutations. This study aims to evaluate the differential prognostic effect of DCIS in breast cancer patients with pathologic variants of BRCA1/2 genes.

METHODS: Breast cancer patients who tested positive for BRCA1/2 mutations between August 2003 and January 2022 at a single tertiary referral center were retrospectively analyzed. Survival outcomes were compared between patients with both invasive ductal carcinoma (IDC) and DCIS (IDC-DCIS group, n = 121) and those with IDC alone (IDC group, n = 36).

RESULTS: Of the 157 patients, 65 (41.4%) exhibited mutations in BRCA1, 90 (57.3%) in BRCA2, and 2 (1.3%) in both BRCA1/2. DCIS components were more frequently found in BRCA2 pathological variants (BRCA1, 46 [38.0%] vs. BRCA2, 76 [62.4%]; P = 0.030). No statistically significant difference was found in 10-year recurrence-free survival (IDC-DCIS, 89.3% vs. IDC, 83.6%; P = 0.989). Subgroup analysis indicated that the DCIS component correlated with improved survival outcomes in the BRCA1 subgroup (BRCA1 IDC-DCIS, 85.5% vs. BRCA1 IDC, 51.0%; P = 0.024). Conversely, in the BRCA2 subgroup, IDC-DCIS patients exhibited a worse prognosis (BRCA1 IDC-DCIS, 85.5% vs. BRCA2 IDC-DCIS, 65.8%; P = 0.045).

CONCLUSION: The presence of a DCIS component carries varied prognostic significance in BRCA1 and BRCA2 mutations. A tailored approach may be necessary when determining treatment options for breast cancer patients with BRCA1/2 mutations based on the presence of DCIS.}, } @article {pmid39665459, year = {2025}, author = {Potter, S and Gulbahce, E and Porretta, J and Lomo, L and Duffy, K and Winkler, N and Coleman, J and Jedrzkiewicz, J}, title = {Invasive Squamous Cell Carcinoma of the Nipple: Case Report With Literature Review.}, journal = {The American Journal of dermatopathology}, volume = {47}, number = {3}, pages = {220-223}, doi = {10.1097/DAD.0000000000002880}, pmid = {39665459}, issn = {1533-0311}, mesh = {Humans ; Female ; Aged ; *Nipples/pathology/surgery ; *Carcinoma, Squamous Cell/pathology/surgery/chemistry ; *Breast Neoplasms/pathology/surgery ; *Skin Neoplasms/pathology/surgery ; Bowen's Disease/pathology ; Mastectomy, Segmental ; Diagnosis, Differential ; Carcinoma, Ductal, Breast/pathology ; Biopsy ; }, abstract = {In this unusual case, a 73-year-old woman presented with bloody discharge from her right breast and skin thickening was observed on subsequent imaging. Clinically, the findings raised concern for Paget disease. A skin punch biopsy was performed, revealing a high-grade infiltrating carcinoma with squamous features. Metaplastic carcinoma was a differential diagnosis, given that this patient had a history of invasive ductal carcinoma and radiation treatment in the same breast. A subsequent central lumpectomy confirmed the diagnosis of invasive squamous cell carcinoma of the nipple, occurring in the context of Bowen disease as a precursor lesion. Notably, there was no evidence of ductal carcinoma in situ in the background breast tissue or conventional invasive ductal carcinoma component. Both in situ and invasive forms of squamous cell carcinomas have been rarely reported in the nipple. This case highlights the importance of considering such a rare diagnosis, especially in patients with a history of breast cancer.}, } @article {pmid39658630, year = {2025}, author = {Papargyriou, A and Najajreh, M and Cook, DP and Maurer, CH and Bärthel, S and Messal, HA and Ravichandran, SK and Richter, T and Knolle, M and Metzler, T and Shastri, AR and Öllinger, R and Jasper, J and Schmidleitner, L and Wang, S and Schneeweis, C and Ishikawa-Ankerhold, H and Engleitner, T and Mataite, L and Semina, M and Trabulssi, H and Lange, S and Ravichandra, A and Schuster, M and Mueller, S and Peschke, K and Schäfer, A and Dobiasch, S and Combs, SE and Schmid, RM and Bausch, AR and Braren, R and Heid, I and Scheel, CH and Schneider, G and Zeigerer, A and Luecken, MD and Steiger, K and Kaissis, G and van Rheenen, J and Theis, FJ and Saur, D and Rad, R and Reichert, M}, title = {Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma.}, journal = {Nature biomedical engineering}, volume = {9}, number = {6}, pages = {836-864}, pmid = {39658630}, issn = {2157-846X}, mesh = {*Carcinoma, Pancreatic Ductal/pathology/genetics/drug therapy/metabolism ; Animals ; Humans ; *Pancreatic Neoplasms/pathology/genetics/drug therapy/metabolism ; Mice ; *Organoids/pathology/drug effects/metabolism ; Phenotype ; Epithelial-Mesenchymal Transition ; Cell Line, Tumor ; }, abstract = {In patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance and mortality rates. However, such morphological and phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the phenotypic landscape seen in murine and human PDAC, that the pronounced molecular and morphological intratumoural and intertumoural heterogeneity of organoids is governed by defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity), and that different organoid phenotypes represent distinct tumour-cell states with unique biological features in vivo. We also show that phenotype-specific therapeutic vulnerabilities and modes of treatment-induced phenotype reprogramming can be captured in phenotypic heterogeneity maps. Our methodology and analyses of tumour-cell heterogeneity in PDAC may guide the development of phenotype-targeted treatment strategies.}, } @article {pmid39654368, year = {2025}, author = {Krings, G and Shamir, ER and Laé, M and Bean, GR and Post, MD and Schnitt, SJ and Chen, YY}, title = {Serous-like breast carcinomas: immunophenotypic, genetic, and clinicopathologic characterization of a morphologically distinct group of tumours.}, journal = {Histopathology}, volume = {86}, number = {5}, pages = {779-792}, doi = {10.1111/his.15385}, pmid = {39654368}, issn = {1365-2559}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/pathology/genetics ; Adult ; Aged ; Biomarkers, Tumor/analysis ; Immunophenotyping ; *Cystadenocarcinoma, Serous/pathology/genetics/diagnosis ; Diagnosis, Differential ; Aged, 80 and over ; }, abstract = {AIMS: Unusual morphologic patterns of breast carcinomas can raise diagnostic consideration for metastasis or special breast cancer subtypes with management implications. We describe rare invasive breast cancers that mimic serous carcinoma of the gynaecologic tract (serous-like breast carcinomas, SLBC) and characterize their clinicopathologic, immunophenotypic, and genetic features.

METHODS AND RESULTS: All patients were female (n = 15, median age 49 years) without a history of gynaecologic malignancy. SLBC were characterized histologically by angulated, branched, sometimes anastomosing glands with micropapillary and/or pseudopapillary luminal projections in desmoplastic stroma. Most SLBC were triple-negative (TN, n = 10) or HER2-positive (n = 2) and grade 2 or 3, while some were oestrogen receptor (ER) low-positive/HER2-negative and low-grade (n = 3). CK5/6 was positive irrespective of grade or receptor status (10/10). All SLBC expressed GATA3 (14/15), TRPS1 (7/7), and/or mammaglobin (4/13). SOX10 was positive in most TN (9/10) and all ER low-positive (3/3) cases, but negative in HER2-positive tumours. WT1 was universally negative, and PAX8 was focal in one mammaglobin-positive tumour. All ER-negative SLBC were p53-aberrant and 9/11 were p16-aberrant, whereas ER-positive tumours were wildtype for both markers (3/3). TP53 was the only frequently mutated gene, altered in all ER-negative (10/10) but no ER-positive (0/4) tumours. Clinical behaviour was variable. Only 1/6 patients achieved pathologic complete response to neoadjuvant chemotherapy.

CONCLUSION: SLBC is a rare morphologic pattern of invasive breast carcinoma that mimics metastatic serous gynaecologic carcinoma, a potential diagnostic pitfall. SLBC are heterogeneous with respect to grade, receptor profile, and oncogenic driver alterations, without specific genetic underpinnings identified. Additional studies are warranted to further evaluate the clinical behaviour of these tumours.}, } @article {pmid39654135, year = {2024}, author = {Rasheed, U and Khalid, M and Noor, A and Saeed, U and Uppal, R and Zafar, S}, title = {Genetic assessment of apolipoprotein E polymorphism and PRNP genotypes in rapidly progressive dementias in Pakistan.}, journal = {Prion}, volume = {18}, number = {1}, pages = {1-7}, pmid = {39654135}, issn = {1933-690X}, mesh = {Humans ; Pakistan ; *Prion Proteins/genetics ; *Genotype ; *Apolipoproteins E/genetics ; Female ; Male ; Polymorphism, Genetic/genetics ; Creutzfeldt-Jakob Syndrome/genetics ; Dementia/genetics ; Mutation/genetics ; Alleles ; Gene Frequency/genetics ; Middle Aged ; Alzheimer Disease/genetics ; Aged ; }, abstract = {Rapidly progressive dementias (RPDs) are a type of fatal dementias that cause rapid progression of neuronal dysfunction. This study aimed to assess the prevalence of APOE genotypes (ε2, ε3, ε4) and PRNP mutations (E200K, M129V) in the general population of Pakistan because of their association with RPDs, including Rapidly Progressive Alzheimer's Disease (rpAD) and Creutzfeldt-Jakob Disease (CJD). Blood samples (n = 100) were collected from healthy Pakistani population and the stated mutations were assessed using polymerase chain reaction. In the analysis of the APOE genotype, ε3/ε3 genotype was the most common (95%), followed by ε3/ε4 (5%) and ε2 allele was completely absent. A low frequency of ε4 allele and the absence of a protective ε2 allele is associated with an increased risk of rpAD. In the case of PRNP mutations, the most common genotype was M129-Ε200 (71%) and V129-Ε200 (29%). E200K mutation was completely absent from the given population. It is noteworthy that the MM homozygous genotype was present in 71 samples, VV genotype was present in 29. Homozygosity on codon 129, as observed in most of our samples, has been associated with more efficient production of PrP[Sc] and disease pathology. This study provides preliminary data indicating that rpAD and CJD pose a significant threat to the Pakistani population.}, } @article {pmid39648131, year = {2024}, author = {Hashimoto, T and Tsuchiya, K and Sakoda, Y and Ogino, M}, title = {[A Case of Locally Advanced Breast Cancer with Ulceration, in Which the Combination of Mohs' Paste and Systemic Drug Therapy Resulted in Improvement of Quality of Life and Disease Control].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {11}, pages = {1153-1155}, pmid = {39648131}, issn = {0385-0684}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/pathology ; *Quality of Life ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Ulcer/drug therapy ; Carcinoma, Ductal, Breast/drug therapy/pathology ; Combined Modality Therapy ; Chlorides ; Zinc Compounds ; }, abstract = {Locally advanced breast cancer can lead to self-destruction, necrosis, and malodor, which may reduce the patients' quality of life. We encountered a case where the combination of Mohs' paste and systemic drug therapy for locally advanced breast cancer improved quality of life and achieved marked disease control. The patient, a woman in her 70s, was referred to our department with suspected right breast cancer. After thorough examination, she was diagnosed with cT4bN3aM1(PUL), cStage Ⅳ, invasive ductal carcinoma, HER2 type. Mohs' paste treatment began on the 8th day, and systemic drug therapy was initiated on the 22nd day. Mohs' paste was applied once a week for a total of 4 times, resulting in significant tumor shrinkage. More than 6 months have passed since the start of treatment, and a complete response has been maintained, including pulmonary metastasis. Mohs' paste is a useful treatment for locally advanced breast cancer with self-destruction and necrosis.}, } @article {pmid39645755, year = {2024}, author = {Parmar, DS and Thakur, MN and Agarwal, I and Ganesh, SR and Vogel, G}, title = {Report of stray sightings of Dendrelaphis proarchos (Wall, 1909) (Serpentes: Colubridae) in Surat, Gujarat, western India.}, journal = {Zootaxa}, volume = {5433}, number = {2}, pages = {231-248}, doi = {10.11646/zootaxa.5433.2.4}, pmid = {39645755}, issn = {1175-5334}, mesh = {Animals ; India ; Male ; *Animal Distribution ; Female ; *Colubridae/anatomy & histology/classification/growth & development ; Animal Structures/anatomy & histology/growth & development ; Body Size ; Ecosystem ; Organ Size ; Humans ; }, abstract = {We here report on likely human-mediated, stray sightings of Dendrelaphis proarchos (Wall, 1909) in an unnatural range-Surat, Gujarat in western India. This population shows the following characters: (1) vertebral scales distinctly enlarged, larger than the dorsals of the first row; (2) 185-194 ventrals; (3) 139-142 divided subcaudals in complete tails; (4) 15 dorsal scale rows at midbody; (5) cloacal shield undivided; (6) one loreal scale; (7) three supralabials touching the eye; (8) a moderate first sublabial that touches two infralabials; (9) 11-12 temporal scales; (10) preoculars 1 or 2; (11) two or three postoculars; (12) maximum total length 1150 mm; (13) interparietal spot absent; (14) a black temporal stripe that does not starts on the postnasal or loreal but starts on the center of the eye follows postoculars (middle or second postocular) covers the majority of the temporal region and extends onto the neck; (15) a distinct, bright ventrolateral stripe bordered by one black line at the bottom; (16) dorsal interstitial color blue and (17) tongue color red with black tip. Data from a partial fragment of the mitochondrial 16S gene also reveal genetic congruence with published sequences from Sagaing and Ayeyarwady in Myanmar and Mizoram, India, further attesting the morphological conclusions. Absence of any sighting of this form in the wild despite long-term (> 15 years) studies in south Gujarat by us, the lack of previous reports of this population especially in natural habitats in Gujarat by colleagues, and reports of many such stray populations of non-native herpetofauna in the coastal port city of Surat together, indicate an unnatural, probably human-mediated, transportation of D. proarchos to Surat. Such likely human-mediated introductions of species outside their native range are a cause for concern and require awareness campaigns among snake rescuers not to 'release' such snakes in the Gujarat forests, but to keep them in zoos or return to the actual point of wild origin, if known or feasible.}, } @article {pmid39644729, year = {2025}, author = {Nguyen, JK and Li, J and Ding, CC and Weight, CJ and McKenney, JK}, title = {Correlation of large cribriform carcinoma and "unfavorable histology" with other Gleason pattern 4 subtypes: A proof-of-principle study evaluating 485 radical prostatectomy specimens with proposal for the concept of "borderline histology".}, journal = {Annals of diagnostic pathology}, volume = {75}, number = {}, pages = {152427}, doi = {10.1016/j.anndiagpath.2024.152427}, pmid = {39644729}, issn = {1532-8198}, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/surgery ; Prostatectomy/methods ; Neoplasm Grading/methods ; Middle Aged ; *Adenocarcinoma/pathology/surgery ; Aged ; Prostate/pathology ; Proof of Concept Study ; }, abstract = {Prostatic adenocarcinomas with large cribriform glands/intraductal carcinoma (LC/IDC), or the recently proposed unfavorable histology, are associated with adverse outcomes after radical prostatectomy. However, Gleason pattern 4 carcinomas without LC/IDC (or unfavorable histology) have minimal risk for aggressive clinical behavior after prostatectomy. As proof-of-principle study, we collected a cohort of 485 radical prostatectomy specimens to assess correlations between different subtypes of Gleason pattern 4 disease and the presence of adjacent high-risk prostatic adenocarcinoma, defined as LC/IDC or unfavorable histology. All prostatectomies were completely embedded, and all slides re-reviewed to record Gleason score/Grade Group, diameter of the largest cribriform gland (i.e. the longest cross-sectional distance), and all architectural patterns of carcinoma utilizing previously described Canary methodology. The presence and percent of LC/IDC (defined as >0.25 mm) was determined. We also evaluated correlation with the recently proposed "unfavorable histology" as a secondary endpoint. Complex Gleason pattern 4 subtypes, distinct from LC/IDC and unfavorable histology, were termed "borderline histology" and defined as the presence of any of the following patterns: small cribriform/glomeruloid architecture (≤0.25 mm), dominant population of poorly formed glands/small nests, simple glomerulations, and epithelial complexity associated with extravasated mucin (beyond typical mucinous fibroplasia pattern and not containing cribriform >0.25 mm). Comparisons between recorded variables and LC/IDC (or unfavorable histology) utilized the Wilcoxon test for continuous variables and chi-squared test or Fisher's test for categorical variables. Pearson or phi correlation coefficients were used to assess the association between two variables. "Borderline histology" was significantly correlated to LC/IDC (r = 0.55) and unfavorable histology (r = 0.607), both p < 0.001. Specifically, small cribriform/small glomeruloid architecture had the strongest correlation, compared to the other "borderline histology" subtypes (r = 0.646). We demonstrate that "borderline histology" has a strong association with the concomitant presence of high-risk prostate cancer by current histologic definitions (i.e. LC/IDC and unfavorable histology). This proof-of-principle study suggests that large cohort biopsy-RP correlation studies are needed, as the presence of these patterns on biopsy could potentially aid preoperative risk stratification for patients without other high-risk features at initial evaluation.}, } @article {pmid39644404, year = {2025}, author = {Wu, M and Huang, Q and Zhang, L and Liu, Y and Zeng, M and Xie, C}, title = {Apo10 and TKTL1 in blood macrophages as potential biomarkers for early diagnosis of operable breast cancer.}, journal = {Breast cancer research and treatment}, volume = {210}, number = {2}, pages = {337-345}, pmid = {39644404}, issn = {1573-7217}, support = {A2022465//the Medical Scientific Research Foundation of Guangdong Province of China/ ; 2022A1515011329//the Guangdong Basic and Applied Basic Research Foundation/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/diagnosis/blood/surgery/pathology ; *Biomarkers, Tumor/blood ; Middle Aged ; *Early Detection of Cancer/methods ; *Macrophages/metabolism ; Adult ; Aged ; ROC Curve ; Retrospective Studies ; Case-Control Studies ; Neoplasm Staging ; }, abstract = {OBJECTIVE: Blood macrophage Apo10 and TKTL1 detection is a novel, noninvasive cancer screening approach, but its relevance in breast cancer remains uncertain. We compared the potential diagnostic value of Apo10 and TKTL1 with commonly used tumor markers in differentiating breast cancer patients.

METHODS: Physical examination and blood sample data from breast cancer patients who did not receive surgery or chemotherapy (retrospective; breast cancer group) and those with benign breast nodules and completely healthy subjects (prospective; control group) were collected from October 2020 to July 2022 at Sun Yat-sen University. Descriptive statistics and receiver operating characteristic (ROC) curves were generated. The area under the ROC curve (AUROC) was calculated to compare the diagnostic efficiency of Apo10 and TKTL1 with conventional biomarkers (carcinoembryonic antigen [CEA], cancer antigens [CA-125, CA-199, CA-153]) in differentiating breast cancer from healthy breasts and benign breast nodules.

RESULTS: From October 2020 to July 2022, 153 breast cancer patients (primarily early-stage disease: n = 113 (73.9%) stage I/II) and 153 control participants (benign breast nodules, n = 56; healthy, n = 97) were included in this study. The breast cancer subtypes were mainly invasive ductal carcinoma (92.8%), with a few cases of DCIS (5.9%), infiltrating lobular carcinoma (0.7%), and mucinous carcinoma (0.7%). Notably, Apo10, TKTL1, and Apo10 + TKTL1 (APT) levels were significantly greater in the cancer group than in the control group (P < 0.001), demonstrating high diagnostic value (AUC = 0.901, 0.871, 0.938) that surpassed CA-125, CA-199, CA-153, and CEA. In a subgroup analysis excluding stage III patients, APT-based breast cancer screening was minimally affected, with the AUROC (0.933-0.938) varying by ≤ 1%.

CONCLUSION: Compared with conventional biomarkers, Apo10, TKTL1, and APT showed superior early-stage breast cancer screening efficacy, potentially emerging as a promising marker for discriminating breast cancer from healthy breasts and nontumoral lesions.}, } @article {pmid39640102, year = {2024}, author = {Waeldner, K and Chin, C and Gilbo, P}, title = {Severe Radiation-Induced Brachial Plexopathy: A Case Report on Radiation Toxicity in a Patient With Invasive Ductal Carcinoma.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e73043}, pmid = {39640102}, issn = {2168-8184}, abstract = {The ataxia-telangiectasia mutated (ATM) gene is an important regulator of cell checkpoint signaling and the repair of double-stranded breaks. When the ATM gene is mutated or damaged, cells are less capable of responding to damage induced by radiation therapy (RT). Here, we present a case of a 50-year-old woman with stage IIIA invasive ductal carcinoma of the left breast who had genetic testing revealing pathogenic ATM mutations (c.5290del and c.4396C>G) and a PALB2 mutation (c.1619dup). While guidelines suggest that adjuvant radiation therapy is safe for patients with ATM mutations, this patient experienced severe radiation-induced toxicities, including brachial plexopathy. These ATM mutations have not previously been described as imparting severe radiation-associated toxicities.}, } @article {pmid39639228, year = {2024}, author = {Hu, J and Ke, J and Xu, S and Pei, L and Cao, L and Zhou, H and Zhu, X}, title = {The combination of focal breast edema and adjacent vessel sign to assess the behavior of mass-type invasive ductal carcinoma.}, journal = {BMC medical imaging}, volume = {24}, number = {1}, pages = {332}, pmid = {39639228}, issn = {1471-2342}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology/complications ; Middle Aged ; Retrospective Studies ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology/complications ; *Magnetic Resonance Imaging/methods ; *Edema/diagnostic imaging/pathology ; Adult ; Aged ; Breast/diagnostic imaging/pathology/blood supply ; Lymphatic Metastasis/diagnostic imaging ; Neoplasm Invasiveness ; Neoplasm Grading ; }, abstract = {BACKGROUND: The objective of this study was to investigate the association between focal breast edema (FBE) and adjacent vessel sign (AVS) with tumor size, histologic grade, lymphovascular invasion, axillary lymph node status, Ki-67 index, and molecular subtype in breast cancer. These findings have provided valuable insights into the biological characteristics and prognosis of mass-type invasive ductal carcinoma (M-IDC).

METHODS: We retrospectively included patients with M-IDC between January 2016 and December 2021. FBE was evaluated using T2-weighted sequence. AVS was assessed using maximum-intensity projection images obtained using early dynamic contrast-enhanced magnetic resonance imaging. The breast peritumor score (BPS) was defined as follows: BPS 1, absence of both edema and AVS; BPS 2, AVS without edema; BPS 3, AVS with peritumoral edema; BPS 4, AVS with prepectoral edema; and BPS 5, AVS with subcutaneous edema. The correlation between different BPS scores and clinicopathological variables was examined using Kendall's tau-b correlation coefficient. The DeLong test was used to compare the performances of three clinicopathological models combined with peritumoral features (FBE, AVS, and BPS) in predicting luminal A-like M-IDC.

RESULTS: In 228 patients with M-IDC, BPS was positively correlated with tumor size, histologic grade, lymphovascular invasion, axillary lymph node status, Ki-67 index, and negatively correlated with estrogen receptor expression (all P < 0.05). Furthermore, BPS 1 was more likely to be present in patients with luminal A-like breast cancer (P < 0.001). Among the three prediction models, the clinicopathological model combined with the BPS model demonstrated superior diagnostic performance for luminal A-like breast cancer.

CONCLUSIONS: The BPS is a valuable, non-invasive biomarker for assessing the aggressiveness of M-IDC and can facilitate treatment planning.}, } @article {pmid39639029, year = {2024}, author = {Nayak, S and Peto, TJ and Kucharski, M and Tripura, R and Callery, JJ and Quang Huy, DT and Gendrot, M and Lek, D and Nghia, HDT and van der Pluijm, RW and Dong, N and Long, LT and Vongpromek, R and Rekol, H and Hoang Chau, N and Miotto, O and Mukaka, M and Dhorda, M and von Seidlein, L and Imwong, M and Roca, X and Day, NPJ and White, NJ and Dondorp, AM and Bozdech, Z}, title = {Population genomics and transcriptomics of Plasmodium falciparum in Cambodia and Vietnam uncover key components of the artemisinin resistance genetic background.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {10625}, pmid = {39639029}, issn = {2041-1723}, mesh = {*Artemisinins/pharmacology/therapeutic use ; *Plasmodium falciparum/genetics/drug effects ; Cambodia ; *Drug Resistance/genetics ; Humans ; *Malaria, Falciparum/parasitology/drug therapy ; *Antimalarials/pharmacology/therapeutic use ; *Polymorphism, Single Nucleotide ; Vietnam ; Protozoan Proteins/genetics/metabolism ; Transcriptome ; Genomics ; Gene Expression Profiling ; }, abstract = {The emergence of Plasmodium falciparum parasites resistant to artemisinins compromises the efficacy of Artemisinin Combination Therapies (ACTs), the global first-line malaria treatment. Artemisinin resistance is a complex genetic trait in which nonsynonymous SNPs in PfK13 cooperate with other genetic variations. Here, we present population genomic/transcriptomic analyses of P. falciparum collected from patients with uncomplicated malaria in Cambodia and Vietnam between 2018 and 2020. Besides the PfK13 SNPs, several polymorphisms, including nonsynonymous SNPs (N1131I and N821K) in PfRad5 and an intronic SNP in PfWD11 (WD40 repeat-containing protein on chromosome 11), appear to be associated with artemisinin resistance, possibly as new markers. There is also a defined set of genes whose steady-state levels of mRNA and/or splice variants or antisense transcripts correlate with artemisinin resistance at the base level. In vivo transcriptional responses to artemisinins indicate the resistant parasite's capacity to decelerate its intraerythrocytic developmental cycle (IDC), which can contribute to the resistant phenotype. During this response, PfRAD5 and PfWD11 upregulate their respective alternatively/aberrantly spliced isoforms, suggesting their contribution to the protective response to artemisinins. PfRAD5 and PfWD11 appear under selective pressure in the Greater Mekong Sub-region over the last decade, suggesting their role in the genetic background of the artemisinin resistance.}, } @article {pmid39637595, year = {2025}, author = {Mahmood, A and Idrees, R and Vohra, LM}, title = {Concurrence of idiopathic granulomatous mastitis and breast cancer in a patient on neoadjuvant chemotherapy: A case report.}, journal = {International journal of surgery case reports}, volume = {126}, number = {}, pages = {110702}, pmid = {39637595}, issn = {2210-2612}, abstract = {INTRODUCTION: Idiopathic Granulomatous Mastitis is a rare benign inflammatory disease of the breast.

PRESENTATION OF THE CASE: We present a case of 45-year-old woman who was diagnosed with stage II invasive ductal carcinoma in the left breast. While receiving neoadjuvant chemotherapy, she developed idiopathic granulomatous mastitis (IGM) in the left breast after the second cycle. She underwent modified radical mastectomy and has been managed with steroids for IGM on the contralateral side, which developed later in the course of the disease. This is a unique finding with limited literature available on similar cases, to the best of our knowledge.

DISCUSSION: IGM poses a diagnostic challenge requiring histopathology for definitive diagnosis.

CONCLUSION: Treatment guidelines of IGM are not established making it difficult to manage.}, } @article {pmid39637037, year = {2024}, author = {Jha, A and Chaudhary, RK and Shrivastav, S and Khanal, U}, title = {Ultrasonographic and pathological correlation of asymmetric retroareolar density on mammogram.}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0301180}, pmid = {39637037}, issn = {1932-6203}, mesh = {Humans ; Female ; Middle Aged ; *Mammography/methods ; Adult ; *Breast Neoplasms/diagnostic imaging/pathology ; Aged ; Nipples/diagnostic imaging/pathology ; Mastitis/diagnostic imaging/pathology ; Ultrasonography/methods ; Breast Density ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Ultrasonography, Mammary/methods ; }, abstract = {BACKGROUND: Retroareolar region refers to the region within two centimeters from the nipple and/or involves the nipple-areolar complex on mammogram. In this study, we graded asymmetric retroareolar density on mammography and determined the underlying cause.

OBJECTIVES: To identify and grade retroareolar densities and evaluate characteristics of lesion using ultrasonography and histopathology.

METHODS: Mammograms with asymmetric retroareolar density done in our tertiary care hospital were included. Retroareolar density was categorized into three grades based on morphological appearance in mammography. Sonography was performed in all patients and tissue diagnosis was obtained for suspicious lesions.

RESULTS: Of the 100 patients included in the study, most of the patients with mammographic grade 1, grade 2 and 3 retroareolar asymmetry had normal sonography, pathologically proven mastitis and invasive ductal carcinoma, respectively. Presenting indication usually was diagnostic (n = 87), lump being most common. Benign (58%) diagnosis was more often present, with equal number of normal studies and malignancies (21%). Frequently pathologically proven malignant lesions (n = 17) had grade 3 asymmetry and none were grade 1. Invasive ductal carcinoma was the most common malignancy while mastitis the most common benign disease.

CONCLUSIONS: Grade I retroareolar asymmetric density on mammography was normal or had a benign etiology while grade 2 or 3 asymmetric density had underlying pathology, often malignancy.

CONTRIBUTION: Grading retroareolar density in mammogram may improve the evaluation of retroareolar region and increase emphasis on higher grades.}, } @article {pmid39627279, year = {2024}, author = {Patil, K and Johnston, E and Novack, J and Wallace, G and Lin, M and Pai, SB}, title = {Multifaceted impact of HIV inhibitor dapivirine on triple negative breast cancer cells reveals potential entities as targets for novel therapy.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {30103}, pmid = {39627279}, issn = {2045-2322}, support = {T32 EB034216/EB/NIBIB NIH HHS/United States ; }, mesh = {Humans ; *Triple Negative Breast Neoplasms/drug therapy/metabolism ; Female ; *Pyrimidines/pharmacology/therapeutic use ; Cell Line, Tumor ; Anti-HIV Agents/pharmacology/therapeutic use ; Apoptosis/drug effects ; Cell Proliferation/drug effects ; MCF-7 Cells ; }, abstract = {Breast cancer is the most common cancer in women worldwide. Many breast cancers originate from the cells lining the milk duct and some become invasive. Breast cancer lacking estrogen, progesterone receptors (ER-, PR-) and epidermal growth factor receptor 2 (HER2-) amplification, termed "Triple negative" (TNBC) is reported to frequently affect Black women and younger women. TNBC is an invasive ductal carcinoma with limited treatment options. To this end, we opted to investigate drugs that could be repurposed because they offer advantages in bringing effective treatments faster to the clinic. We chose to study the effect of the drug, dapivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV because it could be detected in the breast milk of lactating women when treated for HIV and the drug could potentially target the cancer. Here we show the potent impact of dapivirine on MDA-MB-231 TNBC cells, while NNRTI like nevirapine showed marginal effects. When dapivirine was tested on other breast cell lines, MCF-7 and MCF 10A, the inhibition was at higher concentrations. Molecular studies with dapivirine in TNBC cells, revealed an increase in reactive oxygen species (ROS), apoptotic cells, and activation of caspases. Importantly, protein profiling and STRING analysis revealed deregulation of the key molecule, PCNA and impact on pivotal cell signaling circuits including extracellular matrix (ECM), angiogenesis, cell adhesion, and immunomodulation. Of note, is its potential effect on stem-like cells due to downregulation of the basic transcription factor 3 (BTF3) and proteasome activator complex subunit 3; the latter affecting their dependence on the proteasome pathway. Taken together, dapivirine exhibits the potential to be considered as a repurposed drug for TNBC as monotherapy/combination therapy. Notably, it could also potentially be a treatment for individuals with dual ailments, such as HIV and TNBC, if the clinical outcomes with dapivirine for TNBC become favorable.}, } @article {pmid39624628, year = {2024}, author = {Jiao, S and Chen, J and Shen, J and Peng, A and Chen, R and Lai, B and Luo, C and Fan, Y and Pei, X}, title = {Case report: Triple-negative breast cancer with low tumour-infiltrating lymphocytes infiltration and good prognosis: a case of Tall Cell Carcinoma with Reversed Polarity and review of the literature.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1455893}, pmid = {39624628}, issn = {2234-943X}, abstract = {BACKGROUND: Triple-negative breast cancer (TNBC) is a great challenge for clinical management due to the high rate of metastatic recurrence and lack of recognised therapeutic targets, while tumour-infiltrating lymphocytes (TILs) infiltration in TNBC has been discovery provides an opportunity for immunotherapy, and studies have suggested that the level of TILs infiltration is positively correlated with TNBC survival. We found a rare case of TNBC with low TILs infiltration but good prognosis, named Tall Cell Carcinoma with Reversed Polarity (TCCRP), and we investigated it from the perspective of TILs infiltration in order to improve the clinical data of TCCRP.

CASE PRESENTATION: a 54-year-old woman with a left breast mass, breast ultrasound showed BI-RADS IVb, puncture diagnosis of invasive ductal carcinoma, postoperative pathology showed papillary structure, cubic and high columnar arrangement of cells, nuclei far away from the base, interstitial fibroplasia, diagnosed as TCCRP. Immunohistochemistry revealed that the tumours were triple-negative breast cancer (negative for ER, PR, and HER-2), with a low Ki-67 proliferation index. TILs were < 10%, with a small infiltration of CD4[+] and CD8[+] T lymphocytes, positive expression of SMA and FAP, and IDH2, PIK3CA gene mutation. The patient underwent postoperative chemotherapy, 11 months follow-up, no recurrence and metastasis.

CONCLUSION: TCCRP is a rare TNBC with inert biological behaviours and good prognosis. We found low infiltration of TILs in the pathological tissue of this case, which may be a characteristic of TCCRP, and the presence of Cancer-Associated Fibroblasts (CAF) in the interstitium of the tumour in this case may have suppressed the anti-tumour immunity to some extent, and further studies on the immune characteristics of the tumour microenvironment (TME) in TCCRP are needed.}, } @article {pmid39623100, year = {2025}, author = {Lim, CH and Lee, JH and Lee, J and Park, SB}, title = {Predictive value of [18]F-fluorodeoxyglucose uptake for axillary lymph node metastasis in operable breast cancer: impact of molecular subtypes.}, journal = {Annals of nuclear medicine}, volume = {39}, number = {4}, pages = {315-322}, pmid = {39623100}, issn = {1864-6433}, mesh = {Humans ; *Fluorodeoxyglucose F18/metabolism ; Female ; Middle Aged ; Lymphatic Metastasis ; Retrospective Studies ; *Breast Neoplasms/pathology/diagnostic imaging/metabolism/surgery ; Positron Emission Tomography Computed Tomography ; Aged ; Adult ; Axilla ; Biological Transport ; Predictive Value of Tests ; Aged, 80 and over ; }, abstract = {OBJECTIVES: To evaluate the predictive value of standardized uptake value (SUV) in both primary tumors and axillary lymph nodes (ALNs) using FDG PET/CT for lymph node metastasis in breast cancer patients, and to assess the influence of molecular subtypes on this predictive performance.

METHODS: This retrospective study included 287 patients with invasive ductal carcinoma (IDC) who underwent FDG PET/CT prior to surgery between September 2016 and December 2019. The maximum standardized uptake value (SUVmax) of primary tumors (SUV-B) and ALNs (SUV-LN) were analyzed. Molecular subtypes were classified as hormone receptor-positive, HER2-positive, and triple-negative breast cancer (TNBC). Receiver operating characteristic (ROC) curve analysis was performed to assess and compare the diagnostic performance of SUV-B and SUV-LN for predicting ALN metastasis.

RESULTS: Among the 287 patients, 62 (21.6%) had confirmed ALN metastasis. The median SUV-LN was significantly higher in patients with metastasis compared to those without metastasis (1.5 vs. 0.9; P < 0.001). SUV-LN demonstrated good discriminative performance for ALN metastasis (AUC: 0.796), whereas SUV-B did not show significant predictive value (AUC: 0.536). The SUV_LN demonstrated significantly lower predictive performance for ALN metastasis in the hormone-positive group (AUC: 0.796) compared to the excellent discriminative performance in the HER2-positive (AUC: 0.923, P = 0.018) and TNBC (AUC: 0.940, P = 0.004) groups. Hormone receptor-positive tumors also exhibited lower FDG uptake in metastatic lymph nodes compared to HER2-positive and TNBC subtypes (P = 0.031).

CONCLUSION: FDG PET/CT SUV-LN effectively predicts ALN metastasis in HER2-positive and TNBC subtypes. Hormone receptor-positive breast cancers show lower FDG uptake in metastatic ALNs, reducing diagnostic accuracy. This finding may aid in selecting the most appropriate diagnostic modality based on tumor characteristics in the era of personalized medicine.}, } @article {pmid39621168, year = {2024}, author = {Im, YJ and Yoon, YC and Sung, DH}, title = {Brachial plexopathy due to perineural tumor spread: a retrospective single-center experience of clinical manifestations, diagnosis, treatments, and outcomes.}, journal = {Acta neurochirurgica}, volume = {166}, number = {1}, pages = {490}, pmid = {39621168}, issn = {0942-0940}, mesh = {Humans ; Middle Aged ; Female ; Retrospective Studies ; *Brachial Plexus Neuropathies/diagnosis/etiology ; Male ; Adult ; *Positron Emission Tomography Computed Tomography/methods ; Aged ; *Breast Neoplasms/pathology/diagnostic imaging ; *Peripheral Nervous System Neoplasms/diagnostic imaging/pathology/diagnosis ; Lung Neoplasms/pathology/diagnostic imaging/diagnosis ; Treatment Outcome ; Magnetic Resonance Imaging ; Carcinoma, Ductal, Breast/pathology/diagnostic imaging/diagnosis ; Thyroid Cancer, Papillary/pathology/diagnostic imaging/diagnosis/surgery/therapy ; Fluorodeoxyglucose F18 ; Brachial Plexus/pathology/diagnostic imaging ; Adenocarcinoma of Lung/pathology/diagnostic imaging/diagnosis ; }, abstract = {BACKGROUND: Perineural tumor spread (PNTS) to the brachial plexus (BP) is a rare and challenging condition. This study aimed to elucidate the clinical presentations, diagnostic challenges, and outcomes of patients with PNTS to the BP.

METHODS: We retrospectively reviewed patients diagnosed with PNTS to the BP at our institution between January 2009 and June 2024. Clinical characteristics, magnetic resonance imaging (MRI), [18]F-fluorodeoxyglucose ([18]F-FDG) positron emission tomography/computed tomography (PET/CT) findings, and treatment outcomes were analyzed.

RESULTS: Seven patients (mean age, 50.3 years) were identified. The primary cancer diagnoses included invasive ductal carcinoma of the breast (n = 3), metaplastic carcinoma of the breast (n = 1), lung adenocarcinoma (n = 2), and papillary thyroid carcinoma (n = 1). The median time from the initial cancer diagnosis to PNTS symptom onset was 71.0 months. All patients initially presented with progressive unilateral pain or paresthesia, followed by motor weakness. Lower trunk plexopathy was the most common electrodiagnostic finding (n = 5). In most patients, BP MRI showed diffuse tubular enlargement and T2 hyperintensity throughout the BP (n = 6), with gadolinium enhancement primarily in the proximal regions (n = 7). [18]F-FDG PET/CT demonstrated increased uptake in the BP, most prominently at the cervical spinal root or trunk levels (n = 6). Despite treatment, neurological outcomes were generally poor. Six of the seven patients died after a median follow-up of 19 months post-PNTS diagnosis.

CONCLUSIONS: PNTS to the BP can occur years after initial cancer diagnosis and may signify cancer progression. A high index of suspicion is crucial for timely diagnosis, particularly in patients with cancer and progressive upper extremity symptoms. Comprehensive imaging, including BP MRI and PET/CT, is essential for diagnosis. Despite treatment, prognosis remains poor, highlighting the need for improved diagnostic and therapeutic strategies.}, } @article {pmid39616738, year = {2025}, author = {Rivera, A and Plumber, N and Louis, M and Grabill, N and Strom, P}, title = {Surgical stress as a potential trigger for spontaneous coronary artery dissection: A case report.}, journal = {International journal of surgery case reports}, volume = {126}, number = {}, pages = {110644}, pmid = {39616738}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome, predominantly affecting women without traditional cardiovascular risk factors. It is often underdiagnosed, especially in postoperative patients, due to its atypical presentation and the challenges in distinguishing it from other causes of chest pain.

CASE PRESENTATION: We report the case of a 62-year-old woman with type 2 diabetes mellitus, hypertension, hyperlipidemia, and recent bilateral mastectomy for invasive ductal carcinoma, who presented three days post-surgery with sudden onset of chest pain radiating to her left arm. Electrocardiography revealed ST-segment depression suggestive of anterior ischemia, and cardiac biomarkers were significantly elevated. Imaging studies were limited due to recent surgery, but urgent coronary angiography identified spontaneous coronary artery dissections.

CLINICAL DISCUSSION: This case highlights the potential role of surgical stress as a precipitating factor for SCAD in patients without traditional cardiovascular risk factors. The physiological stress of major surgery may contribute to arterial wall vulnerability and dissection. Diagnostic challenges in the postoperative setting necessitate a high index of suspicion for timely identification. Conservative management was pursued, aligning with current guidelines that favor non-invasive treatment in stable SCAD cases to prevent further dissection or complications.

CONCLUSION: SCAD should be considered in the differential diagnosis of acute coronary syndrome in postoperative patients presenting with chest pain, even in the absence of significant cardiovascular risk factors. Early recognition and appropriate management are crucial for improving patient outcomes.}, } @article {pmid39612651, year = {2024}, author = {Shrestha, LB and Tungatt, K and Aggarwal, A and Stubis, A and Fewings, NL and Fichter, C and Akerman, A and Rodrigo, C and Tedla, N and Lee, S and Lloyd, AR and Brilot, F and Britton, WJ and Kelleher, A and Caterson, ID and Douglas, MW and Rockett, R and Tangye, SG and Triccas, JA and Turville, SG and Sandgren, KJ and Bull, RA and Cunningham, AL and , }, title = {Bivalent Omicron BA.1 vaccine booster increases memory B cell breadth and neutralising antibodies against emerging SARS-CoV-2 variants.}, journal = {EBioMedicine}, volume = {110}, number = {}, pages = {105461}, pmid = {39612651}, issn = {2352-3964}, mesh = {Humans ; *COVID-19 Vaccines/immunology/administration & dosage ; *SARS-CoV-2/immunology ; *Memory B Cells/immunology ; *COVID-19/immunology/prevention & control ; *Antibodies, Viral/immunology ; *Antibodies, Neutralizing/immunology ; *Immunization, Secondary ; *Spike Glycoprotein, Coronavirus/immunology ; Adult ; Female ; Male ; Middle Aged ; Immunologic Memory ; B-Lymphocytes/immunology ; }, abstract = {BACKGROUND: Current literature informs us that bivalent vaccines will generate a broader serum neutralizing antibody response to multiple SARS-CoV-2 variants, but studies on how this breadth relates to the memory B cell (MBC) and T cell responses are sparse. This study compared breadth of neutralising antibody, and memory B and T cell responses to monovalent or a bivalent ancestral/Omicron BA.1 COVID-19 booster vaccine.

METHODS: At baseline and 1-month post-booster, neutralisation activity and frequencies of receptor binding domain (RBD)-specific MBCs and Spike-specific memory T cells were measured against a panel of variants.

FINDINGS: Both vaccines boosted neutralising antibodies to 5 variants - Wuhan-Hu-1, Delta, BA.1, BA.5 and JN.1, the latter of which had not yet emerged at the time of sample collection. The bivalent vaccine induced a significantly larger increase in nAb against BA.1 and JN.1. Both vaccines boosted RBD-specific MBC responses to Wuhan-Hu-1, Delta, BA.1 and BA.5 variants with a significantly greater increase for BA.1 in the bivalent group. The breadth of MBCs was significantly higher in those who received the bivalent boost and correlated with nAb breadth. Both vaccines significantly boosted Spike-specific T cell responses to the Wuhan-Hu-1 and BA.5 variants, but only the bivalent vaccine boosted BA.1 responses.

INTERPRETATION: These results suggest that the bivalent vaccine confers an advantage against future novel variants due to increased frequency of broadly reactive RBD-specific B cells.

FUNDING: Work supported by NSW Health for the NSW Vaccine, Infection and Immunology Collaborative (VIIM).}, } @article {pmid39612433, year = {2024}, author = {Tan, M and Luo, L and Wang, T and Zhang, Z and Wei, Y and Long, C}, title = {Two case reports of breast cancer combined with synchronous primary intrahepatic cholangiocarcinoma/mixed liver cancer.}, journal = {Medicine}, volume = {103}, number = {48}, pages = {e40653}, pmid = {39612433}, issn = {1536-5964}, mesh = {Humans ; Female ; *Cholangiocarcinoma/pathology/surgery ; *Neoplasms, Multiple Primary/pathology/surgery ; *Breast Neoplasms/pathology/surgery ; *Bile Duct Neoplasms/pathology/surgery ; *Liver Neoplasms/pathology/surgery ; Middle Aged ; Carcinoma, Hepatocellular/pathology/surgery ; Aged ; Carcinoma, Ductal, Breast/pathology/surgery/diagnosis ; }, abstract = {RATIONALE: This case report discusses multiple primary malignant tumors, which refer to the occurrence of 2 or more different histological types of malignant tumors simultaneously or successively in the same individual.

PATIENT CONCERNS: We present 2 female patients who were admitted to the hospital due to a "left breast mass" and were found to have multiple solid masses in the liver upon imaging.

DIAGNOSES: Postoperative pathology revealed that one patient had breast invasive ductal carcinoma was complicated with primary intrahepatic cholangiocarcinoma and mixed hepatocellular carcinoma with intrahepatic cholangiocarcinoma.

INTERVENTIONS: Both patients underwent extensive resection of the lesion.

OUTCOMES: Regular postoperative checkups and follow-ups have been conducted, and both patient's current conditions are stable.

LESSONS: The treatment approach adopted in this case report may serve as a favorable reference for the management of similar cases. However, further extensive biological studies are still needed to investigate the biological mechanisms of multiple primary malignant tumors and to discover specific therapeutic approaches to achieve more clinical benefits for patients.}, } @article {pmid39610583, year = {2024}, author = {Yasin, R and Zafar, G and Rooman Ali Syed, F and Afzal, S and Fatima, M and Rathore, Z and Chughtai, A and Chughtai, A}, title = {CK5/6 Expression in Molecular Subtypes of Invasive Ductal Carcinoma.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e72608}, pmid = {39610583}, issn = {2168-8184}, abstract = {Background Breast cancer (BC) is the leading cause of cancer-related deaths in women worldwide. There has been a significant increase in the incidence of BC in Pakistan. Family history, older age, obesity, tobacco use, oral contraceptive use, early menarche, and hormonal replacement therapy are among the major risk factors. The most common histological subtype of BC is invasive ductal carcinoma (IDC). Molecular subtypes of BC include mainly Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER-2) enriched, and triple-negative BC subtypes, with the triple-negative subtype having the worst prognosis. CK5/6 serves as a basal keratin biomarker. This aimed to assess the expression of CK5/6 in IDC of the breast belonging to different molecular classes and to compare its expression with traditionally defined prognostic factors for different molecular subtypes. Methodology A cross-sectional, observational study was conducted at the Chughtai Institute of Pathology after approval from the Institutional Review Board (approval number: 1198/IRB/CIP). All cases during a period of six months (April 2023 to September 2023) were sampled using non-probability convenient sampling. All mastectomy samples diagnosed as IDC were included in the study. After standard tissue processing, paraffin tissue blocks and slides were prepared followed by hematoxylin & eosin staining. Hormonal receptors (estrogen receptor, progesterone receptor, HER-2) were assessed for cases to segregate them into molecular subtypes. CK5/6 antibody was then applied and the data were collected on a pre-designed proforma. SPSS version 25.0 (IBM Corp., Armonk, NY, USA) was used for data analysis. Results Of a total of 85 cases, 19 (22.3%) were positive for CK5/6. Of these 19 cases, the majority (68%, p = 0.001) belonged to the triple-negative class of tumors, comprising 13 cases. No case from the Luminal A class showed expression for CK5/6 stain (p = 0.028). Overall, four cases of the Luminal B subtype showed CK5/6 positivity (10.8%, p = 0.022) while two cases of the HER-2-enriched subtype were positive for the stain (33.3%, p > 0.05). These results were analyzed in relation to different prognostic factors. The majority of CK5/6-positive cases showed lymphovascular invasion (42%) and belonged to grade 3 tumors (57.8%). Conclusions The expression of CK5/6 in IDC of the breast is associated with poor prognostic factors such as triple-negative molecular subtypes, high histological grade, lymphovascular invasion, positive nodal status, and high pathological stage.}, } @article {pmid39607443, year = {2024}, author = {Bernardino, RM and Yin, LB and Lajkosz, K and Cockburn, JG and Wettstein, MS and Woon, D and Nguyen, DD and Sayyid, R and Leão, R and van der Kwast, T and Fleshner, N}, title = {Can the free/total psa ratio predict undetected intraductal carcinoma and cribriform pattern at biopsy?.}, journal = {World journal of urology}, volume = {42}, number = {1}, pages = {651}, pmid = {39607443}, issn = {1433-8726}, support = {2022.13386.BD//Fundação para a Ciência e a Tecnologia/ ; }, mesh = {Humans ; Male ; Middle Aged ; *Prostatic Neoplasms/pathology/blood/diagnosis/surgery ; Aged ; *Prostate-Specific Antigen/blood ; *Predictive Value of Tests ; Retrospective Studies ; *Prostatectomy ; Biopsy ; Prostate/pathology ; False Negative Reactions ; Carcinoma, Intraductal, Noninfiltrating/pathology/blood/diagnosis ; }, abstract = {BACKGROUND: Intraductal carcinoma (IDC) and cribriform pattern (Crib) of prostate cancer are recognised as independent prognosticators of poor outcome, both in prostate biopsies and radical prostatectomy (RP) specimens.

OBJECTIVE: This study aimed to determine the predictive value of Free-to-total PSA ratio (FPSAR) in identifying missed IDC/Crib at the time of biopsy as compared to the final surgical specimen.

MATERIALS AND METHODS: Patients who underwent RP between January 2015 and December 2022 were included in the study. Predictors of a false negative biopsy were examined using a multivariate logistic regression. Associations between true positive/true negative/false negative biopsies (for IDC/Crib) with FPSAR as primary outcome parameter were determined using Chi-squared test and Kruskal-Wallis test.

RESULTS: This study included 639 patients who underwent radical prostatectomy between 2015 and 2022 (Table 1) and had available FPSAR- at the time of biopsy. The median age was 63.0 years (IQR: 58.9-68.0). The median serum PSA before RP was 7.0 ng/ml (IQR: 5.3-9.5). Among the 639 patients, 177 (28%) had Crib, and 97 (15%) had IDC on prostate biopsy, with 54 (9%) patients having both IDC and Crib. Concerning Grade Group distribution at biopsy, there was: GG1 in 62 patients (10%), GG2 in 428 (67%), GG3 in 102 (16%), GG4 in 28 (4%), and GG5 in 19 (3%) patients. On multivariate regression analysis, the following were associated with lower odds of a false-negative IDC/Crib biopsy: Percentage of pattern 4 ≥ 10% at biopsy (odds ratio [OR] 0.17, 95% CI 0.10-0.29; p < 0.001); higher Gleason score (grade group 4/5) on biopsy (OR 0.38, 95% CI 0.16-0.91; p = 0.03) and higher percent of positive cores at biopsy ≥ 33% (OR 0.51, 95% CI 0.29-0.88; p = 0.02). FPSAR ≥ 0.10 was not an independent predictor of a false-negative IDC/Crib biopsy (p > 0.05).

CONCLUSIONS: In conclusion, our study's findings suggest that FPSAR is not a reliable biomarker for identifying IDC/Crib status at the time of biopsy. Further research is needed to identify biomarkers or combinations of biomarkers that can improve the diagnostic accuracy for these aggressive variants of PCa. Our study that involved 639 patients shows that FPSAR is not a good marker for detecting aggressive types of PCa, during a biopsy. More research is needed to find better markers or combinations of markers that can help diagnose these aggressive forms of prostate cancer more accurately.}, } @article {pmid39605123, year = {2024}, author = {Noroozpoor, M and Mozdarani, H and Rahbar Parvaneh, R and Lashkari, M}, title = {Evaluation of TP53TG1 and PANDA lncRNAs expression in association with adjuvant chemotherapy response in the peripheral blood of invasive ductal carcinoma patients.}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {70}, number = {10}, pages = {58-63}, doi = {10.14715/cmb/2024.70.10.9}, pmid = {39605123}, issn = {1165-158X}, mesh = {Humans ; Female ; Chemotherapy, Adjuvant ; *RNA, Long Noncoding/genetics/blood ; *Breast Neoplasms/drug therapy/genetics/blood ; Middle Aged ; *Gene Expression Regulation, Neoplastic/drug effects ; Carcinoma, Ductal, Breast/drug therapy/genetics/blood ; Adult ; Biomarkers, Tumor/genetics/blood ; }, abstract = {Breast cancer is the most common malignancy in women. Breast cancer, the second leading cause of cancer deaths, affects 2.1 million women each year and is estimated to have killed 627,000 women worldwide in 2018. Unfortunately, the age of onset of this cancer in our country IRAN is about 10 years lower than the global average and is close to 45 years. Chemotherapy is one of the basic treatments for cancer. Predicting the benefits of chemotherapy is challenging. Studies are now underway to use gene expression tests to pinpoint patients who are most likely to benefit from adjuvant chemotherapy. In the present study, the expression of two long non-coding RNAs TP53TG1 and PANDA in the blood of breast cancer patients before and after receiving chemotherapy compared with this amount in the blood of normal people using Real-Time RT PCR technique to find a meaningful relationship ¬ Compared statistically. Compared to normal samples, the expression level of TP53TG1 in the blood of patients was reduced. Although it was not statistically significant. Its expression also increased after receiving chemotherapy. Compared to normal samples, the expression of PANDA in the blood of patients was increased, which was statistically significant. Also, its expression decreased after receiving chemotherapy. These findings suggest that PANDA and TP53TG1 expression levels may be possible markers associated with tumorigenesis and may also be considered as possible indicators of response to chemotherapy.}, } @article {pmid39602906, year = {2025}, author = {Hrizat, AS and Doxzon, KA and Post, RP and Brachtel, EF}, title = {Diagnostic Accuracy and Clinical Utility of Fine-Needle Aspiration in Breast Lesions: A Correlation with Surgical Pathology.}, journal = {Acta cytologica}, volume = {69}, number = {2}, pages = {114-121}, doi = {10.1159/000542811}, pmid = {39602906}, issn = {1938-2650}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/surgery/diagnosis ; Retrospective Studies ; Middle Aged ; Biopsy, Fine-Needle/methods ; Adult ; Aged ; *Pathology, Surgical/methods ; Predictive Value of Tests ; *Breast/pathology ; Aged, 80 and over ; Reproducibility of Results ; Young Adult ; }, abstract = {INTRODUCTION: Fine-needle aspiration (FNA) is a valuable diagnostic tool for evaluating breast lesions, yet its use is less frequent compared to core needle biopsies in high-resource settings. This study aimed to assess the diagnostic performance and clinical utility of FNA in correlation with surgical pathology outcomes.

METHODS: We performed a 3-year retrospective search (2021-2023) using our institutional database to identify cases of breast mass FNAs performed by interventional radiologists under ultrasound guidance. We retrieved and re-evaluated all glass slides from the archive. Additionally, we reviewed the cytopathology reports and correlated the cytologic diagnoses with concurrent or subsequent surgical pathology results.

RESULTS: A total of 65 breast FNA cases from patients were reviewed. The diagnostic outcomes were 55% negative for malignancy, 23% insufficient for diagnosis, 11% atypical, 8% suspicious for malignancy, and 3% positive for malignancy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value of FNA for detecting malignancy were 76%, 96%, 93%, and 85%, respectively. One false positive case, categorized as atypical due to degenerative changes, was later confirmed as benign apocrine metaplasia. Three false-negative cases, initially categorized as non-diagnostic, were later diagnosed as invasive ductal carcinoma, Hodgkin lymphoma, and papillary carcinoma. An additional false-negative case, categorized under negative for malignancy, was later diagnosed as invasive ductal carcinoma.

CONCLUSION: Breast FNAs, while less frequently performed than core needle biopsies, provide significant diagnostic insights, particularly for cystic lesions. The study demonstrates high specificity and PPV for FNA in detecting malignancy, underscoring its value as a diagnostic tool when integrated with imaging and clinical assessment. These findings support the continued use of FNA in the diagnostic evaluation of breast lesions.}, } @article {pmid39600551, year = {2024}, author = {Dhawan, S and Mattathil, F and Malik, I and Khyathi, M and Bhakar, B}, title = {Leptomeningeal Disease Secondary to Invasive Ductal Carcinoma of the Breast: A Rapidly Progressive and Fatal Complication.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e74421}, pmid = {39600551}, issn = {2168-8184}, abstract = {Leptomeningeal disease (LMD) is a rare yet serious complication of advanced malignancy, often seen in breast cancer and associated with a poor prognosis. This case report highlights the rapid progression and diagnostic challenges encountered in a woman in her 40s with advanced breast cancer who presented with severe headaches, absence seizures, and diplopia. The patient's complex past history included invasive ductal carcinoma, prior brain metastasis, and recent craniotomy, which added significant challenges to diagnosis and management. Clinical investigations included computed tomography (CT) of the head, magnetic resonance imaging (MRI) of the orbit and head, electroencephalography (EEG), and lumbar puncture, which indicated optic nerve sheath enhancement, ventricular prominence, coating of facial and vestibulocochlear nerves, and cerebrospinal fluid abnormalities suggestive of LMD. Although empiric treatment for bacterial and tuberculous meningitis was initiated, the patient's rapid decline necessitated an aggressive multimodal approach. Management included high-dose corticosteroids, broad-spectrum antibiotics, antitubercular drugs, and anticonvulsants, though her seizures persisted. Ultimately, comfort-focused care was prioritized as her condition remained refractory to interventions, and she was transitioned to palliative care. This case emphasizes the need for early suspicion, prompt multidisciplinary involvement, and the challenges in managing complex oncological cases with atypical neurological manifestations. The poor prognosis associated with LMD reflects the limitations of current therapeutic strategies and the need for a nuanced approach to care.}, } @article {pmid39593081, year = {2024}, author = {Trippler, L and Ali, SM and Masoud, MO and Mohammed, ZH and Amour, AK and Suleiman, KR and Ame, SM and Kabole, F and Hattendorf, J and Knopp, S}, title = {Impact of chemical snail control on intermediate host snail populations for urogenital schistosomiasis elimination in Pemba, Tanzania: findings of a 3-year intervention study.}, journal = {Parasites & vectors}, volume = {17}, number = {1}, pages = {489}, pmid = {39593081}, issn = {1756-3305}, support = {PR00P3_179753 / 1//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; }, mesh = {Animals ; Tanzania/epidemiology ; *Schistosomiasis haematobia/prevention & control/epidemiology/drug therapy/transmission ; *Schistosoma haematobium/drug effects/physiology ; *Bulinus/parasitology ; Humans ; *Niclosamide/pharmacology ; Snails/parasitology ; Disease Eradication ; Fresh Water/parasitology ; }, abstract = {BACKGROUND: The World Health Organization (WHO) has set the goal of eliminating schistosomiasis as a public health problem globally by 2030 and to interrupt transmission in selected areas. Chemical snail control is one important measure to reduce transmission and achieve local elimination. We aimed to assess the impact of several rounds of chemical snail control on the presence and number of the Schistosoma haematobium intermediate snail host (Bulinus spp.) in water bodies (WBs) on Pemba Island, Tanzania, a setting targeted for elimination of urogenital schistosomiasis.

METHODS: During the three annual intervention periods of the SchistoBreak study implemented in the north of Pemba from 2020 to 2024, malacological surveys were conducted up to four times per period in WBs of hotspot implementation units (IUs). Present freshwater snail species, vegetation, and WB characteristics were recorded. If Bulinus were found, the snails were inspected for Schistosoma infection and snail control with niclosamide was conducted.

RESULTS: Across the three intervention periods, a total of 112 WBs were identified in 8 hotspots IUs. The spatial distribution of WBs with Bulinus per IU was heterogeneous, ranging from 0.0% (0/15) of WBs infested in one IU in 2022 to 80.0% (8/10) of WBs infested in one IU in 2021. Bulinus presence was significantly associated with lower pH values in WBs (odds ratio: 0.2, 95% confidence interval 0.1-0.4). A total of 0.2% (6/2360) of collected Bulinus were shedding Schistosoma cercariae. Following snail control, the number of Bulinus decreased or remained absent in 56.7% (38/67) of visits at WBs when compared with the previous visit in 2021, 54.9% (28/51) in 2022, and 33.3% (32/96) in 2023. In a total of 43.1% (22/55) of initially infested WBs, no Bulinus were found in the survey round conducted a few weeks after the first application of niclosamide. However, 25.4% (14/55) of WBs showed a pattern of recurring Bulinus presence.

CONCLUSIONS: The distribution of WBs containing Bulinus was very heterogeneous. The percentage of Bulinus with patent Schistosoma infection in our study area was extremely low. Repeated niclosamide application reduced the number of Bulinus in WBs, but snails often recurred after one or multiple treatments. While chemical mollusciciding can reduce snail numbers, to fully break the S. haematobium transmission cycle, timely diagnosis and treatment of infected humans, access to clean water, sanitation, and health communication remain of prime importance.

TRIAL REGISTRATION: ISRCTN, ISRCTN91431493. Registered 11 February. 2020, https://www.isrctn.com/ISRCTN91431493.}, } @article {pmid39592308, year = {2025}, author = {Wang, Y and Teramoto, Y and Miyamoto, H}, title = {Cribriform intraductal carcinoma of the prostate may be more aggressive than cribriform conventional/acinar prostatic adenocarcinoma.}, journal = {Pathology}, volume = {57}, number = {1}, pages = {3-9}, doi = {10.1016/j.pathol.2024.08.012}, pmid = {39592308}, issn = {1465-3931}, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/surgery ; Aged ; Middle Aged ; *Prostatectomy ; Prognosis ; Adenocarcinoma/pathology/surgery ; Neoplasm Grading ; Carcinoma, Acinar Cell/pathology/surgery ; Prostate/pathology/surgery ; Neoplasm Recurrence, Local/pathology ; Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Carcinoma, Ductal/pathology/surgery/mortality ; }, abstract = {It remains to be determined if the prognostic value of cribriform morphology (Crib) associated with intraductal carcinoma of the prostate (IDC) is equivalent to that in conventional/acinar prostatic adenocarcinoma (CPA). We herein assessed radical prostatectomy findings and long-term oncologic outcomes in 732 men with Grade Group 2-4 CPA without any Gleason pattern 5. Our cases were divided into four cohorts according to the absence or presence of Crib within CPA and/or IDC: Cohort-1, no Crib (n=347; 47.4%); Cohort-2, Crib only in CPA (n=203; 27.7%); Cohort-3, Crib only in IDC (n=17; 2.3%); and Cohort-4, Crib in both CPA and IDC (n=165; 22.5%). Compared with that in CPA only (Cohort-2), Crib in both CPA and IDC (Cohort-4) was significantly associated with adverse histopathological features, including higher tumour grade/stage and larger tumour volume. Univariate analysis revealed significantly higher risks of postoperative recurrence in patients with Crib in IDC only [Cohort-3; hazard ratio (HR) 2.450, p=0.022] or both CPA and IDC (Cohort-4; HR 2.835, p<0.001) than in those with Crib in CPA only (Cohort-2), whereas the prognosis was analogous between Cohort-3 and Cohort-4 (p=0.913). In a multivariable analysis [Crib in CPA only (Cohort-2) as a reference], Crib in IDC only (Cohort-3; HR 3.821, p=0.002) or both CPA and IDC (Cohort-4; HR 1.905, p=0.004) showed significantly worse recurrence-free survival. Compared with Crib in CPA only, its presence in both CPA and IDC was thus found to be independently associated with a poorer prognosis, suggesting a potentially greater clinical impact of Crib in IDC than in CPA.}, } @article {pmid39578650, year = {2024}, author = {Berriel Diaz, M and Rohm, M and Herzig, S}, title = {Cancer cachexia: multilevel metabolic dysfunction.}, journal = {Nature metabolism}, volume = {6}, number = {12}, pages = {2222-2245}, pmid = {39578650}, issn = {2522-5812}, support = {949017//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; }, mesh = {Animals ; Humans ; *Cachexia/metabolism/etiology ; *Energy Metabolism ; Metabolic Diseases/etiology/metabolism ; *Neoplasms/complications/metabolism ; }, abstract = {Cancer cachexia is a complex metabolic disorder marked by unintentional body weight loss or 'wasting' of body mass, driven by multiple aetiological factors operating at various levels. It is associated with many malignancies and significantly contributes to cancer-related morbidity and mortality. With emerging recognition of cancer as a systemic disease, there is increasing awareness that understanding and treatment of cancer cachexia may represent a crucial cornerstone for improved management of cancer. Here, we describe the metabolic changes contributing to body wasting in cachexia and explain how the entangled action of both tumour-derived and host-amplified processes induces these metabolic changes. We discuss energy homeostasis and possible ways that the presence of a tumour interferes with or hijacks physiological energy conservation pathways. In that context, we highlight the role played by metabolic cross-talk mechanisms in cachexia pathogenesis. Lastly, we elaborate on the challenges and opportunities in the treatment of this devastating paraneoplastic phenomenon that arise from the complex and multifaceted metabolic cross-talk mechanisms and provide a status on current and emerging therapeutic approaches.}, } @article {pmid39574516, year = {2024}, author = {De la Mata, D and Santiago-Concha, BG and Bargalló-Rocha, JE and Robles-Vidal, CD and Gómez-Pue, D and Castorena-Rojí, G and Hinojosa-Gómez, J and Flores-Vázquez, F and Blake-Cerda, M and Enriquez-Barrera, M and Maffuz-Aziz, A}, title = {Outcomes From Real-World Data on Intraoperative Electronic Radiotherapy for the Treatment of Early-Stage Breast Cancer: Long-Term Recurrence and Survival Outcomes From a Single Center.}, journal = {International journal of breast cancer}, volume = {2024}, number = {}, pages = {6207762}, pmid = {39574516}, issn = {2090-3170}, abstract = {Purpose: This study is aimed at investigating the 10-year outcomes of intraoperative radiotherapy (IORT) in Mexican women with early breast cancer (EBC) treated at the Centro Medico ABC, Mexico City. Methods: A cohort study included women with early-stage invasive ductal carcinoma aged ≥ 45 years without prior oncologic treatment, tumor size ≤ 3.5 cm, cN0M0, positive hormone receptors, margins ≥ 2 mm, negative sentinel lymph nodes, and no extensive lymphovascular invasion. IORT was administered at 20 Gy for 20-30 min after a lumpectomy. Follow-up extended over 10 years and included clinical examinations every 6 months for the first 18 months, followed by annual mammograms and conventional examinations. Patients out of the criteria were excluded from this study because they were referred for additional surgery and/or whole-breast radiation therapy. Results: The study involved 238 patients with an average age of 61.1 years. The mean tumor size was 12 mm, and the percentages of lymphatic invasion, positive hormone receptors, and HER2/neu overexpression were 12.6%, 90.8%, and 2.1%, respectively. The median follow-up was 66.6 months (range: 1-126 months), and the overall survival and mastectomy-free rate reached 95.7% and 90%, respectively. Thirteen patients showed side effects; four recurrences were recorded, of which 50% were out-field relapses. The 5-year Kaplan-Meier probability of local relapses, mastectomy-free, and overall survival reached 97.5%, 100%, and 98%, respectively. Conclusions: This is the first 10-year report about the effect of IORT on Mexican women with EBC in the early stages. Strict adherence to the selection criteria in this study resulted in low rates of side effects, mortality, and local recurrences, demonstrating that IORT is an effective treatment alternative for patients with EBC. Studies with a longer follow-up period should be performed, as recurrences can occur in the long term.}, } @article {pmid39574405, year = {2025}, author = {Yang, X and Duan, S and Zha, J and Jiang, T and Ye, C and Yu, S}, title = {Phosphorylated protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) expression in breast cancer is correlated with malignant proliferation and histological grading.}, journal = {Histology and histopathology}, volume = {40}, number = {7}, pages = {1131-1138}, pmid = {39574405}, issn = {1699-5848}, support = {gxbjZD2022105//Academic sponsorship project for top talents in university disciplines/ ; 2022AH052549//Science Foundation of Anhui Province, China/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/enzymology ; Cell Proliferation ; Phosphorylation ; *eIF-2 Kinase/metabolism/biosynthesis ; *Carcinoma, Ductal, Breast/pathology/enzymology ; Neoplasm Grading ; Middle Aged ; Immunohistochemistry ; *Biomarkers, Tumor/analysis/metabolism ; Aged ; Adult ; *Carcinoma, Lobular/pathology/enzymology ; Ki-67 Antigen/metabolism ; }, abstract = {This study aims to detect the expression of phosphorylated PERK in breast cancer using immunohistochemistry and explore its significance. We examined 134 cases of formalin-fixed and paraffin-embedded breast cancer tissues. It was found that the expression of phosphorylated PERK in ductal carcinoma was higher than that in lobular carcinoma, and the difference between them was statistically significant, suggesting that phosphorylated PERK played different roles in the occurrence and development of different types of breast cancer. Compared with Ki-67-negative breast cancer tissues, phosphorylated PERK has higher expression in Ki-67-positive tissues and is positively correlated with Ki67 expression, indicating that phosphorylated PERK plays an important role in breast cancer's malignant proliferation and progression. We also found a positive correlation between phosphorylated PERK expression and the histological grading of invasive ductal carcinoma, indicating that phosphorylated PERK plays an important role in the differentiation of invasive ductal carcinoma. Our study revealed the differential expression of phosphorylated PERK in subtypes of breast cancer. It contributed to the malignant proliferation of breast cancer and tissue differentiation of invasive ductal carcinoma of the breast.}, } @article {pmid39574126, year = {2024}, author = {Zhang, H and Zhao, T and Ding, J and Wang, Z and Cao, N and Zhang, S and Xie, K and Sun, J and Gao, L and Li, X and Ni, X}, title = {Differentiation between invasive ductal carcinoma and ductal carcinoma in situ by combining intratumoral and peritumoral ultrasound radiomics.}, journal = {Biomedical engineering online}, volume = {23}, number = {1}, pages = {117}, pmid = {39574126}, issn = {1475-925X}, support = {JSDW202237//Jiangsu Provincial Medical Key Discipline Construction Unit (Oncology Therapeutics (Radiotherapy))/ ; BE2022720//Social Development Project of Jiangsu Provincial Key Research & Development Plan/ ; M2020006//General Project of Jiangsu Provincial Health Commission/ ; BK20231190//Natural Science Research of Jiangsu Higher Education Institutions of China/ ; CE20235063//Changzhou Social Development Project/ ; 62371243//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Middle Aged ; *Ultrasonography ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Female ; *Breast Neoplasms/diagnostic imaging ; Diagnosis, Differential ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology ; Retrospective Studies ; Image Processing, Computer-Assisted/methods ; Adult ; Aged ; Machine Learning ; Radiomics ; }, abstract = {BACKGROUND: This study aimed to develop and validate an ultrasound radiomics model for distinguishing invasive ductal carcinoma (IDC) from ductal carcinoma in situ (DCIS) by combining intratumoral and peritumoral features.

METHODS: Retrospective analysis was performed on 454 patients from Chengzhong Hospital. The patients were randomly divided in accordance with a ratio of 8:2 into a training group (363 cases) and validation group (91 cases). In addition, 175 patients from Yanghu Hospital were used as the external test group. The peritumoral ranges were set to 2, 4, 6, 8, and 10 mm. Mann-Whitney U-test, recursive feature elimination, and a least absolute shrinkage and selection operator were used to in the dimension reduction of the radiomics features and clinical knowledge, and machine learning logistic regression classifiers were utilized to construct the diagnostic model. The area under the curve (AUC) of the receiver operating characteristics, accuracy, sensitivity, and specificity were used to evaluate the model performance.

RESULTS: By combining peritumoral features of different ranges, the AUC of the radiomics model was improved in the validation and test groups. In the validation group, the maximum increase in AUC was 9.7% (P = 0.031, AUC = 0.803) when the peritumoral range was 8 mm. Similarly, when the peritumoral range was only 8 mm in the test group, the maximum increase in AUC was 4.9% (P = 0.005, AUC = 0.770). In this study, the best prediction performance was achieved when the peritumoral range was only 8 mm.

CONCLUSIONS: The ultrasound-based radiomics model that combined intratumoral and peritumoral features exhibits good ability to distinguish between IDC and DCIS. The selection of peritumoral range size exerts an important effect on the prediction performance of the radiomics model.}, } @article {pmid39572000, year = {2024}, author = {Sakurai, K and Suzuki, S and Adachi, K and Hirano, T and Kubota, H and Sakamoto, A and Osakaya, A and Fujisaki, S and Ono, T and Tsuji, T}, title = {[Long-Term Response to CDK4/6 Inhibitor for Multiple Metastases of Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {10}, pages = {1071-1073}, pmid = {39572000}, issn = {0385-0684}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/pathology ; *Cyclin-Dependent Kinase 4/antagonists & inhibitors ; *Cyclin-Dependent Kinase 6/antagonists & inhibitors ; Middle Aged ; Time Factors ; Protein Kinase Inhibitors/therapeutic use ; Aminopyridines/therapeutic use/administration & dosage ; Benzimidazoles ; }, abstract = {The patient was a 60-year-old woman. She was diagnosed with hypertension, symptomatic epilepsy, renal failure, and cerebral infarction. During follow-up, she was found to have a mass in her left breast and was referred to our department. An irregular mass measuring 5 cm in diameter was palpated in the C region of the left breast. Multiple enlarged lymph nodes, thought to be metastases, were also palpated in the ipsilateral axillary lymph nodes. A needle biopsy revealed invasive ductal carcinoma, ER positive, PgR positive, HER2 negative, Ki-67 12%. A systemic examination revealed bone metastasis. Surgery was not possible due to comorbidities, so fulvestrant(500 mg/month)+denosumab(120 mg/month)was started. Furthermore, as the tumor markers were elevated, abemaciclib(300 mg/day)was added, which resulted in a decrease in the tumor markers. After 1 month of administration, grade 3 neutropenia was observed, so the dosage was reduced to 200 mg/day. During the course of treatment, the tumor markers rose again, so the dose was increased to 250 mg/day, which resulted in a decrease in the tumor markers and good tolerability. At present, 36 months after the start of treatment, long SD has continued, no adverse events of grade 3 or higher have been observed, and the drug has been well tolerated.}, } @article {pmid39571998, year = {2024}, author = {Adachi, K and Nagae, J and Kubota, H and Suzuki, S and Hirano, T and Saigusa, N and Henmi, T and Yagishita, H and Tsuda, H and Sakurai, K}, title = {[Early Breast Cancer Treated with Adjuvant S-1 plus Endocrine Therapy-A Report of Two Cases].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {10}, pages = {1065-1067}, pmid = {39571998}, issn = {0385-0684}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/pathology/surgery ; *Oxonic Acid/administration & dosage/therapeutic use ; Aged ; *Drug Combinations ; *Tegafur/administration & dosage/therapeutic use ; Middle Aged ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Chemotherapy, Adjuvant ; Antineoplastic Agents, Hormonal/therapeutic use ; }, abstract = {We report 2 cases of early breast cancer treated with adjuvant S-1 plus endocrine therapy. In case 1, a 70-year-old woman was diagnosed with right breast cancer and underwent partial mastectomy. The histopathological diagnosis was invasive ductal carcinoma(solid type), positive for estrogen receptor(ER)and progesterone receptor(PgR), negative for HER2/neu. The Ki-67 labeling index was 14%. The diameter of invasion was 27 mm, no lymph node metastasis was observed, and we confirmed the diagnosis as pT2N0M0, Stage ⅡA. A venous invasion was observed and the histological grade was Ⅱ. In case 2, a 53-year-old woman was diagnosed with left breast cancer and underwent lumpectomy. The histopathological findings showed a solid-tubular carcinoma, characterized by ER-positive, PgR-positive, HER2-negative. The Ki-67 labeling index was 24%. The tumor had an invasion of 20 mm and was diagnosed as Stage Ⅰ early-stage cancer, but there were some venous invasions and the histological grade was Ⅲ. We judged that both patients were at intermediate risk of recurrence and administered S-1 in addition to endocrine therapy. Even in cases without axillary lymph node metastasis, this combination of S-1 with endocrine therapy was considered to be a useful treatment option if the criteria of the POTENT trial were met.}, } @article {pmid39567714, year = {2024}, author = {Khan, B and Qahwaji, R and Alfaifi, MS and Athar, T and Khan, A and Mobashir, M and Ashankyty, I and Imtiyaz, K and Alahmadi, A and Rizvi, MMA}, title = {Deciphering molecular landscape of breast cancer progression and insights from functional genomics and therapeutic explorations followed by in vitro validation.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {28794}, pmid = {39567714}, issn = {2045-2322}, mesh = {Humans ; *Breast Neoplasms/genetics/pathology/drug therapy ; Female ; *Gene Expression Regulation, Neoplastic ; Genomics/methods ; Gene Regulatory Networks ; Disease Progression ; Biomarkers, Tumor/genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/pathology/drug therapy ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/drug therapy ; Molecular Docking Simulation ; Gene Expression Profiling ; Prognosis ; Cell Line, Tumor ; }, abstract = {Breast cancer is caused by aberrant breast cells that proliferate and develop into tumors. Tumors have the potential to spread throughout the body and become lethal if ignored. Metastasis is the process by which invasive tumors move to neighboring lymph nodes or other organs. Metastasis can be lethal and perhaps fatal. The objective of our study was to elucidate the molecular mechanisms underlying the transition of Ductal Carcinoma In Situ (DCIS) to Invasive Ductal Carcinoma (IDC), with a particular focus on hub genes and potential therapeutic agents. Using Weighted Gene Co-expression Network Analysis (WGCNA), we built a comprehensive network combining clinical and phenotypic data from both DCIS and IDC. Modules within this network, correlated with specific phenotypic traits, were identified, and hub genes were identified as critical markers. Receiver Operating Characteristic (ROC) analysis assessed their potential as biomarkers, while survival curve analysis gauged their prognostic value. Furthermore, molecular docking predicted interactions with potential therapeutic agents. Ten hub genes-CDK1, KIF11, NUF2, ASPM, CDCA8, CENPF, DTL, EXO1, KIF2C, and ZWINT-emerged as pivotal fibroblast-specific genes potentially involved in the DCIS to IDC transition. These genes exhibited pronounced positive correlations with key pathways like the cell cycle and DNA repair, Molecular docking revealed Fisetin, an anti-inflammatory compound, effectively binding to both CDK1 and DTL underscoring their role in orchestrating cellular transformation. CDK1 and DTL were selected for molecular docking with CDK1 inhibitors, revealing effective binding of Fisetin, an anti-inflammatory compound, to both. Of the identified hub genes, DTL-an E3 ubiquitin ligase linked to the CRL4 complex-plays a central role in cancer progression, impacting tumor growth, invasion, and metastasis, as well as cell cycle regulation and epithelial-mesenchymal transition (EMT). CDK1, another hub gene, is pivotal in cell cycle progression and associated with various biological processes. In conclusion, our study offers insights into the complex mechanisms driving the transition from DCIS to IDC. It underscores the importance of hub genes and their potential interactions with therapeutic agents, particularly Fisetin. By shedding light on the interplay between CDK1 and DTL expression, our findings contribute to understanding the regulatory landscape of invasive ductal carcinoma and pave the way for future investigations and novel therapeutic avenues.}, } @article {pmid39566250, year = {2025}, author = {Han, M and Schmolze, D and Arias-Stella, JA and Wei, CH and Mortimer, J and Fan, F}, title = {Poor response of HER2-positive mucinous carcinomas of breast to neoadjuvant HER2-targeted therapy: A study of four cases.}, journal = {Annals of diagnostic pathology}, volume = {74}, number = {}, pages = {152396}, doi = {10.1016/j.anndiagpath.2024.152396}, pmid = {39566250}, issn = {1532-8198}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/drug therapy/metabolism ; *Erb-b2 Receptor Tyrosine Kinases/metabolism ; *Neoadjuvant Therapy/methods ; *Adenocarcinoma, Mucinous/pathology/metabolism/drug therapy/therapy ; Middle Aged ; Adult ; Aged ; Carcinoma, Ductal, Breast/pathology/metabolism/drug therapy/therapy ; Treatment Outcome ; Trastuzumab/therapeutic use ; Molecular Targeted Therapy/methods ; }, abstract = {BACKGROUND: Breast mucinous carcinoma (MC) is typically positive for estrogen receptor (ER) and progesterone receptor (PR) expressions and negative for human epidermal growth factor receptor (HER2) overexpression. HER2 positive MC is a rare entity; its response to neoadjuvant HER2-targeted therapy remains unclear.

METHODS: Four cases of HER2 positive MC and seven cases of HER2 positive invasive ductal carcinoma with mucinous features (MCF) were identified. Clinicopathologic features were collected. Patients' germline data was gathered if available. Tumor's response to HER2-directed treatment were recorded and compared.

RESULTS: Two HER2 positive MCs were treated with neoadjuvant HER2-directed treatment and showed no response in the subsequent surgical resection specimens including one positive lymph node showing no treatment effect. One patient had upfront surgery. The fourth patient presented with advanced stage and showed progression on HER2-directed treatment. Six HER2 positive MCFs received neoadjuvant HER2-directed therapy; two cases showed complete pathologic response and four had only minimal residual carcinomas in the breast. Two cases with positive lymph nodes had complete response in the lymph nodes. The seventh patient presented at an advanced stage and was stable on HER2-directed treatment.

CONCLUSIONS: Our findings suggest that HER2 positive MCs may be resistant to HER2-directed treatment. This is in contrast with the excellent treatment response observed in HER2 positive MCFs. It is important to report mucinous carcinoma percentage in biopsies on HER2 positive tumors as it may be related to treatment response. Further investigation of the underlying mechanisms may help optimize clinical management in this patient population.}, } @article {pmid39563922, year = {2024}, author = {Santhanam, H and Muthukumarasamy, N and Hsieh, MK and Brust, K and Wellington, M and Naito, T and Samuelson, RJ and Marra, AR and Kobayashi, T}, title = {Systematic review and meta-analysis of the impact of infectious diseases consultation on outcomes of Staphylococcus aureus bacteremia in children.}, journal = {Antimicrobial stewardship & healthcare epidemiology : ASHE}, volume = {4}, number = {1}, pages = {e199}, pmid = {39563922}, issn = {2732-494X}, abstract = {For adult patients with Staphylococcus aureus bacteremia (SAB), Infectious Diseases consultation (IDC) significantly lowers mortality and recurrence rate. Our systematic review and meta-analysis demonstrate that IDC is also associated with significantly lower mortality in children with SAB. Analysis of the impact of IDC on pediatric recurrence rates revealed moderate heterogeneity.}, } @article {pmid39560723, year = {2024}, author = {Cendrowski, J and Wrobel, M and Mazur, M and Jary, B and Maurya, R and Wang, S and Korostynski, M and Dziewulska, A and Rohm, M and Kuropka, P and Pudelko-Malik, N and Mlynarz, P and Dobrzyn, A and Zeigerer, A and Miaczynska, M}, title = {NFκB and JNK pathways mediate metabolic adaptation upon ESCRT-I deficiency.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {81}, number = {1}, pages = {458}, pmid = {39560723}, issn = {1420-9071}, support = {POIR.04.04.00-00-1C54/16-00//Fundacja na rzecz Nauki Polskiej/ ; POIR.04.04.00-00-20CE/16-00//Fundacja na rzecz Nauki Polskiej/ ; }, mesh = {*Endosomal Sorting Complexes Required for Transport/metabolism/genetics ; Humans ; *NF-kappa B/metabolism ; *Glycolysis/genetics ; Lysosomes/metabolism ; MAP Kinase Signaling System ; Mitochondria/metabolism ; Adaptation, Physiological/genetics ; Transcription Factors/metabolism/genetics ; Glucose/metabolism ; DNA-Binding Proteins ; Tsg101 Protein ; }, abstract = {Endosomal Sorting Complexes Required for Transport (ESCRTs) are crucial for delivering membrane receptors or intracellular organelles for lysosomal degradation which provides the cell with lysosome-derived nutrients. Yet, how ESCRT dysfunction affects cell metabolism remained elusive. To address this, we analyzed transcriptomes of cells lacking TSG101 or VPS28 proteins, components of ESCRT-I subcomplex. ESCRT-I deficiency reduced the expression of genes encoding enzymes involved in oxidation of fatty acids and amino acids, such as branched-chain amino acids, and increased the expression of genes encoding glycolytic enzymes. The changes in metabolic gene expression were associated with Warburg effect-like metabolic reprogramming that included intracellular accumulation of lipids, increased glucose/glutamine consumption and lactate production. Moreover, depletion of ESCRT-I components led to expansion of the ER and accumulation of small mitochondria, most of which retained proper potential and performed ATP-linked respiration. Mechanistically, the observed transcriptional reprogramming towards glycolysis in the absence of ESCRT-I occurred due to activation of the canonical NFκB and JNK signaling pathways and at least in part by perturbed lysosomal degradation. We propose that by activating the stress signaling pathways ESCRT-I deficiency leads to preferential usage of extracellular nutrients, like glucose and glutamine, for energy production instead of lysosome-derived nutrients, such as fatty acids and branched-chain amino acids.}, } @article {pmid39557919, year = {2024}, author = {Rusak, A and Kątnik, E and Górnicki, T and Schmuttermaier, C and Kujawa, K and Piotrowska, A and Ratajczak-Wielgomas, K and Kmiecik, A and Wojnar, A and Dzięgiel, P and Kzhyshkowska, J}, title = {New insights into the role of the CHI3L2 protein in invasive ductal breast carcinoma.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {28529}, pmid = {39557919}, issn = {2045-2322}, support = {2021/05/X/NZ2/01698//National Science Center, Poland (NCN)/ ; }, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/metabolism/pathology/genetics ; *Breast Neoplasms/metabolism/pathology/genetics ; Middle Aged ; STAT3 Transcription Factor/metabolism ; Cell Line, Tumor ; Phosphorylation ; Chitinase-3-Like Protein 1/metabolism/genetics ; Gene Expression Regulation, Neoplastic ; Adult ; Macrophages/metabolism ; Aged ; MAP Kinase Signaling System ; Chitinases ; }, abstract = {Chitinase-like proteins have multiple biological functions that promote tumor growth, angiogenesis and metastasis. Expression of CHI3L2, which is similar in structure to CHI3L1, is detected in glioma cells and tumor-associated macrophages (TAMs) in glioma and breast cancer. However, its exact role remains unclear. We analyzed the expression of CHI3L2 in 74 invasive ductal breast carcinoma (IDC) tumors, breast cancer and macrophages cell cultures using immunohistochemistry, immunofluorescence, Western blot and PCR methods. Clinicopathologic data were included in the analysis. The results obtained show that CHI3L2 expression decreases with increasing degree of tumor grade and negative status of estrogen (ER) and progesterone receptors (PR). Furthermore, CHI3L2 is significantly and positively correlated with phosphorylation of STAT-3 and ERK1/2 signaling pathways, but negatively correlated with macrophage infiltration. CHI3L2 is expressed both in the cytoplasm of cancer cells and in macrophages and may regulate STAT-3 and ERK1/2 phosphorylation in breast cancer cell lines. Analysis of the clinicopathologic data revealed that CHI3L2 levels had no effect on patient survival. CHI3L2 expression may be specific for cancer cells in IDC and involved in cross-talk with the tumor microenvironment. Our study has shown that IDC cancer cells express the CHI3L2 protein, possibly indicating a novel function of this protein.}, } @article {pmid39555338, year = {2024}, author = {Diwaker, P and Jha, T and Gogoi, P and Arora, VK and Ansari, MA and Kaur, N}, title = {Expression of Immune Checkpoint Regulator Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) and Programmed Cell Death Protein Ligand 1 (PD-L1) in Invasive Ductal Carcinoma Breast.}, journal = {Indian journal of surgical oncology}, volume = {15}, number = {4}, pages = {713-720}, pmid = {39555338}, issn = {0975-7651}, abstract = {Despite significant advancement in the diagnostic and therapeutic aspects of breast carcinoma, the prognosis remains dismal. Recently, with advances in its understanding, various immune system-based management strategies have been developed. CTLA-4 suppresses lymphocyte reactivity, IL-2 secretion, and IL-2 receptor expression and triggers cell cycle arrest. PD-L1 inhibits the proliferation and cytotoxicity of T cells and inhibits release of cytokines. Hence, we planned to evaluate the immunoexpression of CTLA-4 and PD-L1 in invasive ductal carcinoma breast and seek correlation between their immunopositivity and the clinicopathological parameters. This was a retrospective study conducted on archival material of 50 cases of breast carcinoma tissue microarrays. Clinicopathological details were recorded. All cases were evaluated for immunohistochemical expression of CTLA-4 and PD-L1. Cytoplasmic expression of CTLA-4 and membranous expression of PD-L1 were considered positive and staining intensity was recorded as mild, moderate, and intense. Data was recorded and analyzed. Immunopositivity for CTLA-4 was seen in 92% of cases of breast carcinoma. CTLA-4 staining intensity showed significant association with TNM staging of breast carcinomas (p = 0.036). Age group of the breast carcinoma cases showed a statistically significant correlation with PD-L1 immunoexpression (p = 0.002). No significant correlation was found between all other clinicopathological characteristics and CTLA-4 or PD-L1 immunostaining. Our study shows that CTLA-4 is a more important immune checkpoint regulator in breast carcinomas in comparison to PD-L1. Thus, anti-CTLA-4 immunotherapy might prove to be of immense help in the treatment of invasive ductal carcinoma breast showing overexpression of CTLA-4.}, } @article {pmid39555003, year = {2025}, author = {Wickins, J and Rickard, CM and Kasper, K and Morton, L and Doellinger, J and Thomas-Gabbett, P and Marsh, N}, title = {Indwelling urinary catheter use and adherence to clinical practice guidelines: A point prevalence study in adult hospital inpatients.}, journal = {Journal of infection prevention}, volume = {26}, number = {1}, pages = {11-18}, pmid = {39555003}, issn = {1757-1774}, abstract = {BACKGROUND: Approximately 25% of hospitalised adults require an indwelling urinary catheter (IDC) during their hospital stay. IDCs expose patients to risks of infectious and non-infectious complications.

AIMS: To identify IDC prevalence, assess adherence to clinical practice guidelines and patient-reported involvement in IDC care for adult hospital inpatients.

METHODS: This point prevalence study was conducted in 22 wards in a single quaternary hospital. Data was collected by clinical and research nurses working in pairs on a single day. Study outcomes were reported descriptively as frequencies and percentages.

RESULTS: Of 502 patients included, 77 (15.3%) had an IDC (median duration 99.6 h). The median age of patients with an IDC was 64 years (interquartile range 22-88 years), 54 (70%) were male and one-quarter (n = 19; 25%) of IDCs were inserted at another hospital. More than half (n = 44; 57%) of the 77 IDCs had no documented removal plan. Three patients were unavailable for review for observed clinical practices, and it was found 43% (n = 32/74) lacked a securement device. Of 77 people with IDCs, there were 44 patient responses, and 27 (61.4%) patients did not know the reason for their catheter.

DISCUSSION: Areas for improvement included securement device use, timely removal plans and patient education for the reason for the device. Regular point prevalence studies to assess use and adherence to clinical practical guidelines can improve safety outcomes for patients requiring IDCs.}, } @article {pmid39553033, year = {2024}, author = {Louis, M and Tapia, R and Grabill, N and Strom, P}, title = {Dormancy Leading to Late Recurrence in Breast Cancer: A Case of Hormone Receptor-Positive Supraclavicular Metastasis 10 Years After the Initial Treatment.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e71586}, pmid = {39553033}, issn = {2168-8184}, abstract = {Breast cancer recurrence can occur many years after the initial treatment, particularly in hormone receptor-positive (HR+) cases, where the risk of late recurrence remains significant. Late recurrences are well documented, with research showing that they can happen even decades after the primary diagnosis, necessitating extended monitoring and personalized therapeutic approaches. A 65-year-old woman with a history of stage IIIC invasive ductal carcinoma, initially treated with neoadjuvant chemotherapy, bilateral mastectomies, adjuvant chemoradiation, and prolonged hormonal therapy, presented 10 years later with metastasis to the left supraclavicular lymph nodes. A biopsy confirmed recurrent ER+/PR+/HER2- (estrogen receptor-positive/progesterone receptor-positive/human epidermal growth factor receptor 2-negative) breast cancer. Her treatment was adjusted to include Faslodex (fulvestrant) and Verzenio (abemaciclib), followed by the surgical resection of the metastatic lymph node. Managing HR+ breast cancer involves significant challenges, mainly due to the potential for late recurrence. Even after aggressive treatment and years of remission, dormant tumor cells may become active again, leading to metastasis in less common sites, like the supraclavicular lymph nodes. This situation demands a tailored therapeutic approach, adjusting treatment strategies to address the specific characteristics of the recurrent tumor. In conclusion, late recurrence in HR+ breast cancer requires vigilant long-term follow-up and personalized treatments to effectively manage recurrence risk. Understanding dormancy and reactivation mechanisms is essential for guiding clinical decisions. Prioritizing individualized follow-up strategies and refining treatment protocols will be key to improving patient outcomes and maintaining quality of life.}, } @article {pmid39546873, year = {2025}, author = {Dong, B and Zhu, X and An, T and Jiang, H and Ma, B}, title = {Barrier-critic-disturbance approximate optimal control of nonzero-sum differential games for modular robot manipulators.}, journal = {Neural networks : the official journal of the International Neural Network Society}, volume = {181}, number = {}, pages = {106880}, doi = {10.1016/j.neunet.2024.106880}, pmid = {39546873}, issn = {1879-2782}, mesh = {*Robotics/instrumentation ; *Neural Networks, Computer ; *Algorithms ; Game Theory ; Computer Simulation ; Feedback ; Torque ; }, abstract = {In this paper, for addressing the safe control problem of modular robot manipulators (MRMs) system with uncertain disturbances, an approximate optimal control scheme of nonzero-sum (NZS) differential games is proposed based on the control barrier function (CBF). The dynamic model of the manipulator system integrates joint subsystems through the utilization of joint torque feedback (JTF) technique, incorporating interconnected dynamic coupling (IDC) effects. By integrating the cost functions relevant to each player with the CBF, the evolution of system states is ensured to remain within the safe region. Subsequently, the optimal tracking control problem for the MRM system is reformulated as an NZS game involving multiple joint subsystems. Based on the adaptive dynamic programming (ADP) algorithm, a cost function approximator for solving Hamilton-Jacobi (HJ) equation using only critic neural networks (NN) is established, which promotes the feasible derivation of the approximate optimal control strategy. The Lyapunov theory is utilized to demonstrate that the tracking error is uniformly ultimately bounded (UUB). Utilizing the CBF's state constraint mechanism prevents the robot from deviating from the safe region, and the application of the NZS game approach ensures that the subsystems of the MRM reach a Nash equilibrium. The proposed control method effectively addresses the problem of safe and approximate optimal control of MRM system under uncertain disturbances. Finally, the effectiveness and superiority of the proposed method are verified through simulations and experiments.}, } @article {pmid39541956, year = {2025}, author = {Abdelwahab, RM and Aghazadeh Mohandesi, N and Sturgis, CD and Alavi, A}, title = {Squamous Metaplasia of Lactiferous Ducts (Zuska's Disease) of the Breast: Clinical and Histopathologic Manifestations.}, journal = {Dermatology (Basel, Switzerland)}, volume = {241}, number = {2}, pages = {210-215}, doi = {10.1159/000542622}, pmid = {39541956}, issn = {1421-9832}, mesh = {Humans ; Female ; Middle Aged ; Adult ; Metaplasia/pathology ; Retrospective Studies ; Aged ; *Breast Diseases/pathology ; Aged, 80 and over ; Smoking/adverse effects ; *Breast/pathology ; *Mammary Glands, Human/pathology ; }, abstract = {INTRODUCTION: Squamous metaplasia of lactiferous duct (SMOLD), also known as Zuska's disease, is an uncommon, recurrent inflammatory fistulizing disease of the breast that strongly correlates with smoking in premenopausal patients. Clinical and imaging findings may overlap with other breast conditions. SMOLD is well recognized by breast pathologists; however, the dermatology literature on this condition remains scarce.

METHODS: In this retrospective study, we reviewed 29 patients with SMOLD diagnosed at Mayo Clinic.

RESULTS: The mean age of the patient cohort is 50.3 with a range of 30 to 81 years. One patient (3.7%) had hidradenitis suppurativa of the retroareolar area. Patient smoking history demonstrated prior/current smokers of 37.9% (11/29), lifetime nonsmokers with significant secondhand exposure 6.9% (2/29), and unknown smoking status 3.4% (1/29). One patient had a personal history of invasive ductal carcinoma, and 10.3% (3/29) had a history of breast cancer in a first-degree relative. The clinical presentation of the patient cohort includes areolar papules, nodules, and draining tract/fistula 13.7% (4/29); pustular cyst/abscess on the breast 13.7% (4/29); breast mass 3.4% (1/29); pain breast discomfort/pain 13.7% (4/29); nipple retraction 3.4% (1/29); and asymptomatic with nipple calcifications on mammogram 3.4% (1/29). A total of 77.8% (7/9) of patients with bacterial cultures demonstrated polymicrobial growth. Overall, 37.9% (11/29) of patients received at least one round of antibiotic therapy. In total, 27.6% (8/29) of patients underwent invasive intervention. Staphylococcus, Streptococcus, and Cutibacterium species were the most frequent causes of infection in our patient cohort.

CONCLUSIONS: We confirm previous findings of strong association between SMOLD and current/former smoking status and a potential, novel correlation between extensive secondhand exposure and SMOLD development. While both medical and surgical interventions are employed in patient management, many patients ultimately require complete excision of the involved duct(s). Dermatologists should consider SMOLD in the differential diagnosis of patients presenting with breast abscess, fistulizing tracts with mass, and breast pain.}, } @article {pmid39520846, year = {2024}, author = {Turk, A and Metin, TO and Kuloglu, T and Yilmaz, M and Artas, G and Ozercan, IH and Hancer, S}, title = {Isthmin-1 and spexin as promising novel biomarker candidates for invasive ductal breast carcinoma.}, journal = {Tissue & cell}, volume = {91}, number = {}, pages = {102601}, doi = {10.1016/j.tice.2024.102601}, pmid = {39520846}, issn = {1532-3072}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/metabolism/pathology ; *Biomarkers, Tumor/metabolism ; *Breast Neoplasms/metabolism/pathology ; Middle Aged ; *Peptide Hormones/metabolism ; Adult ; Aged ; Blood Proteins/metabolism ; Neoplasm Invasiveness ; }, abstract = {INTRODUCTION: Breast cancer is one of the most common malignant tumors and a leading cause of cancer-related death in women. Research is focusing on biomarkers linked to breast cancer, particularly two novel proteins: isthmin-1 (ISM-1) and spexin (SPX), which require further investigation.

MATERIAL AND METHODS: The study involved 20 healthy controls and 60 patients with invasive ductal carcinoma, categorized into three groups: Grade I (n=20), Grade II (n=20), and Grade III (n=20). Levels of ISM-1 and SPX in tissue were analyzed using immunohistochemistry alongside the clinicopathologic data of patients.

RESULTS: There were no statistically significant differences in age, menopausal status, ER, PR, and Cerb-B2 values across grades (p>0.05). Tumor diameters showed a significant increase in Grade I compared to Grade II (p<0.05), while no significant difference was noted between Grade II and Grade III, although diameters were larger in Grade III compared to Grade I (p<0.05). Notably, ISM-1 immunoreactivity decreased, and SPX immunoreactivity increased significantly across all grades compared to normal tissue (p<0.05), with no significant differences between tumor grades for these markers (p>0.05).

CONCLUSIONS: This study presents new findings on ISM-1 and SPX expression in invasive ductal breast carcinoma. The decrease in ISM-1 and increase in SPX suggest a need for further research into the relationship between adipokines and tumor development in breast cancer.}, } @article {pmid39519098, year = {2024}, author = {Kim, YJ and Nanda, SS and Jiang, F and Pyo, SY and Han, JY and Koh, SS and Kang, TH}, title = {Pancreatic Adenocarcinoma Up-Regulated Factor (PAUF) Transforms Human Monocytes into Alternative M2 Macrophages with Immunosuppressive Action.}, journal = {International journal of molecular sciences}, volume = {25}, number = {21}, pages = {}, pmid = {39519098}, issn = {1422-0067}, mesh = {Humans ; *Pancreatic Neoplasms/pathology/metabolism/immunology ; *Monocytes/metabolism/immunology ; *Cell Differentiation ; *Macrophages/metabolism/immunology ; *Tumor Microenvironment/immunology ; Toll-Like Receptor 2/metabolism ; Tumor-Associated Macrophages/metabolism/immunology ; Cell Proliferation ; Adenocarcinoma/pathology/metabolism/immunology ; Cell Line, Tumor ; Intercellular Signaling Peptides and Proteins ; }, abstract = {Tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) promote immune evasion, cancer cell proliferation, and metastasis. Ongoing research is focused on finding ways to prevent tumor growth by inhibiting TAM polarization, which has shown a correlation with unfavorable prognosis in clinical studies. Pancreatic adenocarcinoma up-regulated factor (PAUF) is a protein secreted from pancreatic cancer (PC) and acts as a TME modulator that affects the TME by acting on not only cancer cells but also stromal cells and immune cells. Tumor cells can evade the immune system by PAUF binding to Toll-like receptor (TLR) in monocytes, as this research shows. In this study, the examination centered around the recruitment of human monocytes by PAUF and the subsequent differentiation into macrophages. In an in vitro chemotaxis assay, PAUF induced chemotactic migration of TLR2-mediated monocytes. In addition, PAUF induced differentiation of monocytes into M2 macrophages, which was verified based on expressing surface markers and cytokines and morphological analysis. The inhibition of T cell proliferation and function was observed in differentiated M2 macrophages. To conclude, these findings indicate that PAUF functions as a promoter of cancer progression by regulating the recruitment and differentiation of macrophages within TMEs, ultimately causing immunosuppression.}, } @article {pmid39519012, year = {2024}, author = {Newman, NA and Burke, MA}, title = {Dilated Cardiomyopathy: A Genetic Journey from Past to Future.}, journal = {International journal of molecular sciences}, volume = {25}, number = {21}, pages = {}, pmid = {39519012}, issn = {1422-0067}, mesh = {Humans ; *Cardiomyopathy, Dilated/genetics ; *Genetic Predisposition to Disease ; Genetic Testing ; }, abstract = {Dilated cardiomyopathy (DCM) is characterized by reduced systolic function and cardiac dilation. Cases without an identified secondary cause are classified as idiopathic dilated cardiomyopathy (IDC). Over the last 35 years, many cases of IDC have increasingly been recognized to be genetic in etiology with a core set of definitively causal genes in up to 40% of cases. While over 200 genes have been associated with DCM, the evidence supporting pathogenicity for most remains limited. Further, rapid advances in sequencing and bioinformatics have recently revealed a complex genetic spectrum ranging from monogenic to polygenic in DCM. These advances have also led to the discovery of causal and modifier genetic variants in secondary forms of DCM (e.g., alcohol-induced cardiomyopathy). Current guidelines recommend genetic counseling and screening, as well as endorsing a handful of genotype-specific therapies (e.g., device placement in LMNA cardiomyopathy). The future of genetics in DCM will likely involve polygenic risk scores, direct-to-consumer testing, and pharmacogenetics, requiring providers to have a thorough understanding of this rapidly developing field. Herein we outline three decades of genetics in DCM, summarize recent advances, and project possible future avenues for the field.}, } @article {pmid39518634, year = {2024}, author = {Sicras Mainar, A and Salazar-Mendiguchía, J and Del Campo Alonso, MI and Echeto, A and Vilanova Larena, D and Comín Colet, J}, title = {Consequences of the Poor Anticoagulation Control of Patients with Non-Valvular Atrial Fibrillation Treated with Vitamin K Antagonists.}, journal = {Journal of clinical medicine}, volume = {13}, number = {21}, pages = {}, pmid = {39518634}, issn = {2077-0383}, support = {NA//Bristol Myers Squibb/ ; }, abstract = {Background: The prevention of thromboembolisms through anticoagulation and heart rate control is crucial in managing non-valvular atrial fibrillation (NVAF). This study aimed to analyze the consequences of poor anticoagulation control with vitamin K antagonists (VKAs) in Spanish patients with NVAF, focusing on thrombotic events, bleeding, mortality, healthcare resources (HRU), and costs. Methods: This observational, retrospective study used electronic medical records (BIG-PAC[®] database) of NVAF patients who started VKA treatment between 1 January 2016 and 31 December 2018. Patients were followed up for two years and classified by poor or adequate anticoagulation control. Demographic and clinical characteristics, treatments, incidence of cardiovascular events, mortality rates, HRU, and costs were analyzed. Results: Patients with poor control (n = 2136) had a 75% greater probability of suffering a cardiovascular event compared to patients with adequate control (n = 2351) (HR, 1.75 [95%CI: 1.43-2.14; p < 0.001]). Cardiovascular events, major bleeding, minor bleeding, systemic thromboembolism, and ischemic strokes were reduced by 32.1%, 46.2%, 29.6%, 22.2%, and 16.1%, respectively. It was estimated that adequate anticoagulant control saved EUR 455/patient with NAVF due to reduced hospitalization for cardiovascular events. Conclusions: For VKA-treated NVAF patients, poor anticoagulation control was associated with a higher number of cardiovascular events, greater consumption of HRU, and higher management costs than for patients with adequate control.}, } @article {pmid39513960, year = {2025}, author = {Huang, H and Couch, RE and Karam, R and Hu, C and Boddicker, N and Polley, EC and Na, J and Ambrosone, CB and Yao, S and Trentham-Dietz, A and Eliassen, AH and Penney, K and Brantley, K and Bodelon, C and Teras, LR and Hodge, J and Patel, A and Haiman, CA and John, EM and Neuhausen, SL and Martinez, E and Lacey, JV and O'Brien, KM and Sandler, DP and Weinberg, CR and Palmer, JR and Bertrand, KA and Vachon, CM and Olson, JE and Ruddy, KE and Anton-Culver, H and Ziogas, A and Goldgar, DE and Nathanson, KL and Domchek, SM and Weitzel, JN and Kraft, P and Dolinsky, JS and Pesaran, T and Richardson, ME and Yadav, S and Couch, FJ}, title = {Pathogenic Variants in Cancer Susceptibility Genes Predispose to Ductal Carcinoma In Situ of the Breast.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {31}, number = {1}, pages = {130-138}, pmid = {39513960}, issn = {1557-3265}, support = {R01 CA225662/CA/NCI NIH HHS/United States ; R35CA253187//National Cancer Institute (NCI)/ ; //Breast Cancer Research Foundation (BCRF)/ ; P50CA116201//National Cancer Institute (NCI)/ ; U01 CA164974/CA/NCI NIH HHS/United States ; K12 CA090628/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; R01CA225662//National Cancer Institute (NCI)/ ; P30 CA062203/CA/NCI NIH HHS/United States ; K12CA090628//National Cancer Institute (NCI)/ ; R35 CA253187/CA/NCI NIH HHS/United States ; T32 CA009001/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Genetic Predisposition to Disease ; *Breast Neoplasms/genetics/pathology/epidemiology ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/epidemiology ; Middle Aged ; Adult ; *Germ-Line Mutation ; Aged ; Carcinoma, Ductal, Breast/genetics/pathology/epidemiology ; }, abstract = {PURPOSE: To determine the relationship between germline pathogenic variants (PV) in cancer predisposition genes and the risk of ductal carcinoma in situ (DCIS).

EXPERIMENTAL DESIGN: Germline PV frequencies in breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, PALB2, RAD51C, and RAD51D) were compared between DCIS cases and unaffected controls and between DCIS and invasive ductal breast cancer (IDC) cases from a clinical testing cohort (n = 9,887), a population-based cohort (n = 3,876), and the UK Biobank (n = 2,421). The risk of contralateral breast cancer (CBC) for DCIS cases with PV was estimated in the population-based cohort.

RESULTS: Germline PV were observed in 6.5% and 4.6% of women with DCIS in the clinical testing and population-based cohorts, respectively. BRCA1, BRCA2, and PALB2 PV frequencies were significantly lower among women with DCIS than those with IDC (clinical cohort: 2.8% vs. 5.7%; population-based cohort: 1.7% vs. 3.7%), whereas the PV frequencies for ATM and CHEK2 were similar. ATM, BRCA1, BRCA2, CHEK2, and PALB2 PV were significantly associated with an increased risk of DCIS (OR > 2.0), but only BRCA2 PV were associated with high risk (OR > 4) in both cohorts. The cumulative incidence of CBC among carriers of PV in high-penetrance genes with DCIS was 23% over 15 years.

CONCLUSIONS: The enrichment of PV in ATM, BRCA1, BRCA2, CHEK2, and PALB2 among women with DCIS suggests that multigene panel testing may be appropriate for women with DCIS. Elevated risks of CBC in carriers of PV in high-penetrance genes with DCIS confirmed the utility of testing for surgical decision-making.}, } @article {pmid39512981, year = {2024}, author = {Eshaqi, MJ and Al Shamsi, SA and Al Saidi, AM and Mahesh, S}, title = {Clinical Insights Into Ductal Carcinoma In Situ in Males: A Report of Two Cases From the Sultanate of Oman.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e71071}, pmid = {39512981}, issn = {2168-8184}, abstract = {Breast cancer is a disease that predominantly affects the female population; however, rarely it can manifest in males, yet its etiology remains poorly elucidated. The scarcity of literature reviews and case reports done on male breast cancer in comparison to the female counterpart makes it difficult to understand the risk factors, treatment options, and extension of the disease. Moreover, high-grade ductal carcinoma in situ (DCIS) is exceptionally uncommon among male patients. The prognosis for male patients diagnosed with DCIS is similar to that of females at the same disease stage making early recognition and diagnosis significant. However, more efforts are being made to understand the clinical presentation, increase awareness, and acknowledge the etiology of this disease. This study addresses this gap by presenting two distinctive cases of invasive ductal carcinoma in males from the Sultanate of Oman. The aim of this study is to contribute to the growing efforts in comprehending the unclear landscape of male breast cancer, fostering awareness, and advancing knowledge of its etiology.}, } @article {pmid39506855, year = {2024}, author = {Kook, Y and Lee, YJ and Chu, C and Jang, JS and Baek, SH and Bae, SJ and Cha, YJ and Gong, G and Jeong, J and Lee, SB and Ahn, SG}, title = {Differentiating HER2-low and HER2-zero tumors with 21-gene multigene assay in 2,295 h + HER2- breast cancer: a retrospective analysis.}, journal = {Breast cancer research : BCR}, volume = {26}, number = {1}, pages = {154}, pmid = {39506855}, issn = {1465-542X}, support = {2021M3H9A2096954//National Research Foundation of Korea/ ; RS-2024-00343001//Korean government/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/mortality/drug therapy ; *Erb-b2 Receptor Tyrosine Kinases/genetics/metabolism ; Retrospective Studies ; Middle Aged ; *Biomarkers, Tumor/genetics ; Adult ; Aged ; Gene Expression Profiling ; Immunohistochemistry ; Prognosis ; }, abstract = {BACKGROUND: HER2-positivity is an essential marker for therapeutic decisions, while HER2 expression is heterogenous. In recent years, there has been increasing recognition of a subgroup of breast cancer patients who have low levels of HER2 expression, also known as HER2-low because trastuzumab deruxtecan offers clinical benefit for patients with HER2-low metastatic breast cancer. Despite the growing interest in HER2-low breast cancer, there is limited research on how multigene assays can help differentiate between HER2-low and HER2-negative breast cancer. Among HR + HER2- breast cancer, we compared genomic characteristics between HER2-low and HER2-zero using the 21-gene assay.

METHODS: A retrospective review of clinical records was performed in 2,295 patients who underwent Oncotype DX[®] test in two hospitals between 2013 and 2020. Patients were classified into two groups as the HER2-zero and HER2-low based on HER2 immunohistochemistry. In cases with HER2 2+, no amplification of HER2 gene was confirmed by silver in situ hybridization. High genomic risk was defined as cases with 21-gene recurrence score (RS) > 25. Multivariable binary logistic-regression analysis was performed.

RESULTS: Of these, 944 (41.1%) patients were assigned to the HER2-zero group, while 1351 (58.9%) patients were assigned to the HER2-low group. The average Recurrence Score (RS) was found to be 17.802 in the HER2-zero breast cancer group and 18.503 in the HER2-low group, respectively (p-value < 0.005). When comparing the proportion of high RS between the two groups, the HER2-zero group had a high RS rate of 12.4% (117 out of 944), while the HER2-low group had a high RS rate of 17.0% (230 out of 1351) (p = 0.002). The HER2 score identified by qRT-PCR was 8.912 in the HER2-zero group and 9.337 in the HER2-low group (p < 0.005). In multivariable analysis, HER2-low status was found to be an independent factor for high RS, with an odds ratio of 1.517 (1.172-1.964), independent of ER, PR, and Ki67. Within the subgroup of patients with invasive ductal carcinoma, the high RS rates were 19% in the HER2-low group and 14% in the HER2-zero group. However, when considering all patients, there were no significant differences observed in recurrence-free survival and overall survival between the HER2-low and HER2-zero groups.

CONCLUSION: Within HR + HER2- breast cancer, HER2-low tumors are associated with high RS, especially for histologically invasive ductal carcinoma. A prognostic influence of HER2-low expression among HR + HER2- breast cancer remains as an area that requires further study.}, } @article {pmid39506270, year = {2025}, author = {Li, W and Zhao, Y and Fei, X and Wu, Y and Zhan, W and Zhou, W and Xia, S and Song, Y and Zhou, J}, title = {Image Features and Diagnostic Value of Contrast-Enhanced Ultrasound for Ductal Carcinoma In Situ of the Breast: Preliminary Findings.}, journal = {Ultrasonic imaging}, volume = {47}, number = {2}, pages = {59-67}, doi = {10.1177/01617346241292032}, pmid = {39506270}, issn = {1096-0910}, mesh = {Humans ; Female ; Middle Aged ; *Contrast Media ; *Breast Neoplasms/diagnostic imaging/pathology ; *Ultrasonography, Mammary/methods ; Retrospective Studies ; Aged ; Adult ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology ; *Carcinoma, Ductal, Breast/diagnostic imaging ; Sensitivity and Specificity ; *Image Enhancement/methods ; }, abstract = {To explore the image features and the diagnostic value of contrast-enhanced ultrasound (CEUS) for ductal carcinoma in situ (DCIS) of the breast. A total of 96 female patients with a solitary and histologically proven DCIS were analyzed retrospectively, and 100 female cases of invasive ductal carcinoma (IDC) lesions were used as the control group. The Breast Imaging Reporting and Data System (BI-RADS) category of breast lesions was assessed according to conventional ultrasound features. The DCIS lesions were classified into mass type and non-mass type. The CEUS characteristics of these breast lesions were retrospectively analyzed qualitatively and quantitatively. The final gold standard was biopsy or surgery with histo-pathological examination. Comparing the ultrasound images of DCIS with that of IDC, there were significant differences in echo pattern, calcification morphology, and calcification distribution (p < .05 for all). There was a significant difference between DCIS and IDC in enhancement intensity, perfusion defects, peripheral high enhancement, intratumoral vessels, and arrival time (AT) (p < .05 for all). In the logistic multivariate regression analysis, two indicators linked with DCIS were recognized: perfusion defects (p = .002) and peripheral high enhancement (p < .001). In forecasting DCIS, the logistic regression equation resulted in an AUC of 0.689, a specificity of 0.720, and a sensitivity of 0.563. CEUS showed differences in enhancement characteristics between DCIS and IDC, with perfusion defects and peripheral high enhancement being associated with DCIS.}, } @article {pmid39508178, year = {2024}, author = {Changrong, W and Zhibo, Z and Jufeng, G and Hongju, Y and Feng, Y and Jingjing, X}, title = {Encapsulated Papillary Carcinoma of the Breast: A Review of Clinicopathologic Characteristics, Molecular Mechanisms, and Patient Management.}, journal = {Cancer control : journal of the Moffitt Cancer Center}, volume = {31}, number = {}, pages = {10732748241299071}, pmid = {39508178}, issn = {1526-2359}, mesh = {Humans ; *Breast Neoplasms/pathology/therapy/diagnosis ; Female ; *Carcinoma, Papillary/pathology/therapy/diagnosis ; Prognosis ; }, abstract = {Encapsulated papillary carcinoma (EPC) represents a distinct entity within the spectrum of breast papillary tumors, typically manifesting as a retroareolar mass. This rare subtype can be effectively visualized using ultrasound and magnetic resonance imaging, which reveal characteristic cystic-solid nodules. Histopathologically, EPC is defined by a papillary tumor structure with a well-defined fibrous capsule, devoid of myoepithelial cells both within and around the capsule. Immunohistochemical staining for myoepithelial markers is essential to confirm the absence of these cells, thereby validating the diagnosis of EPC. At the molecular level, EPC exhibits feature similar to estrogen receptor-positive invasive ductal carcinoma (IDC), with a biological behavior that lies between ductal carcinoma in situ (DCIS) and IDC. Generally, EPC has a favorable prognosis, associated with minimal recurrence and metastatic potential. Therapeutic strategies for EPC may parallel those for DCIS, including surgical excision. Adjuvant radiotherapy is recommended following surgery for patients with concurrent DCIS or those who have undergone breast-conserving therapy. In cases with associated IDC, management prioritizes the treatment of the invasive component. High-grade EPC often requires systemic therapies due to its poorer prognosis and increased risk of lymph node involvement.}, } @article {pmid39505971, year = {2024}, author = {Olbromski, M and Mrozowska, M and Smolarz, B and Romanowicz, H and Rusak, A and Piotrowska, A}, title = {ERα status of invasive ductal breast carcinoma as a result of regulatory interactions between lysine deacetylases KAT6A and KAT6B.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {26935}, pmid = {39505971}, issn = {2045-2322}, mesh = {Humans ; Female ; *Estrogen Receptor alpha/metabolism/genetics ; *Breast Neoplasms/pathology/metabolism/genetics ; *Histone Acetyltransferases/metabolism/genetics ; *Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Cell Line, Tumor ; Middle Aged ; Gene Expression Regulation, Neoplastic ; Adult ; Histone Deacetylases/metabolism/genetics ; MCF-7 Cells ; Aged ; Lysine/metabolism ; }, abstract = {Breast cancer (BC) is the leading cause of death among cancer patients worldwide. In 2020, almost 12% of all cancers were diagnosed with BC. Therefore, it is important to search for new potential markers of cancer progression that could be helpful in cancer diagnostics and successful anti-cancer therapies. In this study, we investigated the potential role of the lysine acetyltransferases KAT6A and KAT6B in the outcome of patients with invasive breast carcinoma. The expression profiles of KAT6A/B in 495 cases of IDC and 38 cases of mastopathy (FBD) were examined by immunohistochemistry. KAT6A/B expression was also determined in the breast cancer cell lines MCF-7, BT-474, SK-BR-3, T47D, MDA-MB-231, and MDA-MB-231/BO2, as well as in the human epithelial mammary gland cell line hTERT-HME1 - ME16C, both at the mRNA and protein level. Statistical analysis of the results showed that the nuclear expression of KAT6A/B correlates with the estrogen receptor status: KAT6ANUC vs. ER r = 0.2373 and KAT6BNUC vs. ER r = 0.1496. Statistical analysis clearly showed that KAT6A cytoplasmic and nuclear expression levels were significantly higher in IDC samples than in FBD samples (IRS 5.297 ± 2.884 vs. 2.004 ± 1.072, p < 0.0001; IRS 5.133 ± 4.221 vs. 0.1665 ± 0.4024, p < 0.0001, respectively). Moreover, we noticed strong correlations between ER and PR status and the nuclear expression of KAT6A and KAT6B (nucKAT6A vs. ER, p = 0.0048; nucKAT6A vs. PR p = 0.0416; nucKAT6B vs. ER p = 0.0306; nucKAT6B vs. PR p = 0.0213). Significantly higher KAT6A and KAT6B expression was found in the ER-positive cell lines T-47D and BT-474, whereas significantly lower expression was observed in the triple-negative cell lines MDA-MB-231 and MDA-MB-231/BO2. The outcomes of small interfering RNA (siRNA)-mediated suppression of KAT6A/B genes revealed that within estrogen receptor (ER) positive and negative cell lines, MCF-7 and MDA-MB-231, attenuation of KAT6A led to concurrent attenuation of KAT6A, whereas suppression of KAT6B resulted in simultaneous attenuation of KAT6A. Furthermore, inhibition of KAT6A/B genes resulted in a reduction in estrogen receptor (ER) mRNA and protein expression levels in MCF-7 and MDA-MMB-231 cell lines. Based on our findings, the lysine acetyltransferases KAT6A and KAT6B may be involved in the progression of invasive ductal breast cancer. Further research on other types of cancer may show that KAT6A and KAT6B could serve as diagnostic and prognostic markers for these types of malignancies.}, } @article {pmid39500528, year = {2024}, author = {Degavre, C and Lepez, A and Ibanez, S and François, C and Głowacka, K and Guilbaud, C and Laloux-Morris, F and Esfahani, H and Brusa, D and Bouzin, C and Feron, O}, title = {In situ endoscopic photodynamic therapy combined with immature DC vaccination induces a robust T cell response against peritoneal carcinomatosis.}, journal = {Journal for immunotherapy of cancer}, volume = {12}, number = {11}, pages = {}, pmid = {39500528}, issn = {2051-1426}, mesh = {*Photochemotherapy/methods ; Animals ; Mice ; *Peritoneal Neoplasms/immunology/therapy/secondary ; *Dendritic Cells/immunology ; Humans ; Female ; Cancer Vaccines/therapeutic use/pharmacology/immunology ; Photosensitizing Agents/pharmacology/therapeutic use ; Cell Line, Tumor ; Vaccination/methods ; }, abstract = {BACKGROUND: Immunogenic cell death (ICD) and ferroptosis have recently emerged as key factors in the anticancer immune response. Among the treatments able to induce ICD and the associated release of danger signals is photodynamic therapy (PDT). Ferroptosis for its part results from lipid peroxidation and is induced by CD8[+] T cells to kill nearby cancer cells on IFN-γ production. We aimed to combine the two concepts, that is, to evaluate whether the strong pro-oxidant effects of PDT may promote ferroptosis and antigen release and to develop a procedure for in situ PDT to prepare the soil for highly endocytotic immature dendritic cell (iDC) adoptive transfer. This approach was implemented for managing peritoneal carcinomatosis, a lesion often associated with poor outcomes.

METHODS: We used three-dimensional (3D) heterotypic spheroids made of cancer cells, exposed them to a white light-activated OR141 photosensitizer (PS), and subsequently complexified them by adding iDC and naive lymphocytes. We next used a model of mouse peritoneal carcinomatosis and administered PDT using laparoscopy to locally induce photoactivation using the endoscope light. The immune response following adoptive transfer of iDC was tracked both in vivo and ex vivo using isolated immune cells from in situ vaccinated mice.

RESULTS: Cancer cells undergoing PDT-induced cell death significantly increased ICD markers and the infiltration of iDCs in spheroids, relying on ferroptosis. These actions induced the sequential activation of CD8[+] and CD4[+] T cells as revealed by a significant spheroid 3D structure deterioration and, remarkably, were not recapitulated by conventional ferroptosis inducer RSL3. Using LED light from an endoscope for in situ photoactivation of PS enabled us to apply the vaccination modality in mice with peritoneal tumors. Consecutive intraperitoneal injection of iDCs resulted in delayed tumor growth, increased survival rates, and prevented tumor relapse on rechallenge. CD8[+] T cell response was supported by depletion experiments, nodal detection of early activated T cells, and ex vivo T cell-induced cytotoxicity toward spheroids.

CONCLUSIONS: The combination of in situ PDT locally delivered by an endoscope light and iDC administration induces a durable memory immune response against peritoneal carcinomatosis thereby opening new perspectives for the treatment of a life-threatening condition.}, } @article {pmid39497719, year = {2024}, author = {Yu, J and Yao, T and Zhang, M and Li, B and Yao, Y}, title = {Case report: Advanced breast cancer with scalp metastases: a report of two cases.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1382415}, pmid = {39497719}, issn = {2234-943X}, abstract = {BACKGROUND: Breast cancer, identified as the most prevalent cancer worldwide, presents considerable difficulties in advanced stages, especially when involving metastatic spread. Scalp metastasis from breast cancer represents a rare and insufficiently explored occurrence. This paper seeks to illuminate this uncommon manifestation by presenting two cases of scalp metastatic breast cancer in Chinese women.

CASE REPORT: Case 1: A 45-year-old Chinese woman with a history of invasive ductal carcinoma presented with a scalp lesion indicative of recurrence. Concurrently, she was diagnosed with bone metastases and recurrence at the original site. Despite undergoing various treatments, including chemotherapy and hormonal therapy, her condition worsened, ultimately leading to her passing. Case 2: A 40-year-old Chinese woman was initially diagnosed with bilateral breast invasive mucinous carcinoma presenting with bilateral breast masses and a scalp lesion. She also had multiple bone metastases. Following chemotherapy and hormonal therapy, her disease stabilized.

CONCLUSION: These cases of scalp metastatic breast cancer underscore the complexities involved in managing advanced stages of the disease, especially with rare metastatic manifestations. They highlight the importance of comprehensive diagnostic methods, encompassing full-body skin evaluations, and draw attention to the socioeconomic challenges faced in cancer treatment. These findings point to the necessity for more targeted research on uncommon metastatic forms in breast cancer aiming to enhance patient outcomes and refine management approaches.}, } @article {pmid39495434, year = {2025}, author = {Vadlakonda, A and Chervu, NL and Porter, G and Sakowitz, S and Lee, H and Benharash, P and Kapoor, NS}, title = {Racial disparities in presenting stage and surgical management among octogenarians with breast cancer: a national cancer database analysis.}, journal = {Breast cancer research and treatment}, volume = {210}, number = {1}, pages = {15-25}, pmid = {39495434}, issn = {1573-7217}, mesh = {Aged, 80 and over ; Female ; Humans ; Black or African American/statistics & numerical data ; *Breast Neoplasms/pathology/surgery/mortality/ethnology/epidemiology/therapy ; Databases, Factual ; *Healthcare Disparities/ethnology/statistics & numerical data ; Mastectomy ; Neoplasm Staging ; United States/epidemiology ; White ; }, abstract = {BACKGROUND: As the US faces a diverse aging population, racial disparities in breast cancer outcomes among elderly patients remain poorly understood. We evaluate the association of race with presenting stage, treatment, and survival of invasive breast cancer among octogenarians.

METHODS: Women (≥ 80 years) with invasive breast cancer were identified in 2004-2020 NCDB. To facilitate comparison, only non-Hispanic Black and non-Hispanic White patients were included; patients of Hispanic ethnicity were excluded. Demographics, tumor characteristics, and treatments were assessed by race. Overall survival was compared using the logrank test. Multivariable logistic and Cox proportional hazard regression models were developed to evaluate the independent association of race with outcomes of interest.

RESULTS: Of 222,897 patients, 19,059 (8.6%) were Black. Most patients had stage I ER + HER2- invasive ductal carcinoma. Black patients more frequently had greater comorbidities, low income and education, and advanced stage (p < 0.001 each; ref: White). Following adjustment, Black women had increased likelihood of Stage III/IV over time, as well as increased odds of chemotherapy (AOR 1.22, 95% CI 1.15 - 1.29) and non-operative management (AOR 1.82, 95% CI 1.72 - 1.92; ref: White). Although Black patients had lower survival rates compared to White, race was not associated with 5-year mortality following adjustment for stage, receipt of surgery, and adjuvant treatments (p = 0.34).

CONCLUSIONS: Inferior survival among elderly Black patients appears be driven by advanced stage at presentation. While such disparities are narrowing in the present era, future work must consider upstream interventions to ensure equitable outcomes for all races.}, } @article {pmid39483971, year = {2024}, author = {Erian, S and Davies, R and Morrison, K and West, C and Ruiz, M and Zubik, I and Nhan, J and Thompson, S}, title = {Increasing Accessibility to Intradialytic Cycling in Rural and Remote Settings: Program Report.}, journal = {Canadian journal of kidney health and disease}, volume = {11}, number = {}, pages = {20543581241287591}, pmid = {39483971}, issn = {2054-3581}, abstract = {PURPOSE OF PROGRAM: Access to exercise and rehabilitation is often lower in rural or remote areas and hemodialysis (HD) dependence imposes additional barriers. Intradialytic cycling (IDC) can improve HD-related symptoms, such as leg cramping, restless legs, and symptoms of depression, as well as physical function and fitness, but access to exercise professionals with this expertise is limited. To promote access to IDC in rural and remote HD units, we describe the implementation and initial evaluation of a novel IDC program using virtual assessment to safely prescribe and individualize IDC.

SOURCES OF INFORMATION: We developed and piloted a protocol for virtual IDC assessment and prospectively collected metrics informed by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to support future quality improvement activities.

METHODS: Rural HD units were defined as per Alberta Kidney Care North (AKC-N)'s operations. The virtual IDC program components were: HD unit education sessions, support and interest from local unit staff and those receiving HD, a bike, a supervising kinesiologist, a stable Internet connection, a nurse present during the 25-minute initial virtual assessment, and virtual follow-up every 3 to 4 weeks with the kinesiologist. The initial assessment consists of a virtual bike test where the participant performs a graded, symptom-limited cycling trial with documentation of vital signs and rating of self-perceived exertion (relative intensity). The data are used to prescribe IDC (frequency, intensity, time). The HD unit staff learn participant and bike set-up, confirm safe exercise parameters for that day, adjust the bike intensity, and take vital signs. Outcomes for evaluating the impact of the IDC program using the RE-AIM health framework were selected.

KEY FINDINGS: Out of the 24 HD units in AKC-N, 18 units were defined as either remote or rural (75%). Four of the units (22%) adopted the program, which was less than our target of 30% of units. Individual-level participation (Reach) within those units ranged widely (1-67%) with only one unit reaching the target of at least 30% individual-level participation. Reasons for starting IDC were intradialytic cramping, restless legs, deconditioning, and boredom during HD. Reasons for non-participation were lack of interest and a desire to sleep. Routine exercise program questionnaires on health-related quality of life for program effectiveness were not consistently completed by participants. All virtual assessments were completed as per protocol with a nurse (100% fidelity); however, tests often needed to be re-scheduled due to technical issues with Wi-Fi, limited unit staffing, operational demands, and/or safety concerns. At 1 year, all 4 units continued to participate with 2 additional HD units starting the following year.

LIMITATIONS: Reach could be improved by introducing intradialytic exercise to individuals at HD initiation, prior to moving to their local satellite HD unit. Existing measures of program effectiveness may not be relevant to program participants or feasible to implement without an on-site exercise professional. Technical issues and navigating the busy schedules of unit staff were limitations to completing tests as scheduled.

IMPLICATIONS: Implementing a protocolized approach with virtual support can increase accessibility to an evidence-based treatment in HD units without exercise professionals. For people requiring HD, reach may be improved with early education and exposure at HD start and with orientation sessions for staff. Adding a virtual IDC assessment day for staff as part of their routine monthly task schedule may promote institutionalization. Formalized follow-up sessions for kinesiologists and nurses to discuss program concerns would benefit the program in the future. Completion of program effectiveness measures may be improved by selecting more individualized options, for example, person-reported measures related to the individual's reason for referral.}, } @article {pmid39483603, year = {2024}, author = {Helena, V and Arumugam, S and Muninathan, N and Baskaran, K and Tasneem, A}, title = {Comparative Analysis of Vitamin D, Folic Acid, and Trace Minerals Levels in Various Stages of Invasive Ductal Breast Cancer.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e70593}, pmid = {39483603}, issn = {2168-8184}, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is one of the most commonly diagnosed subtypes of breast cancer, representing the majority of breast cancer cases. This study investigates the levels of vitamin D, folic acid, and antioxidant minerals (zinc (Zn), copper (Cu), and magnesium (Mg)) in IDC patients across different disease stages to explore their potential roles in disease progression.

METHODS: We analyzed a cohort of 150 female patients with IDC, aged between 30 and 67 years (51 ± 15.5 years). Blood samples were collected to measure levels of vitamin D, folic acid, Cu, Mg, and Zn. Patients were categorized into Stage 1 to Stage 4 of cancer. Variations in nutrient levels across these stages were statistically assessed using ANOVA and post-hoc tests.

RESULTS: The study results revealed varying levels of key nutrients across different stages of the disease. Vitamin D levels averaged 17.7 ng/mL, with higher concentrations in early-stage patients, indicating a possible correlation with disease severity. Folic acid levels had a mean of 12.2 ng/mL, showing a decline in later stages, potentially linking it to cancer progression. Copper levels averaged 161.3μg/dL, peaking at 170μg/dL in Stage 3, suggesting a connection with cancer aggressiveness. Magnesium levels, with an average of 1.4 mg/dL, dropped notably to 0.6 mg/dL by Stage 4, highlighting its possible involvement in disease progression. Zinc levels averaged 69.4 μg/dL, with a significant decrease in advanced stages, emphasizing its importance for immune function and cellular health.

CONCLUSION: The study demonstrates significant variations in the levels of vitamin D, folic acid, and antioxidant minerals across different stages of IDC. These nutrients may influence cancer progression, underscoring the potential benefits of nutritional assessments and interventions in managing IDC.}, } @article {pmid39480227, year = {2024}, author = {Samadi, MH and Khezri, S and Rabani Banou, F and Bai, M and Barashki, S}, title = {Radiation Pneumonitis With 99m Tc-MDP Uptake in a Patient With Breast Cancer.}, journal = {Clinical nuclear medicine}, volume = {49}, number = {12}, pages = {e723-e725}, doi = {10.1097/RLU.0000000000005471}, pmid = {39480227}, issn = {1536-0229}, mesh = {Humans ; Female ; *Radiation Pneumonitis/diagnostic imaging ; Middle Aged ; *Breast Neoplasms/diagnostic imaging/radiotherapy ; *Technetium Tc 99m Medronate ; Single Photon Emission Computed Tomography Computed Tomography ; }, abstract = {We present MDP bone scan findings of radiation pneumonitis in a 45-year-old woman with invasive ductal carcinoma of the right breast, classified as stage IIIa, T3N2M0. The patient underwent a modified radical mastectomy, neoadjuvant chemotherapy, and subsequent radiotherapy, receiving the last session 7 months before the bone scan. Whole-body images acquired 3 hours postinjection of 20 mCi (730 MBq) 99m Tc-MDP showed incidentally increased uptake in the right hemithorax, confined to the lung parenchyma of the right lung on SPECT/CT images.}, } @article {pmid39477690, year = {2025}, author = {Borger, J and Zweck, E and Moos, C and Horn, P and Voß, F and Schultheiss, HP and Møller, JE and Boeken, U and Aubin, H and Lichtenberg, A and Kelm, M and Roden, M and Polzin, A and Westenfeld, R and Szendroedi, J and Scheiber, D}, title = {Myocardial inflammation is associated with impaired mitochondrial oxidative capacity in ischaemic cardiomyopathy.}, journal = {ESC heart failure}, volume = {12}, number = {2}, pages = {1246-1255}, pmid = {39477690}, issn = {2055-5822}, support = {236177352//German Research Foundation/ ; 527448911//German Research Foundation/ ; 493659010//German Research Foundation/ ; //Medical Faculty, Heinrich-Heine-University/ ; //German Heart Research Foundation/ ; //German Center for Diabetes Research/ ; //German Diabetes Center/ ; //Federal Ministry of Health/ ; //Ministry of Innovation, Science, Research and Technology of the state North-Rhine Westphalia/ ; }, mesh = {Humans ; Male ; Female ; Middle Aged ; *Myocardial Ischemia/metabolism/complications ; *Mitochondria, Heart/metabolism ; *Cardiomyopathy, Dilated/metabolism ; *Oxidative Stress/physiology ; *Myocarditis/metabolism/etiology ; Aged ; Inflammation/metabolism ; Energy Metabolism ; }, abstract = {AIMS: Myocardial inflammation and impaired mitochondrial oxidative capacity are hallmarks of heart failure (HF) pathophysiology. The extent of myocardial inflammation in patients suffering from ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and its association with mitochondrial energy metabolism are unknown. We aimed at establishing a relevant role of cardiac inflammation in the impairment of mitochondrial energy production in advanced ischaemic and non-ischaemic HF.

METHODS: We included 81 patients with stage D HF (ICM, n = 44; DCM, n = 37) undergoing left ventricular assist device implantation (n = 59) or heart transplantation (n = 22) and obtained left ventricular tissue samples during open heart surgery. We quantified mitochondrial oxidative capacity, citrate synthase activity (CSA) and fibrosis and lymphocytic infiltration. We considered infiltration of >14 CD3[+] cells/mm[2] relevant inflammation.

RESULTS: Patients with ICM or DCM did not differ regarding age (61.5 ± 5.7 vs. 56.5 ± 12.7 years, P = 0.164), sex (86% vs. 84% male, P = 0.725), type 2 diabetes mellitus (34% vs. 18%, P = 0.126) or chronic kidney disease (8% vs. 11%, P = 0.994). ICM exhibited oxidative capacity reduced by 23% compared to DCM (108.6 ± 41.4 vs. 141.9 ± 59.9 pmol/(s*mg), P = 0.006). Maximum production of reactive oxygen species was not significantly different between ICM and DCM (0.59 ± 0.28 vs. 0.69 ± 0.36 pmol/(s*ml), P = 0.196). Mitochondrial content, detected by CSA, was lower in ICM (359.6 ± 164.1 vs. 503.0 ± 198.5 nmol/min/mg protein, P = 0.002). Notably, relevant inflammation was more common in ICM (27% vs. 6%, P = 0.024), and the absolute number of infiltrating leucocytes correlated with lower oxidative capacity (r = -0.296, P = 0.019). Fibrosis was more prevalent in ICM (20.9 ± 21.2 vs. 7.2 ± 5.6% of area, P = 0.002), but not associated with oxidative capacity (r = -0.13, P = 0.327).

CONCLUSIONS: More than every fourth ICM patient with advanced HF displays myocardial inflammation in the range of inflammatory cardiomyopathy associated with reduced mitochondrial oxidative capacity. Future studies may evaluate inflammation in ICM at earlier stages in standardised fashion to explore the therapeutic potential of immunosuppression to influence trajectories of HF in ICM.}, } @article {pmid39474510, year = {2024}, author = {Zhao, X and Guo, H and Shi, G and Li, B and Wang, N}, title = {Case Report: Efficacy of Multiparameter MRI in Diagnosis of Chronic Breast Inflammation Complicated with Invasive Ductal Carcinoma and Ductal Carcinoma in situ.}, journal = {Cancer management and research}, volume = {16}, number = {}, pages = {1517-1521}, pmid = {39474510}, issn = {1179-1322}, abstract = {INTRODUCTION: Incidental Enhancement Lesions (IELs) complicate patient management but may be detected through multiparameter MRI including dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) and synthetic magnetic resonance imaging (syMRI). The multiparameter MRI model gave greater objectivity to avoid unnecessary biopsy.

CASE PRESENTATION: A 60 year-old woman had a history of occasional right breast pain and a mass was identified in the right breast. A thickening in the upper quadrant of the right outer breast was found during physical examination but no mass was palpable. Breast dynamic contrast enhancement MRI and synthetic MRI were performed prior to ultrasound-guided biopsy of the right breast lesion. Resection of the right breast lesion and sentinel lymph node was performed 2 days later. Chronic inflammation, locally invasive ductal carcinoma and high-grade ductal carcinoma in situ were found by pathological examination.

DISCUSSION: Differentiation between benign and malignant breast IELs was facilitated by use of a multiparameter MRI model with DCE-MRI and syMRI, giving greater objectivity in differentiating between benign and malignant lesions.}, } @article {pmid39471024, year = {2024}, author = {Fatima, N and Zaman, U and Ahmed, A and Zaman, S and Khan, K and Zaman, MU}, title = {Impact of 18FDG PET/CT on Clinical Management, Cost Effectiveness, and Radiation Exposure in Newly Diagnosed Breast Cancer Patients.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {25}, number = {10}, pages = {3577-3581}, pmid = {39471024}, issn = {2476-762X}, mesh = {Humans ; Female ; *Positron Emission Tomography Computed Tomography/economics/methods ; *Fluorodeoxyglucose F18/economics ; *Breast Neoplasms/pathology/diagnostic imaging/radiotherapy/economics ; *Cost-Benefit Analysis ; Retrospective Studies ; Middle Aged ; *Radiation Exposure ; *Radiopharmaceuticals ; Adult ; *Neoplasm Staging ; Male ; Aged ; Follow-Up Studies ; Prognosis ; Breast Neoplasms, Male/diagnostic imaging/pathology/radiotherapy/economics ; Cost-Effectiveness Analysis ; }, abstract = {BACKGROUND: For the initial staging of breast cancer (BC), 18FDG PET/CT is recommended by professional guidelines in stage III (except T3N1) and inflammatory BC (T4d) and optional when conventional imaging is equivocal or suspicious. However, growing evidence also supports its role in the staging of intermediate-risk groups (IIA, IIB, T3N1 of IA). This study aimed to compare the impact of 18FDG PET/CT with conventional imaging (CT-chest+abdomen+pelvis and bone scan; CT-CAP+BS) in staging, cost-effectiveness, and radiation exposure in the initial staging of BC.

MATERIAL AND METHOD: A retrospective study (April 2020 2024) included 115 biopsy-proven BC patients who had CT-CAP+BS and 18FDG PET/CT for initial staging. Data were analyzed to see the impact of 18FDG PET/CT on change in staging, cost-effectiveness, and radiation exposure compared to CA-CAP+BS.

RESULTS: Out of 115 patients (113 female and 02 male), 110 had unilateral and 5 had bilateral BC (Invasive Ductal Ca. 107; Non-IDC: 08) with non-significant laterality. The overall upstaging rate for regional nodal and/or distant metastases was 36% (24/66; excluded 49 with stage IV). The overall upstaging rate due to unsuspected higher nodal metastases was 20% (predominantly stage IIA, and IIB). Upstaging rate to stage IV was seen in 17% (11/66; predominantly in IIIA-C). The overall concordance (no change in staging) was seen in 64% (42/66) while no downstaging was found in any patient. In patients with stage-IV disease (n = 49), 18FDG PET/CT identified a higher number of hypermetabolic lesions in 18 (37%), lesser in 07 (14%), and similar in 24 (49%) cases. The estimated cost in Pak rupees for CT-CAP+BS and PET/CT was 139000 and 106000 respectively. The mean effective dose imparted by 18FDG PET/CT was 8.85 mSv compared to the reported 26.6 mSv by CT-CAP+BS.

CONCLUSION: We conclude that in the initial staging of BC, 18FDG PET/CT compared with CT-CAP+BS has a significant impact on decision-making by upstaging the disease in stage II and III and detecting more metastatic lesions in stage-IV disease. Furthermore, 18FDG PET/CT is more cost-effective and imparts significantly lower radiation exposure as compared with CT+CAP+BS. These findings support the inclusion of 18FDG PET/CT in the initial staging of stage II-IV BC.}, } @article {pmid39469406, year = {2024}, author = {Eashwar, P and Yadlapalli, DC and Gullipalli, M}, title = {Experience With Palbociclib in Metastatic Breast Cancer Patients Managed Under a Government Health Scheme at a Cancer Care Center in Southern India.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e70394}, pmid = {39469406}, issn = {2168-8184}, abstract = {Introduction According to Globocan 2022, breast cancer ranks number one among the cancers worldwide. South Asian women have a higher incidence compared to Westerners. Estrogen receptor (ER) and progesterone receptor (PR) positive tumors, termed hormonal receptor-positive tumors, account for most breast cancer presentations. In India, advanced-stage presentations are more common. In metastatic hormone receptor-positive breast cancer, hormonal therapy combined with cyclin-dependent kinase (CDK) 4/6 inhibitors is the standard treatment. Aim This study aimed to analyze the experience with generic palbociclib provided under the Government Health Scheme for metastatic hormone receptor-positive breast cancer at our institution. Methods This retrospective study was conducted on breast cancer patients admitted to a tertiary care center in South India. The data of ER and PR receptor-positive metastatic breast cancer patients who received palbociclib were identified and reviewed using medical records from 2023 to 2024. Results A total of 238 patients were analyzed, of which 41 received palbociclib for hormone receptor-positive metastatic breast cancer. The median age was 49 (33-75), with 53.5% (22) of women above 50. Denovo stage IV presentation was observed in 21 patients (51.2%), while progression to stage IV disease was noted in 11 patients (26.8%), and stages II and III were noted in nine patients (22%). Invasive ductal carcinoma was the most common histology. All patients were ER-positive, and 38 (92.7%) were PR-positive. About 17 patients (41.5%) had visceral metastasis, and 12 (29.3%) had bone-only metastasis. Local recurrence was seen in six patients (14.6%), and bone with visceral metastasis was seen in another six patients (14.6%). Progression within one year of hormonal therapy initiation was observed in 50% (10) of patients. Among 21 patients with upfront metastasis, nine were treated with prior chemotherapy. All patients were given 125 mg of oral palbociclib. Fatigue was the most common side effect in 34.1% (14), followed by myalgia in 21.9% (9), low hemoglobin levels of less than 8 g/dl in 14.6% (6), and nausea and vomiting in only 9.8% (4) of patients. Conclusion Hormone therapy combined with CDK4/6 inhibitors is the backbone of treatment for metastatic hormone-positive breast cancer. However, in developing countries like India, where most patients come from rural areas, using innovator palbociclib may not be feasible for many. With the availability of generic palbociclib under the Government Health Scheme, patients of metastatic hormone receptor-positive breast cancer will receive the protocol-based treatment.}, } @article {pmid39465570, year = {2025}, author = {Wei, X and Zhao, J and Nie, L and Shi, Y and Zhao, F and Shen, Y and Chen, J and Sun, G and Zhang, X and Liang, J and Hu, X and Shen, P and Chen, N and Zeng, H and Liu, Z}, title = {Assessing the predictive value of intraductal carcinoma of the prostate (IDC-P) in determining abiraterone efficacy for metastatic hormone-sensitive prostate cancer (mHSPC) patients.}, journal = {The Prostate}, volume = {85}, number = {2}, pages = {130-139}, pmid = {39465570}, issn = {1097-0045}, support = {//Beijing Bethune Charitable Foundation (mnzl202002, mnzl202007)/ ; //Postdoctoral Research and Development Fund of West China Hospital of Sichuan University (2023HXBH024)/ ; //Science and Technology Support Program of Sichuan Province (2021YFS0119)/ ; //Clinical and Translational Medicine Research Project, Chinese Academy of Medical Sciences (2022-12M-C&T-B-098)/ ; //National Natural Science Foundation of China (NSFC 82203110, 82172785, and 81974398)/ ; }, mesh = {Humans ; Male ; *Prostatic Neoplasms/drug therapy/pathology/mortality ; Aged ; Retrospective Studies ; *Androstenes/therapeutic use ; Middle Aged ; Prostate-Specific Antigen/blood ; Treatment Outcome ; Carcinoma, Intraductal, Noninfiltrating/drug therapy/pathology ; Predictive Value of Tests ; Prostate/pathology/drug effects ; }, abstract = {BACKGROUND: This study explored the value of intraductal carcinoma of the prostate (IDC-P) in predicting the efficacy of abiraterone treatment in metastatic hormone-sensitive prostate cancer (mHSPC) patients.

METHODS: A retrospective study of 925 patients who underwent prostate biopsies to detect IDC-P was conducted, with participants divided into two cohorts. The first cohort of 165 mHSPC patients receiving abiraterone treatment was analyzed to compare therapeutic effectiveness between IDC-P positive and negative cases. Utilizing propensity score matching (PSM) to reduce bias, outcomes such as PSA response, progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival were assessed. Additionally, the second cohort of 760 mHSPC patients compared the efficacy of abiraterone with conventional hormone therapy, focusing on differences between IDC-P positive and negative individuals.

RESULTS: After PSM, our first cohort included 108 patients with similar baseline characteristics. Among them, 50% (54/108) were diagnosed with IDC-P, with 22.2% (12/54) having IDC-P pattern 1 and 77.8% (42/54) with IDC-P pattern 2. While no notable difference was seen in PSA responses between IDC-P positive and negative patients, IDC-P presence linked to worse clinical outcomes (PSA-PFS: 18.6 months vs. not reached [NR], p = 0.009; rPFS: 23.6 months vs. NR, p = 0.020). Further analysis showed comparable outcomes for IDC-P pattern 1 but significantly worse prognosis for IDC-P pattern 2 (PSA-PFS: 18.6 months vs. NR, p = 0.002; rPFS: 22.4 months vs. NR, p = 0.010). Subgroup analysis revealed IDC-P pattern 2 consistently predicted poorer outcomes across patient subgroups. Remarkably, both IDC-P positive and negative patients gained more from androgen deprivation therapy with abiraterone than conventional treatment, with IDC-P negative patients showing a more significant survival advantage, supported by better hazard ratios (0.47 and 0.66).

CONCLUSION: This study found that IDC-P, especially pattern 2, predicts poor prognosis in mHSPC patients on abiraterone therapy. Also, abiraterone's advantage over hormone therapy is reduced in cases with IDC-P compared to those without.}, } @article {pmid39464069, year = {2024}, author = {Young, TA and Bahnassy, S and Abalum, TC and Pope, EA and Rivera, AT and Fernandez, AI and Olukoya, AO and Mobin, D and Ranjit, S and Libbey, NE and Persaud, S and Rozeboom, AM and Chaldekas, K and Harris, BT and Madak-Erdogan, Z and Sottnik, JL and Sikora, MJ and Riggins, RB}, title = {Glutamate Transport Proteins and Metabolic Enzymes are Poor Prognostic Factors in Invasive Lobular Carcinoma.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39464069}, issn = {2692-8205}, support = {R00 CA193734/CA/NCI NIH HHS/United States ; P30 CA051008/CA/NCI NIH HHS/United States ; R01 CA251621/CA/NCI NIH HHS/United States ; T32 CA009686/CA/NCI NIH HHS/United States ; R35 GM154815/GM/NIGMS NIH HHS/United States ; }, abstract = {Invasive Lobular Carcinoma (ILC) is a subtype of breast cancer characterized by distinct biological features, and limited glucose uptake coupled with increased reliance on amino acid and lipid metabolism. Our prior studies highlight the importance of glutamate as a key regulator of ILC tumor growth and therapeutic response. Here we examine the expression of four key proteins involved in glutamate transport and metabolism - SLC3A2, SLC7A11, GPX4, and GLUD1/2 - in a racially diverse cohort of 72 estrogen receptor-positive (ER+) ILC and 50 ER+ invasive ductal carcinoma, no special type (IDC/NST) patients with primary disease. All four proteins are associated with increased tumor size in ILC, but not IDC/NST, with SLC3A2 also specifically linked to shorter overall survival and the presence of comorbidities in ILC. Notably, GLUD1/2 expression is associated with ER expression in ILC, and is most strongly associated with increased tumor size and stage in Black women with ILC from our cohort and TCGA. We further explore the effects of GLUD1 inhibition in endocrine therapy-resistant ILC cells using the small-molecule inhibitor R162, which reduces ER protein levels, increases reactive oxygen species, and inhibits oxidative phosphorylation. These findings highlight a potentially important role for glutamate metabolism in ILC, particularly for Black women, and position several of these glutamate-handling proteins as potential targets for therapeutic intervention in ILC.}, } @article {pmid39463552, year = {2024}, author = {Hobbs, L and Tiwari, N}, title = {Hemorrhagic Bullous Lichen Sclerosus of the Breast: A Rare Complication of Radiotherapy.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e70194}, pmid = {39463552}, issn = {2168-8184}, abstract = {Cutaneous side effects from radiotherapy are commonly reported in breast cancer patients. Radiation-induced hemorrhagic bullous lichen sclerosus (RHBLS) of the breast is a rare, but important, complication of radiotherapy. RHBLS typically presents as painful, hemorrhagic bullae with surrounding sclerotic tissue. A 71-year-old female with a history of whole breast radiotherapy for invasive ductal carcinoma of the right breast and ductal carcinoma in situ (DCIS) of the left breast presented to the clinic with pruritic, firm, and erythematous plaques involving the inframammary folds that progressed into large, painful, hemorrhagic bullae surrounded by porcelain-white skin over several weeks. Biopsy was consistent with RHBLS. She was initially treated with systemic steroids and Clobetasol 0.05% ointment twice daily with partial improvement. To the best of our knowledge, only three definitive cases have been previously reported in the literature making this the fourth case.}, } @article {pmid39455907, year = {2024}, author = {Yang, L and Ding, H and Gao, X and Xu, Y and Xu, S and Wang, K}, title = {Can we skip invasive biopsy of sentinel lymph nodes? A preliminary investigation to predict sentinel lymph node status using PET/CT-based radiomics.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {1316}, pmid = {39455907}, issn = {1471-2407}, support = {JJMS-2023-05//Haiyan Fund of Harbin Medical University Cancer Hospital/ ; GA21C001//Provincial Key Research and Development Program of Heilongjiang Province/ ; }, mesh = {Humans ; Female ; *Positron Emission Tomography Computed Tomography/methods ; Middle Aged ; Retrospective Studies ; *Sentinel Lymph Node Biopsy/methods ; *Breast Neoplasms/pathology/diagnostic imaging/surgery ; *Fluorodeoxyglucose F18 ; Aged ; Adult ; *Lymphatic Metastasis/diagnostic imaging/pathology/diagnosis ; *Sentinel Lymph Node/diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology/surgery ; Radiopharmaceuticals/administration & dosage ; ROC Curve ; Radiomics ; }, abstract = {BACKGROUND: Sentinel lymph node (SLN) biopsy (SLNB) is considered the gold standard for detecting SLN metastases in patients with invasive ductal breast cancer (IDC). However, SLNB is invasive and associated with several complications. Thus, this study aimed to evaluate the diagnostic performance of a non-invasive radiomics analysis utilizing 2-deoxy-2-[[18]F]fluoro-d-glucose positron emission tomography/computed tomography ([18]F-FDG-PET/CT) for assessing SLN metastasis in IDC patients.

METHODS: This retrospective study included 132 patients with biopsy-confirmed IDC, who underwent [18]F-FDG PET/CT scans prior to mastectomy or breast-conserving surgery with SLNB. Tumor resection or SLNB was conducted within one-week post-scan. Clinical data and metabolic parameters were analyzed to identify independent SLN metastasis predictors. Radiomic features were extracted from each PET volume of interest (VOI) and CT-VOI. Feature selection involved univariate and multivariate logistic regression analysis, and the least absolute shrinkage and selection operator (LASSO) method. Three models were developed to predict SLN status using the random forest (RF), decision tree (DT), and k-Nearest Neighbors (KNN) classifiers. Model performance was assessed using the area under the receiver operating characteristic curve (AUC).

RESULTS: The study included 91 cases (32 SLN-positive and 59 SLN-negative patients) in the training cohort and 41 cases (29 SLN-positive and 12 SLN-negative patients) in the validation cohort. Multivariate logistic regression analysis identified Ki 67 and TLG as independent predictors of SLN status. Five PET-derived features, three CT-derived features, and two clinical variables were selected for model development. The AUC values of the RF, KNN, and DT models for the training cohort were 0.887, 0.849, and 0.824, respectively, and for the validation cohort were 0.856, 0.830, and 0.819, respectively. The RF model demonstrated the highest accuracy for the preoperative prediction of SLN metastasis in IDC patients.

CONCLUSION: The PET-CT radiomics approach may offer robust and non-invasive predictors for SLN status in IDC patients, potentially aiding in the planning of personalized treatment strategies for IDC patients.}, } @article {pmid39445843, year = {2025}, author = {Anampa, JD and Lin, S and Obeng-Gyasi, S and Xue, X}, title = {Treatment and Survival Differences between Patients with Invasive Lobular Carcinoma Versus Invasive Ductal Carcinoma of the Breast.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {34}, number = {1}, pages = {125-132}, doi = {10.1158/1055-9965.EPI-24-1250}, pmid = {39445843}, issn = {1538-7755}, support = {5K12CA132783-08//National Institutes of Health (NIH)/ ; UL1 TR002556/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Female ; *Carcinoma, Lobular/mortality/pathology/therapy ; *Breast Neoplasms/mortality/pathology/therapy ; *Carcinoma, Ductal, Breast/mortality/pathology/therapy ; Middle Aged ; Aged ; *SEER Program ; Adult ; Survival Rate ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) exhibits differences in molecular and biological characteristics compared with invasive ductal carcinoma (IDC). We aim to compare breast cancer-specific survival (BCSS) between patients with ILC and IDC.

METHODS: We used data from the Surveillance, Epidemiology, and End Results database (1992-2020). Logistic regression analyses were conducted to identify factors associated with treatment modalities. We examined BCSS at different time points using a cox regression model with time-dependent coefficient.

RESULTS: A total of 343,397 patients with IDC and 39,859 patients with ILC were included. Patients with ILC had more advanced-stage disease (stage II, 35% vs. 34%; stage III, 16% vs. 11%) and a higher rate of hormone receptor-positive disease (97% vs. 81%). Compared with patients with IDC, patients with ILC had better BCSS in the first five years (HR = 0.71; P < 0.001) but worse BCSS in later years (HR = 1.30, P < 0.001 in years 6-10; HR = 1.75, P < 0.001 in years 11-15; and HR = 2.17, P < 0.001 in years 16-20).

CONCLUSIONS: Patients with ILC survive better in early years but worse in later years compared with patients with IDC. Future studies are required to identify patients with ILC who are at risk of late recurrence or mortality.

IMPACT: The results of this study add to the currently conflicting literature of survival of ILC and demonstrate the importance of evaluating novel therapeutic approaches and extended therapy for patients with ILC.}, } @article {pmid39445545, year = {2025}, author = {Wu, B and Gao, A and He, B and Chen, Y and Kong, X and Wen, F and Gao, H}, title = {RNA-seq analysis of mitochondria-related genes regulated by AMPK in the human trophoblast cell line BeWo.}, journal = {Animal models and experimental medicine}, volume = {8}, number = {4}, pages = {649-661}, pmid = {39445545}, issn = {2576-2095}, support = {R16 HD116702/HD/NICHD NIH HHS/United States ; RCMI/IDC Award U54MD007597//National Center on Minority Health and Health Disparities/ ; R16HD116702//National Institute of Child Health and Human Development/ ; U54 MD007597/MD/NIMHD NIH HHS/United States ; R03HD095417//National Institute of Child Health and Human Development/ ; Bridge Fund/Pilot Study Award//Dean's Office Howard University College of Medicine/ ; }, mesh = {Humans ; *Trophoblasts/metabolism ; *Mitochondria/genetics/metabolism ; *AMP-Activated Protein Kinases/metabolism/genetics ; RNA-Seq ; Adenosine Triphosphate/metabolism ; Cell Line ; Gene Expression Regulation ; Protein Interaction Maps ; Signal Transduction ; Pregnancy ; Female ; Gene Expression Profiling ; }, abstract = {BACKGROUND: How AMP activated protein kinase (AMPK) signaling regulates mitochondrial functions and mitophagy in human trophoblast cells remains unclear. This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq.

METHODS: We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2 (PRKAA1/2) knockdown (AKD) and control BeWo cells using the Seahorse real-time ATP rate test, then analyzed gene expression profiling by RNA-seq. Differentially expressed genes (DEG) were examined by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Then protein-protein interactions (PPI) among mitochondria related genes were further analyzed using Metascape and Ingenuity Pathway Analysis (IPA) software.

RESULTS: Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells (CT), with a greater reduction of mitochondrial ATP production. A total of 1092 DEGs were identified, with 405 upregulated and 687 downregulated. GO analysis identified 60 genes associated with the term 'mitochondrion' in the cellular component domain. PPI analysis identified three clusters of mitochondria related genes, including aldo-keto reductase family 1 member B10 and B15 (AKR1B10, AKR1B15), alanyl-tRNA synthetase 1 (AARS1), mitochondrial ribosomal protein S6 (MRPS6), mitochondrial calcium uniporter dominant negative subunit beta (MCUB) and dihydrolipoamide branched chain transacylase E2 (DBT).

CONCLUSIONS: In summary, this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells, and among them, three clusters of genes may potentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.}, } @article {pmid39445528, year = {2024}, author = {Zhao, Z and Li, L and He, M and Li, Y and Ma, X and Zhao, B}, title = {Prognostic and Predictive Markers for Early Stage Triple-Negative Breast Cancer Treated With Platinum-Based Neoadjuvant Chemotherapy.}, journal = {Cancer medicine}, volume = {13}, number = {20}, pages = {e70336}, pmid = {39445528}, issn = {2045-7634}, support = {2019D01C258//The Natural Science Foundation of Xinjiang Uygur Autonomous Region/ ; }, mesh = {Humans ; *Triple Negative Breast Neoplasms/drug therapy/genetics/mortality/pathology ; Female ; *Neoadjuvant Therapy/methods ; Middle Aged ; *Polymorphism, Single Nucleotide ; Prognosis ; *BRCA1 Protein/genetics ; *Biomarkers, Tumor/genetics ; Adult ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Neoplasm Staging ; BRCA2 Protein/genetics ; Aged ; X-ray Repair Cross Complementing Protein 1/genetics ; Prospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Emerging evidence has indicated possible efficacy benefit of platinum-based chemotherapy as neoadjuvant treatment for invasive ductal carcinoma triple-negative breast cancer (TNBC). However, it has not been endorsed by current guidelines due to highly controversial results.

MATERIALS AND METHODS: Present study aims to investigate predictive and prognostic roles concerning single nucleotide polymorphisms (SNPs) in XRCC1 and BRCA1, BRCA2 genes for early stage TNBC patients that received platinum-based neoadjuvant treatment. We prospectively enrolled women with stage IIB-IIIB TNBC that had progressed on neoadjuvant taxane and anthracycline-based chemotherapy at Xinjiang Medical University Affiliated Cancer Hospital. Tumor response and pathological complete response (pCR) rate were assessed. Invasive disease-free survival (iDFS) and overall survival (OS) were analyzed. Patients' blood samples were subject to Sanger sequencing to genotype XRCC1 Arg194Trp and Arg399Gln, BRCA1 s1799949, and BRCA2 rs206115. Univariate and multivariate logistic regressions were employed to investigate associations between SNPs and clinical characteristics with treatment response and pCR. A total of 45 patients were enrolled.

RESULTS: The cohort showcased ORR of 44.4%, pCR of 28.9%, median iDFS of 22 months, and a 3-year OS of 73.3%. The A/G and G/G genotypes of BRCA1 rs1799949, and the T/T genotype of BRCA2 rs206115 were associated with higher responsive rate. Histologic grade of III and Ki67 expression > 65% were associated with low responsive rate. Moreover, the A/G genotype of BRCA1 rs1799949 and T/T genotype of BRCA2 rs206115 correlated to high pCR. The histologic III and T4 stage correlated to inferior iDFS. Carrier of BRCA1 rs1799949 G/G had the most favorable OS, carriers of A/A showed the poorest OS, and those with A/G genotype showed an intermediate OS.

CONCLUSIONS: Platinum-based chemotherapy might serve as a therapeutic option for TNBC patients who were resistant to anthracycline- and taxane-based neoadjuvant therapy. Our study identified several genetic and clinical features that might function as prognostic and predictive markers.}, } @article {pmid39443544, year = {2024}, author = {Bernardino, R and Carvalho, AS and Hall, MJ and Alves, L and Leão, R and Sayyid, R and Pereira, H and Beck, HC and Pinheiro, LC and Henrique, R and Fleshner, N and Matthiesen, R}, title = {Profiling of urinary extracellular vesicle protein signatures from patients with cribriform and intraductal prostate carcinoma in a cross-sectional study.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {25065}, pmid = {39443544}, issn = {2045-2322}, support = {UIDB/04462/2020 and UIDP/04462/2020//iNOVA4Health/ ; UIDB/04462/2020 and UIDP/04462/2020//iNOVA4Health/ ; UIDB/04462/2020 and UIDP/04462/2020//iNOVA4Health/ ; 2022.13386.BD//Fundação para a Ciência e a Tecnologia/ ; 10.54499/DL57/2016/CP1457/CT0013//Fundação para a Ciência e a Tecnologia/ ; 10.54499/CEECIND/03906/2017/CP1421/CT0004//Fundação para a Ciência e a Tecnologia/ ; PTDC/BTM-TEC/1746/2021//Portuguese Foundation for Science and Technology/ ; PTDC/BTM-TEC/1746/2021//Portuguese Foundation for Science and Technology/ ; CA20113388//COST Action "PROTEOCURE/ ; CA20113388//COST Action "PROTEOCURE/ ; n° 101079264//Horizon2020 GA, EVCA/ ; n° 101079264//Horizon2020 GA, EVCA/ ; }, mesh = {Humans ; Male ; *Prostatic Neoplasms/urine/pathology/metabolism/diagnosis ; *Extracellular Vesicles/metabolism ; Cross-Sectional Studies ; Aged ; Middle Aged ; Proteome/analysis ; Tandem Mass Spectrometry ; Neoplasm Grading ; Biomarkers, Tumor/urine ; Chromatography, Liquid ; Proteomics/methods ; }, abstract = {Prognostic tests and treatment approaches for optimized clinical care of prostatic neoplasms are an unmet need. Prostate cancer (PCa) and derived extracellular vesicles (EVs) proteome changes occur during initiation and progression of the disease. PCa tissue proteome has been previously characterized, but screening of tissue samples constitutes an invasive procedure. Consequently, we focused this study on liquid biopsies, such as urine samples. More specifically, urinary small extracellular vesicle and particles proteome profiles of 100 subjects were analyzed using liquid chromatography coupled to high-resolution mass spectrometry (LC-MS/MS). We identified 171 proteins that were differentially expressed between intraductal prostate cancer/cribriform (IDC/Crib) and non-IDC/non-Crib after correction for multiple testing. However, the strong correlation between IDC/Crib and Gleason Grade complicates the disentanglement of the underlying factors driving this association. Nevertheless, even after accounting for multiple testing and adjusting for ISUP (International Society of Urological Pathology) grading, two proteins continued to exhibit significant differential expression between IDC/Crib and non-IDC/non-Crib. Functional enrichment analysis based on cancer hallmark proteins disclosed a clear pattern of androgen response down-regulation in urinary EVs from IDC/Crib compared to non-IDC/non-Crib. Interestingly, proteome differences between IDC and cribriform were more subtle, suggesting high proteome heterogeneity. Overall, the urinary EV proteome reflected partly the prostate pathology.}, } @article {pmid39443503, year = {2024}, author = {Murugesan, GK and McCrumb, D and Aboian, M and Verma, T and Soni, R and Memon, F and Farahani, K and Pei, L and Wagner, U and Fedorov, AY and Clunie, D and Moore, S and Van Oss, J}, title = {AI-Generated Annotations Dataset for Diverse Cancer Radiology Collections in NCI Image Data Commons.}, journal = {Scientific data}, volume = {11}, number = {1}, pages = {1165}, pmid = {39443503}, issn = {2052-4463}, support = {75N91019D00024/CA/NCI NIH HHS/United States ; U01 CA142565/CA/NCI NIH HHS/United States ; U01 CA151261/CA/NCI NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Neoplasms/diagnostic imaging ; *National Cancer Institute (U.S.) ; United States ; Tomography, X-Ray Computed ; Magnetic Resonance Imaging ; Artificial Intelligence ; Positron-Emission Tomography ; Cloud Computing ; }, abstract = {The National Cancer Institute (NCI) Image Data Commons (IDC) offers publicly available cancer radiology collections for cloud computing, crucial for developing advanced imaging tools and algorithms. Despite their potential, these collections are minimally annotated; only 4% of DICOM studies in collections considered in the project had existing segmentation annotations. This project increases the quantity of segmentations in various IDC collections. We produced high-quality, AI-generated imaging annotations dataset of tissues, organs, and/or cancers for 11 distinct IDC image collections. These collections contain images from a variety of modalities, including computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). The collections cover various body parts, such as the chest, breast, kidneys, prostate, and liver. A portion of the AI annotations were reviewed and corrected by a radiologist to assess the performance of the AI models. Both the AI's and the radiologist's annotations were encoded in conformance to the Digital Imaging and Communications in Medicine (DICOM) standard, allowing for seamless integration into the IDC collections as third-party analysis collections. All the models, images and annotations are publicly accessible.}, } @article {pmid39443384, year = {2025}, author = {João, D and Feltri, M and Klubickova, N and Michal, M and Kacerovská, D and Skálová, A}, title = {Apocrine variant of intraductal carcinoma of the parotid gland with sebaceous-like differentiation: expanding morphological and molecular spectrum of an enigmatic entity.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {487}, number = {1}, pages = {215-219}, pmid = {39443384}, issn = {1432-2307}, mesh = {Humans ; Male ; Middle Aged ; *Parotid Neoplasms/pathology/genetics ; Cell Differentiation ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins B-raf/genetics ; Sebaceous Glands/pathology ; Mutation ; Biomarkers, Tumor/analysis/genetics ; *Carcinoma, Ductal/pathology/genetics ; *Apocrine Glands/pathology ; }, abstract = {Intraductal carcinoma (IDC) is a rare tumor of the salivary glands. Here, we report a unique case of apocrine IDC of the parotid gland of a 60-year-old male, exhibiting a striking sebaceous-like differentiation. Microscopically, the tumor displayed a papillary growth pattern with apocrine cells (AR-positive; S100/SOX10-negative) and distinct areas harboring clear, vacuolated cells resembling sebaceous cells (CK7/S100/SOX10-positive; AR negative). Molecular genetic analysis revealed mutations in AKT1 and BRAF genes. An AKT1 gene mutation has earlier been described in sclerosing polycystic adenoma (SPA), suggesting a possible link between IDC and SPA, while BRAF V600E mutations were reported in an oncocytic subtype of IDC, but not in the apocrine one. Since IDC is an indolent disease, its recognition is a key to prevent unwarranted overtreatment. Further evidence is needed to determine whether apocrine IDC with sebaceous-like differentiation represents a novel morphological variant of the apocrine subtype of IDC or a novel salivary gland entity.}, } @article {pmid39441969, year = {2025}, author = {Hill, M and Aripoli, A}, title = {Unknown Case: Implant Protocol Breast MRI-Looking Beyond the Implants.}, journal = {Journal of breast imaging}, volume = {7}, number = {5}, pages = {619-621}, doi = {10.1093/jbi/wbae067}, pmid = {39441969}, issn = {2631-6129}, } @article {pmid39440077, year = {2024}, author = {Breit, C and Gorman, V}, title = {Utility of [18]F-fluoroestradiol over [18]F-fluorodeoxyglucose positron emission tomography/computed tomography in the initial diagnosis of over 90 metastatic lesions in a patient with metastatic estrogen receptor-positive breast cancer.}, journal = {Proceedings (Baylor University. Medical Center)}, volume = {37}, number = {6}, pages = {984-986}, pmid = {39440077}, issn = {0899-8280}, abstract = {Approximately 6% of women with newly diagnosed breast cancer will present with metastatic disease. Proper staging workup and diagnosis of metastatic lesions is crucial prior to surgical treatment.[18]F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is often included in the staging workup of locally advanced breast cancer. Recently, PET/CT with [18]F-fluoroestradiol ([18]F-FES), a radiolabeled form of estradiol that binds to the estrogen receptor, has been approved as an additional imaging technique for the detection of estrogen receptor-positive lesions in patients with metastatic breast cancer. Though the two have been shown to have comparable sensitivity for diagnosis of metastatic lesions, there is still much debate regarding when to use [18]F-FES PET/CT over [18]F-FDG PET/CT imaging. We present the case of a 68-year-old patient diagnosed with estrogen and progesterone receptor-positive invasive ductal carcinoma of the left breast. Her staging workup included an [18]F-FDG PET/CT that did not demonstrate any evidence of metastatic lesions. Due to discordant imaging findings, the patient then underwent [18]F-FES PET/CT, which demonstrated over 90 metastatic osseous lesions. This study highlights the utility of [18]F-FES PET/CT over [18]F-FDG PET/CT in diagnosis of metastatic osseous lesions in a patient with metastatic estrogen receptor-positive breast cancer.}, } @article {pmid39437744, year = {2025}, author = {Zhang, H and Zhang, A and Wei, T and Huang, H and Huang, Y and Zhang, Z and Xu, Y and Kong, L and Li, Y and Li, F}, title = {Long-Term Survival Outcomes in Locally Advanced Breast Cancer after Mastectomy with or without Breast Reconstruction.}, journal = {Oncology}, volume = {103}, number = {6}, pages = {477-489}, doi = {10.1159/000541771}, pmid = {39437744}, issn = {1423-0232}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery/mortality/pathology ; *Mammaplasty/methods/mortality ; Middle Aged ; SEER Program ; *Mastectomy/methods ; Adult ; Aged ; Kaplan-Meier Estimate ; Propensity Score ; Treatment Outcome ; Retrospective Studies ; }, abstract = {INTRODUCTION: There is ongoing debate about the safety of breast reconstruction for patients with locally advanced breast cancer (LABC) who have undergone total mastectomy (TM). More and more LABC patients are undergoing breast reconstruction after TM, but its long-term survival outcomes remain unclear. This study aimed to compare the survival outcomes of LABC patients who underwent breast reconstruction after TM with those who did not, based on a large sample.

METHODS: We collected data for all LABC patients who underwent TM with or without breast reconstruction in the Surveillance, Epidemiology, and End Results (SEER) database. We divided patients into two groups: TM group and total mastectomy with reconstruction (TM+R) group. The primary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS). Propensity score matching (PSM) analysis was used to eliminate imbalances of baseline data between the two groups. Data were analyzed using χ2 tests, Kaplan-Meier methods, and univariate and multivariate Cox regression analyses.

RESULT: We identified 39,112 eligible patients (33,169 patients received TM and 5,943 received TM+R), and 8,680 patients were matched after PSM (4,340 patients received TM and 4,340 received TM+R). Patients with middle age, white, married, lived in urban, IIB-IIIA stage, invasive ductal carcinoma, pathological grade II-III, hormone receptor-positive, and undergone chemotherapy were more likely to receive breast reconstruction. After PSM, Kaplan-Meier survival analysis showed better OS and BCSS in the TM+R group versus the TM group (OS: p < 0.001; BCSS: p = 0.008). Multivariate Cox regression analysis showed that TM+R significantly improved OS and BCSS (OS: hazard ratio 0.73, 95% confidence interval [CI] [0.68, 0.79], p < 0.001; BCSS: 95% CI [0.79, 0.94], p = 0.001). Subgroup analysis showed that patients with old age, white, and hormone receptor-positive had better OS and BCSS by TM+R compared to TM.

CONCLUSIONS: Breast reconstruction after TM is associated with better OS and BCSS in patients with LABC.}, } @article {pmid39435217, year = {2024}, author = {Kumaravel, A and Esakki, M}, title = {Comparing CD10 Expression With the Clinicopathological Features and Hormone Status of Invasive Breast Cancer.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e69836}, pmid = {39435217}, issn = {2168-8184}, abstract = {Background Worldwide, female breast cancer is the most common cancer (11.7%), followed by lung (11.4%), colorectal, prostate, and stomach. Breast cancer is the fifth most common cause of cancer-related mortality, with lung cancer being the leading cause. In India, breast and cervical cancers are the two most common cancers among women. This study was undertaken to analyse the expression of CD10 in invasive duct cancer (IDC) and its correlation with the various clinicopathological features and hormone status. Materials and methods This study was conducted in the Department of Pathology, Saveetha Medical College and Hospital on 42 cases of invasive ductal carcinoma - no special type (IDC NST). The clinical and histopathologic parameters such as age, tumor site, tumor size, histologic type, histologic grade, lymph node metastases, lymphovascular invasion, and perineural invasion were assessed in hematoxylin and eosin-stained sections of the tumor tissue along with the hormone status of positivity for ER, PR and Her2Neu. These parameters were subsequently compared with the expression of CD10 in the corresponding slides and statsitical correlation was done using the chi square test. Results The most common age group was more than 40 years, with 41-50 years, and 51-60 years in particular. CD10 was positive in 93% of cases. There was a positive correlation between CD 10 expression and lymphovascular invasion in the study (p-0.006). There was no significant relationship between hormone status and CD10 expression. Conclusion A significant association was seen between CD10 expression and lymphovascular invasion. No relation was found between CD10 and the other parameters such as tumour grade, lymph node metastases, lymphovascular invasion, perineural invasion and hormone status. Further studies are required to explore the potential of CD10 as a prognostic marker for IDC.}, } @article {pmid39433886, year = {2025}, author = {Bernardino, RM and Yin, LB and Lajkosz, K and Cockburn, JG and Wettstein, M and Sayyid, RK and Henrique, R and Pinheiro, LC and van der Kwast, T and Fleshner, NE}, title = {Undetected Cribriform and Intraductal Prostate Cancer at biopsy is associated with adverse outcomes.}, journal = {Prostate cancer and prostatic diseases}, volume = {28}, number = {1}, pages = {187-192}, pmid = {39433886}, issn = {1476-5608}, support = {BD2022.13386//Ministry of Education and Science | Fundação para a Ciência e a Tecnologia (Portuguese Science and Technology Foundation)/ ; }, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/surgery/mortality/diagnosis ; Middle Aged ; Aged ; Prognosis ; Prostatectomy ; Biopsy ; False Negative Reactions ; Retrospective Studies ; *Prostate/pathology/surgery ; Neoplasm Grading ; Follow-Up Studies ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; }, abstract = {BACKGROUND: Intraductal carcinoma (IDC) and cribriform pattern (Crib) of prostate cancer are increasingly recognized as independent prognosticators of poor outcome, both in prostate biopsies and radical prostatectomy (RP) specimens.

OBJECTIVE: The aim of our project is to assess the impact of false negative biopsies for these two characteristics on oncological outcomes.

MATERIAL AND METHODS: Patients who underwent RP between January 2015 and December 2022 were included in the study. Predictors of Biochemical Failure were examined using a multivariate Cox proportional hazards model.

RESULTS AND LIMITATION: Among the 836 patients who underwent RP, 233 (27.9%) had Crib, and 125 (15.0%) had IDC on prostate biopsy, with 71 (8.5%) patients having both IDC and Crib. Concerning IDC/Crib status at biopsy, 217 (26%) patients had a false-negative biopsy, 332 (39.7%) had a true-negative biopsy, 256 (30.6%) showed a true-positive biopsy, and 24 (3.7%) exhibited a false-positive biopsy, with respect to either pattern. When comparing false-negative, false-positive, true-negative and true-positive biopsies for IDC/Crib, we found that patients with a false-negative biopsy for IDC/Crib versus those with a true-negative biopsy for IDC/Crib disclosed a rate of advanced pathological stage (≥pT3) which was twice that of patients with a true-negative biopsy for IDC/Crib: 56.8% versus 28.1%, respectively (p < 0.001). On multivariate Cox analysis, log PSA before RP (hazard ratio [HR] 2.07, 95% CI 1.53-2.82; p < 0.001), a higher percentage of positive cores at biopsy ( ≥ 33%) (HR 1.68, 95% CI 1.07-2.63; p = 0.024), and false negative biopsy for IDC/Crib (HR 2.14, 95% CI 1.41-3.25; p < 0.001), were each significantly associated with an increased risk of BCR.

CONCLUSIONS: A false-negative biopsy for IDC/Crib is independently associated with higher risk of BCR and advanced pathological stage compared to a true negative biopsy.}, } @article {pmid39432469, year = {2024}, author = {Anh, NK and Lee, A and Phat, NK and Yen, NTH and Thu, NQ and Tien, NTN and Kim, HS and Kim, TH and Kim, DH and Kim, HY and Phuoc Long, N}, title = {Combining metabolomics and machine learning to discover biomarkers for early-stage breast cancer diagnosis.}, journal = {PloS one}, volume = {19}, number = {10}, pages = {e0311810}, pmid = {39432469}, issn = {1932-6203}, mesh = {Humans ; *Breast Neoplasms/diagnosis/metabolism ; Female ; *Biomarkers, Tumor/metabolism ; *Metabolomics/methods ; *Machine Learning ; Middle Aged ; *Early Detection of Cancer/methods ; Adult ; Aged ; ROC Curve ; Neoplasm Staging ; }, abstract = {There is an urgent need for better biomarkers for the detection of early-stage breast cancer. Utilizing untargeted metabolomics and lipidomics in conjunction with advanced data mining approaches for metabolism-centric biomarker discovery and validation may enhance the identification and validation of novel biomarkers for breast cancer screening. In this study, we employed a multimodal omics approach to identify and validate potential biomarkers capable of differentiating between patients with breast cancer and those with benign tumors. Our findings indicated that ether-linked phosphatidylcholine exhibited a significant difference between invasive ductal carcinoma and benign tumors, including cases with inconsistent mammography results. We observed alterations in numerous lipid species, including sphingomyelin, triacylglycerol, and free fatty acids, in the breast cancer group. Furthermore, we identified several dysregulated hydrophilic metabolites in breast cancer, such as glutamate, glycochenodeoxycholate, and dimethyluric acid. Through robust multivariate receiver operating characteristic analysis utilizing machine learning models, either linear support vector machines or random forest models, we successfully distinguished between cancerous and benign cases with promising outcomes. These results emphasize the potential of metabolic biomarkers to complement other criteria in breast cancer screening. Future studies are essential to further validate the metabolic biomarkers identified in our study and to develop assays for clinical applications.}, } @article {pmid39430818, year = {2024}, author = {Zhou, R and Liu, M and Li, M and Peng, Y and Zhang, X}, title = {BUB1 as a novel marker for predicting the immunotherapy efficacy and prognosis of breast cancer.}, journal = {Translational cancer research}, volume = {13}, number = {9}, pages = {4534-4554}, pmid = {39430818}, issn = {2219-6803}, abstract = {BACKGROUND: Budding uninhibited by benzimidazole 1 (BUB1) is a highly conserved serine/threonine kinase, showing prominent importance for proper function during mitosis. However, little is known about BUB1 mRNA expression in breast cancer (BRCA) and its correlation with prognosis and immune infiltration. Hence, we aimed to unveil its potential as groundbreaking biomarkers for immunotherapy efficacy and the prognosis of BRCA.

METHODS: Database for Annotation, Visualization, and Integrated Discovery (DAVID) is a potent tool for identifying significant clusters of genes and pathways in the resulting dataset. In this study, gene set enrichment analysis of BUB1 was conducted using DAVID. The clinical characteristics of patients with or without altered BUB1 mRNA expression were compared using cBioPortal. Tumor Immune Estimation Resource (TIMER) is a known as database for comprehensive analysis of tumor-infiltrating immune cells in various cancers. In the present study, the relationship between BUB1 expression and the abundance of immune infiltrates was explored using TIMER in BRCA. Immunohistochemistry staining was performed to analyze the protein expression of BUB1 in tumor tissue specimens. We used PrognoScan and Kaplan-Meier Plotter to evaluate the prognosis of patients with different BUB1 expression levels.

RESULTS: The expression of BUB1 in various tumor tissues was higher than that in adjacent normal tissues. BUB1 was mainly localized to the nucleoplasm and additionally localized to the cytosol. Functional enrichment analyses revealed that the cell cycle was the most significant pathway. Abnormal BUB1 mRNA expression was more frequently detected in invasive ductal carcinoma with higher histological grades and BRCAs with estrogen receptor (ER)-negative, human epidermal growth receptor 2 (HER2)-negative, and basal-like phenotypes. The BUB1 expression was correlated positively with tumor purity, B cells, CD8[+] T cells, CD4[+] T cells, neutrophils, and dendritic cells, while BUB1 had no significant correlation with macrophages. The results of immunohistochemical staining from clinical samples further confirmed that BUB1 was overexpressed in BRCA compared to benign tumor (fibroadenoma of breast) (P<0.01). BRCA patients with lower BUB1 expression had a better prognosis than those with higher BUB1 expression in overall survival (OS) curves, distant metastasis-free survival (DMFS) curves, and relapse-free survival (RFS) curves (P<0.05).

CONCLUSIONS: Our results suggest that BUB1 is a potential molecular biomarker for evaluating the prognosis and predicting the effectiveness of immunotherapy for BRCA.}, } @article {pmid39426973, year = {2024}, author = {Wojtowicz, W and Tarkowski, R and Olczak, A and Szymczycha-Madeja, A and Pohl, P and Maciejczyk, A and Trembecki, Ł and Matkowski, R and Młynarz, P}, title = {Serum metabolite and metal ions profiles for breast cancer screening.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {24559}, pmid = {39426973}, issn = {2045-2322}, support = {WCB KNOW 2014-2018//Politechnika Wrocławska/ ; }, mesh = {Humans ; *Breast Neoplasms/blood/diagnosis/metabolism ; Female ; *Early Detection of Cancer/methods ; *Metabolomics/methods ; Middle Aged ; *Metals/blood ; Biomarkers, Tumor/blood ; Adult ; Aged ; Ions/blood ; Metabolome ; Magnetic Resonance Spectroscopy/methods ; }, abstract = {Enhancing early-stage breast cancer detection requires integrating additional screening methods with current diagnostic imaging. Omics screening, using easily collectible serum samples, could serve as an initial step. Alongside biomarker identification capabilities, omics analysis allows for a comprehensive analysis of prevalent histological types-DCIS and IDC. Employing metabolomics, metallomics, and machine learning, could yield accurate screening models with valuable insights into organism responses. Serum samples of confirmed breast cancer patients were utilized to analyze metabolite and metal ion profiles, using two distinct analysis methods, proton NMR for metabolomics and ICP-OES for metallomics. The resulting responses were then subjected to discriminant analysis, progression biomarker exploration, examination of correlations between patients' metabolites and metal ions, and the impact of age and menopause status. Measured NMR spectra and metabolite relative integrals were used to achieve statistically significant discrimination through MVA between breast cancer and control groups. The analysis identified 24 metabolites and 4 metal ions crucial for discrimination. Furthermore, four metabolites were associated with disease progression. Additionally, there were important correlations and relationships between metabolite relative integrals, metal ion concentrations, and age/menopausal status subgroups. Quantified relative integrals allowed for discrimination between studied subgroups, validated with a holdout set. Feature importance and statistical analysis for metabolomics and metallomics extracted a set of common entities which in combination provides valuable insights into ongoing molecular disturbances and disease progression.}, } @article {pmid39418320, year = {2025}, author = {Schwarz, D and Le Marois, M and Sturm, V and Peters, AS and Longuespée, R and Helm, D and Schneider, M and Eichmüller, B and Hidmark, AS and Fischer, M and Kender, Z and Schwab, C and Hausser, I and Weis, J and Dihlmann, S and Böckler, D and Bendszus, M and Heiland, S and Herzig, S and Nawroth, PP and Szendroedi, J and Fleming, T}, title = {Exploring Structural and Molecular Features of Sciatic Nerve Lesions in Diabetic Neuropathy: Unveiling Pathogenic Pathways and Targets.}, journal = {Diabetes}, volume = {74}, number = {1}, pages = {65-74}, pmid = {39418320}, issn = {1939-327X}, support = {GRK 1874/2//DFG/ ; //Deutsche Forschungsgemeinschaft/ ; //German Centre for Diabetes Research/ ; }, mesh = {*Diabetic Neuropathies/metabolism/pathology ; Humans ; *Sciatic Nerve/metabolism/pathology ; Male ; *Diabetes Mellitus, Type 2/metabolism/complications ; Middle Aged ; *Proteomics ; Female ; Aged ; Blood-Nerve Barrier/metabolism ; Magnetic Resonance Imaging ; Adult ; }, abstract = {Lesioned fascicles (LFs) in the sciatic nerves of individuals with diabetic neuropathy (DN) correlate with clinical symptom severity. This study aimed to characterize the structural and molecular composition of these lesions to better understand DN pathogenesis. Sciatic nerves from amputees with and without type 2 diabetes (T2D) were examined using ex vivo magnetic resonance neurography, in vitro imaging, and proteomic analysis. Lesions were only found in T2D donors and exhibited significant structural abnormalities, including axonal degeneration, demyelination, and impaired blood-nerve barrier (BNB). Although non-LFs from T2D donors showed activation of neuroprotective pathways, LFs lacked this response and instead displayed increased complement activation via the classical pathway. The detection of liver-derived acute-phase proteins suggests that BNB disruption facilitates harmful interorgan communication between the liver and nerves. These findings reveal key molecular mechanisms contributing to DN and highlight potential targets for therapeutic intervention.}, } @article {pmid39410615, year = {2024}, author = {Usul, G and Kelten Talu, EC and Yılmaz, İ and Issın, GN and Bektaş, S and Can Trabulus, D}, title = {The Association of Neuroendocrine Differentiation with MicroRNA 21 and MicroRNA let7f Expression and the Clinicopathological Parameters in Primary Invasive Breast Carcinomas with Neuroendocrine Features.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {19}, pages = {}, pmid = {39410615}, issn = {2075-4418}, abstract = {MiRNAs have been reported as biomarkers with diagnostic, prognostic, and predictive value for many different diseases. Therapeutic agents targeting some miRNAs are currently being developed. We aimed to compare BC-NEFs (carcinoma of the breast with neuroendocrine features) with IDC (invasive ductal carcinoma) cases without neuroendocrine features in terms of the level of miRNA expression known to show the oncogenic (miR-21) and tumor-suppressor effects (miR-let7f) and the clinicopathological features. A total of 29 patients with a diagnosis of BC-NEFs (15 cases with neuroendocrine differentiation >50% of the whole section of tumor and 14 cases with neuroendocrine differentiation 10-50% of the tumor) and 30 patients with a diagnosis of IDC (no neuroendocrine differentiation) were retrospectively re-evaluated. Expression levels of miR-21 and miR-let7f were determined by the qRT-PCR method in paraffin tissue blocks. MiR-21 expression was significantly higher in the IDC group than in the group with BC-NEFs. miR-let7f expression was significantly lower in the group with BC-NEFs compared to the IDC group. A high expression level of miR-21 was found to be associated with progesterone receptor (PR) negativity. Our findings show that the presence of NEFs in breast carcinomas makes a significant difference in the expression levels of the investigated oncogenic (miR-21) and tumor-suppressor (miR-let7f) miRNAs. These findings suggest that miRNAs may be a potential biomarker in BC-NEFs and would benefit from targeted therapy.}, } @article {pmid39399800, year = {2024}, author = {Noto, M and Satake, T and Taki, K and Ikeda, T and Tsukura, K and Ikusaka, K and Katsuragi, R and Onoda, S}, title = {Breast Reconstruction Using Combined Unilateral Hemiabdominal DIEP Flap with Lipofilling from the Contralateral Abdomen.}, journal = {Plastic and reconstructive surgery. Global open}, volume = {12}, number = {10}, pages = {e6239}, pmid = {39399800}, issn = {2169-7574}, abstract = {The deep inferior epigastric perforator (DIEP) flap is the gold standard breast reconstruction procedure for patients with adequate lower abdominal tissue and is often elevated, including the unilateral DIEP. In patients with a lower midline abdominal surgical scar, the volume of the DIEP flap used for breast reconstruction may be limited because of the cessation of blood perfusion over the scar. Several options have been used for increasing the flap volume using bipedicled flaps; however, they are more invasive for the abdominal donor site and require longer operation time for complex vascular anastomoses. To overcome these disadvantages, we propose immediate breast reconstruction with simultaneous fat grafting combined with a DIEP flap, which can achieve an adequate breast volume. The patient was a 46-year-old woman with left-sided invasive ductal carcinoma. She underwent a left nipple-sparing mastectomy, sentinel lymph node biopsy, and one-stage immediate DIEP flap breast reconstruction. Indocyanine green angiography was used to evaluate the blood supply to the DIEP flap, and lipofilling was performed from the unstained flap area. The fat was injected into and under the pectoralis major muscle, and the total volume of the fat graft was 66 mL. The advantages of immediate lipofilling harvested from the unstained flap area include minimal sacrifice, the expectation of simultaneous restoration of the overall appearance of the breast with a minimal number of operations, the simplicity of the procedure, and the best use of viable tissues. Therefore, breast reconstruction combined with fat grafting is effective for volume augmentation.}, } @article {pmid39399621, year = {2024}, author = {Moradian Haft Cheshmeh, Z and Ostovar, A and Ghanbari Motlagh, A and Asadi-Lari, M}, title = {Examining the Completeness of Breast Cancer Pathology Reports Registered in the Population-Based Cancer Registration System in Iran during 2016 to 2018.}, journal = {Medical journal of the Islamic Republic of Iran}, volume = {38}, number = {}, pages = {61}, pmid = {39399621}, issn = {1016-1430}, abstract = {BACKGROUND: Ensuring the comprehensive and accurate representation of data within cancer registries holds paramount significance across various facets of public health decision-making. This study delves into the evaluation of data completeness in breast cancer (BC) pathology reports within a population-based cancer registration system in Iran, spanning the period from 2016 to 2018.

METHODS: Employing a retrospective and descriptive analytical approach, we harnessed secondary data extracted from pathology reports encompassing breast cancer diagnoses, which were duly recorded in the Integrated Cancer Information Management System database during 2016-2018. A total of 4000 pathology reports were thoughtfully selected from each of the three years. The spectrum of pathology information encompassed tumor type, site grade, size (T), and involvement of lymph nodes (N). Summary statistics were provided as percentages of categorical variables and mean with standard deviation of continuous variables. A comparison of categorical variables was performed using the Chi-squared test.

RESULTS: The participants' mean age was 51.8±12.5 years. Among the 12,000 studied patients, 5744 (47.9%) were ≤ 50 years old, 5233 (43.6%) were aged 50-69 years, and 1023 (8.5%) were >60 years old. The completeness of BC pathology reports varied for different variables. Interestingly, the completeness of these variables increased with older age groups. The proportion of specific tumor types differed significantly among age groups (P = 0.001). Notably, the prevalence of invasive ductal carcinoma was higher in the ≤ 50 years age group compared to the older cohorts. Likewise, notable variations in tumor sizes were observed (P = 0.009), with a higher prevalence of missing tumor size data noted in the age group ≤ 50 years. On the other hand, pathologic T stage also demonstrated age-dependent variations (P = 0.014), indicating a higher prevalence of missing stages in the ≤ 50 years age group. Finally, tumor grade exhibited a statistically significant difference (P < 0.001), with a higher proportion of grade 1 tumors observed in the 50-69 years age group.

CONCLUSION: Tumor grade had the highest completeness rate, while tumor size, pathologic T stage, and pathologic N stage had the lowest. Therefore, a good understanding of completeness of pathology reports, as well as improvement in the registration of stage, integrated system at the national level for BC is warranted.}, } @article {pmid39398724, year = {2024}, author = {Troelstra, JM and Murphy, E and Tousimis, E}, title = {Invasive Ductal Carcinoma of the Breast Presenting With Contralateral Axillary Lymph Node Metastasis: A Case Report.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e69359}, pmid = {39398724}, issn = {2168-8184}, abstract = {This is a case of a 71-year-old Caucasian female presenting with invasive carcinoma of the breast with contralateral axillary lymph node metastasis. This unique presentation presents clinicians with difficulty staging and, therefore, predicting patient prognosis. This patient had a history of right ER/PR positive HER2 negative stage 1 breast cancer s/p lumpectomy with sentinel lymph node biopsy and radiation plus tamoxifen x6 months in 2017. She is now presenting with a recurrence of right breast cancer along with additional metastatic disease to the contralateral (left) axilla. She was treated with a skin-sparing mastectomy along with a contralateral lymph node dissection. A negative sentinel lymph node was seen, representing the dilemma of non-contiguous metastatic spread. Histological pathology of the right breast masses revealed multifocal invasive carcinoma of no special type (ductal), along with two of five left axillary lymph nodes positive for metastatic mammary carcinoma. No right-sided sentinel node was identified. The right breast lesions and the left axillary lymph node metastases are all morphologically similar and showed strong ER expression, the results of which are compatible with spreading to the contralateral axilla.}, } @article {pmid39387224, year = {2025}, author = {Walsh, AR and Spiars, DE and Loder, C and Dove-Medows, E and Kalpakjian, C and Hess, A and Postler, K and Munro-Kramer, ML and Ernst, S}, title = {Sexual and Gender Identity-Associated Disparities in University Students' Experiences with Inappropriate, Disrespectful, and Coercive Health Care.}, journal = {LGBT health}, volume = {12}, number = {4}, pages = {295-305}, doi = {10.1089/lgbt.2023.0373}, pmid = {39387224}, issn = {2325-8306}, mesh = {Humans ; Female ; Male ; *Students/psychology/statistics & numerical data ; Cross-Sectional Studies ; Universities ; Young Adult ; *Coercion ; *Gender Identity ; *Sexual and Gender Minorities/statistics & numerical data/psychology ; Adult ; Adolescent ; }, abstract = {Purpose: Inappropriate, disrespectful, or coercive health care (IDCH) is associated with patient age and sexual orientation and gender identity (SOGI) and can impact healthcare engagement and outcomes. Emerging adulthood is a critical period for establishing trust in health care, yet little is known about university students' IDCH experiences. This study assessed the IDCH prevalence and identified IDCH-SOGI associations in a university student sample. Methods: Using data from the cross-sectional IDC Survey (2021), we quantified the lifetime prevalence of 18 IDCH items in a sample of 3403 university students. Chi-squared and Kruskal-Wallis tests were used to assess bivariate associations between IDCH items and SOGI. We modeled associations between demographic characteristics and two types of provider-sexual misconduct using logistic regression. Results: Statistically significant associations between SOGI and 17 of the analyzed IDCH items were identified. Self-reported IDCH experiences were more prevalent among minoritized SOGI students than heterosexual cisgender students, including receiving inappropriate/harmful treatment and dismissive or biased provider communication. Gender minority and sexual minority cisgender male and female students had significantly higher odds of ever being touched inappropriately during an exam, compared with heterosexual cisgender males (adjusted odds ratios [95% confidence interval]: 3.07 [1.59-5.93], 2.34 [1.24-4.41], and 1.85 [1.16-2.90], respectively). SOGI was not significantly associated with experiencing a provider's sexual advances. Conclusion: University students with historically minoritized SOGIs may be particularly vulnerable to IDCH experiences; research is needed to understand differential experiences within minoritized sexual and gender subpopulations. Patient and provider education about healthcare norms and trauma-centered care could potentially reduce IDCH and its harms.}, } @article {pmid39393363, year = {2025}, author = {Xu, J and Accola, MA and Rehrauer, WM and Weisman, PS}, title = {Pilomatrix-like breast carcinoma: A mammary analog of pilomatrix-like high-grade endometrioid carcinoma (PiMHEC).}, journal = {American journal of clinical pathology}, volume = {163}, number = {3}, pages = {388-394}, doi = {10.1093/ajcp/aqae132}, pmid = {39393363}, issn = {1943-7722}, support = {//University of Wisconsin-Madison/ ; //School of Medicine and Public Health/ ; //Department of Pathology and Laboratory Medicine/ ; }, mesh = {Female ; Humans ; beta Catenin/genetics ; Biomarkers, Tumor/metabolism/analysis ; *Breast Neoplasms/pathology/genetics ; *Carcinoma, Endometrioid/pathology/genetics/metabolism ; Mutation ; *Pilomatrixoma/pathology/genetics ; *Triple Negative Breast Neoplasms/pathology/genetics/metabolism ; Aged ; }, abstract = {OBJECTIVES: To describe what is, to our knowledge, the first recognized case of a triple-negative breast carcinoma (TNBC) with a PiMHEC-like phenotype. Pilomatrix-like high-grade endometrioid carcinoma (PiMHEC) is a high-grade carcinoma with divergent differentiation resembling cutaneous pilomatrix carcinoma that was recently described in the endometrium and ovary. For reference, pertinent features of PiMHEC include (1) high-grade basaloid to squamoid morphology with the presence of ghost cells; (2) only focal p63 and/or p40 expression despite a squamoid appearance; (3) CTNNB1 mutation, accompanied by diffusely aberrant β-catenin expression and LEF1 and/or CDX2 expression; and (4) loss of site-specific markers (ie, PAX8, ER).

METHODS: Here we report the histologic, immunophenotypic and molecular genetic features of a case of a triple-negative breast carcinoma (TNBC) with a PiMHEC-like phenotype.

RESULTS: The tumor developed immediately adjacent to a HER2+, androgen receptor (AR)+, GATA3+ conventional grade 3 invasive ductal carcinoma (IDC) with only membranous β-catenin expression. The PiMHEC-like component had all of the above-noted morphologic and immunophenotypic features of endometrial PiMHEC but with loss of GATA3 and AR rather than PAX8 and ER. Molecular analysis performed on both tumor components demonstrated a shared TP53 point mutation and an exon 3 CTNNB1 mutation restricted to the PiMHEC-like component, implying a clonal relationship with secondary acquisition of CTNNB1. Following neoadjuvant chemotherapy, the HER2+ conventional component had completely resolved, but the PiMHEC-like component had very little response.

CONCLUSIONS: This case demonstrates that a PiMHEC-like phenotype may be seen as a form of TNBC that can develop from conventional IDC, with loss of site-specific biomarkers, acquisition of CTNNB1 mutation, and resistance to conventional chemotherapy.}, } @article {pmid39392173, year = {2024}, author = {Huang, YJ and Lin, JA and Chen, WM and Shia, BC and Wu, SY}, title = {Statin Therapy Reduces Radiation-Induced Cardiotoxicity in Patients With Breast Cancer Receiving Adjuvant Radiotherapy.}, journal = {Journal of the American Heart Association}, volume = {13}, number = {20}, pages = {e036411}, pmid = {39392173}, issn = {2047-9980}, mesh = {Humans ; Female ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Middle Aged ; Retrospective Studies ; *Cardiotoxicity ; Radiotherapy, Adjuvant/adverse effects ; Taiwan/epidemiology ; Aged ; Breast Neoplasms/radiotherapy ; Incidence ; Mastectomy, Segmental ; Registries ; Risk Assessment ; Radiation Injuries/epidemiology/prevention & control/etiology ; Adult ; Carcinoma, Ductal, Breast/radiotherapy ; Risk Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: To evaluate the efficacy of statin therapy in reducing major adverse cardiovascular event (MACE) risk among patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy.

METHODS AND RESULTS: A retrospective cohort study was conducted using data from the Taiwan Cancer Registry Database linked to the National Health Insurance Research Database. Patients diagnosed with left-sided early breast invasive ductal carcinoma between 2016 and 2019 were included. Propensity score matching was employed to compare MACE risk between statin users and nonusers. Cox regression models were used to estimate adjusted hazard ratios (aHRs) for MACE, considering cumulative defined daily doses and daily defined doses of statins. Among 1481 patients undergoing breast-conserving surgery and adjuvant whole breast radiotherapy, statin use significantly reduced MACE risk (aHR, 0.34 [95% CI, 0.25-0.44]). Hydrophilic statins, particularly rosuvastatin and pravastatin, demonstrated the greatest risk reduction. Higher cumulative defined daily doses and daily intensity doses of statins were associated with lower MACE risk, indicating a dose-response relationship. The 5-year cumulative incidence of MACE was significantly lower in statin users compared with nonusers (12.24% versus 31.70%).

CONCLUSIONS: Statin therapy is associated with a reduced risk of MACE in patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy. Hydrophilic statins rosuvastatin and pravastatin exhibit the most pronounced cardioprotective effects. These findings suggest a potential role for statins in mitigating cardiovascular complications in this population and highlight the need for further research to optimize statin therapy in survivors of breast cancer undergoing radiotherapy.}, } @article {pmid39385889, year = {2024}, author = {Arunachalam Jeykumar, NS and Sacratice, S and Thirugnanam, T and Vadivel, P}, title = {Inflammatory Breast Carcinoma in Pregnancy: A Curious Case of a High-Grade Invasive Ductal Carcinoma Masquerading as a Breast Abscess in the Second Trimester.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e68984}, pmid = {39385889}, issn = {2168-8184}, abstract = {Inflammatory breast carcinoma is an uncommon presentation of carcinoma breast characterised by tumour cell emboli invading the dermal lymphatics and manifesting as skin oedema and redness, closely resembling acute mastitis. We report the case of a 37-year-old pregnant female in the second trimester (at 16 weeks) with a left breast inflammatory carcinoma deceptively presenting as a breast abscess leading to a late diagnosis, delayed definitive management, and having profound psychological, therapeutic, and prognostic implications. Given its tendency to be clinically misleading and often disregarded until late stages, much emphasis has to be placed on a low threshold of suspicion when suggestive clinical signs are encountered.}, } @article {pmid39384955, year = {2025}, author = {Ofoghi, A and Kotschi, S and Lemmer, IL and Haas, DT and Willemsen, N and Bayer, B and Jung, AS and Möller, S and Haberecht-Müller, S and Krüger, E and Krahmer, N and Bartelt, A}, title = {Activating the NFE2L1-ubiquitin-proteasome system by DDI2 protects from ferroptosis.}, journal = {Cell death and differentiation}, volume = {32}, number = {3}, pages = {480-487}, pmid = {39384955}, issn = {1476-5403}, support = {BA4925/2-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; RTG2719 PRO//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; PROTEOFIT//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; }, mesh = {*Ferroptosis/drug effects ; *Proteasome Endopeptidase Complex/metabolism ; Humans ; *NF-E2-Related Factor 1/metabolism ; *Ubiquitin/metabolism ; Ubiquitination ; HEK293 Cells ; }, abstract = {Ferroptosis is an iron-dependent, non-apoptotic form of cell death initiated by oxidative stress and lipid peroxidation. Recent evidence has linked ferroptosis to the action of the transcription factor Nuclear factor erythroid-2 derived,-like-1 (NFE2L1). NFE2L1 regulates proteasome abundance in an adaptive fashion, maintaining protein quality control to secure cellular homeostasis, but the regulation of NFE2L1 during ferroptosis and the role of the ubiquitin-proteasome system (UPS) herein are still unclear. In the present study, using an unbiased proteomic approach charting the specific ubiquitylation sites, we show that induction of ferroptosis leads to recalibration of the UPS. RSL3-induced ferroptosis inhibits proteasome activity and leads to global hyperubiquitylation, which is linked to NFE2L1 activation. As NFE2L1 resides in the endoplasmic reticulum tethered to the membrane, it undergoes complex posttranslational modification steps to become active and induce the expression of proteasome subunit genes. We show that proteolytic cleavage of NFE2L1 by the aspartyl protease DNA-damage inducible 1 homolog 2 (DDI2) is a critical step for the ferroptosis-induced feed-back loop of proteasome function. Cells lacking DDI2 cannot activate NFE2L1 in response to RSL3 and show global hyperubiquitylation. Genetic or chemical induction of ferroptosis in cells with a disrupted DDI2-NFE2L1 pathway diminishes proteasomal activity and promotes cell death. Also, treating cells with the clinical drug nelfinavir, which inhibits DDI2, sensitized cells to ferroptosis. In conclusion, our results provide new insight into the importance of the UPS in ferroptosis and highlight the role of the DDI2-NFE2L1 as a potential therapeutic target. Manipulating DDI2-NFE2L1 activity through chemical inhibition might help sensitizing cells to ferroptosis, thus enhancing existing cancer therapies.}, } @article {pmid39382167, year = {2024}, author = {Koumantou, D and Adiko, AC and Bourdely, P and Nugue, M and Boedec, E and El-Benna, J and Monteiro, R and Saveanu, C and Laffargue, M and Wymann, MP and Dalod, M and Guermonprez, P and Saveanu, L}, title = {Specific Requirement of the p84/p110γ Complex of PI3Kγ for Antibody-Activated, Inducible Cross-Presentation in Murine Type 2 DCs.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {11}, number = {44}, pages = {e2401179}, pmid = {39382167}, issn = {2198-3844}, support = {ANR-11-IDEX-0005-02//Agence Nationale de la Recherche/ ; ANR-15-CE15-0005//Agence Nationale de la Recherche/ ; ANR-17-CE11-0001//Agence Nationale de la Recherche/ ; //Fondation pour la Recherche Medicale/ ; ANR-10-EQPX-03//ICGex NGS platform of the Institut Curie/ ; ANR-10-INBS-09-08//ICGex NGS platform of the Institut Curie/ ; INCa-DGOS-465//SiRIC-Curie program/ ; INCa-DGOS- Inserm_12554//SiRIC-Curie program/ ; SNF-310030-189065/SNSF_/Swiss National Science Foundation/Switzerland ; }, mesh = {Animals ; Mice ; *Dendritic Cells/immunology/metabolism ; *Cross-Priming/immunology ; *Mice, Inbred C57BL ; Class Ib Phosphatidylinositol 3-Kinase/metabolism/immunology/genetics ; Antigen Presentation/immunology ; }, abstract = {Cross-presentation by MHCI is optimally efficient in type 1 dendritic cells (DC) due to their high capacity for antigen processing. However, through specific pathways, other DCs, such as type 2 DCs and inflammatory DCs (iDCs) can also cross-present antigens. FcγR-mediated uptake by type 2 DC and iDC subsets mediates antibody-dependent cross-presentation and activation of CD8[+] T cell responses. Here, an important role for the p84 regulatory subunit of PI3Kγ in mediating efficient cross-presentation of exogenous antigens in otherwise inefficient cross-presenting cells, such as type 2 DCs and GM-CSF-derived iDCs is identified. FcγR-mediated cross-presentation is shown in type 2 and iDCs depend on the enzymatic activity of the p84/p110γ complex of PI3Kγ, which controls the activity of the NADPH oxidase NOX2 and ROS production in murine spleen type 2 DCs and GM-CSF-derived iDCs. In contrast, p84/p110γ is largely dispensable for cross-presentation by type 1 DCs. These findings suggest that PI3Kγ-targeted therapies, currently considered for oncological practice, may interfere with the ability of type 2 DCs and iDCs to cross-present antigens contained in immune complexes.}, } @article {pmid39381035, year = {2024}, author = {Bhimani, F and McEvoy, M and Chen, Y and Gupta, A and Pastoriza, J and Fruchter, S and Bitan, ZC and Tomé, WA and Mehta, K and Fox, J and Feldman, S}, title = {Case report: IORT as an alternative treatment option for breast cancer patients with difficulty staying still.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1429326}, pmid = {39381035}, issn = {2234-943X}, abstract = {BACKGROUND: Administering radiation therapy to individuals with intellectual disabilities (ID) and psychiatric patients taking antipsychotics poses challenges, especially with whole breast irradiation (WBI) due to difficulty staying still (DSS). In such scenarios, intraoperative radiotherapy (TARGIT-IORT) provides an alternative. Although prior studies have shown its applicability in special cases where WBI may be contraindicated, there is a paucity of literature emphasizing its role in patients with ID and psychiatric conditions who have DSS. Therefore, our case series aims to highlight the applicability of administering TARGIT-IORT in such patients.

CASE REPORTS: Four breast cancer patients underwent lumpectomy and TARGIT-IORT. Among them, two patients had ID, with one experiencing a decreased range of motion. The other two had psychiatric disorders, including schizophrenia and bipolar disorder, both manifesting involuntary movements and DSS. Three patients had invasive ductal carcinoma (IDC), and one had invasive lobular carcinoma (ILC). All patients undergoing TARGIT-IORT tolerated the procedure well. Notably, none of the patients exhibited evidence of disease on follow-up.

CONCLUSION: Our study underscores the potential use of TARGIT-IORT as a viable treatment option for breast cancer patients with intellectual and psychiatric disabilities. Unlike traditional EBRT, TARGIT-IORT offers a single radiation dose, addressing challenges associated with compliance or DSS. Our findings demonstrate positive outcomes and tolerance, especially in patients where standard oncologic procedures are difficult to achieve. TARGIT-IORT could also benefit breast cancer patients with concurrent movement disorders like Parkinson's disease and other movement disorders. Nonetheless, future studies are needed to reinforce its applicability for patients with DSS.}, } @article {pmid39379117, year = {2024}, author = {Salih, MM and Abdulgafor, DA and Dahlawi, HA and Khalifa, EH}, title = {The value and significance of nucleolar organizer region proteins as markers of malignancy in breast cancer patients.}, journal = {Saudi medical journal}, volume = {45}, number = {10}, pages = {1028-1033}, pmid = {39379117}, issn = {1658-3175}, mesh = {Humans ; *Breast Neoplasms/pathology/metabolism ; Female ; Middle Aged ; *Biomarkers, Tumor/metabolism ; Adult ; *Nucleolus Organizer Region/metabolism/pathology ; Aged ; Antigens, Nuclear/metabolism/analysis ; Carcinoma, Ductal, Breast/pathology/metabolism ; }, abstract = {OBJECTIVES: To assess argyrophilic nucleolar organizer regions (AgNORs) in 60 patients with primary breast carcinoma and evaluated their association with clinical prognostic parameters of breast cancer.

METHODS: Argyrophilic nucleolar organizer regions were stained in paraffin sections of the tissues using Ploton's silver method. For each sample, the number of AgNORs within the nuclei of 100 tumor cells was counted. The average number of AgNORs per nucleus was calculated, and the results were expressed as mean.

RESULTS: The number of AgNORs was significantly higher in breast invasive ductal carcinoma (6.6) compared to benign breast tumors (fewer than 2.0). However, differences in AgNOR counts across different age groups were not statistically significant.

CONCLUSION: This study suggests that AgNOR counts could be used as a potential procedure for estimating proliferation characteristics in histopathological sections of benign and malignant breast lesions. Argyrophilic nucleolar organizer region counts may also be valuable for identifying high-risk patients and indicating tumor aggressiveness. A larger study with an increased sample size that incorporates both AgNOR numbers and Ki67 scores for assessing cell kinetics is needed to confirm our findings.}, } @article {pmid39378121, year = {2024}, author = {Xu, Y and Yuan, L and Liu, Z and Long, J and Luo, Y and Chen, C and Niu, C}, title = {Value of contrast-enhanced ultrasound in differentiating granulomatous mastitis from invasive ductal carcinoma.}, journal = {The British journal of radiology}, volume = {97}, number = {1164}, pages = {2033-2041}, doi = {10.1093/bjr/tqae199}, pmid = {39378121}, issn = {1748-880X}, support = {2022JJ30827//Hunan Provincial Natural Science Foundation of China/ ; A202309026329//Natural Science Foundation of Hunan Provincial Health Commission/ ; }, mesh = {Humans ; Female ; *Granulomatous Mastitis/diagnostic imaging/pathology ; Diagnosis, Differential ; *Contrast Media ; Retrospective Studies ; Middle Aged ; *Breast Neoplasms/diagnostic imaging/pathology ; Adult ; *Ultrasonography, Mammary/methods ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Aged ; }, abstract = {OBJECTIVE: This study aims to analyse the imaging manifestations of granulomatous mastitis (GM) and invasive ductal carcinoma (IDC) using conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). The objective is to investigate the clinical value of CEUS in differentiating between GM and IDC.

METHODS: We retrospectively enrolled 39 GM patients and 64 IDC patients between January 2020 and June 2023. All diagnoses were confirmed via core needle biopsy or surgical pathology. The characteristics of both conventional US and CEUS in these patients were analysed to distinguish GM from IDC.

RESULTS: Based on CEUS features, GM lesions most commonly presented as hypoechoic areas (43.6%), followed by pseudocysts (28.2%), hypoechoic nodules (15.4%), and honeycomb cysts (12.8%). The diffuse enhancement pattern was an independent characteristic for distinguishing GM from IDC, with the ROC analysis revealing an area under the curve (AUC) value of 0.794.

CONCLUSION: US is the preferred initial examination for GM, and both its conventional and CEUS features can enhance diagnostic accuracy and guide clinical treatment. CEUS demonstrates high differential diagnostic value in distinguishing GM from IDC.

ADVANCES IN KNOWLEDGE: This study categorizes GM manifestations on CEUS into four types, each corresponding to different pathological stages of GM. We identified that the diffuse enhancement pattern on CEUS is a distinctive characteristic associated with GM, aiding in its differentiation from IDC.}, } @article {pmid39375162, year = {2024}, author = {Salem, R and Wu, F and Andaleeb, U and Ahmed, I}, title = {Coexisting invasive ductal carcinoma arising within a benign phyllodes tumour.}, journal = {BMJ case reports}, volume = {17}, number = {10}, pages = {}, doi = {10.1136/bcr-2024-262414}, pmid = {39375162}, issn = {1757-790X}, mesh = {Humans ; Female ; *Phyllodes Tumor/pathology/surgery ; *Breast Neoplasms/pathology ; Adult ; Carcinoma, Ductal, Breast/pathology/surgery/diagnosis ; Neoplasms, Multiple Primary/pathology/diagnostic imaging ; Magnetic Resonance Imaging ; Sentinel Lymph Node Biopsy ; }, abstract = {A woman in her 40s presented to the breast clinic with a 2-year history of an enlarging right breast lump. Examination revealed a 10 cm firm mass in the upper outer quadrant of the right breast. MRI and ultrasonography results revealed an 8 cm mass in the right breast and suspicious axillary nodes. Biopsy results of this mass revealed a sclerosed fibroadenoma (B2). Excision of the right breast lump had shown a benign phyllodes tumour, containing an incidental invasive ductal carcinoma and high-grade ductal carcinoma in situ. The patient underwent a right breast cavitectomy and sentinel lymph node biopsy, which revealed no further disease. She received adjuvant radiotherapy, chemotherapy and anti-HER2 treatment, and has remained disease-free at 20-month follow-up. The coexistence of an invasive carcinoma arising within a benign phyllodes tumour is rare. This case report underscores the importance of thoroughly examining excised specimens for phyllodes tumour to exclude malignant components.}, } @article {pmid39371729, year = {2024}, author = {Kepuladze, S and Burkadze, G and Kokhreidze, I}, title = {Epithelial-Mesenchymal Transition Indexes in Triple-Negative Breast Cancer Progression and Metastases.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e68761}, pmid = {39371729}, issn = {2168-8184}, abstract = {Background Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer characterized by the lack of expression of estrogen and progesterone receptors and the absence of HER2 protein overexpression or gene amplification. How TNBC becomes so aggressive at the molecular level is not yet fully understood. The epithelial-mesenchymal transition (EMT) has been increasingly recognized as playing a pivotal role in cancer progression and metastasis. This study aimed to elucidate the connection between TNBC progression with EMT-related markers, including vimentin, beta-catenin, and E-cadherin. Methodology Rigorous immunohistochemical analysis was employed to assess the expression of vimentin, beta-catenin, and E-cadherin in primary tumors, tumor buds, and lymph node metastases (LNMs) from 137 cases with an invasive ductal carcinoma triple-negative phenotype diagnosed between 2018 and 2024. The EMT index, which was especially important in our work, is the sum of vimentin and beta-catenin expression divided by that of E-cadherin. Estimated Pearson correlation, multiple linear regression, and Kruskal-Wallis tests were used to determine the relationships of the EMT index with tumor buds and tumor-infiltrating lymphocytes (TILs). Results Vimentin highly correlated within separate regions of interest with Pearson correlation ranging from 0.90 to 0.92 (p < 0.001). Strong negative correlations between E-cadherin and vimentin (r = -0.81 to - 0.89, p < 0.001) showed its role in preserving the epithelial phenotype. The presence of tumor buds, aggregates, or clusters of cancer cells shed from the primary tumor mass invading the connective tissue showed very strong associations with the EMT index (r = 0.91, p < 0.001). Its presence is suggestive of aggressive disease and may identify a high-risk subpopulation that may benefit from more active surveillance or adjuvant treatment. Similarly, TILs correlated inversely with the EMT index (r = -0.90, p < 0.001). The most significant predictor of the EMT index, i.e., vimentin, had a model R-squared value of 1.000 in the regression analysis. Conclusions This study brings to light the importance of EMT-related markers in TNBC progression, with special emphasis on tumor buds as possible prognostic indicators for aggressive disease. The negative correlation of TILs with the EMT index indicates that an effective immune response could antagonize EMT-mediated tumor progression. These results suggest that EMT-based treatments in TNBC should be designed from a multimarker perspective by including interactions among several markers to optimize predictions and therapeutics. The results hold the potential to set future research directions and actionable outcomes that could influence clinical utility in the battle against TNBC.}, } @article {pmid39368973, year = {2024}, author = {Elias, AD and Staley, AW and Fornier, M and Vidal, GA and Alami, V and Sams, S and Spoelstra, NS and Goodspeed, A and Kabos, P and Diamond, JR and Shagisultanova, E and Gallagher, RI and Wulfkuhle, JD and Petricoin, EF and Zolman, KL and McSpadden, T and Jordan, KR and Slansky, JE and Borges, VF and Gao, D and Richer, JK}, title = {Clinical and immune responses to neoadjuvant fulvestrant with or without enzalutamide in ER+/Her2- breast cancer.}, journal = {NPJ breast cancer}, volume = {10}, number = {1}, pages = {88}, pmid = {39368973}, issn = {2374-4677}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA046934/CA/NCI NIH HHS/United States ; BCRP BC120183 W81XWH-13-1-0090/91//U.S. Department of Defense (United States Department of Defense)/ ; }, abstract = {Most ER+ breast cancers (BC) express androgen receptors (AR). This randomized phase II trial of 4 months of neoadjuvant fulvestrant (Fulv) alone or with enzalutamide (Combo) assessed whether adding AR blockade to Fulv would limit residual tumor at the time of surgery, as measured by modified preoperative endocrine predictive index (PEPI) score. Eligible patients were women with ER+/HER2- primary BC cT2 or greater. Stratification factors were clinical node and T-stage. Fresh tumor biopsies were required at study entry, after 4 weeks on therapy (W5), and at surgery. Laboratory analyses on tumors included immunochemistry (IHC) for ER/PR/AR/GR and Ki67 protein, evaluation of gene expression, multiplex for myeloid lineage immune cells, reverse-phase protein array, and plasma metabolomic analyses. Of 69 consented patients, 59 were evaluable. Toxicity was as expected with endocrine therapy. Combo achieved PEPI = 0 more frequently (24%: 8/33) than Fulv (8%: 2/26). Ki67 was ≤10% across arms by W5 in 76% of tumors. Activation of mTOR pathway proteins was elevated in tumors with poor Ki67 response. Tumors in both arms showed decreased estrogen-regulated and cell division gene sets, while Combo arm tumors uniquely exhibited enrichment of immune activation gene sets, including interferon gamma, complement, inflammation, antigen processing, and B and T cell activation. Multiplex IHC showed significantly reduced tumor-associated macrophages and CD14+/HLADR-/CD68- MDSCs in Combo tumors at W5. In summary, Combo tumors showed a higher PEPI = 0 response, Ki67 response, and more activated tumor immune microenvironment than Fulv. The odds of response were 4.6-fold higher for patients with ILC versus IDC. (Trial registration: This trial is registered at Clinicaltrials.gov (https://www.clinicaltrials.gov/study/NCT02955394?id=16-1042&rank=1). The trial registration number is NCT02955394. The full trial protocol is available under Study Details at the Clinicaltrials.gov link provided).}, } @article {pmid39365417, year = {2025}, author = {Taira, S and Kawagoe, M and Anzai, H and Yasukawa, M and Asakawa, S and Arai, S and Yamazaki, O and Tamura, Y and Oshima, Y and Numakura, S and Ohashi, R and Shibata, S and Fujigaki, Y}, title = {Immunoglobulin A-dominant membranoproliferative glomerulonephritis-like pattern of injury as a possible paraneoplastic nephropathy in a breast cancer patient.}, journal = {CEN case reports}, volume = {14}, number = {2}, pages = {217-223}, pmid = {39365417}, issn = {2192-4449}, mesh = {Humans ; Female ; *Breast Neoplasms/complications/therapy/pathology ; *Glomerulonephritis, Membranoproliferative/diagnosis/pathology/etiology ; Middle Aged ; *Immunoglobulin A ; *Paraneoplastic Syndromes/diagnosis/pathology/etiology ; Hematuria/etiology ; *Glomerulonephritis, IGA/diagnosis/pathology ; Proteinuria/etiology ; *Carcinoma, Ductal, Breast/complications/therapy/pathology ; Biopsy ; Kidney/pathology ; }, abstract = {A middle-aged woman was found to have proteinuria during a health check-up. About sixteen months later, she was diagnosed with stage IIA invasive ductal carcinoma of the right breast. Her proteinuria progressed to nephrotic syndrome with significant hematuria. Hormone therapy was initiated for her estrogen and progesterone receptor-positive breast cancer. A kidney biopsy performed 47 days after starting the therapy revealed an IgA-dominant membranoproliferative glomerulonephritis-like pattern of injury. Electron microscopy showed subendothelial-dominant electron-dense deposits (EDD), with small amounts of mesangial EDD and a single occurrence of subepithelial hump-like EDD, along with occasional mesangial interpositions. Similar pathology can be caused by IgA vasculitis with nephritis, IgA-dominant infection-associated glomerulonephritis, and liver disease-associated glomerulopathy, but all of these were ruled out. The deposited IgA was found to be galactose-deficient IgA1. Thus, IgA nephropathy with glomerular capillary IgA deposition was considered. She underwent a right partial mastectomy and sentinel lymph node biopsy in the right axilla 75 days after starting hormone therapy, followed by adjuvant radiation. Proteinuria and hematuria tended to decrease after the treatment, and this trend continued even after corticosteroid therapy for glomerulonephritis, which was administered 156 days after starting hormone therapy. Approximately 15 months after starting hormone therapy, her proteinuria had reduced to around 1.0 g/g of creatinine, and her hematuria was negative. IgA nephropathy with glomerular capillary IgA deposition is known to be resistant to corticosteroid therapy. The favorable clinical course of the rare glomerulopathy following breast cancer treatment suggested a diagnosis of paraneoplastic glomerulopathy secondary to breast cancer in our patient.}, } @article {pmid39363164, year = {2024}, author = {Sun, Y and Pan, Z and Wang, Z and Wang, H and Wei, L and Cui, F and Zou, Q and Zhang, Z}, title = {Single-cell transcriptome analysis reveals immune microenvironment changes and insights into the transition from DCIS to IDC with associated prognostic genes.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {894}, pmid = {39363164}, issn = {1479-5876}, support = {62102064//National Natural Science Foundation of China/ ; 62261018//National Natural Science Foundation of China/ ; 62262015//National Natural Science Foundation of China/ ; ZDYF2024GXJS01//Science and Technology special fund of Hainan Province/ ; 324MS009//Hainan Provincial Natural Science Foundation of China/ ; }, mesh = {Humans ; *Single-Cell Analysis ; Female ; *Tumor Microenvironment/genetics/immunology ; *Gene Expression Profiling ; Prognosis ; *Carcinoma, Intraductal, Noninfiltrating/genetics/immunology/pathology ; *Breast Neoplasms/genetics/immunology/pathology ; *Gene Expression Regulation, Neoplastic ; *Carcinoma, Ductal, Breast/genetics/pathology/immunology ; *Disease Progression ; Transcriptome/genetics ; Single-Cell Gene Expression Analysis ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast is an early stage of breast cancer, and preventing its progression to invasive ductal carcinoma (IDC) is crucial for the early detection and treatment of breast cancer. Although single-cell transcriptome analysis technology has been widely used in breast cancer research, the biological mechanisms underlying the transition from DCIS to IDC remain poorly understood.

RESULTS: We identified eight cell types through cell annotation, finding significant differences in T cell proportions between DCIS and IDC. Using this as a basis, we performed pseudotime analysis on T cell subpopulations, revealing that differentially expressed genes primarily regulate immune cell migration and modulation. By intersecting WGCNA results of T cells highly correlated with the subtypes and the differentially expressed genes, we identified six key genes: FGFBP2, GNLY, KLRD1, TYROBP, PRF1, and NKG7. Excluding PRF1, the other five genes were significantly associated with overall survival in breast cancer, highlighting their potential as prognostic biomarkers.

CONCLUSIONS: We identified immune cells that may play a role in the progression from DCIS to IDC and uncovered five key genes that can serve as prognostic markers for breast cancer. These findings provide insights into the mechanisms underlying the transition from DCIS to IDC, offering valuable perspectives for future research. Additionally, our results contribute to a better understanding of the biological processes involved in breast cancer progression.}, } @article {pmid39353633, year = {2024}, author = {Li, CL and Wu, CY}, title = {Invasive ductal carcinoma of the nipple in a man.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {196}, number = {32}, pages = {E1121}, pmid = {39353633}, issn = {1488-2329}, mesh = {Humans ; Male ; *Nipples/pathology ; *Breast Neoplasms, Male/pathology/diagnosis ; *Carcinoma, Ductal, Breast/pathology/diagnosis ; Middle Aged ; }, } @article {pmid39355216, year = {2024}, author = {Callaud, A and Dupont, AC and By, MA and Zemmoura, I and Santiago-Ribeiro, MJ}, title = {Case Report: Contribution of [[18]F]FET PET in differential diagnosis between radionecrosis and progression in metastasis-reproducibility and superiority of dynamic acquisitions.}, journal = {Frontiers in nuclear medicine}, volume = {4}, number = {}, pages = {1287240}, pmid = {39355216}, issn = {2673-8880}, abstract = {We present the case of a 67-year-old woman with metastatic invasive ductal carcinoma of the left breast, in whom a follow-up magnetic resonance imaging, 3 months after encephalic radiotherapy, revealed a significant increase in the size of two brain metastases, potentially indicating progressive disease within the radiation field. Subsequent [[18]F] fluorodeoxyglucose ([[18]F]FDG) and [[18]F] fluoroethyl-L-tyrosine positron emission tomography ([[18]F]FET PET) scans were performed to distinguish radionecrosis from tumor progression. Despite a dynamic [[18]F]FET time-activity curve (TAC) against progression, the exceeding of the 1.9 cutoff by mean tumor to brain ratio (TBR) and interdisciplinary considerations led to the resection of one lesion. Histopathology revealed necrosis due to radiotherapy, without viable tumor proliferation. To verify radionecrosis, a second [[18]F]FET PET scan was conducted, showing consistent findings. In metastasis differentiation, the mean TBR cutoff of 1.9 and TAC analysis achieved a sensitivity of 95% and specificity of 91%. The discrepancy between the TAC and TBR emphasizes the need for consideration, and a time delay between radiotherapy and PET may impact TBR cutoffs. In addition, differences in radiosensitivity suggest a lower metastasis pre-test probability of progression, and it might be why a TAC analysis could be more effective in distinguishing true progression from treatment related changes in metastasis. This case demonstrates the accuracy of dynamic [[18]F]FET PET and suggests its utility for post-treatment metastasis evaluation, and further research on post-treatment delay could lead to improved performances of dynamic [[18]F]FET PET.}, } @article {pmid39351744, year = {2024}, author = {Azad, SA and Rahman, MS and Bhuiyan, AKM and Islam, MJ and Ahmed, SU and Hossain, AFM}, title = {Evaluation of Primary and Recurrent Breast Cancer after Giving Adjuvant Therapy in Correlation with the Receptor Status.}, journal = {Mymensingh medical journal : MMJ}, volume = {33}, number = {4}, pages = {1204-1210}, pmid = {39351744}, issn = {2408-8757}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/therapy/metabolism/drug therapy ; *Neoplasm Recurrence, Local ; *Receptors, Progesterone/metabolism ; Middle Aged ; *Erb-b2 Receptor Tyrosine Kinases/metabolism ; *Receptors, Estrogen/metabolism ; Adult ; Chemotherapy, Adjuvant ; Aged ; }, abstract = {Breast cancer is the most common type of cancer among women. The molecular subtypes of breast cancer, depending on the Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor (HER-2) status, usually play a vital role for the adjuvant treatment. Interestingly, there is a good possibility of change of receptor status in the recurrence of same primary tumor. The study is designed April 2018 to March 2019 to see the concordance in triple-receptor expression (ER, PR, and HER-2) between the primary and the locally recurrent breast cancer patient and the results can be able to influence the management and prognosis of the breast cancer patients. This observational study was carried out in the department of surgical oncology, NICRH where total 48 patients were studied who were subjected to core biopsy of recurrent lesion for ER, PR and HER-2 status. A structured case record form was used to interview and collect data. Data analysis was done using SPSS version 26.0 to see concordance and discordance in triple-receptor expression between the primary and the locally recurrent breast cancer patient. Among 48 cases, 12(25.0%), 10(20.83%) and 2(4.16%) patients showed Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor (Her-2) discordance that are statistically significant in every receptor status. Majority discordance of ER, PR and Her-2 were associated with invasive duct cell carcinoma (IDC); ER & Her-2 discordance was equally associated with histological grade 2 and 3 whereas PR discordance had significant association with grade 3. Staging of disease showed that all ER, PR and Her-2 discordance were associated with stage (p<0.05). Besides, majority discordance was mostly associated with lumpectomy except Her-2 discordance. Besides, among the adjuvant treatment regimen chemotherapy along with radiotherapy was mostly associated with discordance of all receptors (p<0.05). Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor (HER-2) status of primary breast cancer showed 25.0%, 20.83% and 4.16% discordant in recurrent episodes in this study. Invasive duct cell carcinoma, histological grade 2 and 3, stage II, stage III, MRM and CT along with RT are major attributable factors in this study.}, } @article {pmid39349666, year = {2025}, author = {Bernhardt, M and Hommerding, O and Kreft, T and Weinhold, L and Schmid, M and Kristiansen, G}, title = {Prospective selective embedding of radical prostatectomy specimens is not inferior to full embedding regarding established and new prognostic parameters.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {486}, number = {5}, pages = {931-940}, pmid = {39349666}, issn = {1432-2307}, mesh = {Humans ; Male ; *Prostatectomy/methods ; *Prostatic Neoplasms/pathology/surgery ; Prognosis ; *Specimen Handling/methods ; Neoplasm Grading ; Middle Aged ; Aged ; *Paraffin Embedding/methods ; Prospective Studies ; }, abstract = {The histopathological examination of radical prostatectomy specimens is essential for assessing critical tumor characteristics, including stage, grade, and margins, all of which impact patient prognosis. However, the extent of embedding the prostate has long been a subject of debate, with some advocating partial/selective embedding and others favoring complete embedding. This study establishes a standardized and time-efficient protocol for processing radical prostatectomy specimens with limited embedding while maintaining diagnostic accuracy. Two hundred twenty-six prostatectomy specimens were analyzed, and the results of a highly standardized selective embedding protocol, systematically embedding the apex, the base, the transition to the seminal vesicles, and selected horizontal sections, were compared with full embedding as the gold standard. Non-inferiority testing was conducted by one-sided binomial tests and Pearson-Clopper confidence intervals. Selective embedding provided consistent and accurate diagnostic information with up to 90-98% concordance in pT, margins, ISUP-grade groups, and presence of IDC-P and cribriform tumor growth. In summary, this study establishes an economical standardized protocol for selective embedding of radical prostatectomy specimens with only minimal loss of information.}, } @article {pmid39345847, year = {2024}, author = {Jaheddine, F and Cherif, A and Rabilleh, M and Lanjeri, S and El Houss, S and El Bakkari, A and Omor, Y and Latib, R and Amalik, S}, title = {Axillary skin lesion: A rare presentation of metastatic male breast cancer.}, journal = {Radiology case reports}, volume = {19}, number = {12}, pages = {6053-6056}, pmid = {39345847}, issn = {1930-0433}, abstract = {Male breast cancer is an uncommon condition, accounting for less than 1% of all breast carcinomas and under 1.5% of all malignant tumors in men. Skin lesions can often be the initial reason for consultation. At this advanced stage, diagnosis is typically delayed, leading to a poor prognosis. Herein, we report the case of a 66-year-old man who presented with a dermo-epidermal axillary mass, indicative of cutaneous metastasis from an invasive ductal carcinoma.}, } @article {pmid39342818, year = {2024}, author = {Sivarajah, RT and Bean, TR and Chetlen, AL}, title = {Diffuse unilateral MRI breast entities.}, journal = {Clinical imaging}, volume = {115}, number = {}, pages = {110305}, doi = {10.1016/j.clinimag.2024.110305}, pmid = {39342818}, issn = {1873-4499}, mesh = {Humans ; Female ; *Magnetic Resonance Imaging/methods ; *Breast Neoplasms/diagnostic imaging ; Diagnosis, Differential ; Breast Diseases/diagnostic imaging ; Breast/diagnostic imaging/pathology ; }, abstract = {Many benign and malignant breast entities can present with diffuse unilateral magnetic resonance imaging (MRI) findings. The unilateral breast findings can be broken down into three broad categories including asymmetric diffuse masses/non-mass enhancement (NME), diffuse unilateral skin thickening, and diffuse asymmetric background enhancement. Although correlation with clinical history is always necessary, biopsy is often needed to make a definitive diagnosis. There are some findings on MRI which can help narrow the differential including morphology, distribution, T2W signal, enhancement kinetics, and associated skin thickening. Malignant entities which will be discussed in this review include ductal carcinoma in situ, invasive ductal carcinoma, invasive lobular carcinoma, Paget disease, inflammatory breast cancer, and locally advanced breast cancer. Benign entities which will be discussed in this review include idiopathic granulomatous mastitis (IGM), infectious mastitis, pseudoangiomatous stromal hyperplasia, giant fibroadenoma, early and late radiation changes, unilateral breast feeding, and central venous obstruction, all which have varied MRI appearances. It is important for radiologists to be familiar with the common entities that can present with diffuse asymmetric unilateral MRI breast findings to ensure the correct diagnosis and management is undertaken.}, } @article {pmid39342513, year = {2024}, author = {Cho, SM and Khanduja, S and Wilcox, C and Dinh, K and Kim, J and Kang, JK and Chinedozi, ID and Darby, Z and Acton, M and Rando, H and Briscoe, J and Bush, EL and Sair, HI and Pitts, J and Arlinghaus, LR and Wandji, AN and Moreno, E and Torres, G and Akkanti, B and Gavito-Higuera, J and Keller, S and Choi, HA and Kim, BS and Gusdon, A and Whitman, GJ and , }, title = {Clinical Use of Bedside Portable Ultra-Low-Field Brain Magnetic Resonance Imaging in Patients on Extracorporeal Membrane Oxygenation: Results From the Multicenter SAFE MRI ECMO Study.}, journal = {Circulation}, volume = {150}, number = {24}, pages = {1955-1965}, pmid = {39342513}, issn = {1524-4539}, support = {L30 NS134072/NS/NINDS NIH HHS/United States ; R21 NS135045/NS/NINDS NIH HHS/United States ; K23 NS121628/NS/NINDS NIH HHS/United States ; K23 HL157610/HL/NHLBI NIH HHS/United States ; L30 HL165486/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Extracorporeal Membrane Oxygenation/adverse effects/instrumentation ; Male ; Female ; Middle Aged ; *Magnetic Resonance Imaging/adverse effects ; Prospective Studies ; Aged ; Adult ; Brain/diagnostic imaging ; Brain Injuries/diagnostic imaging ; Point-of-Care Testing ; }, abstract = {BACKGROUND: Early detection of acute brain injury (ABI) at the bedside is critical in improving survival for patients with extracorporeal membrane oxygenation (ECMO) support. We aimed to examine the safety of ultra-low-field (ULF; 0.064-T) portable magnetic resonance imaging (pMRI) in patients undergoing ECMO and to investigate the ABI frequency and types with ULF-pMRI.

METHODS: This was a multicenter prospective observational study (SAFE MRI ECMO study [Assessing the Safety and Feasibility of Bedside Portable Low-Field Brain Magnetic Resonance Imaging in Patients on ECMO]; NCT05469139) from 2 tertiary centers (Johns Hopkins, Baltimore, MD and University of Texas-Houston) with specially trained intensive care units. Primary outcomes were safety of ULF-pMRI during ECMO support, defined as completion of ULF-pMRI without significant adverse events.

RESULTS: Of 53 eligible patients, 3 were not scanned because of a large head size that did not fit within the head coil. ULF-pMRI was performed in 50 patients (median age, 58 years; 52% male), with 34 patients (68%) on venoarterial ECMO and 16 patients (32%) on venovenous ECMO. Of 34 patients on venoarterial ECMO, 11 (22%) were centrally cannulated and 23 (46%) were peripherally cannulated. In venovenous ECMO, 9 (18%) had single-lumen cannulation and 7 (14%) had double-lumen cannulation. Of 50 patients, adverse events occurred in 3 patients (6%), with 2 minor adverse events (ECMO suction event; transient low ECMO flow) and one serious adverse event (intra-aortic balloon pump malfunction attributable to electrocardiographic artifacts). All images demonstrated discernible intracranial pathologies with good quality. ABI was observed in 22 patients (44%). Ischemic stroke (36%) was the most common type of ABI, followed by intracranial hemorrhage (6%) and hypoxic-ischemic brain injury (4%). Of 18 patients (36%) with both ULF-pMRI and head computed tomography within 24 hours, ABI was observed in 9 patients with a total of 10 events (8 ischemic, 2 hemorrhagic events). Of the 8 ischemic events, pMRI observed all 8, and head computed tomography observed only 4 events. For intracranial hemorrhage, pMRI observed only 1 of them, and head computed tomography observed both (2 events).

CONCLUSIONS: Our study demonstrates that ULF-pMRI can be performed in patients on ECMO across different ECMO cannulation strategies in specially trained intensive care units. The incidence of ABI was high, seen in 44% of ULF-pMRI studies. ULF-pMRI imaging appears to be more sensitive to ABI, particularly ischemic stroke, compared with head computed tomography.}, } @article {pmid39341718, year = {2024}, author = {Drake, MJ and Clavica, F and Murphy, C and Fader, MJ}, title = {Innovating Indwelling Catheter Design to Counteract Urinary Tract Infection.}, journal = {European urology focus}, volume = {10}, number = {5}, pages = {713-719}, doi = {10.1016/j.euf.2024.09.015}, pmid = {39341718}, issn = {2405-4569}, mesh = {Humans ; *Catheters, Indwelling/adverse effects/microbiology ; *Urinary Tract Infections/prevention & control ; *Equipment Design ; Urinary Catheters/adverse effects ; Catheter-Related Infections/prevention & control ; Urinary Catheterization/adverse effects ; Stents/adverse effects ; Biofilms ; Bacteriuria/prevention & control ; }, abstract = {BACKGROUND AND OBJECTIVE: Bacteriuria is anticipated in long-term indwelling catheter (IDC) use, and urinary tract infections (UTIs) and related issues are common. Defence mechanisms against infection are undermined by the presence of a Foley catheter, and adjustments to design could influence UTI risk.

METHODS: We reviewed the various aspects of IDCs and ureteric stent designs to discuss potential impact on UTI risk.

KEY FINDINGS AND LIMITATIONS: Design adaptations have focussed on reducing the sump of undrained urine, potential urinary tract trauma, and bacterial adherence. Experimental and computational studies on ureteral stents found an interplay between urine flow, bacterial microcolony formation, and accumulation of encrusting particles. The most critical regions for biofilm and crystal accumulation are associated with low shear stress. The full drainage system is the functioning unit, not just the IDC in isolation. This means reliably keeping the drainage system closed and considering whether a valve is preferred to a collection bag. Other developments may include one-way valves, obstacles to "bacterial swimming", and ultrasound techniques. Preventing or clearing IDC blockage can exploit access via the lumen or retaining balloon. Progress in computational fluid dynamics, energy delivery, and soft robotics may increase future options. Clinical data on the effectiveness of IDC design features are lacking, which is partly due to reliance on proxy measures and the challenges of undertaking trials.

Design changes are legitimate lines of development, but are only indirect for UTI prevention. Modifications may be advantageous, but might potentially bring problems in other ways. Education of health care professionals can improve UTIs and should be prioritised.

PATIENT SUMMARY: Catheters used to help bladder drainage can cause urinary infections, and improvements in design might reduce the risk. Several approaches are described in this review. However, proving that these approaches work is a challenge. Training professionals in the key aspects of catheter care is important.}, } @article {pmid39341603, year = {2024}, author = {Pereira, LHS and Alves, ADC and Lopes, GFM and da Silva, BF and Vieira, MS and Lopes, DO and Ferreira, JMS and Lara Dos Santos, L}, title = {Soluble isoforms of the DC-SIGN receptor can increase the dengue virus infection in immature dendritic cells.}, journal = {The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases}, volume = {28}, number = {6}, pages = {103873}, pmid = {39341603}, issn = {1678-4391}, mesh = {*Cell Adhesion Molecules/metabolism ; *Receptors, Cell Surface/metabolism ; *Lectins, C-Type/metabolism ; *Dengue Virus/immunology ; *Dendritic Cells/virology/immunology ; Humans ; Animals ; *Protein Isoforms ; Viral Load ; Dengue/immunology ; Aedes/virology ; DC-Specific ICAM-3 Grabbing Nonintegrin ; }, abstract = {Dengue is a disease with a high-impact on public health worldwide. Many researches have focused on the cell receptors involved in its pathogenesis. The role of soluble isoforms of DC-SIGN (Dendritic Cell-Specific ICAM-3 Grabbing Non-integrin) receptor in the process of Dengue Virus (DENV) infection is not well understood. This work proposes to evaluate changes in the infection process of Immature Dendritic Cells (iDCs) by DENV in the presence of DC-SIGN recombinant soluble isoforms 8, 10, and 12. The recombinant isoforms were built by heterologous expression, the DENV-2 was multiplied in the Aedes albopictus C6/36 cells and quantified in BHK-21 cells, and the iDCs were produced from the THP-1 strain. Infection assays were performed in the presence of iDCs, DENV-2, and isoforms 8, 10, and 12 separately at 25, 50 and 100 ng/mL. The final viral load was estimated by qPCR and statistical analysis was performed by Kruskal-Wallis and ANOVA tests. The iDC profile was confirmed by increasing expression of CD11c, CD86, and CD209 surface markers and maintaining CD14 expression. Infection assays demonstrated a 23-fold increase in DENV viral load in the presence of isoforms 8 and 10 at 100 ng/mL compared to the viral control (p < 0.05), while isoform 12 did not alter the viral load. It was possible to conclude that at 100 ng/mL isoforms (8 and 10) can interact with DENV, increasing viral infection, and potentially acting as opsonins.}, } @article {pmid39331289, year = {2024}, author = {Vasigh, M and Mohamed, A and Jacobs, L and Lange, J and Camp, M and Sun, B and Wright, P and O'Donnell, M and Tran, HT and Sogunro, O and Habibi, M and Johnston, F and Euhus, D}, title = {The Association Between Breast Cancer Predisposing Genetic Variants and Multifocal, Multicentric Breast Cancer.}, journal = {Annals of surgical oncology}, volume = {31}, number = {13}, pages = {8891-8899}, pmid = {39331289}, issn = {1534-4681}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology ; Retrospective Studies ; Middle Aged ; *Genetic Predisposition to Disease ; Adult ; Prognosis ; Follow-Up Studies ; Carcinoma, Ductal, Breast/genetics/pathology ; Aged ; Biomarkers, Tumor/genetics ; Genetic Variation ; }, abstract = {BACKGROUND: Breast-conserving surgery is often discouraged in BRCA gene carriers with early onset breast cancer. The genetic variant carrier breast cancers are more likely to be multifocal or multicentric (MFMC).

PATIENTS AND METHOD: This retrospective study includes newly diagnosed patients with breast cancer undergoing genetic testing between 2010 and 2021 within the Johns Hopkins Regional Health System. After excluding patients who received neoadjuvant chemotherapy or stage IV breast cancers, patients were divided into two groups: those who tested positive for a variant recognized by the National Comprehensive Cancer Network as predisposing the patient to breast cancer (ATM, BRCA1, BRCA2, CHEK2, NF1, PALB2, RAD51C, RAD51D, and TP53) and those who tested negative. Pathologic features of the tumors were compared, focusing on evidence for MFMC disease, defined as more than one malignant foci more than 5 mm apart.

RESULTS: Among the 282 eligible cases, 69 (24%) were positive for a genetic variant. The variant carriers were younger at diagnosis (p < 0.001), more likely to have invasive ductal carcinoma (p = 0.03), more likely to have undergone mastectomy (p = 0.03), and more likely to have a grade 3 cancer (p = 0.003). Variant carriers were not more likely to have MFMC disease (28% vs. 22%, p = 0.4). A positive genetic variant was not a predictor of MFMC within the entire cohort [odds ratio (OR):1.3, 95% confidence interval (CI) 0.6-2.6, p = 0.5).

CONCLUSION: Genetic variant carrier cancers are not more likely to be MCMF than sporadic cancers.}, } @article {pmid39328281, year = {2024}, author = {Shrestha, P and Hsieh, MC and Ferguson, T and Peters, ES and Trapido, E and Yu, Q and Chu, QD and Wu, XC}, title = {Higher 10-Year Survival with Breast-Conserving Therapy over Mastectomy for Women with Early-Stage (I-II) Breast Cancer: Analysis of the CDC Patterns of Care Data Base.}, journal = {Breast cancer : basic and clinical research}, volume = {18}, number = {}, pages = {11782234241273666}, pmid = {39328281}, issn = {1178-2234}, support = {R15 MD012387/MD/NIMHD NIH HHS/United States ; }, abstract = {BACKGROUND: Studies in the United States are scarce that assess the survival differences between breast-conserving surgery plus radiation (Breast-Conserving Therapy; BCT) and mastectomy groups using population-based data while accounting for sociodemographic and clinical factors that affect the survival of women with early-stage breast cancer (ESBC).

OBJECTIVE: To assess whether BCT provides superior long-term overall survival (OS) and breast cancer-specific survival (BCSS) compared with mastectomy in women with ESBC, while considering key factors that impact survival.

DESIGN: Cohort study.

METHODS: We analyzed data on women aged 20 years and older diagnosed with stage I-II breast cancer (BC) in 2004 who received either BCT or mastectomy. The data were collected by 5 state cancer registries through the Centers for Disease Control and Prevention-funded Patterns of Care study. Multivariable Cox proportional hazard models, accounting for sociodemographic and clinical factors, were used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). Sensitivity analysis involved optimal caliper propensity score (PS) matching to address residual confounding.

RESULTS: Of the 3495 women, 41.5% underwent mastectomy. The 10-year OS and BCSS were 82.7% and 91.1% for BCT and 72.3% and 85.7% for mastectomy, respectively. Adjusted models showed that mastectomy recipients had a 22% higher risk of all-cause deaths (ACD) (HR = 1.22, 95% CI = [1.06, 1.41]) and a 26% higher risk of breast cancer-specific deaths (BCD) (HR = 1.26, 95% CI = [1.02, 1.55]) than BCT recipients. Sensitivity analysis demonstrated that mastectomy was associated with a higher risk of ACD (P < .05) but did not exhibit a statistically significant risk for BCD. Women with HR+/HER2+ (luminal B) or invasive ductal carcinoma BC who underwent mastectomy had higher risks of ACD and BCD compared with BCT recipients, while the hazards for ACD in triple-negative BC did not remain significant after adjusting for covariates.

CONCLUSION: ESBC BCT recipients demonstrate superior OS and BCSS compared with mastectomy recipients.}, } @article {pmid39320077, year = {2024}, author = {Hadad, Z and Wahid, W and Afzelius, P}, title = {[Not Available].}, journal = {Ugeskrift for laeger}, volume = {186}, number = {36}, pages = {}, doi = {10.61409/V01240024}, pmid = {39320077}, issn = {1603-6824}, mesh = {Female ; Humans ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/secondary/pathology/diagnostic imaging ; *Liver Neoplasms/secondary/diagnostic imaging ; *Lymphatic Metastasis/diagnostic imaging ; *Neoplasm Recurrence, Local/pathology ; }, abstract = {Breast cancer usually metastasizes by haematogenous spread. This is a case report of a woman with unusual liver metastases from a recurrent invasive ductal carcinoma via a lymphatic route draining the outer part of the breast to the liver running parallelly with the right rectus abdominis muscle, depicted by preoperative sentinel node lymphoscintigraphy. Realizing this route of metastasis can impact survival, as it has a favourable prognosis compared with haematogenous metastasis, we want to draw attention to this.}, } @article {pmid39319200, year = {2024}, author = {Heyvaert, M and Denys, H and Van Dorpe, J and Roels, D}, title = {Management of severe capecitabine-induced corneal toxicity.}, journal = {American journal of ophthalmology case reports}, volume = {36}, number = {}, pages = {102174}, pmid = {39319200}, issn = {2451-9936}, abstract = {PURPOSE: To describe the clinical presentation and management of severe capecitabine-induced corneal toxicity.

OBSERVATIONS: A 71-year-old woman presented with severe bilateral vision loss. Four months earlier, capecitabine was initiated for a metastatic invasive ductal carcinoma. Biomicroscopy revealed bilateral whorl-like corneal epitheliopathy accompanied by metaplasia, keratinization and subepithelial fibrosis. After consulting the treating oncologist, capecitabine treatment was discontinued. Initially, a non-surgical approach was adopted and intensive topical dexamethasone treatment was applied. Despite capecitabine discontinuation and topical steroid treatment, visual acuity progressively declined. Bilateral corneal scraping and bandage contact lens fitting was performed. This resulted in significant improvement of visual acuity, corneal surface regularity and quality of life.

CONCLUSION AND IMPORTANCE: We report the first case of severe visual impairment due to capecitabine-induced corneal toxicity. Early corneal scraping, especially when confronted with profound vision loss, may yield better outcomes compared to relying on spontaneous recovery after capecitabine discontinuation. Patients experiencing ocular discomfort and vision loss, while receiving capecitabine therapy, should be referred for semi-urgent ophthalmological examination.}, } @article {pmid39317017, year = {2024}, author = {Louis, M and Fang, J and Grabill, N and Singh, H and Strom, P}, title = {Her2-positive breast cancer in a young patient with Li-Fraumeni syndrome: A comprehensive case study.}, journal = {International journal of surgery case reports}, volume = {124}, number = {}, pages = {110323}, pmid = {39317017}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Li-Fraumeni syndrome (LFS) is a rare hereditary disorder caused by mutations in the TP53 gene, leading to a significantly increased risk of developing various cancers at a young age, including breast cancer.

CLINICAL PRESENTATION: This case report details the clinical journey of a 21-year-old female diagnosed with Grade 3 invasive ductal carcinoma, which was estrogen receptor low positive and progesterone receptor negative but positive for Her2 (3+) with a high Ki67 proliferation index.

CLINICAL DISCUSSION: Genetic testing confirmed a TP53 mutation, establishing the diagnosis of LFS. The patient underwent neoadjuvant chemotherapy with TCHP (docetaxel, carboplatin, trastuzumab, pertuzumab), resulting in a complete clinical response. This was followed by bilateral skin-sparing and nipple-sparing mastectomy with sentinel lymph node biopsy and immediate reconstruction. Postoperative pathology confirmed a complete response to neoadjuvant therapy. The patient's treatment plan includes 12 cycles of trastuzumab and pertuzumab, with regular echocardiograms to monitor cardiac function and fertility preservation strategies involving monthly Lupron injections. Given the association of LFS with a high risk of multiple primary cancers, a rigorous surveillance strategy is essential. The psychological impact of a cancer diagnosis and the burden of living with a hereditary cancer syndrome were significant, necessitating comprehensive psychosocial support.

CONCLUSION: Managing Li-Fraumeni syndrome (LFS) and its associated cancers, particularly in young patients, necessitates a comprehensive and multidisciplinary approach. Early genetic testing for TP53 mutations is crucial in identifying LFS, enabling personalized treatment plans and proactive surveillance strategies.}, } @article {pmid39316204, year = {2025}, author = {Samaha, M and Fellner, A and Raque, K and Kuritzky, A and Wexelman, B}, title = {Magnetic lymphatic tracing for omission of sentinel lymph node biopsies in mastectomy patients: a community cancer center experience.}, journal = {Breast cancer research and treatment}, volume = {209}, number = {1}, pages = {161-166}, pmid = {39316204}, issn = {1573-7217}, mesh = {Humans ; Female ; *Sentinel Lymph Node Biopsy/methods ; *Breast Neoplasms/surgery/pathology/diagnostic imaging ; Middle Aged ; *Carcinoma, Intraductal, Noninfiltrating/surgery/pathology/diagnostic imaging ; *Mastectomy/methods ; Aged ; Retrospective Studies ; Adult ; Sentinel Lymph Node/pathology/diagnostic imaging ; Prophylactic Mastectomy ; Lymph Nodes/pathology/diagnostic imaging ; Axilla ; }, abstract = {BACKGROUND: Patients with ductal carcinoma in situ (DCIS) and patients undergoing risk reduction mastectomy may undergo sentinel lymph node biopsy (SLNB) at the time of mastectomy to complete axillary staging were an underlying invasive malignancy to be found on final pathology. Among patients with DCIS undergoing mastectomy, 15-29% of patients will have invasive disease on final pathology; therefore, approximately 70-85% of patients may benefit from avoiding SLNB. Superparamagnetic tracers (SPMT) have been proven to be non-inferior to the standard radioisotope and blue dye combination. SPMT remains active for several weeks, allowing a large proportion of DCIS and genetic carrier patients to potentially avoid SLNB in the setting of mastectomy. We hypothesize the use of SPMT will reduce the number of SLNB performed in patients undergoing mastectomy for DCIS and risk reduction, ultimately reducing the number of complications associated with axillary surgery. We seek to report our community cancer center's experience with SPMT and omission of SLNB in the DCIS and prophylactic mastectomy patient population.

METHODS: We performed a retrospective review of 52 female patients with DCIS or known genetic predisposition undergoing mastectomy. SPMT (Magtrace®, Endomag Ltd, Cambridge, UK) was injected ipsilateral to DCIS and bilaterally for prophylactic mastectomy patients. Our primary outcome was rate of return to the operating room (OR) for delayed SLNB. Secondary outcomes included post-operative complications within 30 days of surgery and operative time. We compared outcomes to a control group of 28 women undergoing mastectomy for DCIS or for risk reduction who underwent SLNB at their index operation in traditional fashion. Continuous variables were reported using median and interquartile ranges (IQR) and were compared using the Mann-Whitney U test. Categorical data were reported using frequency and percent and were compared using Pearson's Chi-Square or Fisher's Exact test, as appropriate. Alpha was set to 0.05 to determine statistical significance.

RESULTS: There was a total of 80 patients (52 SPMT, 28 control). Median age of SPMT patients was 49.5 (IQR 40-60.75) vs. 54.5 (48 - 65) in the traditional tracer group. vs. control group. 57.7% of SPMT patients underwent mastectomy for DCIS vs. 89.3% in the control group. Eight SPMT patients (15.4%) had invasive ductal carcinoma (IDC) on final pathology and seven of those patients underwent delayed SLNB (87.5%). None of the delayed SLNB were positive for metastatic disease. Rates of post-operative complications were similar between the two groups, including hematoma, seroma, and surgical site infection. OR times were also similar with median OR time 202 min (min) for the SPMT group vs. 195 min for the control group.

CONCLUSION: Use of SPMT avoided SLNB in 84.6% of our patients. We found no difference in rates of post-operative complications or operative times in patients using SPMT for omission of SLNB at time of mastectomy compared to the control group. Our findings suggest SLNB can be avoided in a majority of patients undergoing mastectomy for DCIS or risk reduction in the setting of genetic predisposition.}, } @article {pmid39315404, year = {2024}, author = {Liu, Y and Lin, D and Najam, SS and Huang, S and Song, M and Sirakawin, C and Zhao, C and Jiang, H and Konopka, W and Herzig, S and Vinnikov, IA}, title = {Functional redundancy between glucocorticoid and mineralocorticoid receptors in mature corticotropin-releasing hormone neurons protects from obesity.}, journal = {Obesity (Silver Spring, Md.)}, volume = {32}, number = {10}, pages = {1885-1896}, doi = {10.1002/oby.24116}, pmid = {39315404}, issn = {1930-739X}, support = {31771433//National Natural Science Foundation of China/ ; 32241020//National Natural Science Foundation of China/ ; 32350610254//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Male ; Mice ; *Corticosterone/blood/metabolism ; *Corticotropin-Releasing Hormone/metabolism ; *Energy Metabolism ; Insulin Resistance ; Mice, Inbred C57BL ; *Mice, Knockout ; *Neurons/metabolism ; *Obesity/metabolism ; Paraventricular Hypothalamic Nucleus/metabolism ; *Receptors, Glucocorticoid/metabolism/genetics ; *Receptors, Mineralocorticoid/metabolism/genetics ; Female ; }, abstract = {OBJECTIVE: Here, we aimed to investigate the role of glucocorticoid and mineralocorticoid receptors (GRs and MRs, respectively) in the regulation of energy homeostasis.

METHODS: We used three mouse models with simultaneous deletion of GRs and MRs in either forebrain neurons, the paraventricular nucleus, or corticotropin-releasing hormone (CRH) neurons and compared them with wild-type controls or isolated knockout groups. In addition to body weight, food intake, energy expenditure, insulin sensitivity, fat/lean mass distribution, and plasma corticosterone levels, we also performed transcriptomic analysis of CRH neurons and assessed their response to melanocortinergic stimulation.

RESULTS: Similar to global double-knockout models, deletion of GRs and MRs specifically in mature CRH neurons resulted in obesity. Importantly, the latter was accompanied by insulin resistance, but not increased plasma corticosterone levels. Transcriptomic analysis of these neurons revealed upregulation of several genes involved in postsynaptic signal transduction, including the Ptk2b gene, which encodes proline-rich tyrosine kinase 2. Knockout of both nuclear receptors leads to upregulation of Ptk2b in CRH neurons, which results in their diminished responsiveness to melanocortinergic stimulation.

CONCLUSIONS: Our data demonstrate the functional redundancy of GRs and MRs in CRH neurons to maintain energy homeostasis and prevent obesity. Simultaneous targeting of both receptors might represent an unprecedented approach to counteract obesity.}, } @article {pmid39314558, year = {2024}, author = {Altamirano, GA and Romero, CK and Moreno Cabrera, CS and Aragón Conrado, LE}, title = {Mucinous Carcinoma in a Male: First Documented Case in Nicaragua.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e67674}, pmid = {39314558}, issn = {2168-8184}, abstract = {Breast malignancy in men is an exceedingly rare condition, representing a small fraction of all diagnosed breast cancer cases. The most common histological subtype is invasive ductal carcinoma, while the mucinous type is extremely rare. This pathology has a high mortality rate due to its poor prognosis and diagnosis in advanced stages, often initially overlooked with limited screening. Surprisingly, more men have died from breast cancer than from testicular cancer. This report details a case of invasive mucinous carcinoma in a 75-year-old male who presented with a five-week history of chronic non-productive cough and signs of pleural effusion. A breast magnetic resonance imaging (MRI) revealed a retroareolar breast tumor, and a second-look ultrasound confirmed the presence of a BI-RADS 4C solid nodule. Histopathological and immunohistochemical results were confirmed by ultrasound-guided tru-cut biopsy, identifying invasive mucinous carcinoma and luminal B (HER2+) subtype. Staging studies were negative for metastasis, and a modified radical mastectomy was performed, yielding favorable intraoperative findings. The incidental diagnosis in this patient highlights the necessity of comprehensive imaging in atypical presentations. Despite its rarity, awareness and early detection of mucinous carcinoma are essential for optimizing patient outcomes. This case also underscores the disparity in breast cancer outcomes between low gross domestic product (GDP) and high-GDP countries, emphasizing the need for improved access to diagnostic and therapeutic resources. Enhanced clinical awareness and early detection are crucial for improving outcomes in patients with rare histological subtypes, particularly in underserved regions.}, } @article {pmid39301202, year = {2024}, author = {Han, B and Han, X and Luo, H and Nasir, J and Chen, C and Shao, Z and Ling, H and Hu, X}, title = {Multiomics and single-cell sequencings reveal the specific biological characteristics of low Ki-67 triple-negative breast cancer.}, journal = {Cancer innovation}, volume = {3}, number = {5}, pages = {e146}, pmid = {39301202}, issn = {2770-9183}, abstract = {BACKGROUND: Triple-negative breast cancer (TNBC) displays high heterogeneity. The majority of TNBC cases are characterized by high Ki-67 expression. TNBC with low Ki-67 expression accounts for only a small fraction of cases and has been relatively less studied.

METHODS: This study analyzed a large single-center multiomics TNBC data set, combined with a single-cell data set. The clinical, genomic, and metabolic characteristics of patients with low Ki-67 TNBC were analyzed.

RESULTS: The clinical and pathological characteristics were analyzed in 2217 TNBC patients. Low Ki-67 TNBC was associated with a higher patient age at diagnosis, a lower proportion of invasive ductal carcinoma, increased alterations in the PI3K-AKT-mTOR pathway, upregulated lipid metabolism pathways, and enhanced infiltration of M2 macrophages. High Ki-67 TNBC exhibited a higher prevalence of TP53 gene mutations, elevated nucleotide metabolism, and increased infiltration of M1 macrophages.

CONCLUSIONS: We identified specific genomic and metabolic characteristics unique to low Ki-67 TNBC, which have implications for the development of precision therapies and patient stratification strategies.}, } @article {pmid39302353, year = {2024}, author = {Ben Kridis, W and Lajnef, M and Khanfir, A}, title = {Synchronous primary breast angiosarcoma with invasive ductal carcinoma.}, journal = {Breast disease}, volume = {43}, number = {1}, pages = {271-274}, pmid = {39302353}, issn = {1558-1551}, mesh = {Humans ; Female ; *Hemangiosarcoma/secondary/pathology ; *Breast Neoplasms/pathology ; Middle Aged ; *Carcinoma, Ductal, Breast/pathology/secondary ; *Neoplasms, Multiple Primary/pathology ; Ovarian Neoplasms/pathology/secondary ; }, abstract = {Primary angiosarcoma (PAS) of the breast is an extremely uncommon variant of breast malignancies. Highly aggressiveness and dismal prognosis characterize this endothelial neoplasm. We report here an unusual case of PAS of the breast occurring in a 46-year-old woman associated with concurrent bilateral invasive ductal carcinoma and ovarian metastases.}, } @article {pmid39296436, year = {2024}, author = {Mihai, AM and Ianculescu, LM and Suciu, N}, title = {MiRNAs as potential biomarkers in early breast cancer detection: a systematic review.}, journal = {Journal of medicine and life}, volume = {17}, number = {6}, pages = {549-554}, pmid = {39296436}, issn = {1844-3117}, mesh = {Female ; Humans ; *Biomarkers, Tumor/blood/genetics ; *Breast Neoplasms/blood/diagnosis/genetics ; *Early Detection of Cancer/methods ; *Circulating MicroRNA/blood/genetics ; }, abstract = {Breast cancer remains a significant global health challenge, with high incidence and mortality rates. While mammography has contributed to declining mortality, its limitations in sensitivity and specificity for early detection, particularly in distinguishing between pure atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC), highlight the need for more precise tools. Even with core needle biopsy (CNB), conclusive diagnoses often require surgical excision. This underscores the urgency for non-invasive biomarkers to improve early detection and differentiation, potentially reducing invasive procedures. Recent research has shifted focus from mRNA to microRNAs (miRNAs) as promising biomarkers for breast cancer screening. These small non-coding RNAs, which exhibit abnormal expression patterns in breast cancer patients' tissue and serum/plasma, play crucial roles in early breast cancer development by modulating proto-oncogenes or tumor suppressor genes at the post-transcriptional level. Notably, miRNAs such as miR-21, miR-155, and miR-200c are key regulators of cell proliferation and apoptosis, with the potential to distinguish between normal tissue and various stages of breast lesions, including ADH, DCIS, and IDC. Additionally, miRNAs in serum and plasma offer a non-invasive method to differentiate breast cancer stages. This review aims to consolidate current knowledge on early breast lesions and explore the potential of miRNAs as biomarkers for early breast cancer detection, which could enhance risk prediction and reduce reliance on invasive diagnostic procedures.}, } @article {pmid39286469, year = {2024}, author = {Bailey, RE and Mazo Canola, M}, title = {Acute Lymphoblastic Leukemia in a Patient With Advanced Breast Cancer Treated With Cyclin-Dependent Kinase 4/6 Inhibitors and Endocrine Therapy.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e69548}, pmid = {39286469}, issn = {2168-8184}, abstract = {This case shares the case of a post-menopausal woman who develops Philadelphia chromosome-positive B cell acute lymphoblastic leukemia (B-ALL) while receiving treatment for invasive ductal carcinoma (IDC) of the breast. The patient received a cyclin-dependent kinase (CDK) 4/6 inhibitor + aromatase inhibitor (AI) for the IDC; hyperfractionate cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride (Adriamycin), methotrexate, and cytarabine (hyperCVAD), and the steroid hormone dexamethasone were added to treat the B-ALL. HyperCVAD combined with CDK 4/6 inhibitor + AI was very well tolerated. The CDK 4/6 inhibitor and AI were only held once in the treatment course due to adverse effect (AE) intolerance. The patient remains on a CDK 4/6 inhibitor and ponatinib with only low-grade fatigue as an AE. This case underscores the importance of a concurrent approach to managing hematologic and breast malignancies. The combined treatment regimens were effective and well-tolerated. Vigilant follow-up is essential for patients in remission from both malignancies, ensuring effective disease surveillance and treatment management. Integrated care remains pivotal for optimal outcomes.}, } @article {pmid39286022, year = {2024}, author = {Ge, Y and Wei, X and Liu, JN and Sun, PL and Gao, H}, title = {New insights into acinic cell carcinoma of the breast: clinicopathology, origin of histology, molecular features, prognosis, and treatment.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1438179}, pmid = {39286022}, issn = {2234-943X}, abstract = {Acinic cell carcinoma (AciCC) of the breast is a rare malignant epithelial neoplasm, with approximately 60 cases reported in the literature. It predominantly affects women and exhibits significant histological heterogeneity. The diagnosis of breast AciCC is primarily based on the presence of eosinophilic and/or basophilic granular cytoplasm and markers of serous acinar differentiation. Despite being considered a low-grade variant of conventional triple-negative breast cancer (TNBC), over 25% of patients with breast AciCC have adverse clinical outcomes. Additionally, in early research, microglandular adenosis (MGA) and atypical MGA were considered potential precursors for various breast cancers, including intraductal carcinoma, invasive ductal carcinoma, adenoid cystic carcinoma, metaplastic carcinoma, and AciCC. Similarly, some studies have proposed that breast AciCC should be considered a type of carcinoma developing in MGA with acinic cell differentiation rather than a distinct entity. Therefore, the pathogenesis of breast AciCC has not yet been clarified. Moreover, to the best of our knowledge, the literature has not summarized the latest prognosis and treatment of breast AciCC. In this review, we synthesized the current literature and the latest developments, aiming at exploring the clinicopathology, histological origin, molecular features, prognosis, and treatment of breast AciCC from a novel perspective.}, } @article {pmid39286019, year = {2024}, author = {Guo, F and Fu, H and Wang, Y and Hua, Y and Wang, X and Zhang, Y and Jian, J and Jia, Z and Zhang, G}, title = {Clinical features and prognosis of parotid metastasis of breast cancer: retrospective analysis of 57 cases.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1442713}, pmid = {39286019}, issn = {2234-943X}, abstract = {PURPOSE: Parotid gland metastases originating from breast origin are extremely rare, with their clinical presentation, therapeutic approaches, and prognostic indicators remaining to be elucidate.

METHODS: A comprehensive retrospective review was conducted, analyzing the clinical characteristics and prognostic factors of 57 patients diagnosed with parotid metastasis of breast cancer in the existing literature. Notably, our study included two unique cases of patients who developed contralateral and ipsilateral parotid metastases, occurring 5 years and 32 years respectively after primary surgery. This analysis aimed to provide a deeper understanding of the disease presentation and identify potential prognostic indicators.

RESULTS: The primary clinical manifestation presented in breast cancer patients with parotid metastases was painless masses in the parotid glands, synchronously or metachronously occurred with primary breast tumors. The predominant pathological subtype among these patients was invasive ductal carcinoma. Out of the 57 patients studied, 24 (42.1%) exhibited metastases solely in the ipsilateral parotid gland, while 18 cases (31.6%) involved either the contralateral or bilateral parotid gland. Patients may solely exhibit metastasis in the parotid gland, or they may present with concurrent multiple metastases in other organs. Patients who suffered from parotid metastases, either merely or accompanied with bone-only metastasis, exhibited significantly longer overall survival (OS) rates compared to those who had concomitant metastases in other organs (1.23 ± 0.26 years vs 4.46 ± 0.77 years, P=0.046). While no statistically significant differences in OS were observed among patients presenting with metastases in the ipsilateral, contralateral, or bilateral parotid glands, a notable variance could be discerned from the Kaplan-Meier curve analysis. Additionally, no significant difference in survival was exhibited between patients with different interval of progression from primary breast sites to initial diagnosis of parotid metastases (uDF), nor for patients who were treated with surgery or palliative therapy.

CONCLUSION: Parotid metastasis, a rare and distinctive form of breast cancer metastasis, demands particular scrutiny in patients exhibiting metastasis to multiple organs or contralateral or bilateral parotid glands.}, } @article {pmid39285422, year = {2024}, author = {Xiao, C and Guo, Y and Xu, Y and Huang, J and Li, J}, title = {Clinicopathological characteristics and survival analysis of different molecular subtypes of breast invasive ductal carcinoma achieving pathological complete response through neoadjuvant chemotherapy.}, journal = {World journal of surgical oncology}, volume = {22}, number = {1}, pages = {250}, pmid = {39285422}, issn = {1477-7819}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/mortality/drug therapy/metabolism ; *Neoadjuvant Therapy/methods/mortality ; *Carcinoma, Ductal, Breast/pathology/drug therapy/mortality/metabolism ; Middle Aged ; Survival Rate ; Prognosis ; *Erb-b2 Receptor Tyrosine Kinases/metabolism ; Follow-Up Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Adult ; Receptors, Progesterone/metabolism ; SEER Program ; Receptors, Estrogen/metabolism ; Aged ; Biomarkers, Tumor/metabolism/analysis ; Chemotherapy, Adjuvant/methods ; Retrospective Studies ; }, abstract = {BACKGROUND: To investigate the prognostic differences following the achievement of a pathological complete response (pCR) through neoadjuvant chemotherapy across different molecular subtypes of breast invasive ductal carcinoma.

METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) were identified for patients undergoing neoadjuvant chemotherapy who achieved pathological complete response for invasive ductal carcinoma of the breast between 2010 and 2019.Comparing the clinicopathological characteristics of patients across different molecular subtypes. Univariate and Cox multivariate analyses were utilized to identify independent predictors of overall survival (OS) and cancer-specific survival (CSS). The Kaplan-Meier method is used to compare OS and CSS among different molecular subtypes. After propensity score matching, subgroup analysis results were presented through forest plots.

RESULTS: This study included 9,380 patients diagnosed with invasive ductal carcinoma, who were categorized into four molecular subtypes: 2,721 (29.01%) HR + /HER-2 + , 1,661 (17.71%) HR + /HER2-, 2,082 (22.20%) HR-/HER2 + , and 2,916 (31.08%) HR-/HER-2-. HR + /HER-2- subgroup exhibited a significantly higher proportion of patients under 50 years old than the other subtype groups (54.67% vs 40.2%, 50.35% and 51.82%, p < 0.01), and had a higher N2 + N3 stage (11.2% vs 7.24%, 8.69% and 7.48%, p < 0.01). Univariate and multivariate analysis revealed that molecular subtype was the independent risk factor for OS and CSS in patients(p < 0.05). The Kaplan-Meier curves indicated that the HR + /HER-2 + subtype had the highest OS and CSS(p < 0.05). Next, were the HR-/HER-2 + and HR-/HER-2- subtypes, with the HR + /HER-2- group having the lowest OS and CSS(p < 0.05). After propensity score matching, the OS and CSS of patients in the HR + /HER-2 + group remained higher compared to HR + /HER-2- group(p < 0.05).

CONCLUSIONS: Patients with invasive ductal carcinoma of different molecular subtypes exhibit varying prognoses after achieving pCR to neoadjuvant chemotherapy. Those in the HR + /HER-2- group are younger, have a higher lymph node stage, and the lowest OS and CSS, whereas patients in the HR + /HER-2 + group have the highest OS and CSS.}, } @article {pmid39285012, year = {2025}, author = {Birnbaum, GE and Kanat-Maymon, Y and Zholtack, K and Avidan, R and Reis, HT}, title = {The Power to Flirt: Power within Romantic Relationships and Its Contribution to Expressions of Extradyadic Desire.}, journal = {Archives of sexual behavior}, volume = {54}, number = {1}, pages = {139-156}, pmid = {39285012}, issn = {1573-2800}, support = {1158/22//Israel Science Foundation/ ; 2016405//United States - Israel Binational Science Foundation/ ; }, mesh = {Humans ; Male ; Female ; *Power, Psychological ; *Sexual Partners/psychology ; *Interpersonal Relations ; *Sexual Behavior/psychology ; Adult ; Young Adult ; Motivation ; *Libido ; Fantasy ; Adolescent ; }, abstract = {Power in non-romantic contexts makes people confident in their ability to attract potential partners, increasing their mating motivation and the likelihood of acting on this motivation. Four studies investigated whether perceptions of power within romantic relationships would also activate mating goals, intensifying desires for alternative partners. In Studies 1 and 2, participants underwent power manipulation and then described a sexual fantasy or evaluated photos of attractive strangers. Studies 3 and 4 used face-to-face interaction and daily experiences methods to examine the mechanisms underlying the link between power and extradyadic desires. Overall, high perceived relationship power was associated with increased interest in alternatives. Perceived relative mate value explained this association, suggesting that what determines whether power elicits extradyadic interest is not power perceptions alone but rather the feeling of having a higher mate value than one's partner that accompanies elevated power and affects whether high-power individuals will prioritize their own needs in ways that may hurt their partners.}, } @article {pmid39284909, year = {2024}, author = {Brunetta, HS and Jung, AS and Valdivieso-Rivera, F and de Campos Zani, SC and Guerra, J and Furino, VO and Francisco, A and Berçot, M and Moraes-Vieira, PM and Keipert, S and Jastroch, M and Martinez, LO and Sponton, CH and Castilho, RF and Mori, MA and Bartelt, A}, title = {IF1 is a cold-regulated switch of ATP synthase hydrolytic activity to support thermogenesis in brown fat.}, journal = {The EMBO journal}, volume = {43}, number = {21}, pages = {4870-4891}, pmid = {39284909}, issn = {1460-2075}, support = {2022/00358-1//Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)/ ; 852742//EC | European Research Council (ERC)/ ; BA4925/2-1//Deutsche Forschungsgemeinschaft (DFG)/ ; 81X3600212//Deutsches Zentrum für Herz-Kreislaufforschung (DZHK)/ ; 310287/2018-9//Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)/ ; 88881.143924/2017-01//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)/ ; }, mesh = {Animals ; *Thermogenesis/genetics ; Mice ; *Adipose Tissue, Brown/metabolism ; *Cold Temperature ; *ATPase Inhibitory Protein ; *Mitochondrial Proton-Translocating ATPases/metabolism/genetics ; Hydrolysis ; Mitochondria/metabolism ; Mice, Inbred C57BL ; Male ; Adipocytes, Brown/metabolism ; Membrane Potential, Mitochondrial ; Energy Metabolism ; }, abstract = {While mechanisms controlling uncoupling protein-1 (UCP1) in thermogenic adipocytes play a pivotal role in non-shivering thermogenesis, it remains unclear whether F1Fo-ATP synthase function is also regulated in brown adipose tissue (BAT). Here, we show that inhibitory factor 1 (IF1, encoded by Atp5if1), an inhibitor of ATP synthase hydrolytic activity, is a critical negative regulator of brown adipocyte energy metabolism. In vivo, IF1 levels are diminished in BAT of cold-adapted mice compared to controls. Additionally, the capacity of ATP synthase to generate mitochondrial membrane potential (MMP) through ATP hydrolysis (the so-called "reverse mode" of ATP synthase) is increased in brown fat. In cultured brown adipocytes, IF1 overexpression results in an inability of mitochondria to sustain the MMP upon adrenergic stimulation, leading to a quiescent-like phenotype in brown adipocytes. In mice, adeno-associated virus-mediated IF1 overexpression in BAT suppresses adrenergic-stimulated thermogenesis and decreases mitochondrial respiration in BAT. Taken together, our work identifies downregulation of IF1 upon cold as a critical event for the facilitation of the reverse mode of ATP synthase as well as to enable energetic adaptation of BAT to effectively support non-shivering thermogenesis.}, } @article {pmid39283572, year = {2024}, author = {Fine, RE and Gilmore, RC and Tomkovich, KR and Dietz, JR and Berry, MP and Hernandez, LE and Columbus, KS and Seedman, SA and Fisher, CS and Han, LK and Manahan, ER and Hicks, RD and Vaidya, RP and Curcio, LD and Sevrukov, AB and Kenler, AS and Taback, B and Chen, M and Miller, ME and Gold, L and Anglin, BV and Aoun, HD and Simmons, RM and Feldman, SM and Boolbol, SK}, title = {Cryoablation Without Excision for Early-Stage Breast Cancer: ICE3 Trial 5-Year Follow-Up on Ipsilateral Breast Tumor Recurrence.}, journal = {Annals of surgical oncology}, volume = {31}, number = {11}, pages = {7273-7283}, pmid = {39283572}, issn = {1534-4681}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Breast Neoplasms/pathology/surgery ; Female ; Aged ; *Cryosurgery/methods ; Middle Aged ; Follow-Up Studies ; *Neoplasm Recurrence, Local/pathology/surgery ; Prospective Studies ; *Carcinoma, Ductal, Breast/surgery/pathology ; Aged, 80 and over ; *Neoplasm Staging ; Survival Rate ; Prognosis ; Neoplasm Grading ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; }, abstract = {BACKGROUND: The ICE3 trial evaluated the safety and efficacy of cryoablation in women aged ≥60 years with low-risk, early-stage breast cancers, aiming to provide a non-operative treatment option and avoid potential surgical risks. This study presents 5-year follow-up trial results.

METHODS: The ICE3 trial is an Institutional Review Board-approved, prospective, multicentered, non-randomized trial including women ≥ 60 years of age with unifocal, ultrasound visible, invasive ductal carcinoma ≤ 1.5 cm in size, histologic grade 1-2, hormone receptor (HR)-positive, and human epidermal growth factor receptor 2 (HER2)-negative. The primary study endpoint of 5-year ipsilateral breast tumor recurrence (IBTR) was evaluated based on Kaplan-Meier estimates.

RESULTS: Overall, 194 patients meeting eligibility received successful cryoablation treatment per protocol and were included for analysis. The mean age was 74.9 years (55-94) with a mean tumor size of 7.4 mm transverse (2.8-14.0 mm) and 8.1 mm sagittal (2.5-14.9 mm). With a mean follow-up period of 54.16 months, the IBTR rate at 5 years was 4.3% and breast cancer survival was 96.7%. Of the 124 patients who received endocrine therapy only, the IBTR was 3.7%. No serious device-related adverse events were reported. Minor (88.2%) and moderate (9.6%) adverse events were mild in severity and resolved without residual effects. Quality-of-life score demonstrated statistically significant improvement (p < 0.001) in distress at 6 months as compared with baseline.

CONCLUSIONS: Breast cryoablation presents a promising alternative to surgery in selected patients, offering the benefits of a minimally invasive procedure with minimal risks. Further studies are encouraged to confirm cryoablation as a viable alternative to surgical excision low-risk patients.}, } @article {pmid39283254, year = {2024}, author = {Cai, F and Li, Y and Liu, H and Luo, J}, title = {Single-cell and Spatial Transcriptomic Analyses Implicate Formation of the Immunosuppressive Microenvironment during Breast Tumor Progression.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {213}, number = {9}, pages = {1392-1401}, doi = {10.4049/jimmunol.2400025}, pmid = {39283254}, issn = {1550-6606}, support = {62072058//MOST | National Natural Science Foundation of China (NSFC)/ ; 82073339//MOST | National Natural Science Foundation of China (NSFC)/ ; BK20231271//JST | Natural Science Foundation of Jiangsu Province (Jiangsu Natural Science Foundation)/ ; }, mesh = {Humans ; *Tumor Microenvironment/immunology/genetics ; *Breast Neoplasms/immunology/genetics/pathology ; Female ; *Single-Cell Analysis ; *Disease Progression ; *Transcriptome ; Gene Expression Profiling ; Carcinoma, Intraductal, Noninfiltrating/immunology/genetics/pathology ; Carcinoma, Ductal, Breast/immunology/genetics/pathology ; Gene Expression Regulation, Neoplastic/immunology ; }, abstract = {Ductal carcinoma in situ and invasive ductal carcinoma represent two stages of breast cancer progression. A multitude of studies have shown that genomic instability increases during tumor development, as manifested by higher mutation and copy number variation rates. The advent of single-cell and spatial transcriptomics has enabled the investigation of the subtle differences in cellular states during the tumor progression at single-cell level, thereby providing more nuanced understanding of the intercellular interactions within the solid tumor. However, the evolutionary trajectory of tumor cells and the establishment of the immunosuppressive microenvironment during breast cancer progression remain unclear. In this study, we performed an exploratory analysis of the single-cell sequencing dataset of 13 ductal carcinoma in situ and invasive ductal carcinoma samples. We revealed that tumor cells became more malignant and aggressive during their progression, and T cells transited to an exhausted state. The tumor cells expressed various coinhibitory ligands that interacted with the receptors of immune cells to create an immunosuppressive tumor microenvironment. Furthermore, spatial transcriptomics data confirmed the spatial colocalization of tumor and immune cells, as well as the expression of the coinhibitory ligand-receptor pairs. Our analysis provides insights into the cellular and molecular mechanism underlying the formation of the immunosuppressive landscape during two typical stages of breast cancer progression.}, } @article {pmid39280872, year = {2024}, author = {Jackson, I and Isern, R and Jesina, S and Velagapudi, M and Pruett, W}, title = {Pneumocystis jirovecii Pneumonia in Patients Treated for Solid Organ Malignancy.}, journal = {Ochsner journal}, volume = {24}, number = {3}, pages = {225-228}, pmid = {39280872}, issn = {1524-5012}, abstract = {Background: Pneumocystis jirovecii is a fungal pathogen that can present as an opportunistic cause of pneumonia and can occur in individuals with various causes of immunosuppression, including malignancy and treatments for malignancy that confer increased risk. Although the guidelines for use of Pneumocystis prophylaxis in certain populations are clear, the rapid development of novel cancer therapies elicits the need to accurately assess the degree of immunosuppression conferred by these regimens and to determine if patients receiving these therapies warrant Pneumocystis prophylaxis. Case Series: We present 2 cases of Pneumocystis jirovecii pneumonia in patients with invasive ductal carcinoma of the breast treated with a dose-dense chemotherapy regimen consisting of doxorubicin, cyclophosphamide, and paclitaxel. Conclusion: The use of a dose-dense regimen, in which the interval between doses is shortened compared to a standard regimen, has become a common therapy for patients diagnosed with early breast cancer. Although this approach leads to improved disease-free and overall survival, it has also been associated with an increased risk of developing Pneumocystis jirovecii pneumonia. Further research involving patients receiving dose-dense chemotherapy regimens is needed to determine their risk of developing opportunistic infections and whether that risk warrants changes in clinical management.}, } @article {pmid39274541, year = {2024}, author = {Esin, E and Yildirim, HC and Oksuzoglu, B and Markoc, F and Guntekin, S and Bilgetekin, I and Yildiz, F and Yukruk, F and Demirci, U and Cetin-Atalay, R}, title = {Prosigna Assay for Treatment Decisions in Early Breast Cancer: A Decision Impact Study.}, journal = {Journal of clinical medicine}, volume = {13}, number = {17}, pages = {}, pmid = {39274541}, issn = {2077-0383}, abstract = {Introduction: Therapeutic decisions in early breast cancer are based on clinico-pathological features which are subject to intra- and inter-observer variability. This single-center decision impact study aimed to evaluate the effects of the Prosigna assay on physicians' adjuvant treatment choices. Methods: Between 09/2017 and 02/2018, formalin-fixed tumor samples from 52 newly diagnosed, postmenopausal, hormone receptor-positive, HER2-negative breast cancer (T1-T2; pN0-N1a) patients were analyzed. Pre-test clinical judgements and Prosigna test results were compared. Results: The mean age was 59 (42-77). Invasive ductal carcinoma (79.2%), grade 2 (52.8%) and T1c-N0 tumors (43.4%) were represented. There was 40.4% discordance between the pre- and post-test risk of recurrences. No significant change was observed in the clinical intermediate risk category, while there was a net reclassification of low-risk patients into a high Prosigna recurrence risk group. In addition, clinically determined intrinsic subtypes were 34.6% discordant with the Prosigna results, which is largely driven by the reclassification of the luminal A tumors into the Prosigna-assessed luminal B group. Before the Prosigna test, endocrine treatment was the primary choice in 20 patients (39.2%), and chemotherapy was recommended to 31 patients (60.8%). Overall, the Prosigna assay led to a change in treatment choice for one patient. Conclusions: Although conventional risk assessment methods are relatively inexpensive with shorter turnaround times, their accuracy and value for risk reduction are suboptimal. According to our results, the Prosigna assay was found to be a relevant tool for the clinical decision making process. Long-term follow-up of these patients will elucidate the potential benefits of using multigene molecular tests as biomarkers for treatment.}, } @article {pmid39266381, year = {2025}, author = {Cilla, S and Macchia, G and Bonome, P and Pezzulla, D and Romano, C and Boccardi, M and Viola, P and Galietta, E and Donati, CM and Morganti, AG and Deodato, F}, title = {Automated single-isocenter stereotactic body radiotherapy for multiple metastases from breast cancer: A case study.}, journal = {Medical dosimetry : official journal of the American Association of Medical Dosimetrists}, volume = {50}, number = {1}, pages = {57-62}, doi = {10.1016/j.meddos.2024.08.001}, pmid = {39266381}, issn = {1873-4022}, mesh = {Humans ; Female ; *Radiosurgery/methods ; Adult ; *Breast Neoplasms/pathology/radiotherapy ; Radiotherapy Planning, Computer-Assisted/methods ; }, abstract = {Oligometastatic breast cancer patients can today could benefit from a multimodal approach, combining systemic therapy with metastasis-directed treatment using stereotactic body radiotherapy (SBRT). However, the possibility to synchronously treat multiple lesions is still challenging, needing the ability to generate complex dose distributions with steep dose gradients outside the lesions and major sparing of surrounding organs at risk and accurately track and reproduce the patient's position before and during radiation therapy. We report the case of an oligometastatic patient from left breast cancer, which occurred after a full course of whole breast radiotherapy, treated using the potential of modern technology including single-isocenter setup, plan automation, breath-hold technique and surface guided tracking and reproducibility of patient's position before and during radiation therapy. A 44-year-old female patient with a history of left breast cancer, specifically a luminal-B-like invasive ductal carcinoma with Her2 overexpression, was admitted to our department. The patient previously underwent a left mastectomy (pT2N0M0), 4 cycles of adjuvant chemotherapy, adjuvant radiotherapy on the chest wall and lymph nodes drainage, and 5 years of hormonal therapy. A chest wall ultrasound and positron emission tomography revealed the presence of new lesions in the area of the surgical scar from the previous mastectomy, internal mammary, axillary and retropectoral levels. The 3 lesions were simultaneously treated with a mono-isocentric VMAT plan using SBRT technique with a total dose of 30 Gy delivered in 5 fractions. Due to the technical challenges, this treatment was supported by the use of planning automation, breath-hold technique and surface-guided radiation therapy to improve the accuracy of the dose delivery. Two different plans were generated and compared to pursue the best dosimetric result, including a summed plan obtained from 3 individual SBRT plans for each lesion with a separate isocenter placed in each of them (MIP), and a single-isocenter SBRT plan able to treat multiple lesions synchronously (SIP). Because of the advantages in terms of dosimetry and dose delivery efficiency, the patient was successfully treated with the SIP plan. The treatment time was reduced to about 4.5 minutes, allowing the comfortably use of breath-hold technique. After treatment, the condition of the patient was normal, and no toxicities have been observed in follow-up. SBRT with mono isocentric VMAT planning represents the recommended approach to simultaneously treat multiple lesions in close proximity in the thoracic district.}, } @article {pmid39260386, year = {2024}, author = {Setyawan, G and Ibrahim, KA and Ogawa, R and Sejati, PA and Fujimoto, H and Yamamoto, H and Takei, M}, title = {Detection of invasive ductal carcinoma by electrical impedance spectroscopy implementing gaussian relaxation-time distribution (EIS-GRTD).}, journal = {Biomedical physics & engineering express}, volume = {10}, number = {6}, pages = {}, doi = {10.1088/2057-1976/ad795f}, pmid = {39260386}, issn = {2057-1976}, mesh = {Humans ; *Dielectric Spectroscopy/methods ; Female ; *Breast Neoplasms ; *Carcinoma, Ductal, Breast/pathology ; *Adipose Tissue ; Normal Distribution ; Breast/diagnostic imaging ; Electric Impedance ; Mastectomy ; }, abstract = {Breast cancer detection and differentiation of breast tissues are critical for accurate diagnosis and treatment planning. This study addresses the challenge of distinguishing between invasive ductal carcinoma (IDC), normal glandular breast tissues (nGBT), and adipose tissue using electrical impedance spectroscopy combined with Gaussian relaxation-time distribution (EIS-GRTD). The primary objective is to investigate the relaxation-time characteristics of these tissues and their potential to differentiate between normal and abnormal breast tissues. We applied a single-point EIS-GRTD measurement to ten mastectomy specimens across a frequency rangef= 4 Hz to 5 MHz. The method calculates the differential ratio of the relaxation-time distribution functionΔγbetween IDC and nGBT, which is denoted byΔγIDC-nGBT,andΔγbetween IDC and adipose tissues, which is denoted byΔγIDC-adipose.As a result, the differential ratio ofΔγbetween IDC and nGBTΔγIDC-nGBTis 0.36, and between IDC and adiposeΔγIDC-adiposeis 0.27, which included in theα-dispersion atτpeak1=0.033±0.001s.In all specimens, the relaxation-time distribution functionγof IDCγIDCis higher, and there is no intersection withγof nGBTγnGBTand adiposeγadipose.The difference inγsuggests potential variations in relaxation properties at the molecular or structural level within each breast tissue that contribute to the overall relaxation response. The average mean percentage errorδfor IDC, nGBT, and adipose tissues are 5.90%, 6.33%, and 8.07%, respectively, demonstrating the model's accuracy and reliability. This study provides novel insights into the use of relaxation-time characteristic for differentiating breast tissue types, offering potential advancements in diagnosis methods. Future research will focus on correlating EIS-GRTD finding with pathological results from the same test sites to further validate the method's efficacy.}, } @article {pmid39256827, year = {2024}, author = {Phung, AT and Shah, JR and Dong, T and Reid, T and Larson, C and Sanchez, AB and Oronsky, B and Trogler, WC and Kummel, AC and Aisagbonhi, O and Blair, SL}, title = {CAR expression in invasive breast carcinoma and its effect on adenovirus transduction efficiency.}, journal = {Breast cancer research : BCR}, volume = {26}, number = {1}, pages = {131}, pmid = {39256827}, issn = {1465-542X}, mesh = {Humans ; Female ; *Breast Neoplasms/therapy/genetics/metabolism/pathology ; *Adenoviridae/genetics ; *Transduction, Genetic ; *Coxsackie and Adenovirus Receptor-Like Membrane Protein/metabolism/genetics ; Cell Line, Tumor ; Carcinoma, Lobular/metabolism/therapy/genetics/pathology ; Carcinoma, Ductal, Breast/metabolism/genetics/pathology/therapy ; Cadherins/metabolism/genetics ; Genetic Vectors/genetics/administration & dosage ; Liposomes ; }, abstract = {BACKGROUND: Breast cancer is the second leading cause of death in women, with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) as the two most common forms of invasive breast cancer. While estrogen receptor positive (ER+) IDC and ILC are treated similarly, the multifocality of ILC presents challenges in detection and treatment, worsening long-term clinical outcomes in patients. With increasing documentation of chemoresistance in ILC, additional treatment options are needed. Oncolytic adenoviral therapy may be a promising option, but cancer cells must express the coxsackievirus & adenovirus receptor (CAR) for adenoviral therapy to be effective. The present study aims to evaluate the extent to which CAR expression is observed in ILC in comparison to IDC, and how the levels of CAR expression correlate with adenovirus transduction efficiency. The effect of liposome encapsulation on transduction efficiency is also assessed.

METHODS: To characterize CAR expression in invasive breast carcinoma, 36 formalin-fixed paraffin-embedded (FFPE) human breast tumor samples were assayed by CAR immunohistochemistry (IHC). Localization of CAR in comparison to other junctional proteins was performed using a multiplex immunofluorescence panel consisting of CAR, p120-catenin, and E-cadherin. ILC and IDC primary tumors and cell lines were transduced with E1- and E3-deleted adenovirus type 5 inserted with a GFP transgene (Ad-GFP) and DOTAP liposome encapsulated Ad-GFP (DfAd-GFP) at various multiplicities of infection (MOIs). Transduction efficiency was measured using a fluorescence plate reader. CAR expression in the human primary breast carcinomas and cell lines was also evaluated by IHC.

RESULTS: We observed membranous CAR, p120-catenin and E-cadherin expression in IDC. In ILC, we observed cytoplasmic expression of CAR and p120-catenin, with absent E-cadherin. Adenovirus effectively transduced high-CAR IDC cell lines, at MOIs as low as 12.5. Ad-GFP showed similar transduction as DfAd-GFP in high-CAR IDC cell lines. Conversely, Ad-GFP transduction of ILC cell lines was observed only at MOIs of 50 and 100. Furthermore, Ad-GFP did not transduce CAR-negative IDC cell lines even at MOIs greater than 100. Liposome encapsulation (DfAd-GFP) improved transduction efficiency 4-fold in ILC and 17-fold in CAR-negative IDC cell lines.

CONCLUSION: The present study demonstrates that oncolytic adenoviral therapy is less effective in ILC than IDC due to differences in spatial CAR expression. Liposome-enhanced delivery may be beneficial for patients with ILC and tumors with low or negative CAR expression to improve adenoviral therapeutic effectiveness.}, } @article {pmid39254403, year = {2024}, author = {Agosti, V and Munari, E}, title = {Histopathological evaluation and grading for prostate cancer: current issues and crucial aspects.}, journal = {Asian journal of andrology}, volume = {26}, number = {6}, pages = {575-581}, pmid = {39254403}, issn = {1745-7262}, mesh = {Humans ; *Prostatic Neoplasms/pathology ; Male ; *Neoplasm Grading ; Prognosis ; Observer Variation ; Prostate/pathology ; Reproducibility of Results ; }, abstract = {A crucial aspect of prostate cancer grading, especially in low- and intermediate-risk cancer, is the accurate identification of Gleason pattern 4 glands, which includes ill-formed or fused glands. However, there is notable inconsistency among pathologists in recognizing these glands, especially when mixed with pattern 3 glands. This inconsistency has significant implications for patient management and treatment decisions. Conversely, the recognition of glomeruloid and cribriform architecture has shown higher reproducibility. Cribriform architecture, in particular, has been linked to the worst prognosis among pattern 4 subtypes. Intraductal carcinoma of the prostate (IDC-P) is also associated with high-grade cancer and poor prognosis. Accurate identification, classification, and tumor size evaluation by pathologists are vital for determining patient treatment. This review emphasizes the importance of prostate cancer grading, highlighting challenges like distinguishing between pattern 3 and pattern 4 and the prognostic implications of cribriform architecture and intraductal proliferations. It also addresses the inherent grading limitations due to interobserver variability and explores the potential of computational pathology to enhance pathologist accuracy and consistency.}, } @article {pmid39253883, year = {2024}, author = {Paz, Y and Frenkel, TI}, title = {Infant sensitivity to social contingency moderates the predictive link between early maternal reciprocity and infants' emerging social behavior.}, journal = {Developmental science}, volume = {27}, number = {6}, pages = {e13563}, doi = {10.1111/desc.13563}, pmid = {39253883}, issn = {1467-7687}, support = {//Ziama Arkin Infancy Institute at Reichman University/ ; }, mesh = {Humans ; Female ; Infant ; *Mother-Child Relations ; Male ; *Maternal Behavior/physiology ; *Social Behavior ; *Child Development/physiology ; Child, Preschool ; Infant Behavior/physiology ; }, abstract = {The scientific study of love underscores the importance of dyadic reciprocity in laying the foundation for infants' social development. While research establishes links between early reciprocity and children's social capacities, some infants appear to benefit from reciprocity more than others. A central feature of reciprocity is its contingent structure, that is, the extent to which maternal behaviors are temporally associated with and contingent upon infants' dynamically changing cues. As such, infants' sensitivity to social contingencies may define the extent to which an infant benefits from maternal reciprocity. The current study examined the role of infants' sensitivity to social contingency (SC) in moderating associations between early maternal reciprocity and subsequent infants' social behavior. The study followed 157 children (47% females), across the first year of life (4, 10, and 12 months) and at preschool age (48 months). Infants' SC at 4 and 10 months moderated the link between early maternal reciprocity and infants' prosocial behavior observed at 12 months. SC at 10 months moderated the link between early reciprocity and reported peer problems at 48 months. Maternal reciprocity predicted more helping behavior in infancy and fewer peer problems at preschool, but only for infants who displayed high SC. Findings highlight the contingent nature of reciprocal mother-infant interactions revealing that an infant's sensitivity to breaks in social-contingency moderates the developmental benefit of reciprocity. Future research is necessary to directly test the underlying mechanisms of these processes and better understand the individual characteristics of infants' sensitivity to social contingency and its' role in typical and atypical development. RESEARCH HIGHLIGHTS: Individual differences in infants' sensitivity to breaks in social contingencies may moderate the extent to which infants benefit from contingent reciprocal maternal behavior (i.e., maternal reciprocity). Maternal reciprocity predicted more helping behavior in infancy and fewer peer problems at preschool, but only for infants who displayed high sensitivity to breaks in social contingency. Findings highlight the contingent nature of reciprocal mother-infant interactions revealing that infants' sensitivity to breaks in social-contingency moderates the developmental benefit of reciprocity. Findings emphasize the need to develop measurement methods and direct empirical attention to the important yet understudied individual characteristic of infants' sensitivity to social contingency and its role in shaping social development.}, } @article {pmid39241864, year = {2024}, author = {Dobato Portoles, O and Aparicio Lopez, D and Ibañez Carreras, R and Aguirre Ortega, E and Eizaguirre Zarza, B and García Mur, C and Carrasquer Puyal, A and Cebollero Benito, MP and Comín Novella, LI and Allue Cabañuz, M and Martinez Ubieto, F and Sousa Domínguez, R and Torcal Aznar, J and Casamayor Franco, C}, title = {Male breast cancer: A multicenter study in Aragon over 27 years.}, journal = {Cirugia espanola}, volume = {102}, number = {10}, pages = {524-532}, doi = {10.1016/j.cireng.2024.09.001}, pmid = {39241864}, issn = {2173-5077}, mesh = {Humans ; *Breast Neoplasms, Male/pathology/epidemiology/surgery ; Retrospective Studies ; Spain/epidemiology ; Male ; Middle Aged ; Aged ; Adult ; Prevalence ; Aged, 80 and over ; Prognosis ; Mastectomy/statistics & numerical data/methods ; Neoplasm Recurrence, Local/epidemiology/pathology ; Carcinoma, Ductal, Breast/pathology/epidemiology/mortality ; Time Factors ; }, abstract = {INTRODUCTION: Male breast cancer accounts for 1% of all breast cancers. Its low frequency leads to a lack of awareness, resulting in significant diagnostic delays. Additionally, this limits the available evidence, which primarily uses diagnostic-therapeutic algorithms based on women.

OBJECTIVES: To analyze the prevalence, clinical presentation, anatomical and pathological characteristics, and prognosis of male breast cancer using one of the largest series available. Secondarily, to compare our data with studies conducted in women.

MATERIALS AND METHODS: A multicenter, observational, descriptive, retrospective study was conducted in the autonomous community of Aragon, Spain, from 1995 to 2022 including men with a pathological diagnosis of breast cancer.

RESULTS: A total of 148 patients were included, with a prevalence of 1%. The most common clinical presentation was a palpable retroareolar mass. Invasive ductal carcinoma was the most frequent type (88.89%), and luminal B was the predominant subtype (47.76%). Surgery was the most utilized treatment; mastectomy was performed in 90.34% and AL in 46.89%. At diagnosis, 52.46% had extramammary involvement. The recurrence rate was 24.1%, and the mortality attributed to the disease was 14.6%.

CONCLUSIONS: There is a high rate of metastatic involvement at diagnosis, a high percentage of mutilating surgeries, and a high number of recurrences compared to available studies on males. Additionally, a worse prognosis is observed compared to breast cancer in women, despite these tumors having a less aggressive molecular subtype. These findings highlight the importance of conducting studies focused on men to develop specific protocols.}, } @article {pmid39241826, year = {2024}, author = {Han, Z and Ding, S and Liu, B and Tang, Y and Qiu, X and Wang, E and Zhao, H}, title = {Histopathologic Differential Diagnosis and Estrogen Receptor/Progesterone Receptor Immunohistochemical Evaluation of Breast Carcinoma Using a Deep Learning-Based Artificial Intelligence Architecture.}, journal = {The American journal of pathology}, volume = {194}, number = {12}, pages = {2313-2325}, doi = {10.1016/j.ajpath.2024.08.011}, pmid = {39241826}, issn = {1525-2191}, mesh = {Humans ; *Deep Learning ; *Breast Neoplasms/pathology/metabolism/diagnosis ; *Receptors, Progesterone/metabolism ; *Receptors, Estrogen/metabolism ; Female ; *Immunohistochemistry/methods ; *Artificial Intelligence ; *Carcinoma, Ductal, Breast/pathology/metabolism/diagnosis ; Diagnosis, Differential ; Biomarkers, Tumor/metabolism/analysis ; Carcinoma, Intraductal, Noninfiltrating/pathology/metabolism/diagnosis ; }, abstract = {In breast carcinoma, invasive ductal carcinoma (IDC) is the most common histopathologic subtype, and ductal carcinoma in situ (DCIS) is a precursor of IDC. These two often occur concomitantly. The immunohistochemical staining of estrogen receptor (ER)/progesterone receptor (PR) in IDC/DCIS on histopathologic whole slide images (WSIs) can predict the prognosis of patients. Artificial intelligence (AI) technology has the potential to substantially reduce the interobserver variability among pathologists reading WSIs. Herein, IDC/DCIS detection was conducted by a deep learning approach, including faster region-based convolutional neural network (Faster R-CNN), RetinaNet, single-shot multibox detector 300 (SSD300), you only look once (YOLO) v3, YOLOv5, YOLOv7, YOLOv8, and Swin transformer. Their performance was estimated by mean average precision (mAP) values. Cell recognition and counting were performed using AI technology to evaluate the intensity and proportion of ER/PR-immunostained cancer cells in IDC/DCIS. A three-round ring study (RS) was conducted to assess WSIs. A database for modelling the underlying probability distribution of a data set with labels was established. YOLOv8 exhibited the highest detection performance with an mAP at 0.5 of 0.944 and an mAP at 0.5 to 0.95 of 0.790. With the assistance of YOLOv8, the scoring concordance across all pathologists was boosted to excellent in RS3 (0.970) from moderate in RS1 (0.724) and good in RS2 (0.812). Deep learning detection can be applied in the clinicopathologic field. Herein, a novel AI architecture and well-organized data set were developed to facilitate the histopathologic diagnosis of IDC/DCIS and immunostaining scoring of ER/PR.}, } @article {pmid39241490, year = {2024}, author = {Vanni, G and Pellicciaro, M and Materazzo, M and Berretta, M and Meucci, R and Perretta, T and Portarena, I and Pistolese, CA and Buonomo, OC}, title = {Radiological and pathological predictors of post-operative upstaging of breast ductal carcinoma in situ (DCIS) to invasive ductal carcinoma and lymph-nodes metastasis; a potential algorithm for node surgical de-escalation.}, journal = {Surgical oncology}, volume = {56}, number = {}, pages = {102128}, doi = {10.1016/j.suronc.2024.102128}, pmid = {39241490}, issn = {1879-3320}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/surgery ; Retrospective Studies ; Middle Aged ; *Carcinoma, Intraductal, Noninfiltrating/surgery/pathology/secondary ; *Lymphatic Metastasis ; *Carcinoma, Ductal, Breast/surgery/pathology/secondary ; *Algorithms ; Adult ; Aged ; Sentinel Lymph Node Biopsy/methods ; Prognosis ; Follow-Up Studies ; Mammography ; Mastectomy ; Neoplasm Staging ; }, abstract = {BACKGROUND/AIM: Ductal carcinoma in situ is considered a local disease with no metastatic potential, thus sentinel lymph node biopsy (SLNB) may be deemed an overtreatment. SLNB should be reserved for patients with invasive cancer, even though the risk of upstaging rises to 25 %. We aimed to identify clinicopathological predictors of post-operative upstaging in invasive carcinoma.

METHODS: We retrospectively analyzed patients with a pre-operative diagnosis of DCIS subjected to breast surgery between January 2017 to December 2021, and evaluated at the Breast Unit of PTV (Policlinico Tor Vergata, Rome).

RESULTS: Out of 267 patients diagnosed with DCIS, 33(12.4 %) received a diagnosis upstaging and 9(3.37 %) patients presented with sentinel lymph node (SLN) metastasis. In multivariate analysis, grade 3 tumor (OR 1.9; 95 % CI 1.2-5.6), dense nodule at mammography (OR 1.3; 95 % CI 1.1-2.6) and presence of a solid nodule at ultrasonography (OR 1.5; 95 % CI 1.2-2.6) were independent upstaging predictors. Differently, the independent predictors for SLNB metastasis were: upstaging (OR 2.1.; 95 % CI 1.2-4.6; p = 0.0079) and age between 40 and 60yrs (OR 1.4; 95 % CI 1.4-2.7; p = 0.027). All 9 patients with SLN metastasis received a diagnosis upstaging and were aged between 40 and 60 years old.

CONCLUSION: We identified pre-operative independent predictors of upstaging to invasive ductal carcinoma. The combined use of different predictors in an algorithm for surgical treatments of DCIS could reduce the numbers of unnecessary SLNB.}, } @article {pmid39238959, year = {2024}, author = {Hou, T and Shen, G and Hu, X and Bai, T and He, H and Zhang, Z and Bao, W and Tian, R and Yu, X and Sun, T and Ding, X and Wang, X and Zhang, Y}, title = {A case report of breast cancer metastasis to the bladder from invasive ductal carcinoma.}, journal = {Annals of medicine and surgery (2012)}, volume = {86}, number = {9}, pages = {5529-5534}, pmid = {39238959}, issn = {2049-0801}, abstract = {INTRODUCTION AND IMPORTANCE: Breast cancer is the most common malignancy among women worldwide, predominantly manifesting as invasive ductal carcinoma (IDC), which usually metastasizes to the bones, lungs, and liver. However, metastasis to the bladder is exceedingly rare, with few documented cases and limited understanding in the existing literature.

CASE PRESENTATION: A 57-year-old woman with a history of IDC presented with a lump in her left breast and was initially treated with chemotherapy and a modified radical mastectomy. Years later, she developed urinary symptoms, which upon investigation revealed multiple bladder tumors and right kidney hydronephrosis. Diagnostic imaging, including ultrasound and computed tomography (CT) scans, supported these findings.

CLINICAL DISCUSSION: The discovery of bladder metastasis from IDC highlights significant diagnostic challenges due to the atypical presentation. The case underscores the importance of considering unusual metastatic sites in patients with known breast cancer, especially when they present with non-specific urinary symptoms. This report explores the potential pathophysiological mechanisms of such rare metastatic occurrences and discusses the implications for clinical practice.

CONCLUSION: This case exemplifies the critical need for heightened awareness and thorough evaluation in patients with unusual symptoms and a history of breast cancer. It calls for more comprehensive diagnostic approaches and possibly adjusted treatment protocols to better manage atypical metastases, ultimately aiming to improve patient outcomes and contribute to a deeper understanding of metastatic breast cancer behavior.}, } @article {pmid39234434, year = {2024}, author = {Farghadani, M and Sanei, P}, title = {MRI Evaluation of Mass-Like and None-Mass-Like-Proven Breast Cancer from Moderate-to-High Background Enhancement.}, journal = {Advanced biomedical research}, volume = {13}, number = {}, pages = {36}, pmid = {39234434}, issn = {2277-9175}, abstract = {BACKGROUND: Breast cancer is considered one of the most prevalent cancers among females worldwide. The aim of this study was to assess the magnetic resonance imaging (MRI) patterns of female breast cancer, and also the prevalence of mass-like and nonmass-like lesions among these patients.

MATERIALS AND METHODS: 32 patients with proven breast cancer (based on their pathologic findings and background parenchymal enhancement [BPE] of their magnetic resonance [MR] images) were included in this cross-sectional study which was performed from 2017 to 2019 in Isfahan, Iran, using a1.5 Tesla (Achieva Philips, Netherland) MRI scanner system. The MR sequences (noncontrast image and at least two contrast-enhanced images) were done in the prone position for studied patients.

RESULTS: It was found that 68.8% (n = 44) and 31.2% (n = 20) of breast cancers were suffered from moderate and severe BPE, respectively. Furthermore, the prevalence of mass-like nonmass-like and both tumors were 43.8%, 43.8%, and 12.4%, respectively. Pathological studies indicated that 50%, 37.5%, and 12.5% of cancers were ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and DCIS, respectively. In addition, a significant relationship between MRI characteristics and pathologic findings was found for IDC and DCIS (P = 0.03).

CONCLUSION: Based on the results of this study, the relationship between BPE level and MRI finding including mass-like or nonmass-like lesions in biopsy-proven breast cancers was not significant.}, } @article {pmid39233942, year = {2024}, author = {McGrath, J and Rhatigan, DJ and Donahue, D and Fannin, M and Lawson, N}, title = {Infiltrating Ductal Breast Carcinoma in a Male Patient With Associated BARD1 Mutation.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e66216}, pmid = {39233942}, issn = {2168-8184}, abstract = {Male breast cancer is an uncommon diagnosis with limited research on management and prognosis due to its rarity. We discuss a case of a 55-year-old male with a non-contributory past medical history who presented with an enlarging palpable mass of his right breast tissue at the 10:00 position. The ultrasound of the right breast showed a 2.8 cm heterogenous mass with irregular borders highly suspicious for malignancy. The follow-up sonogram-guided core biopsy was performed, and the pathology of the mass confirmed high-grade infiltrating ductal carcinoma. A modified radical mastectomy of the right breast with extensive axillary lymph node excision was performed. Genetic testing of the excised tumor revealed a MUTYH gene mutation and a BARD1 (BRCA1-associated RING domain 1) gene mutation of unknown significance. Histopathological analysis confirmed a Grade 2, ER/PR-positive, KI 67-positive, and HER2-negative tumor.}, } @article {pmid39233823, year = {2024}, author = {Sun, K and Zhu, M and Chen, G and Liu, B}, title = {Neoadjuvant chemotherapy for primary invasive ductal carcinoma of the nipple: A case report.}, journal = {Oncology letters}, volume = {28}, number = {5}, pages = {506}, pmid = {39233823}, issn = {1792-1082}, abstract = {Breast cancer typically arises from the terminal duct-lobular unit of the mammary gland and rarely from the ducts inside the nipple. The present paper reports a rare case of primary invasive ductal carcinoma of the papilla, which was a locally advanced triple-negative breast cancer that was treated with 6 cycles of neoadjuvant chemotherapy with a nab-paclitaxel, epirubicin and cyclophosphamide regimen. Surgical pathology confirmed that a pathological complete response was achieved and adjuvant radiotherapy was performed postoperatively. No recurrence or metastasis occurred as of April 2024. A review of previous similar cases revealed that primary invasive breast cancer of the nipple has several manifestations. Changes in the nipple should be treated cautiously and a pathological biopsy should be performed in a timely manner. Breast cancer occurring in the nipple can be treated with reference to the same type of common breast cancer, and neoadjuvant chemotherapy can also be performed first if neoadjuvant chemotherapy is indicated.}, } @article {pmid39226766, year = {2024}, author = {Madrigal, JM and Pruitt, CN and Fisher, JA and Liao, LM and Graubard, BI and Gierach, GL and Silverman, DT and Ward, MH and Jones, RR}, title = {Carcinogenic industrial air pollution and postmenopausal breast cancer risk in the National Institutes of Health AARP Diet and Health Study.}, journal = {Environment international}, volume = {191}, number = {}, pages = {108985}, pmid = {39226766}, issn = {1873-6750}, support = {Z99 CA999999/ImNIH/Intramural NIH HHS/United States ; ZIA CP010125/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/chemically induced ; *Postmenopause ; Middle Aged ; United States/epidemiology ; Aged ; *Air Pollution/statistics & numerical data ; Air Pollutants/analysis ; Prospective Studies ; Carcinogens/analysis ; Risk Factors ; National Institutes of Health (U.S.) ; Environmental Exposure/statistics & numerical data ; Benzene/analysis ; }, abstract = {BACKGROUND: Chemicals emitted from industrial facilities include known or suspected mammary carcinogens and endocrine disruptors, but epidemiologic studies are limited. We evaluated associations between air emissions of multiple carcinogenic chemicals and postmenopausal breast cancer risk in a large prospective U.S.

METHODS: We used the U.S. Environmental Protection Agency's Toxics Release Inventory to estimate historical airborne emissions (1987-1995) of 19 known and probable carcinogens for participants enrolled (1995-1996) in the NIH-AARP Diet and Health Study. Among 170,402 women, 15,124 breast cancers were diagnosed through 2018. We constructed inverse distance- and wind-weighted average emissions metrics within 1, 2, 5, and 10 km of the enrollment address for each chemical. We estimated multivariable adjusted HRs and 95 % CIs for categories (quartiles, tertiles, medians) of each chemical in association with breast cancer overall and separately by type (invasive, ductal carcinoma in situ) and estrogen receptor (ER) status.

RESULTS: We observed an association between benzene emissions and breast cancer risk that was strongest at 1 km (HRQ4 vs. non-exposed = 2.06, 95 %CI: 1.34-3.17; p-trend = 0.001). The magnitude of the association weakened with increasing distance (2 km HRQ4 vs. non-exposed = 1.17, 95 %CI=0.92-1.49; p-trend = 0.19; 5 km HRQ4 vs. non-exposed = 1.05, 95 %CI=0.94-1.16; p-trend = 0.37; 10 km HRQ4 vs. non-exposed = 0.95, 95 %CI=0.89-1.02; p-trend = 0.19) and appeared to be most relevant for invasive rather than intraductal disease. Overall risk was also elevated for vinyl chloride at 5 km (HR≥median vs. non-exposed = 1.20, 95 %CI=1.01-1.43; p-trend = 0.04), but not 2 km or 10 km. We observed suggestive associations for asbestos, trichloroethylene, and styrene in different subgroup analyses, but risk patterns were not clear across distances. Associations with other chemicals were generally null, with limited evidence of heterogeneity by disease type or ER status.

CONCLUSIONS: An increased risk of breast cancer associated with relatively high levels of industrial benzene emissions warrants additional study, particularly among participants with diverse sociodemographic characteristics that live in areas with higher density of industrial facilities.}, } @article {pmid39219256, year = {2024}, author = {Lu, N and Zhang, M and Lu, L and Liu, YZ and Zhang, HH and Liu, XD}, title = {[Retracted] miRNA‑490‑3p promotes the metastatic progression of invasive ductal carcinoma.}, journal = {Oncology reports}, volume = {52}, number = {5}, pages = {}, doi = {10.3892/or.2024.8802}, pmid = {39219256}, issn = {1791-2431}, abstract = {Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the western blotting data shown in Fig. 2D, the cell migration and invasion assay data in Fig. 3C, the mouse imaging pictures in Fig. 4C and D, and the H&E‑stained images in Fig. 4E and F were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had already been submitted or published elsewhere prior to the submission of this paper to Oncology Reports. Given that the abovementioned data had already apparently been submitted or published prior to the receipt of this paper at Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 45: 706‑716, 2021; DOI: 10.3892/or.2020.7880].}, } @article {pmid39219019, year = {2025}, author = {Harel-Arbeli, T and Shaposhnik, H and Palgi, Y and Ben-David, BM}, title = {Taking the Extra Listening Mile: Processing Spoken Semantic Context Is More Effortful for Older Than Young Adults.}, journal = {Ear and hearing}, volume = {46}, number = {2}, pages = {315-324}, pmid = {39219019}, issn = {1538-4667}, mesh = {Humans ; Aged ; Adult ; *Speech Perception/physiology ; Young Adult ; *Semantics ; Male ; Female ; *Aging/physiology ; Pupil/physiology ; Reaction Time ; Eye-Tracking Technology ; Age Factors ; }, abstract = {OBJECTIVES: Older adults use semantic context to generate predictions in speech processing, compensating for aging-related sensory and cognitive changes. This study aimed to gauge aging-related changes in effort exertion related to context use.

DESIGN: The study revisited data from Harel-Arbeli et al. (2023) that used a "visual-world" eye-tracking paradigm. Data on efficiency of context use (response latency and the probability to gaze at the target before hearing it) and effort exertion (pupil dilation) were extracted from a subset of 14 young adults (21 to 27 years old) and 13 older adults (65 to 79 years old).

RESULTS: Both age groups showed a similar pattern of context benefits for response latency and target word predictions, however only the older adults group showed overall increased pupil dilation when listening to context sentences.

CONCLUSIONS: Older adults' efficient use of spoken semantic context appears to come at a cost of increased effort exertion.}, } @article {pmid39218040, year = {2024}, author = {Mahmoud, D and Yassa, M and Alvarado, L and Lambert, C and Meterissian, S and Anderson, D and Tremblay, F and Otaky, N and Keyserlingk, J and Panet-Raymond, V and Kopek, N and David, M and Duclos, M and Pembroke, C and Fleiszer, D and Meguerditchian, AN and Loutfi, A and Lavigne, D and Hijal, T}, title = {Single pre-operative radiation therapy (SPORT-CK) trial for low-risk breast cancer: Early results of a phase 2 study.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {200}, number = {}, pages = {110510}, doi = {10.1016/j.radonc.2024.110510}, pmid = {39218040}, issn = {1879-0887}, mesh = {Humans ; *Breast Neoplasms/radiotherapy/pathology/surgery ; Female ; Aged ; Middle Aged ; Mastectomy, Segmental ; Carcinoma, Ductal, Breast/radiotherapy/surgery/pathology ; Radiotherapy, Intensity-Modulated/adverse effects/methods ; Sentinel Lymph Node Biopsy ; Preoperative Care ; Aged, 80 and over ; }, abstract = {BACKGROUND AND PURPOSE: Preoperative partial breast irradiation (PBI) is a novel technique that can be used in patients with early-stage breast cancer with the goal of limiting the irradiated breast volume, toxicity and number of fractions. The aim of this trial is to assess the toxicity, surgical, oncologic and cosmetic outcomes of preoperative PBI.

MATERIALS AND METHODS: In this single-arm phase II trial, we enrolled women ≥ 60 years, with unifocal low-risk breast invasive ductal carcinoma (cT1N0, grade 1-2, ER+, Her2-). Patients were treated with a single fraction of 20 Gy of preoperative PBI using volumetric modulated arc therapy (VMAT). Patients then underwent breast-conserving surgery (BCS) +/- sentinel lymph node biopsy within 72 h of radiation. Primary outcomes were rate of surgical complications and early toxicity. Secondary outcomes were cosmesis at 12 months, chronic toxicity and ipsilateral breast tumor recurrence.

RESULTS: Twenty-five patients were recruited with a median age of 67 years, and a median follow-up of 60 months. Sentinel biopsy was positive in 1 out of 24 patients (4 %). Two patients received adjuvant RT for close margins or positive lymph nodes. Within the first 90 days, none of the patients had surgical complications; almost all had grade 0 to 1 acute and late RTOG skin toxicity. The cosmetic outcome was rated between good and excellent in all cases by physicians and patients, except for one patient who self-rated her cosmesis as fair as of the third year. There were no recurrences.

CONCLUSION: Preoperative single-fraction PBI is a safe and feasible treatment for elderly patients with low-risk early-stage breast cancer, with no surgical complications, very low rates of acute and late radiation toxicity, and excellent cosmetic outcomes. Randomized controlled trials are needed to compare preoperative to adjuvant PBI in this patient population.}, } @article {pmid39215495, year = {2024}, author = {Islam, T and Hoque, ME and Ullah, M and Islam, T and Nishu, NA and Islam, R}, title = {CNN-based deep learning approach for classification of invasive ductal and metastasis types of breast carcinoma.}, journal = {Cancer medicine}, volume = {13}, number = {16}, pages = {e70069}, pmid = {39215495}, issn = {2045-7634}, mesh = {Humans ; Female ; *Deep Learning ; *Breast Neoplasms/pathology/classification/diagnostic imaging ; *Neural Networks, Computer ; *Carcinoma, Ductal, Breast/pathology/classification/diagnostic imaging/secondary ; Neoplasm Metastasis ; }, abstract = {OBJECTIVE: Breast cancer is one of the leading cancer causes among women worldwide. It can be classified as invasive ductal carcinoma (IDC) or metastatic cancer. Early detection of breast cancer is challenging due to the lack of early warning signs. Generally, a mammogram is recommended by specialists for screening. Existing approaches are not accurate enough for real-time diagnostic applications and thus require better and smarter cancer diagnostic approaches. This study aims to develop a customized machine-learning framework that will give more accurate predictions for IDC and metastasis cancer classification.

METHODS: This work proposes a convolutional neural network (CNN) model for classifying IDC and metastatic breast cancer. The study utilized a large-scale dataset of microscopic histopathological images to automatically perceive a hierarchical manner of learning and understanding.

RESULTS: It is evident that using machine learning techniques significantly (15%-25%) boost the effectiveness of determining cancer vulnerability, malignancy, and demise. The results demonstrate an excellent performance ensuring an average of 95% accuracy in classifying metastatic cells against benign ones and 89% accuracy was obtained in terms of detecting IDC.

CONCLUSIONS: The results suggest that the proposed model improves classification accuracy. Therefore, it could be applied effectively in classifying IDC and metastatic cancer in comparison to other state-of-the-art models.}, } @article {pmid39207954, year = {2024}, author = {Yates, ME and Waltermire, H and Mori, K and Li, Z and Li, Y and Guzolik, H and Wang, X and Liu, T and Atkinson, JM and Hooda, J and Lee, AV and Oesterreich, S}, title = {ESR1 Fusions Invoke Breast Cancer Subtype-Dependent Enrichment of Ligand-Independent Oncogenic Signatures and Phenotypes.}, journal = {Endocrinology}, volume = {165}, number = {10}, pages = {}, pmid = {39207954}, issn = {1945-7170}, support = {R01 CA181368/CA/NCI NIH HHS/United States ; R01 CA183976/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; S10OD028483/NH/NIH HHS/United States ; S10 OD028483/OD/NIH HHS/United States ; F30CA250167/CA/NCI NIH HHS/United States ; R01 CA256161/CA/NCI NIH HHS/United States ; //The Breasties/ ; P30CA047904-31//UPMC Hillman Cancer Biology Program/ ; //Hillman Foundation/ ; //Breast Cancer Alliance/ ; //Shear Family Foundation/ ; //Pennsylvania Department of Health/ ; R21 CA237964/CA/NCI NIH HHS/United States ; //PA Breast Cancer Coalition/ ; F30 CA250167/CA/NCI NIH HHS/United States ; RRID:SCR_022735//University of Pittsburgh/ ; }, mesh = {Humans ; *Breast Neoplasms/genetics/pathology/metabolism ; Female ; *Estrogen Receptor alpha/genetics/metabolism ; Cell Line, Tumor ; Phenotype ; YAP-Signaling Proteins/genetics/metabolism ; SOX9 Transcription Factor/genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/pathology/metabolism ; Oncogene Proteins, Fusion/genetics/metabolism ; Signal Transduction/genetics ; Carcinoma, Lobular/genetics/metabolism/pathology ; Transcription Factors/genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Adaptor Proteins, Signal Transducing/genetics/metabolism ; Ligands ; Cell Proliferation/genetics ; }, abstract = {Breast cancer is a leading cause of female mortality and despite advancements in personalized therapeutics, metastatic disease largely remains incurable due to drug resistance. The estrogen receptor (ER, ESR1) is expressed in two-thirds of all breast cancer, and under endocrine stress, somatic ESR1 mutations arise in approximately 30% of cases that result in endocrine resistance. We and others reported ESR1 fusions as a mechanism of ER-mediated endocrine resistance. ER fusions, which retain the activation function 1- and DNA-binding domains, harbor ESR1 exons 1 to 6 fused to an in-frame gene partner resulting in loss of the ER ligand-binding domain (LBD). We demonstrate that in a no-special type (invasive ductal carcinoma [IDC]-NST) and an invasive lobular carcinoma (ILC) cell line, ER fusions exhibit robust hyperactivation of canonical ER signaling pathways independent of estradiol or antiendocrine therapies. We employ cell line models stably overexpressing ER fusions with concurrent endogenous ER knockdown to minimize endogenous ER influence. Cell lines exhibited shared transcriptomic enrichment in pathways known to be drivers of metastatic disease, notably MYC signaling. Cells expressing the 3' fusion partners SOX9 and YAP1 consistently demonstrated enhanced growth and cell survival. ILC cells expressing the DAB2 fusion led to enhanced growth, survival, and migration, phenotypes not appreciated in the IDC-NST DAB2 model. Herein, we report that cell line activity is subtype-, fusion-, and assay-specific, suggesting that LBD loss, the fusion partner, and the cellular landscape all influence fusion activities. Therefore, it will be critical to assess fusion frequency in the context of the clinicopathology.}, } @article {pmid39207921, year = {2024}, author = {Oriakhi, S and Nwashilli, NJ and Ohanaka, CE and Osifo, OD}, title = {Diagnostic Accuracy of Mammographic Findings in Patients 35 Years and Older Presenting with Palpable Breast Lump in University of Benin Teaching Hospital, Benin City.}, journal = {West African journal of medicine}, volume = {41}, number = {5}, pages = {548-554}, pmid = {39207921}, issn = {0189-160X}, mesh = {Humans ; Female ; *Mammography/methods ; Middle Aged ; *Breast Neoplasms/diagnostic imaging/pathology/diagnosis ; Adult ; Prospective Studies ; *Hospitals, Teaching ; *Sensitivity and Specificity ; Nigeria ; Breast Diseases/diagnostic imaging/diagnosis/pathology ; Aged ; Breast/pathology/diagnostic imaging ; Predictive Value of Tests ; }, abstract = {BACKGROUND: Mammography has become an invaluable tool for diagnosing breast lesions and detecting early breast cancer in women of 35 years and above.

AIMS: To correlate the mammography Breast Imaging Reporting and Data System (BI-RADS) categories with the histology in breast lesions and to determine the predictive values, sensitivity, specificity and accuracy of mammography.

PATIENTS AND METHOD: This was a one- year prospective study carried out from March 2015 to February 2016. Consecutive female patients of 35 years and above with breast lesions at the University of Benin Teaching Hospital, Benin-City were recruited. Patients with fungating breast lesions and those who declined recruitment were excluded. All patients had mammography and core biopsy of the breast lesion which was examined histologically.

RESULTS: A total of 101 patients were studied. Five patients had bilateral breast lesions making a total of 106 biopsies that were performed. The mean age of patients with benign breast disease was 47.0 ± 4.9 years while those with malignant breast disease was 49.9 ± 8.5 years; P-value was 0.080 which was not statistically significant. Fibrocystic disease 6 (5.6%) was the most common benign disease while invasive ductal carcinoma was the most common malignant breast disease 84(79.2%). BI-RADS 5 correlated mostly with malignant breast disease (97.0%); P value < 0.001 and was statistically significant.

CONCLUSION: This study showed that mammography is useful in the diagnosis of breast lesions in women who are 35 years and older. Patients with BI-RADS category 3, 4 and 5 had an increasing correlation with malignant breast disease.}, } @article {pmid39206518, year = {2024}, author = {Schwieger, L and Switchenko, JM and Cao, Y and Amaniera, I and Phillips-Reed, R and Godette, K and Rizzo, M}, title = {Intraoperative radiation therapy for early-stage breast cancer.}, journal = {Journal of surgical oncology}, volume = {130}, number = {5}, pages = {997-1005}, doi = {10.1002/jso.27814}, pmid = {39206518}, issn = {1096-9098}, mesh = {Humans ; Female ; *Breast Neoplasms/radiotherapy/pathology/surgery/mortality ; Middle Aged ; Retrospective Studies ; *Intraoperative Care ; *Mastectomy, Segmental ; Aged ; Adult ; Carcinoma, Ductal, Breast/radiotherapy/surgery/pathology/mortality ; Radiotherapy, Adjuvant ; Survival Rate ; Neoplasm Recurrence, Local/pathology ; Follow-Up Studies ; Neoplasm Staging ; Carcinoma, Intraductal, Noninfiltrating/radiotherapy/surgery/pathology/mortality ; Prognosis ; }, abstract = {BACKGROUND: Intraoperative radiotherapy (IORT) offers more convenience compared to external beam radiotherapy (EBRT) following breast-conserving surgery for early-stage breast cancer. This study describes the implementation of IORT at a metropolitan academic cancer center.

METHODS: Demographics, tumor characteristics, margin status, adjunct EBRT, and cosmetic results were retrospectively analyzed in patients undergoing BCS with IORT. IORT consists of 20 gray delivered to the partial mastectomy cavity.

RESULTS: From 2015 to 2020, 171 patients (65.5% African American) were included. Histologically, 104 (60.8%) patients had invasive ductal carcinoma (IDC), while 67 (39%) patients had DCIS only. Seventeen (15.9%) patients with IDC and 12 (8.6%) patients with DCIS had positive margins. There were 15 ipsilateral breast recurrences (8.8%) and three patients (20%) developed systemic disease. Twenty-five patients (14.6%) underwent adjuvant EBRT. The local recurrence-free survival at 60 months from date of IORT was 89.4% (95% CI 82.7%-93.6%). For overall survival (OS), 168 (98.2%) patients were alive at a median follow-up of 51.4 months, and three total deaths were recorded.

CONCLUSIONS: IORT is a highly desirable and convenient alternative to EBRT for early-stage breast cancer especially for patients with poor compliance. IORT has an acceptable ipsilateral recurrence while not precluding adjunct EBRT based upon the final pathologic report.}, } @article {pmid39205706, year = {2024}, author = {Puvvada, P and Nirhale, DS and Gaudani, RH and Mane, P}, title = {Bilateral Infiltrating Ductal Carcinoma With Adrenal Metastasis: A Rare Case Report.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e65635}, pmid = {39205706}, issn = {2168-8184}, abstract = {Adrenal gland metastasis is rare, often associated with invasive lobular carcinoma (ILC) rather than infiltrating ductal carcinoma (IDC). This report presents a case of a 43-year-old female with bilateral breast IDC and metastasis to the adrenal gland, with bilateral axillary and supraclavicular node involvement. Initial symptoms included a nipple discharge and a palpable lump. Diagnostic imaging and biopsy confirmed IDC, grade 2, with positive estrogen receptor (ER) and progesterone receptor (PR) status and negative human epidermal growth factor receptor 2 (HER2) status. The patient is undergoing chemotherapy and radiotherapy, with adrenalectomy planned post chemotherapy. The case underscores the need for early diagnosis and rapid treatment to improve outcomes, highlighting the paucity of data on managing solitary adrenal metastasis from IDC. Further research and clinical trials are essential to develop standardized treatment protocols.}, } @article {pmid39202750, year = {2024}, author = {Iorga, C and Iorga, CR and Grigorescu, A and Bengulescu, I and Constantin, T and Strambu, V}, title = {Synchronous Breast and Colorectal Malignant Tumors-A Systematic Review.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {8}, pages = {}, pmid = {39202750}, issn = {2075-1729}, abstract = {UNLABELLED: The incidence of breast and colorectal cancers is well established in studies, but the synchronous occurrence of the two types of tumors is a rarity. In general, they are discovered during screening investigations following the diagnosis of an initial tumor.

OBJECTIVE: Our aim is to describe the main diagnostic and therapeutic challenges for synchronous breast and colorectal tumors.

MATERIALS AND METHODS: We performed a systematic review of the literature for cases or case series, using established keywords (synchronous breast and colon tumor and synonyms) for the period of 1970-2023. Five reviewers independently screened the literature, extracted data, and assessed the quality of the included studies. The results were processed according to the PRISMA 2020 guidelines.

RESULTS: A total of 15 cases were included in the study, including 2 males (age 50 and 57) and 13 females (median age 60, with range from 40 to 79). In a vast majority of the cases, the diagnosis of synchronous tumor was prompted by the first tumor's workup. The first diagnosed tumor was colorectal in nine cases and a breast tumor in six cases. The most common histopathological type of breast tumor was invasive ductal carcinoma, and the colon tumors were exclusively adenocarcinomas. All cases had a surgical indication for both breast and colorectal tumor, except one case, in which the breast tumor had multiple metastasis. In four cases, the surgery was performed concomitantly (colectomy and mastectomy). In three cases, surgery was initially carried out for the breast tumor, followed by colon surgery. Oncological treatment was indicated depending on the tumor stage.

CONCLUSIONS: For the treatment of synchronous tumors, the Tumor Board (T.B) decision is mandatory and must be personalized for each patient. Developing new methods of treatment and investigation may play an important role in the future for understanding synchronous tumor development, incidence, and outcome.}, } @article {pmid39197222, year = {2024}, author = {Choudhury, D and Dolezal, JM and Dyer, E and Kochanny, S and Ramesh, S and Howard, FM and Margalus, JR and Schroeder, A and Schulte, J and Garassino, MC and Kather, JN and Pearson, AT}, title = {Developing a low-cost, open-source, locally manufactured workstation and computational pipeline for automated histopathology evaluation using deep learning.}, journal = {EBioMedicine}, volume = {107}, number = {}, pages = {105276}, pmid = {39197222}, issn = {2352-3964}, mesh = {Humans ; *Deep Learning ; Image Processing, Computer-Assisted/methods ; Computational Biology/methods/economics ; Algorithms ; Neoplasms/pathology/diagnosis ; }, abstract = {BACKGROUND: Deployment and access to state-of-the-art precision medicine technologies remains a fundamental challenge in providing equitable global cancer care in low-resource settings. The expansion of digital pathology in recent years and its potential interface with diagnostic artificial intelligence algorithms provides an opportunity to democratize access to personalized medicine. Current digital pathology workstations, however, cost thousands to hundreds of thousands of dollars. As cancer incidence rises in many low- and middle-income countries, the validation and implementation of low-cost automated diagnostic tools will be crucial to helping healthcare providers manage the growing burden of cancer.

METHODS: Here we describe a low-cost ($230) workstation for digital slide capture and computational analysis composed of open-source components. We analyze the predictive performance of deep learning models when they are used to evaluate pathology images captured using this open-source workstation versus images captured using common, significantly more expensive hardware. Validation studies assessed model performance on three distinct datasets and predictive models: head and neck squamous cell carcinoma (HPV positive versus HPV negative), lung cancer (adenocarcinoma versus squamous cell carcinoma), and breast cancer (invasive ductal carcinoma versus invasive lobular carcinoma).

FINDINGS: When compared to traditional pathology image capture methods, low-cost digital slide capture and analysis with the open-source workstation, including the low-cost microscope device, was associated with model performance of comparable accuracy for breast, lung, and HNSCC classification. At the patient level of analysis, AUROC was 0.84 for HNSCC HPV status prediction, 1.0 for lung cancer subtype prediction, and 0.80 for breast cancer classification.

INTERPRETATION: Our ability to maintain model performance despite decreased image quality and low-power computational hardware demonstrates that it is feasible to massively reduce costs associated with deploying deep learning models for digital pathology applications. Improving access to cutting-edge diagnostic tools may provide an avenue for reducing disparities in cancer care between high- and low-income regions.

FUNDING: Funding for this project including personnel support was provided via grants from NIH/NCIR25-CA240134, NIH/NCIU01-CA243075, NIH/NIDCRR56-DE030958, NIH/NCIR01-CA276652, NIH/NCIK08-CA283261, NIH/NCI-SOAR25CA240134, SU2C (Stand Up to Cancer) Fanconi Anemia Research Fund - Farrah Fawcett Foundation Head and Neck Cancer Research Team Grant, and the European UnionHorizon Program (I3LUNG).}, } @article {pmid39195215, year = {2024}, author = {Zavaglio, F and Cassaniti, I and d'Angelo, P and Zelini, P and Comolli, G and Gregorini, M and Rampino, T and Del Frate, L and Meloni, F and Pellegrini, C and Abelli, M and Ticozzelli, E and Lilleri, D and Baldanti, F}, title = {Immune Control of Human Cytomegalovirus (HCMV) Infection in HCMV-Seropositive Solid Organ Transplant Recipients: The Predictive Role of Different Immunological Assays.}, journal = {Cells}, volume = {13}, number = {16}, pages = {}, pmid = {39195215}, issn = {2073-4409}, support = {FRRB 2015-043//Fondazione Regionale per la ricerca Biomedica/ ; PE 2016-02362470//Ministero della salute Ricerca Finalizzata/ ; 1032-rcr2023-43//Ministero della salute Ricerca Corrente/ ; 20179JHAM//Ministero dell'Università e della Ricerca, PRIN/ ; }, mesh = {Humans ; *Cytomegalovirus Infections/immunology/virology ; *Cytomegalovirus/immunology ; Female ; Male ; Middle Aged ; *Transplant Recipients ; Adult ; Organ Transplantation/adverse effects ; CD8-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/immunology ; Aged ; DNA, Viral ; Dendritic Cells/immunology ; Enzyme-Linked Immunospot Assay ; Immunologic Tests/methods ; Cytokines/metabolism ; }, abstract = {Human cytomegalovirus (HCMV) infection remains a major complication for solid organ transplant recipients (SOTRs). The aim of this study was to evaluate the role of HCMV-specific T cell immunity measured at the time of the HCMV-DNA peak in predicting the spontaneous clearance of infection. The performance of cytokine flow cytometry using infected dendritic cells (CFC-iDC), infected cell lysate (CFC-iCL) and pp65 peptide pool (CFC-pp65 pool) as stimuli, as well as ELISPOT assays using infected cell lysate (ELISPOT-iCL) and the pp65 peptide pool (ELISPOT-pp65 pool), was analysed. Among the 40 SOTRs enrolled, 16 patients (40%) required antiviral treatment for an HCMV infection (Non-Controllers), while the others spontaneously cleared the infection (Controllers). At the HCMV-DNA peak, the number of HCMV-specific CD4[+] T cells detected by the CFC-iDC, CFC-iCL and CFC-pp65 pool assays in Controllers was higher than that detected in Non-Controllers, while no difference was observed in terms of HCMV-specific CD8[+] T cell response. The same trend was observed when the HCMV-specific T cell response was measured by ELISPOT-iCL and ELISPOT-pp65 pool. We observed that the CD4[+] CFC-pp65 pool assay was the best predictor of self-resolving HCMV infection at the time of the HCVM-DNA peak. The CFC-pp65 pool assay is able to discriminate between CD4[+] and CD8[+] T cell responses and could be used in daily clinical practice.}, } @article {pmid39194971, year = {2024}, author = {Conti, M and Morciano, F and Amodeo, S and Gori, E and Romanucci, G and Belli, P and Tommasini, O and Fornasa, F and Rella, R}, title = {Special Types of Breast Cancer: Clinical Behavior and Radiological Appearance.}, journal = {Journal of imaging}, volume = {10}, number = {8}, pages = {}, pmid = {39194971}, issn = {2313-433X}, abstract = {Breast cancer is a complex disease that includes entities with different characteristics, behaviors, and responses to treatment. Breast cancers are categorized into subgroups based on histological type and grade, and these subgroups affect clinical presentation and oncological outcomes. The subgroup of "special types" encompasses all those breast cancers with insufficient features to belong to the subgroup "invasive ductal carcinoma not otherwise specified". These cancers account for around 25% of all cases, some of them having a relatively good prognosis despite high histological grade. The purpose of this paper is to review and illustrate the radiological appearance of each special type, highlighting insights and pitfalls to guide breast radiologists in their routine work.}, } @article {pmid39191695, year = {2024}, author = {Nakamura, K and Nio, Y and Imai, S and Sakamoto, M and Sakamoto, T and Kamei, M and Maruyama, R and Soh, H}, title = {[A Case Report of Adenomyoepithelioma Coexisting with Apocrine Carcinoma in Contralateral Breasts].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {7}, pages = {757-761}, pmid = {39191695}, issn = {0385-0684}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/pathology/surgery ; *Adenomyoepithelioma/pathology/surgery ; Apocrine Glands/pathology/surgery ; Neoplasms, Multiple Primary/pathology/surgery ; Sweat Gland Neoplasms/pathology/surgery ; }, abstract = {Adenomyoepithelioma(AME)of the breast is a rare condition, and comorbidity with carcinoma is even more unusual. Herein, we report a case of both AME and apocrine carcinoma in different breasts of a single patient. A 48-year-old woman presented to our clinic with a right breast tumor. Fine needle aspiration cytology(FNAC)was indeterminate and suspicious for both papilloma and non-invasive ductal carcinoma, but excisional biopsy indicated an AME. Immuno-histochemical staining showed EMA(+), AE1/3(+), and CK7(+)mammary duct cells and αSMA(+), CK5/6(+), and p63(+) myoepithelial cells. Six months later, the patient noticed a left breast tumor, and although FNAC indicated no malignancy, after 6 additional months, the tumor size had increased and a mammography revealed tumor microcalcification, suggesting malignancy. Vacuum-assisted biopsy revealed an apocrine carcinoma. The patient underwent partial mastectomy and sentinel node biopsy, followed by radiotherapy and chemotherapy. The post-surgical pathology was pT1pN0M0, Stage Ⅰ, triple- negative, and the patient was disease-free for 12 years postoperatively. To our knowledge, this is only the second case of AME and breast cancer in different breasts reported in Japan.}, } @article {pmid39188883, year = {2024}, author = {Murillo-Ortiz, BO and García-Corrales, K and Martínez-Garza, S and Romero-Vázquez, MJ and Agustín-Godínez, E and Escareño-Gómez, A and Silva-Guerrero, DG and Mendoza-Ramírez, S and Murguia-Perez, M}, title = {Association of hTERT expression, Her2Neu, estrogen receptors, progesterone receptors, with telomere length before and at the end of treatment in breast cancer patients.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1450147}, pmid = {39188883}, issn = {2296-858X}, abstract = {BACKGROUND: Breast cancer shows significant clinical, morphologic, and molecular variation. Telomeres are nucleoprotein complexes composed of hexanucleotide repeat DNA sequence, TTAGGG, and numerous telomere-associated proteins. The maintenance of telomere length is carried out by a ribonucleoprotein called telomerase, which consists of two main components: a catalytic subunit called hTERT (human telomerase reverse transcriptase) and an RNA template called hTR (human telomerase RNA). The importance of evaluating hTERT expression lies in its potential therapeutic application, being an attractive target due to its almost non-existent expression in normal somatic cells. It is also expected that the anti-neoplastic effect would appear earlier in neoplastic cells with shorter telomeres. Additionally, a significant relationship has been observed between Her2-Neu overexpression and Her2-Neu positivity, which could suggest new combined therapies.The aim of this study was to detect the expression of hTERT, estrogen receptor (ER), progesterone receptor (PR), and HER2-Neu in neoplastic breast tissue embedded in paraffin before treatment and to investigate the relationship between them and with baseline and post-treatment telomere length, as well as with various clinicopathological parameters.

MATERIALS AND METHODS: A cross-sectional-correlational, 21 women diagnosed with breast cancer at the Oncology Service of the High Specialty Medical Unit No. 1 of Bajio of the Mexican Institute of Social Security. The study complies with the Helsinki Declaration and was approved by the Institutional Ethical Committee of the Mexican Institute of Social Security (R-2019-1001-127). A peripheral blood sample was obtained before oncological treatment and at the end of oncological treatment for the measurement of telomere length by extracting DNA from leukocytes, was performed by the quantitative polymerase chain reaction (PCR) method described by Cawthon. Tumor samples were collected from each patient at the oncology department for immunohistochemical determination of biomarker expression (ER, PR, Her2/neu) and hTERT.

RESULTS: Of the 21 cases included in the study, the median age was 57.57 years. Eighteen cases were classified as invasive ductal carcinoma NOS (85.71%), 10 were histologic grade 2 (47.61%), 16 cases were hormone receptor positive (76.19%), 7 were Her2Neu positive (33.33%), and only 2 cases were triple negative (9.52%). Positive hTERT expression was detected in 11 cases (52.38%) and was negative in the remaining cases. A significant association was identified between hTERT-positive cases and Her2-Neu positive cases (p = 0.04). Baseline and post-treatment telomere lengths showed a significant difference using the non-parametric Wilcoxon t-test (p = 0.002). In hTERT-positive cases, there was significant telomere shortening at the end of oncological treatment (6.14 ± 1.54 vs. 4.75 ± 1.96 Kb, p = 0.007).

CONCLUSION: Positive hTERT immunostaining cases were associated with poor prognostic factors, such as Her2-Neu overexpression and post-treatment telomere shortening. In the future, hTERT immunostaining could be used to select patients for therapies with antagonistic effects on hTERT, as well as in the selection of more appropriate chemotherapy regimens for patients who express it.}, } @article {pmid39188507, year = {2024}, author = {Suliman, A and Osman, M and Ali, S and Hussein, S and Osman, RM and Tageldin, E and Ali, LE}, title = {Challenges in diagnosis and management of invasive ductal carcinoma in axillary ectopic breast tissue: a case study.}, journal = {Journal of surgical case reports}, volume = {2024}, number = {8}, pages = {rjae531}, pmid = {39188507}, issn = {2042-8812}, abstract = {Ectopic breast tissue (EBT) is breast tissue located outside the normal anatomic boundaries of the breasts, developing due to incomplete embryological regression of the mammary ridges. EBT can develop anywhere along the milk line, with the axilla being the most common site. While generally benign, EBT can undergo malignant transformation. This case report discusses a 24-year-old female with locally advanced invasive ductal carcinoma in the axillary EBT, highlighting its clinical presentation, diagnostic process, and management in a resource-limited setting. The patient underwent wide local excision and axillary lymph node dissection followed by adjuvant chemotherapy and radiotherapy, achieving a favorable short-term outcome. This case underscores the importance of considering EBT in differential diagnosis of axillary masses and the need for tailored treatment strategies in such settings.}, } @article {pmid39188449, year = {2024}, author = {Scott-Emuakpor, R and Reza-Soltani, S and Altaf, S and Nr, K and Kołodziej, F and Sil-Zavaleta, S and Nalla, M and Ullah, MN and Qureshi, MR and Ahmadi, Y and Rezvani, A and Siddiqui, HF}, title = {Mammary Paget's Disease Mimicking Benign and Malignant Dermatological Conditions: Clinical Challenges and Diagnostic Considerations.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e65378}, pmid = {39188449}, issn = {2168-8184}, abstract = {Mammary Paget's disease (MPD) or Paget's disease of the breast is a rare dermatological malignancy of the nipple-areolar complex that manifests with a spectrum of symptoms spanning from itching and redness to more severe indications such as breast lump, nipple-areolar complex destruction, or nipple discharge. It is predominantly associated with an underlying ductal carcinoma in situ or invasive ductal carcinoma. MPD often masquerades as other benign and malignant dermatological conditions, including eczema, atopic dermatitis, psoriasis, and squamous and basal cell carcinomas, leading to delayed diagnosis and inappropriate treatment. Only one-third of the patients present with a palpable lump; therefore, advanced age with chronic and unilateral lesions should raise concern for MPD. Our review article presents case reports of MPD imitating other skin conditions and underscores the key findings of clinical features and diagnostic workup to help differentiate the condition. A literature review revealed that studies emphasize caution regarding the sole use of mammography and ultrasound in diagnosing MPD, particularly in cases lacking a palpable lump. This highlights the MRI as a superior and more accurate imaging tool. However, any suspicious lesion must be biopsied to allow histopathological and immunohistochemical examination, since there are some cases where MRI findings were negative in the presence of a biopsy-proven MPD. This highlights the need for clinicians to investigate any suspicious lesion of the nipple or breast using the complete triple assessment approach to exclude an underlying malignancy. It is imperative to establish therapeutic guidelines to approach any nipple lesion to minimize the risk of misdiagnosing any underlying cancer, which can be potentially fatal if left alone.}, } @article {pmid39187318, year = {2024}, author = {Kolia, A and Frountzas, M and Liatsou, E and Samelis, G and Zagouri, F and Zografos, GC and Gazouli, M and Michalopoulos, NV}, title = {The Role of Serum Nestin in Diagnosis and Prognosis of Breast Cancer: A Prospective Observational Study.}, journal = {In vivo (Athens, Greece)}, volume = {38}, number = {5}, pages = {2399-2403}, pmid = {39187318}, issn = {1791-7549}, mesh = {Humans ; *Breast Neoplasms/blood/diagnosis/pathology/metabolism ; Female ; *Nestin/metabolism/blood ; Middle Aged ; Prognosis ; *Biomarkers, Tumor/blood ; Aged ; Adult ; Prospective Studies ; Neoplasm Staging ; Erb-b2 Receptor Tyrosine Kinases/metabolism/genetics ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Aged, 80 and over ; }, abstract = {BACKGROUND/AIM: The molecular classification of breast cancer has enabled targeted therapy for specific molecular subtypes. Nestin, which has been studied for its role in oncogenesis, could contribute to this direction. This study aimed to investigate the differences between serum nestin levels and molecular profiling, as well as histopathological tumor types, in women who underwent surgery for breast cancer.

PATIENTS AND METHODS: Women who underwent surgery for breast cancer at the Breast Unit of the 1[st] Propaedeutic Department of Surgery, Hippocration General Hospital, National and Kapodistrian University of Athens were prospectively included. Patients' demographic data were recorded and serum nestin levels were measured. Molecular biomarker analysis was performed, as well as histopathologic assessment.

RESULTS: Seventy patients were included in the analysis. Among patients with breast cancer, 93% were estrogen receptor (ER) positive, 91% were progesterone receptor (PR) positive, and 43% were human epidermal growth factor receptor 2 (HER2) positive. Ki67 was expressed in 16% of patients and p53 was expressed in 32% of patients. Invasive ductal carcinoma was diagnosed in 80% of patients, with 44% of tumors classified as T1 and 46% as T2. Additionally, 43% were G1 and 56% were N0, while 34% were N1. No statistically significant difference was observed between serum nestin levels and ER, PR, HER2, Ki67, and p53 expression. Furthermore, no difference was observed between serum nestin levels and breast cancer histological type, size, N-stage, and grading.

CONCLUSION: The diagnostic and prognostic role of circulating nestin for breast cancer was not confirmed and no correlation with immunohistochemistry results was observed. Thus, the necessity of larger prospective studies is enhanced.}, } @article {pmid39185299, year = {2024}, author = {Alamri, AM and AlWadai, HH and Almowallad, SM and AlKulayb, SM and Abdalwahab, ZE and Alzahuf, SM and Alshaiban, SH}, title = {The Pathological Pattern of Breast Cancer in the Najran Region of Saudi Arabia: A Retrospective Study.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e67621}, pmid = {39185299}, issn = {2168-8184}, abstract = {Background Breast cancer (BC) is the most widespread cancer on a global scale, and its prevalence is likewise significant in the Kingdom of Saudi Arabia. Nevertheless, the data accessible regarding the epidemiology and histopathological characteristics of BC in clinical practice is restricted and primarily confined to research endeavors. Aim This study aims to investigate the histopathological profile of women diagnosed with BC seeking treatment at King Khalid Hospital in the Najran region of the Kingdom of Saudi Arabia. Methods In this retrospective study, BC biopsies performed on Saudi patients at King Khalid Hospital between January 2018 and December 2022 were examined. All records of breast biopsies from this timeframe were extracted from the hospital's histopathology laboratory computer database after written permission from the head of the laboratory department. For all neoplastic lesions, the World Health Organization's 2012 categorization of breast tumors was applied. Results A total of 61 women with BC were included. Women's age ranged from 30 to 89 years, with a mean age of 49.6 ± 12.3 years. The most reported BC was invasive ductal carcinoma (IDC; 70.5%). Other types reported included invasive papillary carcinoma (8.2%), ductal carcinoma in situ (4.9%), and invasive lobular carcinoma (3.3%). A total of 14 (23%) of the study women had multifocal cancer. Ki-67 was high in 19 cases (31.1%); six (9.8%) had BRCA1 mutations, and six (9.8%) had BRCA2 mutations. Conclusion The current study revealed that BC was frequent among young females, mainly IDC, which was reported on both sides at different sizes and grades. Breast lump was the most commonly presented symptom and had a high representation in women with hormonal receptors, mainly estrogen receptors, but positive genetic testing was infrequent.}, } @article {pmid39184925, year = {2024}, author = {Morecroft, R and Logothetics, CN and Tarnawsky, SP and Davis, AA}, title = {Chemotherapy-induced neutropenia management in a patient with metastatic breast cancer and Shwachman-Diamond syndrome (SDS): a case report.}, journal = {Translational breast cancer research : a journal focusing on translational research in breast cancer}, volume = {5}, number = {}, pages = {26}, pmid = {39184925}, issn = {2218-6778}, abstract = {BACKGROUND: Shwachman-Diamond syndrome (SDS) is a rare inherited bone marrow failure syndrome associated with cytopenia and the development of hematologic malignancies. Solid tumor occurrence is rare and, historically, these patients have had poor outcomes due to chemotherapy-induced myelosuppression and increased susceptibility to infections. We report the administration of cytotoxic systemic therapy with granulocyte colony-stimulating factor (G-CSF) in a patient with SDS and metastatic breast cancer. We describe the risk-benefit profile of utilizing G-CSF in managing this patient to improve her therapeutic outcome and review the prior literature.

CASE DESCRIPTION: A 41-year-old Caucasian female with SDS developed stage IV triple-positive [estrogen positive, progesterone positive, and human epidermal growth factor receptor 2 (HER2) positive] invasive ductal carcinoma of the left breast with liver metastases. She had lifelong thrombocytopenia with other hematologic parameters within normal limits, no tumor protein 53 (TP53) mutation, and no history of marrow dysplasia. Based on her underlying SDS, paclitaxel was favored over docetaxel due to the reduced risk of myelosuppression and weekly dosing schedule. Her regimen included weekly paclitaxel with trastuzumab and pertuzumab every 21 days. She experienced chemotherapy-induced neutropenia with an absolute neutrophil count of less than 1,500 leading to the utilization of G-CSF support. She received chemotherapy with twice-weekly G-CSF and did not experience severe infections. After nine cycles of therapy, she had no evidence of metastatic disease on imaging. The patient has an ongoing complete response at 18 months since treatment initiation.

CONCLUSIONS: This case report describes the treatment of a patient with SDS and metastatic breast cancer with cytotoxic chemotherapy and G-CSF. G-CSF facilitated ongoing chemotherapy administration and reduced the risk of infection leading to an optimal therapeutic outcome. There should be careful consideration of early G-CSF use in patients with SDS to optimize continuous chemotherapy dosing.}, } @article {pmid39177919, year = {2024}, author = {Yamazaki, A and Tada, H and Muroyama, Y and Yamazaki, Y and Miyashita, M and Harada-Shoji, N and Hamanaka, Y and Ebata, A and Sato, M and Motonari, T and Yanagaki, M and Kon, T and Sakamoto, A and Suzuki, T and Ishida, T}, title = {Surgical and irradiated case of early breast cancer in a patient with Ehlers-Danlos syndrome.}, journal = {Surgical case reports}, volume = {10}, number = {1}, pages = {195}, pmid = {39177919}, issn = {2198-7793}, abstract = {BACKGROUND: Ehlers-Danlos syndrome (EDS) is a rare inherited connective tissue disease characterized by hyperextensibility of the skin and joints and tissue fragility of the skin and blood vessels, Vascular EDS is the most severe form of EDS, with abnormal arterial fragility. There have been no reports of breast cancer occurring in patients with vascular EDS. Here, we report here a very rare case of breast cancer in a patient with vascular EDS.

CASE PRESENTATION: A 46-year-old woman with vascular EDS underwent partial left mastectomy and sentinel lymph node biopsy for left breast cancer (cStage 0) detected by medical examination. The final pathological diagnosis was invasive ductal carcinoma of the breast (pStage IA) [hormone receptor-positive, HER2 score 2 equivocal (FISH-positive), Ki-67LI 18%, luminal-HER2 type]. BluePrint was submitted as an aid in determining the postoperative treatment strategy, BluePrint Molecular Subtype HER2-type. However, the 10-year breast cancer mortality risk using Predict was low (5%). After consultation with the patient, the decision was made to administer postoperative radiation to the preserved breast along with hormone therapy only. There was no delay in postoperative wound healing, and the patient was free of metastatic recurrence for 9 months after surgery.

CONCLUSION: We performed surgery, postoperative radiotherapy, and hormonal therapy in a breast cancer patient with vascular EDS without major complications.}, } @article {pmid39172028, year = {2025}, author = {Birnbaum, GE and Friedman, D and Zholtack, K and Gilad, N and Bergman, N and Pollak, D and Reis, HT}, title = {When Your Partner is Being Flirted With: The Impact of Unsolicited Attention on Perceived Partner Desirability and Mate Retention Efforts.}, journal = {Journal of sex research}, volume = {62}, number = {8}, pages = {1598-1611}, doi = {10.1080/00224499.2024.2391105}, pmid = {39172028}, issn = {1559-8519}, mesh = {Humans ; Male ; *Sexual Partners/psychology ; Adult ; Female ; Young Adult ; *Interpersonal Relations ; *Social Perception ; *Attention/physiology ; *Marriage/psychology ; *Sexual Behavior/psychology ; *Social Desirability ; }, abstract = {When searching for a partner, people often rely on social cues to determine partners' suitability, finding those who attract attention from others particularly appealing. While people continue to evaluate their partners beyond relationship initiation, existing research has predominantly concentrated on the effects of observing others' choices during the stage of partner selection, neglecting to consider whether viewing others' attention toward current partners yields similar effects or instead elicits defensive devaluation. In three experiments, we exposed Israeli participants to situations where their partners received unsolicited flirtatious advances, utilizing visualization, virtual reality, and recall techniques. Participants then rated their desire for their partner and mate retention efforts. Results indicated that attention to partners led to decreased desire for them, subsequently predicting reduced relationship investment. These findings suggest that witnessing current partners receiving attention holds a different meaning than observing potential partners in a similar situation, making salient the risk of losing the partner.}, } @article {pmid39170836, year = {2024}, author = {Gunasekaran, G and Amalachandran, J}, title = {[68] Ga-FAPI PET/CT versus [18] F-FDG PET/CT: Differentiating Metastatic Disease and Reactive Lymph Nodes in a Case of Carcinoma of Breast/Acquired Immunodeficiency Syndrome.}, journal = {World journal of nuclear medicine}, volume = {23}, number = {3}, pages = {217-219}, pmid = {39170836}, issn = {1450-1147}, abstract = {Gallium-68 ([68] Ga)-fibroblast activation protein inhibitor (FAPI) positron emission tomography (PET) images the cancer-associated fibroblast that forms a vital component of the tumor microenvironment. It is known that [68] Ga-FAPI PET can aid in differentiating reactive lymph nodes from metastatic lymph nodes. [18] F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) is still the most commonly used PET radiopharmaceutical in the evaluation of a wide range of malignancies including breast carcinoma. Reactive lymph nodes may also show FDG uptake which can hinder optimal assessment for metastatic involvement. We report an interesting case of invasive ductal carcinoma of the right breast with associated World Health Organization clinical stage I acquired immunodeficiency syndrome for which [18] F-FDG PET/CT and [68] Ga-FAPI PET/CT were done.}, } @article {pmid39166665, year = {2024}, author = {Kaundiyal, S and Chandra, S and Arora, A}, title = {Study of tumor budding and its association with clinicopathological parameters in breast carcinoma.}, journal = {Revista da Associacao Medica Brasileira (1992)}, volume = {70}, number = {7}, pages = {e20240173}, pmid = {39166665}, issn = {1806-9282}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Middle Aged ; *Carcinoma, Ductal, Breast/pathology ; *Neoplasm Grading ; *Lymphatic Metastasis/pathology ; *Neoplasm Invasiveness ; Adult ; *Neoplasm Staging ; *Ki-67 Antigen/analysis ; Aged ; Immunohistochemistry ; Prognosis ; }, abstract = {OBJECTIVE: Tumor budding is a phenomenon in which the tumor cells detach from the main mass and are present at the invasive front. The present study was conducted to study tumor budding in invasive breast carcinoma and to correlate it with clinicopathological parameters and molecular subtypes.

METHODS: The study was conducted over a period of 1 year, and tumor budding was studied as a single or group of cells at the invasive front of breast carcinoma counted in a high-power field (40×). The grading was statistically correlated with tumor size, grade, lymph node status, lymphovascular invasion, pathological TNM staging, molecular subtype, and survival of patients.

RESULTS: A total of 50 cases of invasive breast carcinoma were included, out of which 66% (n=33) showed high-grade tumor budding, which was statistically significantly higher in grade 2 invasive ductal carcinoma (p<0.05). High tumor budding was associated with lymphovascular invasion, lymph node metastasis, and a high Ki-67 proliferative index. All cases showing low-grade budding were alive until 6 months of diagnosis, but there was no statistically significant association between stage and budding.

CONCLUSION: Tumor buds are significantly higher in grade 2 invasive ductal carcinoma with lymphovascular invasion, lymph node metastasis, and a high Ki-67 proliferative index. Immunohistochemistry may prove helpful in distinguishing tumor buds from their mimickers. Further studies with extended follow-up are recommended to predict tumor budding as a prognostic marker in breast carcinoma, which may play an important role in cancer therapy.}, } @article {pmid39165702, year = {2024}, author = {Gul, SK and Tepetam, H and Yavuz, BB and Gursel, OK and Altinok, A and Yuksel, I and Alomari, O and Atalar, B and Gorken, IB}, title = {General analysis of breast cancer patients tested for BRCA mutations and evaluation of acute radiotherapy toxicity.}, journal = {Northern clinics of Istanbul}, volume = {11}, number = {4}, pages = {302-308}, pmid = {39165702}, issn = {2536-4553}, abstract = {OBJECTIVE: The objective of our study is to evaluate breast cancer patients with BRCA1 or BRCA2 gene mutations and compare them with patients without these mutations. Specifically, we aim to assess the acute side effects of radiotherapy in both groups.

METHODS: Data were collected from four participating centers, comprising information from 73 patients who underwent known mutation analysis and had complete data. Patients were monitored on a weekly basis throughout their treatment for acute toxicity, which was evaluated using the Radiation Therapy Oncology Group (RTOG) acute toxicity criteria.

RESULTS: The median age of the 73 patients included in our study was 43. Among them, 17 had BRCA1-positive mutations and 19 had BRCA2-positive mutations. Invasive ductal carcinoma was present in 67 patients, all of whom underwent surgery. Of the patients, 57 received conventional radiotherapy doses, while 16 received hypofractionated radiotherapy doses. During follow-up, metastasis occurred in three patients. In BRCA-positive patients, those under 40 years of age (p<0.001), with high nodal positivity (p=0.008), grade 2-3 (p=0.022), and lymphovascular invasion (p=0.002) were significantly more frequent compared to BRCA-negative patients (p<0.001). The median survival was 35.8 months. Grade 1 dysphagia developed in seven BRCA-negative patients and four BRCA-positive patients, with no significant difference observed between the two groups (p=0.351). There was also no statistical difference observed in the occurrence of grade 2-3 skin reactions, with 11 BRCA-negative patients and eight BRCA-positive patients experiencing these side effects.

CONCLUSION: Our study supports existing literature by identifying an association between the presence of BRCA mutations and young age, nodal status, grade, and lymphovascular invasion. Additionally, we found no significant difference in the occurrence of radiotherapy toxicity between BRCA-positive and BRCA-negative patients. These findings suggest that radiotherapy can be safely administered to BRCA-positive patients after breast-conserving surgery or mastectomy. Keywords for our study include breast cancer, BRCA mutation, radiotherapy, and side effects.}, } @article {pmid39161776, year = {2024}, author = {Abdullah, AM and Omar, SS and Qadir, AA and Salih, AM and Pshtiwan, LRA and Ahmed, RS and Ali, RM and Baba, HO and Mohammed, RO and Ali, HO and Kakamad, FH}, title = {Epidermal inclusion cyst in an axillary lymph node with breast cancer: A case report.}, journal = {Molecular and clinical oncology}, volume = {21}, number = {4}, pages = {72}, pmid = {39161776}, issn = {2049-9469}, abstract = {Epidermal inclusion cyst (EIC) is a benign lesion rarely discovered within lymph nodes. The present case report introduces an EIC incidentally discovered during an axillary lymph node biopsy in a patient with invasive ductal carcinoma of the breast. A 55-year-old woman presented with a breast mass. Ultrasound revealed a suspicious mass, and a core needle biopsy confirmed the diagnosis of invasive ductal carcinoma. Lumpectomy and sentinel lymph node biopsies were performed. Histopathological examination revealed tumor-free lymph nodes, with one of them harboring a keratinous EIC. EICs typically arise from entrapped epidermal cells. Their presence in lymph nodes is exceptionally rare. While the origin of such inclusions remains unclear, various theories exist, including anomalous embryonic development, implantation, and metaplasia. This report highlights the unique presentation of an EIC within an axillary lymph node. Recognizing this entity is crucial to avoid misdiagnosis of malignancy and unnecessary interventions.}, } @article {pmid39156944, year = {2024}, author = {Yasmeen, T and Umar, S and Razi, MM}, title = {Synchronous Invasive Ductal Carcinoma of Breast and Diffuse Large B-cell Lymphoma: A Case Report.}, journal = {Journal of cancer & allied specialties}, volume = {10}, number = {2}, pages = {655}, pmid = {39156944}, issn = {2411-989X}, abstract = {INTRODUCTION: It is uncommon for breast cancer and non-Hodgkin lymphoma to present simultaneously. An increase in the rate of simultaneous malignancy identification has resulted from adopting more sensitive staging imaging techniques.

CASE DESCRIPTION: Here, we describe a patient who was diagnosed with axillary diffuse large B cell lymphoma (DLBCL) in a cancer hospital during a staging work-up for suspected breast cancer. Breast cancer was staged as Stage IIA and DLBCL as Stage IE. She was given three cycles of rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone (R-CHOP) protocol. Interim positron emission tomography scan showed a complete metabolic response (Deauville score 2). She was given one more cycle of R-CHOP. Then, she had right breast-conserving surgery with axillary lymph node dissection in August 2023. Histopathology report showed residual disease with ductal carcinoma in situ. She was recommended weekly paclitaxel for 12 cycles and trastuzumab and pertuzumab for 1 year. She is currently having her adjuvant systemic therapy, after which she will be planned for local radiation. Endocrine treatment will be started once chemotherapy is completed.

PRACTICAL IMPLICATIONS: Complete baseline work-up per standard protocols/guidelines should be done in each malignancy. Biopsy of metastatic sites should be done wherever possible. All histopathologies should be reviewed thoroughly before treatment initiation, as they may significantly alter patient management.}, } @article {pmid39154567, year = {2024}, author = {Shinzaki, W and Terashita, D and Kanaizumi, H and Wakasa, T and Kimura, Y and Komoike, Y}, title = {Coexistence of benign phyllodes tumor and invasive ductal cancer in the ipsilateral breast: A case report.}, journal = {International journal of surgery case reports}, volume = {122}, number = {}, pages = {110162}, pmid = {39154567}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Phyllodes tumors (PTs) are rare breast neoplasms, with an incidence rate of <1 %. Further, the coexistence of PTs and carcinoma is also uncommon. In this report, we describe a rare case of the synchronous coexistence of a benign PT and invasive ductal carcinoma (IDC) of the ipsilateral breast.

CASE PRESENTATION: A 42-year-old woman presented with a 6-month history of a tumor in her right breast. Mammography and ultrasonography revealed a 9.0 cm breast lump, and core biopsy revealed a benign PT. A simple mastectomy of the right breast revealed IDC foci in the mammary area, close to the benign PT. Right axillary lymph node staging was performed by surgery. However, no lymph node metastasis was observed. Subsequently, appropriate adjuvant therapy was initiated. Currently, the patient is doing well.

CLINICAL DISCUSSION: Breast cancer may be located close to the PT of the ipsilateral breast and is difficult to detect preoperatively, especially in cases of large PTs. Early detection of the presence of a coexisting carcinoma is clinically important because it can alter patient management.

CONCLUSION: Careful assessment of the PT using additional breast imaging tools might help identify their coexistence with breast cancer in cases of difficult diagnosis of coexistent tumors using standard breast imaging tools such as mammography or ultrasound.}, } @article {pmid39154565, year = {2024}, author = {Almass, AA and Boumarah, DN and Al-Ali, Z and Salim, AA and Dohal, AA and Al Duhileb, M}, title = {Trichoblastoma and breast carcinoma as metachronous primary tumors: Case report.}, journal = {International journal of surgery case reports}, volume = {122}, number = {}, pages = {110166}, pmid = {39154565}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: The occurrence of more than one tumor originating from the same or different organs is the definition of multiple primary tumors. According to the time of diagnosis, these tumors are classified into two types: metachronous and synchronous tumors. Trichoblastoma is a rare benign skin tumor that is rarely involved in multiple primary tumors, especially in patients with breast cancer.

CASE PRESENTATION: A 60-year-old male with left breast and lateral chest wall masses. Lastly, he has been diagnosed with invasive ductal carcinoma of the left breast and chest wall trichoblastoma as metachronous primary tumors with no significant genetic background.

CLINICAL DISCUSSION: With the development in the medical field, such tumors are being encountered more. Some authors suggest a relationship between these tumors and genetic mutations. Although rare trichoblastomas can be transformed into malignant tumors and get metastasized.

CONCLUSION: The diagnosis and management of primary tumors can be challenging in some cases. Researchers should focus on further exploration of the genetic bases and risk factors of such tumors.}, } @article {pmid39149534, year = {2024}, author = {Luo, HJ and Ren, JL and Mei Guo, L and Liang Niu, J and Song, XL}, title = {MRI-based machine learning radiomics for prediction of HER2 expression status in breast invasive ductal carcinoma.}, journal = {European journal of radiology open}, volume = {13}, number = {}, pages = {100592}, pmid = {39149534}, issn = {2352-0477}, abstract = {BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is a tumor biomarker with significant prognostic and therapeutic implications for invasive ductal breast carcinoma (IDC).

OBJECTIVE: This study aimed to explore the effectiveness of a multisequence magnetic resonance imaging (MRI)-based machine learning radiomics model in classifying the expression status of HER2, including HER2-positive, HER2-low, and HER2 completely negative (HER2-zero), among patients with IDC.

METHODS: A total of 402 female patients with IDC confirmed through surgical pathology were enrolled and subsequently divided into a training group (n = 250, center I) and a validation group (n = 152, center II). Radiomics features were extracted from the preoperative MRI. A simulated annealing algorithm was used for key feature selection. Two classification tasks were performed: task 1, the classification of HER2-positive vs. HER2-negative (HER2-low and HER2-zero), and task 2, the classification of HER2-low vs. HER2-zero. Logistic regression, random forest (RF), and support vector machine were conducted to establish radiomics models. The performance of the models was evaluated using the area under the curve (AUC) of the operating characteristics (ROC).

RESULTS: In total, 4506 radiomics features were extracted from multisequence MRI. A radiomics model for prediction of expression state of HER2 was successfully developed. Among the three classification algorithms, RF achieved the highest performance in classifying HER2-positive from HER2-negative and HER2-low from HER2-zero, with AUC values of 0.777 and 0.731, respectively.

CONCLUSIONS: Machine learning-based MRI radiomics may aid in the non-invasive prediction of the different expression status of HER2 in IDC.}, } @article {pmid39148033, year = {2024}, author = {Chen, JH and Addanki, S and Roy, D and Bassett, R and Kalashnikova, E and Spickard, E and Kuerer, HM and Meas, S and Sarli, VN and Korkut, A and White, JB and Rauch, GM and Tripathy, D and Arun, BK and Barcenas, CH and Yam, C and Sethi, H and Rodriguez, AA and Liu, MC and Moulder, SL and Lucci, A}, title = {Monitoring response to neoadjuvant chemotherapy in triple negative breast cancer using circulating tumor DNA.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {1016}, pmid = {39148033}, issn = {1471-2407}, support = {T32 CA009599/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Triple Negative Breast Neoplasms/drug therapy/blood/mortality/genetics/pathology ; *Circulating Tumor DNA/blood/genetics ; Female ; *Neoadjuvant Therapy/methods ; Middle Aged ; Adult ; *Neoplastic Cells, Circulating/pathology/metabolism ; Biomarkers, Tumor/blood ; Aged ; Prognosis ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Treatment Outcome ; }, abstract = {BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. We aimed to determine whether circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) could predict response and long-term outcomes to neoadjuvant chemotherapy (NAC).

METHODS: Patients with TNBC were enrolled between 2017-2021 at The University of Texas MD Anderson Cancer Center (Houston, TX). Serial plasma samples were collected at four timepoints: pre-NAC (baseline), 12-weeks after NAC (mid-NAC), after NAC/prior to surgery (post-NAC), and one-year after surgery. ctDNA was quantified using a tumor-informed ctDNA assay (Signatera[TM], Natera, Inc.) and CTC enumeration using CellSearch. Wilcoxon and Fisher's exact tests were used for comparisons between groups and Kaplan-Meier analysis used for survival outcomes.

RESULTS: In total, 37 patients were enrolled. The mean age was 50 and majority of patients had invasive ductal carcinoma (34, 91.9%) with clinical T2, (25, 67.6%) node-negative disease (21, 56.8%). Baseline ctDNA was detected in 90% (27/30) of patients, of whom 70.4% (19/27) achieved ctDNA clearance by mid-NAC. ctDNA clearance at mid-NAC was significantly associated with pathologic complete response (p = 0.02), whereas CTC clearance was not (p = 0.52). There were no differences in overall survival (OS) and recurrence-free survival (RFS) with positive baseline ctDNA and CTC. However, positive ctDNA at mid-NAC was significantly associated with worse OS and RFS (p = 0.0002 and p = 0.0034, respectively).

CONCLUSIONS: Early clearance of ctDNA served as a predictive and prognostic marker in TNBC. Personalized ctDNA monitoring during NAC may help predict response and guide treatment.}, } @article {pmid39145500, year = {2024}, author = {Zakaria, MH and Shaharudin, S and Ahmad Saad, FF}, title = {The Utility of [18]F-Fluorocholine Positron Emission Computed Tomography and [18]F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Evaluating Breast Cancer Phenotypes: A Pilot Study.}, journal = {The Eurasian journal of medicine}, volume = {56}, number = {2}, pages = {78-85}, pmid = {39145500}, issn = {1308-8734}, abstract = {The utility of the [18]F fluorodeoxyglucose positron emission tomography-computed tomography ([18]F FDG PET-CT) marker for breast cancer is well established. Given its limitations in localizing FDG-negative malignant tumors, the expression of [18]F-fluorocholine ([18]-FCH) may potentially be helpful to improve the overall accuracy in evaluating breast cancer. This study determined the potential of [18]- FCH PET CT as a potential marker in assessing breast cancer phenotypes. We recruited consecutive patients with biopsy-proven breast carcinoma who underwent [18] F-FCH PET-CT following the [18]F-FDG PET-CT imaging. The subjects were dichotomized into human epidermal growth factor receptor 2 (HER2)-negative and HER2-positive genotypes. The maximum standardized uptake value (SUVmax; g/dL) was used to predict the two groups of variables. Global health status (GHS) score based on the EORTC quality of life questionnaire (QLQ) was used to evaluate the outcome of the cohort subjects at 6, 12, and 24 months. There were 21 females with a mean age of 54.48 ± 12.17 years. Eighteen patients had invasive ductal carcinoma (18/21;85.8%) on histology, with 11 (52.4%) were HER2-negative genotype. There was higher sensitivity and specificity of [18]-FCH-PET/CT in breast lesions at 40% and 68.8% compared to [18]FDGPET/CT with 33.3% and 66.7%, respectively. There were significant differences between [18]F-FCH SUVmax (g/dL) of the HER-negative as compared to the HER2- positive group (1.99 g/dL vs. 0.2 g/dL; P < .05). High SUVmax (g/dL) of [18]F-FCH had predicted the HER-negative genotype at the cutoff value of 0.75 (P < .05). High [18]F-FCH showed significantly poor scoring of GHS parameters compared to low FCH at 6 months (mean SUVmax 8.06 vs. 5.40 respectively; P < .05). [18]F-FCH PET-CT is a potential marker in localizing and predicting aggressive breast carcinoma phenotypes.}, } @article {pmid39144911, year = {2024}, author = {Jawale, D and Bhoj, P and Pandagle, A and Sharma, A and Kulshrestha, A}, title = {An Unusual Occurrence of Tamoxifen-Induced Maculopathy in a Young Woman With Hormone Receptor-Positive Post-mastectomy Breast Carcinoma.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e64545}, pmid = {39144911}, issn = {2168-8184}, abstract = {Tamoxifen, a selective estrogen receptor modulator (SERM), is a hormone therapy used for the treatment of estrogen receptor (ER)-positive breast cancer. We report the case of a 29-year-old premenopausal lady with a history of infertility treatments who was diagnosed with ER-positive infiltrating ductal carcinoma (IDC) of the breast. Following a modified radical mastectomy (MRM) and adjuvant systemic chemotherapy, tamoxifen was recommended as part of her adjuvant hormonal therapy. After over three years of tamoxifen use, the patient complained of gradual blurring of vision in both eyes. Ophthalmological examinations indicated bilateral maculopathy, a rare but alarming ocular side effect attributed to tamoxifen use. This case report emphasizes the significance of ophthalmic tests in patients on tamoxifen therapy to monitor any potential ocular side effects. While tamoxifen has shown remarkable benefits in the adjuvant treatment of ER-positive breast cancer, including lowering the chance of recurrence and increasing survival rates, clinicians must be acquainted with rare but potential vision-threatening consequences such as tamoxifen-induced maculopathy. Early detection and timely management are critical in reducing the risk of vision loss in patients receiving tamoxifen for breast cancer.}, } @article {pmid39142851, year = {2024}, author = {Kosáč, P and Zábojníková, M and Vážan, P and Petrů, V and Ratajský, M and Lajmar, K and Dudešek, B and Kudlová, P and Duben, J and Podrazká, L and Gatěk, J}, title = {Breast cancer in 80+ year olds.}, journal = {Rozhledy v chirurgii : mesicnik Ceskoslovenske chirurgicke spolecnosti}, volume = {103}, number = {7}, pages = {258-262}, doi = {10.48095/ccrvch2024258}, pmid = {39142851}, issn = {0035-9351}, mesh = {Humans ; Aged, 80 and over ; *Breast Neoplasms/pathology/surgery ; Female ; Retrospective Studies ; Male ; Axilla ; Breast Neoplasms, Male/pathology/surgery ; Lymph Node Excision ; Carcinoma, Ductal, Breast/surgery/pathology/mortality ; Sentinel Lymph Node Biopsy ; Chemotherapy, Adjuvant ; Radiotherapy, Adjuvant ; Mastectomy, Segmental ; }, abstract = {INTRODUCTION: The risk of breast cancer increases with increasing age. The aim of our retrospective study was to determine the extent of breast and axillary surgery, including subsequent adjuvant therapy, in 80-year and older patients.

METHODS: Between 2017 and 2021, 834 breast cancer patients were operated in the Surgical Department of the EUC Clinic. Ninety-eight women (2× with bilateral cancer) and 2 men were included in this retrospective study. A total of 102 breast cancer cases in patients older than 80 years were analyzed. The surgical procedure corresponded to the stage of the disease and the general condition of the patient. Adjuvant systemic therapy was indicated according to the same principles.

RESULTS: At the time of surgery, the patients were more than 80 years old (80-96 years). The predominant type of invasive ductal carcinoma was diagnosed 83×, lobular carcinoma 6×, mucinous 6×, papillary carcinoma 4×, other 3×, with luminal A, B predominating (89×). The breast-conserving procedures were performed 63×. Sentinel node biopsy was performed 65×, supplemented by axillary lymph node dissection 13×. Primary axillary lymph node dissection was performed 15×. No axillary procedure was performed 23×. Radiotherapy was given 49×, chemotherapy 9× and hormonal therapy 82×. Local and regional recurrences were each observed 2×. A total of 37 patients died, 10 of them from breast cancer.

CONCLUSION: The most common cause of death in patients aged 80+ years is a cardiovascular disease, not breast cancer itself. This fact should be taken into account when determining the treatment plan.}, } @article {pmid39138705, year = {2025}, author = {Taha, SR and Boulos, F}, title = {E-cadherin staining in the diagnosis of lobular versus ductal neoplasms of the breast: the emperor has no clothes.}, journal = {Histopathology}, volume = {86}, number = {3}, pages = {327-340}, pmid = {39138705}, issn = {1365-2559}, mesh = {Female ; Humans ; *Biomarkers, Tumor/analysis/metabolism ; *Breast Neoplasms/diagnosis/pathology/metabolism ; *Cadherins/metabolism/analysis ; *Carcinoma, Ductal, Breast/diagnosis/pathology/metabolism ; *Carcinoma, Lobular/diagnosis/metabolism/pathology ; Immunohistochemistry ; Antigens, CD ; }, abstract = {Categorizing breast neoplasia as ductal or lobular is a daily exercise that relies on a combination of histologic and immunohistochemical tools. The historically robust link between loss of the E-cadherin molecule and lobular neoplasia has rendered staining for E-cadherin by immunohistochemistry a staple of this diagnostic process. Unfortunately, discordances between E-cadherin expression and histomorphology, and variations in E-cadherin staining patterns and intensities abound in clinical practice, but are often neglected in favour of a binary interpretation of the E-cadherin result. In this article, we highlight the complexities of E-cadherin expression through a review of the E-cadherin protein and its associated gene (CDH1), the mechanisms leading to aberrant/absent E-cadherin expression, and the implications of these factors on the reliability of the E-cadherin immunohistochemical stain in the classification of ductal versus lobular mammary neoplasia.}, } @article {pmid39138514, year = {2024}, author = {Moragas, N and Fernandez-Nogueira, P and Recalde-Percaz, L and Inman, JL and López-Plana, A and Bergholtz, H and Noguera-Castells, A and Del Burgo, PJ and Chen, X and Sorlie, T and Gascón, P and Bragado, P and Bissell, M and Carbó, N and Fuster, G}, title = {The SEMA3F-NRP1/NRP2 axis is a key factor in the acquisition of invasive traits in in situ breast ductal carcinoma.}, journal = {Breast cancer research : BCR}, volume = {26}, number = {1}, pages = {122}, pmid = {39138514}, issn = {1465-542X}, support = {Juan de la Cierva//Agencia Estatal de Investigación,Spain/ ; Postdoctoral grant//Asociación Española contra el cáncer (AECC)/ ; 201915-30-31//La Marató TV3/ ; FPU//Spanish Ministry of Education/ ; PREDOCS-UB fellowship//Universitat de Barcelona (UB)/ ; PID2019-104991RB-I00//Spanish Ministry of Economy and Competitiveness/ ; BBM-TRA-0041//Becas Leonardo 2018/ ; }, mesh = {Humans ; *Neuropilin-1/metabolism/genetics ; Female ; *Breast Neoplasms/pathology/metabolism/genetics ; *Neuropilin-2/metabolism/genetics ; *Neoplasm Invasiveness ; *Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology/genetics ; Cell Line, Tumor ; *Nerve Tissue Proteins/metabolism/genetics ; Epithelial-Mesenchymal Transition/genetics ; Animals ; Membrane Proteins/metabolism/genetics ; Mice ; Carcinoma, Ductal, Breast/pathology/metabolism/genetics ; Gene Expression Regulation, Neoplastic ; Signal Transduction ; }, abstract = {BACKGROUND: A better understanding of ductal carcinoma in situ (DCIS) is urgently needed to identify these preinvasive lesions as distinct clinical entities. Semaphorin 3F (SEMA3F) is a soluble axonal guidance molecule, and its coreceptors Neuropilin 1 (NRP1) and NRP2 are strongly expressed in invasive epithelial BC cells.

METHODS: We utilized two cell line models to represent the progression from a healthy state to the mild-aggressive or ductal carcinoma in situ (DCIS) stage and, ultimately, to invasive cell lines. Additionally, we employed in vivo models and conducted analyses on patient databases to ensure the translational relevance of our results.

RESULTS: We revealed SEMA3F as a promoter of invasion during the DCIS-to-invasive ductal carcinoma transition in breast cancer (BC) through the action of NRP1 and NRP2. In epithelial cells, SEMA3F activates epithelialmesenchymal transition, whereas it promotes extracellular matrix degradation and basal membrane and myoepithelial cell layer breakdown.

CONCLUSIONS: Together with our patient database data, these proof-of-concept results reveal new SEMA3F-mediated mechanisms occurring in the most common preinvasive BC lesion, DCIS, and represent potent and direct activation of its transition to invasion. Moreover, and of clinical and therapeutic relevance, the effects of SEMA3F can be blocked directly through its coreceptors, thus preventing invasion and keeping DCIS lesions in the preinvasive state.}, } @article {pmid39130797, year = {2024}, author = {Kim, JH}, title = {Concurrent Invasive Carcinoma and Fibroadenoma Arising from Bilateral Ectopic Breast Tissue in the Chest Wall: A Case Report and Literature Review.}, journal = {Journal of the Korean Society of Radiology}, volume = {85}, number = {4}, pages = {813-819}, pmid = {39130797}, issn = {2951-0805}, abstract = {Ectopic breast tissue, which results from incomplete regression of the mammary line during embryogenesis, is observed in 0.2%-6% of the population. Carcinoma development in ectopic breast tissue, especially in the abdominal or chest wall, is rare. Here we present the unusual case of a 38-year-old woman with invasive ductal carcinoma in the ectopic breast tissue on the left side of the chest wall and concurrent fibroadenoma in the ectopic breast tissue on the right side. We also describe the US and MR findings of these masses.}, } @article {pmid39129012, year = {2024}, author = {Elzohery, YHAM and Radwan, AH and Gareer, SWY and Mamdouh, MM and Moaz, I and Khalifa, AM and Mohen, OA and Elithy, MFAA and Hassaan, M}, title = {Micropapillary breast carcinoma in comparison with invasive duct carcinoma. Does it have an aggressive clinical presentation and an unfavorable prognosis?.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {992}, pmid = {39129012}, issn = {1471-2407}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/mortality/surgery ; Middle Aged ; Prognosis ; *Carcinoma, Ductal, Breast/pathology/mortality/surgery/therapy ; Aged ; *Carcinoma, Papillary/pathology/mortality/surgery ; Adult ; Lymphatic Metastasis ; Neoplasm Invasiveness ; }, abstract = {BACKGROUND: Invasive micropapillary carcinoma (IMPC) was first proposed as an entity by Fisher et al. In the 2003 World Health Organization (WHO) guidelines for histologic classification of the breast tumors. IMPC was recognized as a distinct, rare histological subtype of breast cancer. IMPC is emerging as a surgical and oncological challenge due to its tendency to manifest as a palpable mass, larger in size and higher in grade than IDC with more rate of lymphovascular invasion (LVI) and lymph node (LN) involvement, which changes the surgical and adjuvant management plans to more aggressive, with comparative prognosis still being a point of ongoing debate.

AIM OF THE STUDY: In this study, we compared the clinicopathological characteristics, survival and surgical management of breast cancer patients having invasive micropapillary carcinoma pathological subtype in comparison to those having invasive duct carcinoma.

METHOD: This is a comparative study on female patients presented to Baheya center for early detection and treatment of breast cancer, in the period from 2015 to 2022 diagnosed with breast cancer of IMPC subtype in one group compared with another group of invasive duct carcinoma. we analyzed 138 cases of IMPC and 500 cases of IDC.

RESULTS: The incidence of LVI in the IMPC group was 88.3% in comparison to 47.0% in the IDC group (p < 0.001). IMPC had a higher incidence of lymph node involvement than the IDC group (68.8% and 56% respectively). IMPC had a lower rate of breast conserving surgery (26% vs.37.8%) compared with IDC. The survival analysis indicated that IMPC patients had no significant difference in overall survival compared with IDC patients and no differences were noted in locoregional recurrence rate and distant metastasis rate comparing IMPCs with IDCs.

CONCLUSION: The results from our PSM analysis suggested that there was no statistically significant difference in prognosis between IMPC and IDC patients after matching them with similar clinical characteristics. However, IMPC was found to be more aggressive, had larger tumor size, greater lymph node metastasis rate and an advanced tumor stage.}, } @article {pmid39127596, year = {2024}, author = {O'Connor, DJ and Davey, MG and McFeetors, C and McLaughlin, RP and Sweeney, KJ and Barry, MK and Malone, CM and Wahab, SAE and Lowery, AJ and Kerin, MJ}, title = {Evaluating Surgical Outcomes Between Estrogen Receptor Positive Invasive Lobular and Invasive Ductal Carcinoma of the Breast-A Propensity Matched Analysis.}, journal = {Clinical breast cancer}, volume = {24}, number = {8}, pages = {e655-e662}, doi = {10.1016/j.clbc.2024.06.012}, pmid = {39127596}, issn = {1938-0666}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/surgery/mortality/metabolism ; *Carcinoma, Lobular/surgery/pathology/metabolism/mortality ; *Carcinoma, Ductal, Breast/surgery/pathology/mortality/metabolism ; Middle Aged ; *Receptors, Estrogen/metabolism ; Aged ; Propensity Score ; Mastectomy ; Adult ; Retrospective Studies ; Disease-Free Survival ; Prognosis ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Mastectomy, Segmental ; Treatment Outcome ; Follow-Up Studies ; }, abstract = {INTRODUCTION: Invasive lobular carcinoma (ILC) contributes significantly to the global cancer burden and is the most common of the histological "special types" of breast cancer. ILC has unique features setting it apart from the more common invasive ductal carcinoma (IDC). Despite differences, treatment algorithms do not consider histological differences.

AIM: To determine the differences in treatment and outcomes of ILC relative to IDC in a strict case-matched cohort study at a tertiary referral, specialist, breast cancer center.

METHODS: All Estrogen receptor positive (ER+) ILCs from 1999 to 2015 were matched for; age, tumor size, grade, PR/HER2 status, nodal stage and metastases with ER+ IDCs from the same period. Surgical and systemic treatments were assessed along with overall (OS) and disease-free survival (DFS).

RESULTS: 762 cases in total were analyzed (1:1 matching; ILC:IDC). ILC cases were more often treated with mastectomy (37.5% vs. 28.6%, P .009) and those who received breast conserving surgery (BCS) more often had an incomplete resection (30.2% vs. 19.6%, P .01). IDC were more often treated with NACT (5.5% vs. 14.4%, P < .001). Mean DFS were similar between ILC and IDC; 148.3 vs. 141.4 months (P .112) but OS was significantly longer in the ILC group; 165.7 vs. 134 months (P .002). This trend was consistent among the subset of patients undergoing BCS. For ILC undergoing BCS, mean DFS was 129.8 vs. 128.3 months for IDC (P .418) and OS was 155.4 and 110.7 months respectively (P < .001). Incomplete resection at the time of index surgery did not alter the disease free or overall survival in either the ILC or IDC patients to a level that reached statistical significance.

CONCLUSION: In this cohort study, the strict matching of ILC and IDCs for a number of prognostic indicators, demonstrates the impact of lobular histology with a clarity not previously observed. ILCs have comparable survival outcomes to patients with IDC but at the expense of more extensive index and revisional surgery. There is a need for awareness of these facts among surgeons and patients for optimal treatment prioritization and provision.}, } @article {pmid39126401, year = {2024}, author = {Mujahid, M and Khan, AR and Kolivand, M and Alamri, FS and Saba, T and Bahaj, SAO}, title = {Breast histopathological imaging using ultra-fast fluorescence confocal microscopy to identify cancer lesions at early stage.}, journal = {Microscopy research and technique}, volume = {87}, number = {12}, pages = {3047-3063}, doi = {10.1002/jemt.24677}, pmid = {39126401}, issn = {1097-0029}, support = {PNURSP2024R346//Princess Nourah Bint Abdulrahman University/ ; }, mesh = {*Microscopy, Confocal/methods ; *Breast Neoplasms/pathology/diagnostic imaging/diagnosis ; Humans ; Female ; *Neural Networks, Computer ; Microscopy, Fluorescence/methods ; Breast/diagnostic imaging/pathology ; Early Detection of Cancer/methods ; Image Processing, Computer-Assisted/methods ; }, abstract = {Ultrafast fluorescent confocal microscopy is a hypothetical approach for breast cancer detection because of its potential to achieve instantaneous, high-resolution images of cellular-level tissue features. Traditional approaches such as mammography and biopsy are laborious, invasive, and inefficient; confocal microscopy offers many benefits over these approaches. However, confocal microscopy enables the exact differentiation of malignant cells, the expeditious examination of extensive tissue sections, and the optical sectioning of tissue samples into tiny slices. The primary goal should be to prevent cancer altogether, although detecting it early can help achieve that objective. This research presents a novel Breast Histopathology Convolutional Neural Network (BHCNN) for feature extraction and recursive feature elimination method for selecting the most significant features. The proposed approach utilizes full slide images to identify tissue in regions affected by invasive ductal carcinoma. In addition, a transfer learning approach is employed to enhance the performance and accuracy of the models in detecting breast cancer, while also reducing computation time by modifying the final layer of the proposed model. The results showed that the BHCNN model outperformed other models in terms of accuracy, achieving a testing accuracy of 98.42% and a training accuracy of 99.94%. The confusion matrix results show that the IDC positive (+) class achieved 97.44% accuracy and 2.56% inaccurate results, while the IDC negative (-) class achieved 98.73% accuracy and 1.27% inaccurate results. Furthermore, the model achieved less than 0.05 validation loss. RESEARCH HIGHLIGHTS: The objective is to develop an innovative framework using ultra-fast fluorescence confocal microscopy, particularly for the challenging problem of breast cancer diagnosis. This framework will extract essential features from microscopy and employ a gradient recurrent unit for detection. The proposed research offers significant potential in enhancing medical imaging through the provision of a reliable and resilient system for precise diagnosis of breast cancer, thereby propelling the progression of state-of-the-art medical technology. The most suitable feature was determined using BHRFE optimization techniques after retrieving the features by proposed model. Finally, the features chosen are integrated into a proposed methodology, which is then classified using a GRU deep model. The aforementioned research has significant potential to improve medical imaging by providing a complex and reliable system for precise evaluation of breast cancer, hence advancing the development of cutting-edge medical technology.}, } @article {pmid39123374, year = {2024}, author = {Muñoz-Casares, FC and Martín-Broto, J and Cascales-Campos, P and Torres-Melero, J and López-Rojo, I and Gómez-Barbadillo, J and González-Bayón, L and Sebio, A and Serrano, C and Carvalhal, S and Abreu de Souza, J and Souza, A and Flores-Ayala, G and Palacios Fuenmayor, LJ and Lopes-Bras, R and González-López, JA and Vasques, H and Asencio-Pascual, JM}, title = {Ibero-American Consensus for the Management of Peritoneal Sarcomatosis: Updated Review and Clinical Recommendations.}, journal = {Cancers}, volume = {16}, number = {15}, pages = {}, pmid = {39123374}, issn = {2072-6694}, abstract = {Peritoneal sarcomatosis is a rare malignant disease with a poor prognosis, secondary to peritoneal dissemination of abdominopelvic soft tissue sarcomas. Its rarity, together with the characteristic histological heterogeneity and the historically poor response to systemic treatments, has prevented the establishment of widely accepted treatment criteria with curative intent. In this sense, radical cytoreductive surgery (CRS) with peritonectomy procedures and hyperthermic intraperitoneal chemotherapy (HIPEC), widely used in peritoneal carcinomatosis with excellent results, have not had the same evolutionary development in patients with peritoneal sarcomatosis. A multidisciplinary working group of experts in sarcomas and peritoneal oncological surgery established a series of recommendations based on current scientific evidence for the management of peritoneal sarcomatosis, taking into account the different histological subgroups of abdominopelvic sarcomas that can cause it depending on their origin: retroperitoneal sarcomas, uterine sarcomas, and visceral/peritoneal sarcomas of GIST (gastrointestinal stromal tumor) and non-GIST origin. This article shows the results of sarcoma experts' voting on the recommendations presented during the I Ibero-American Consensus on the Management of Peritoneal Sarcomatosis, which took place during the recent celebration of the III Hispanic-Portuguese Meeting for Updates on the Treatment of Sarcomas.}, } @article {pmid39121465, year = {2024}, author = {Pavunkumar, V and Harikrishnan, K and Mohanakrishnan, AK}, title = {Synthesis of Indolo[2,3/3,2-c]quinoline through Complementary PIDA/BF3·OEt2 as Well as Pd(0)-Mediated Intramolecular Cyclization of Isomeric N-((Aryl)-N-(phenylsulfonyl)indolyl)methylbenzenesulfonamides.}, journal = {The Journal of organic chemistry}, volume = {89}, number = {17}, pages = {12204-12227}, doi = {10.1021/acs.joc.4c01113}, pmid = {39121465}, issn = {1520-6904}, abstract = {Herein, a straightforward facile synthesis of indolo[2,3-c]quinoline analogues was reported from 2-arylamino(phenylsulfonyl)methylindoles involving PIDA/BF3·OEt2-mediated intramolecular dehydrogenative coupling (IDC) as a key step. Even though isomeric 3-arylamino(phenylsulfonyl)methylindoles, upon interaction with PIDA/BF3·OEt2, led to complications, synthesis of the indolo[3,2-c]quinoline framework could be easily achieved from N-(2-iodoaryl)-N-indolylmethylbenzenesulfonamide by employing a Pd(0)-mediated intramolecular cyclization reaction. Under identical conditions, synthesis of indolo[2,3-c]quinolines was also accomplished from the respective N-(2-iodoaryl)-N-indolylmethylbenzenesulfonamides. The SRB assay of fluorine-bound indoloquinolines displayed nanomolar-level cytotoxicity against a nonsmall lung cancer cell line, NCI-H460.}, } @article {pmid39118792, year = {2024}, author = {Hemida, AS and Abdelaziz, RA and Abd El-Wahed, MM and Asaad, NY and Serag El-Dien, MM and Elshahat Ali, HA}, title = {Significance of RCC2, Rac1 and p53 Expression in Breast Infiltrating Ductal Carcinoma; An Immunohistochemical Study.}, journal = {Iranian journal of pathology}, volume = {19}, number = {2}, pages = {177-192}, pmid = {39118792}, issn = {1735-5303}, abstract = {BACKGROUND & OBJECTIVE: The regulator of chromosome condensation 2 (RCC2) and RAS-related C3 botulinum toxin substrate 1 (Rac1) have been implicated in the promotion of breast cancer cell proliferation and migration. The signaling pathway involving p53/RCC2/Rac1 has been proposed to contribute to the regulation of colon cancer metastasis. However, until now, this pathway has not been thoroughly investigated in breast cancer. This study seeks to explore the influence of immunohistochemical expression and the correlation among RCC2, Rac1, and p53 in breast infiltrating ductal carcinoma (IDC).

METHODS: Immunostaining was performed on 120 breast IDC specimens using RCC2, Rac1, and p53 antibodies. Statistical analyses were conducted to examine the correlations between these antibodies.

RESULTS: A Positive expression of RCC2, Rac1, and p53 was observed in 116 (96.7%), 120 (100%), and 33 (27.5%) of the breast cancer cases, respectively. RCC2, Rac1, and p53 demonstrated association with poor prognostic parameters such as frequent mitoses, high Ki-67 status, positive lymphovascular invasion (LVI), and advanced tumor stage. A highly significant direct correlation was found between each immunohistochemical marker and the other two markers. Shorter overall survival was linked to multifocal tumors (P=0.017), advanced tumor stage (T3) (P=0.010), Luminal B subtype (P=0.015), progressive disease (P=0.003), positive Her2neu status (P=0.008), and metastasis to distant organs (P<0.001). However, RCC2, Rac1, and p53 did not exhibit a significant association with overall survival.

CONCLUSION: The high expression levels of RCC2, Rac1, and p53 in breast IDC suggest their potential role in tumor behavior. The association of RCC2 and Rac1 with poor prognostic parameters may serve as predictive indicators for aggressive tumors, thus implying that targeted therapy could be beneficial in the treatment of breast cancer.}, } @article {pmid39107186, year = {2024}, author = {Huang, ML and Lane, DL and Chang Sen, LQ and Candelaria, RP and Kuerer, HM and Hunt, KK and Akay, C and Lim, B and Shaitelman, S and Hwang, RF and Chen, H and Katta, R and Santiago, L}, title = {Defining Breast Cryoablation Treatment Success: A Guide for the Curative and Palliative Treatment of Breast Cancer.}, journal = {Academic radiology}, volume = {31}, number = {12}, pages = {4759-4771}, pmid = {39107186}, issn = {1878-4046}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Breast Neoplasms/surgery/diagnostic imaging ; *Cryosurgery/methods ; Female ; Middle Aged ; *Palliative Care/methods ; Retrospective Studies ; Aged ; Treatment Outcome ; Adult ; Aged, 80 and over ; Ultrasonography, Interventional ; }, abstract = {RATIONALE AND OBJECTIVES: Recent ICE3 trial of breast cryoablation for breast cancer demonstrated 98% success rate, similar to breast-conserving surgery. However, ICE3 and other published studies did not differentiate curative from palliative treatment nor define patient-specific treatment objectives. We sought to define treatment success of curative and palliative breast cryoablation for breast cancer in meeting procedure objectives and patient-specific treatment objectives.

MATERIALS AND METHODS: We conducted a retrospective analysis of breast cancer patients who underwent breast cryoablation during 2021-2024. Breast radiologists performed outpatient cryoablation using local anesthesia and argon gas cryoprobes under ultrasound or MRI guidance. Patient demographics, referral indications, tumor characteristics, procedure details, and imaging follow-up findings were analyzed. Cryoablation was categorized as curative or palliative. Treatment success was defined as achievement of both procedure and patient-specific treatment objectives.

RESULTS: Breast cryoablation was performed for 34 lesions in 29 patients with N0M0 (n = 25), N1M0 (n = 2), N2M0 (n = 1), and N0M1 (n = 1) disease. Most tumors were invasive ductal carcinoma (IDC), low to intermediate grade, estrogen receptor (ER) and progesterone receptor (PR) positive and HER2 negative (23 tumors, 68%). Tumor size ranged from 0.4-1.9 (median 0.8) cm for curative cryoablation and 0.6-6.0 (median 1.3) cm for palliative cryoablation. For 27 patients with follow-up imaging, ablation was curative in 14 patients, 14 tumors and palliative in 13 patients, 18 lesions. Imaging follow-up time ranged from 3 to 26 (median 16) months, > 12 months in 22 of 27 patients and 25 of 32 tumors. Complications were limited to 2 cases of skin frost injury, 1 mild and 1 moderate. Treatment success was achieved in 13 of 14 patients with curative and all 13 patients with palliative cryoablation.

CONCLUSION: Our study defines treatment success for curative and palliative breast cryoablation, demonstrates breast cryoablation achieves not only procedure (technical) but also patient-specific treatment objectives without significant complications, and may serve as guide for integrating breast cryoablation in the treatment of breast cancer patients.}, } @article {pmid39106425, year = {2024}, author = {Banks, SA and Brinjikji, W and Giannini, C and Syc-Mazurek, SB and Xeros, HK and Toledano, M and Mustafa, R and Carabenciov, ID and Tobin, WO}, title = {Intra-arterial Melphalan as Targeted Therapy for Tumefactive Multiple Sclerosis Lesions.}, journal = {Neurology}, volume = {103}, number = {5}, pages = {e209739}, doi = {10.1212/WNL.0000000000209739}, pmid = {39106425}, issn = {1526-632X}, mesh = {Humans ; *Melphalan/administration & dosage/therapeutic use ; *Multiple Sclerosis/drug therapy/diagnostic imaging ; Female ; Adult ; Myeloablative Agonists/administration & dosage ; Magnetic Resonance Imaging ; Male ; }, } @article {pmid39103259, year = {2024}, author = {Wang, DH and Yin, WL and Pan, XY and Zhang, MN and Nie, L and Chen, XQ and Zeng, H and Zhou, Q and Chen, N}, title = {[Prostate cancer with BRCA2 pathogenic mutation: a clinicopathological analysis].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {53}, number = {8}, pages = {789-796}, doi = {10.3760/cma.j.cn112151-20240402-00216}, pmid = {39103259}, issn = {0529-5807}, support = {82273047, 82273073, 82203280//National Natural Science Foundation of China/ ; 24SYSX0223, 2022YFS0305//Foundation of Science and Technology Department of Sichuan Province/ ; }, mesh = {Humans ; Male ; *Prostatic Neoplasms/genetics/pathology ; *BRCA2 Protein/genetics ; Aged ; Retrospective Studies ; Middle Aged ; *Mutation ; Prognosis ; Aged, 80 and over ; Bone Neoplasms/genetics/secondary/pathology ; }, abstract = {Objective: To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations, and the association between BRCA2 pathogenic mutation and clinicopathological characteristics. Patient survivals were also examined. Methods: Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University, Chengdu, China from June 2014 to August 2021 were collected. A retrospective analysis of histopathological morphology, clinicopathological characteristics, and patient survivals was conducted. Results: The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene (DRG) in 73 cases (73/249, 29.3%), including 22 cases (8.8%) with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG. Among the 22 patients with BRCA2 pathogenic mutation, 14 patients (5.6%) harbored germline mutations and 8 patients (3.2%) somatic mutations. Their ages ranged from 48 to 91 years, with a median of 67 years. Seventeen patients (77.3%) had distant metastasis, including 16 cases with bone metastasis and 1 case with multiple metastases. Thirteen patients (59.1%) were castration-resistant prostate cancer. The histological type was mainly classical prostatic acinar adenocarcinoma, including 16 cases (72.7%) with intraductal carcinoma of the prostate (IDC-P). Six cases (27.3%) showed focal neuroendocrine differentiation. Perineural/vascular invasion and extraprostatic extension were seen in 11 cases (50.0%) and 8 cases (36.4%), respectively. The Gleason scores of 19 patients (86.4%) were≥8. IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.002). With a total follow-up time of 189 months, the median overall survival (OS) was 132.3 months. Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation (P=0.040). The OS of patients with BRCA2 germline pathogenic mutation did not significantly differ from that of patients with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.216). Conclusions: The presence of BRCA2 gene pathogenic mutation is common in the prostate cancers with high Gleason grade, advanced clinical stage, and castration resistance. IDC-P is more commonly noted in cases with BRCA2 germline pathogenic mutation than those without. Patients with DRG pathogenic mutation have shorter OS than those with no-DRG pathogenic mutation, but there is no significant association between BRCA2 pathogenic mutations and OS.}, } @article {pmid39101021, year = {2024}, author = {Sood, A and Mishra, G and Khandelwal, S and Bhoyar, M and Manuja, N}, title = {Tumour thrombosis of the left axillary vein due to infiltrative ductal carcinoma causing superior vena cava obstruction.}, journal = {Radiology case reports}, volume = {19}, number = {10}, pages = {4195-4200}, pmid = {39101021}, issn = {1930-0433}, abstract = {Invasive ductal carcinoma is the most common type of breast cancer and can affect any age group, predominantly females older than 55 years of age. We present a case of a female in her mid-30s complaining of a fungating mass in the upper outer quadrant of the left anterior chest wall. On workup of the patient, it was histopathologically found that the patient was affected by infiltrating ductal carcinoma of the left breast, which was causing tumoral thrombosis of the left axillary vein. Also, thrombosis of the right axillary vein, bilateral brachiocephalic veins, and superior vena cava with a focal hepatic hotspot sign were appreciated on contrast-enhanced computed tomography scan. No such case of tumoral thrombosis of the axillary vein causing superior vena cava obstruction has been reported in recent literature.}, } @article {pmid39099972, year = {2024}, author = {Asafu Adjaye Frimpong, G and Aboagye, E and Owusu-Afriyie, O and Bonsu, EO and Mahama, F and Asante, E and Asafu Adjaye Frimpong, BG}, title = {Shear Wave Elastography in Breast Cancer: Unveiling Correlations With Histopathological Grades and Subtypes.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e63759}, pmid = {39099972}, issn = {2168-8184}, abstract = {Objective This study explores the correlation between shear wave elastography (SWE) features and histopathological grades and subtypes in breast cancer, aiming to enhance diagnostic accuracy and personalized treatment strategies. Methods The study retrospectively analyzed 59 consecutive women with breast cancer who underwent breast ultrasound with SWE. SWE parameters and histopathologic information, including histological type and grade, were recorded. Qualitative and quantitative SWE findings were analyzed, and B-mode findings were evaluated. Sociodemographic and clinical factors and B-mode findings were assessed as predictors of elastography stiffness using logistic regression analysis. Results Of the 59 participants diagnosed with breast cancer, invasive ductal carcinoma of no special type (IDC-NST) was predominantly found in 50 (84.7%) cases, followed by invasive medullary carcinoma in 5 (8.5%) cases. The majority of participants belonged to the 50-59 age group, comprising 19 (32.2%) patients. Histopathological grading revealed grade II tumors in 27 (45.8%) cases and grade III tumors in 24 (40.7%) cases. Notably, grade III tumors exhibited higher tissue stiffness compared to grade II tumors. Out of 36 stiff lesions, 30 (83.3%%) were IDC-NST while 3 (8.3%) were invasive medullary carcinoma. A significant association was observed between higher histopathological grade (grade III) and increased tissue stiffness (p < 0.05). Furthermore, among participants with stiff lesions, 21 (58.3%) exhibited color defects while 4 (23.5%) cases with soft lesions also displayed color defects Conclusion The correlation between SWE findings and histopathological grades and subtypes underscores the potential of SWE as a valuable tool for predicting tumor aggressiveness and characterizing specific subtypes. SWE enhances diagnostic accuracy and complements traditional imaging modalities, holding promise for personalized treatment strategies.}, } @article {pmid39099625, year = {2024}, author = {Xu, W and Wang, X and Yang, L and Meng, M and Sun, C and Li, W and Li, J and Zheng, L and Tang, T and Jia, W and Chen, X}, title = {Consistency of CSCO AI with Multidisciplinary Clinical Decision-Making Teams in Breast Cancer: A Retrospective Study.}, journal = {Breast cancer (Dove Medical Press)}, volume = {16}, number = {}, pages = {413-422}, pmid = {39099625}, issn = {1179-1314}, abstract = {BACKGROUND: The Chinese Society of Clinical Oncology Artificial Intelligence System (CSCO AI) serves as a clinical decision support system developed utilizing Chinese breast cancer data. Our study delved into the congruence between breast cancer treatment recommendations provided by CSCO AI and their practical application in clinical settings.

METHODS: A retrospective analysis encompassed 537 breast cancer patients treated at the Second Affiliated Hospital of Anhui Medical University between January 2017 and December 2022. Proficient senior oncology researchers manually input patient data into the CSCO AI system. "Consistent" and "Inconsistent" treatment categories were defined by aligning our treatment protocols with the classification system in the CSCO AI recommendations. Cases that initially showed inconsistency underwent a second evaluation by the Multi-Disciplinary Treatment (MDT) team at the hospital. Concordance was achieved when MDTs' treatment suggestions were in the 'Consistent' categories.

RESULTS: An impressive 80.4% concurrence was observed between actual treatment protocols and CSCO AI recommendations across all breast cancer patients. Notably, the alignment was markedly higher for stage I (85.02%) and stage III (88.46%) patients in contrast to stage II patients (76.06%, P=0.023). Moreover, there was a significant concordance between invasive ductal carcinoma and lobular carcinoma (88.46%). Interestingly, triple-negative breast cancer (TNBC) exhibited a high concordance rate (87.50%) compared to other molecular subtypes. When contrasting MDT-recommended treatments with CSCO AI decisions, an overall 92.4% agreement was established. Furthermore, a logistic multivariate analysis highlighted the statistical significance of age, menstrual status, tumor type, molecular subtype, tumor size, and TNM stage in influencing consistency.

CONCLUSION: In the realm of breast cancer treatment, the alignment between recommendations offered by CSCO AI and those from MDT is predominant. CSCO AI can be a useful tool for breast cancer treatment decisions.}, } @article {pmid39098868, year = {2024}, author = {Greenwood, HI and Maldonado Rodas, CK and Freimanis, RI and Glencer, AC and Miller, PN and Mukhtar, RA and Brabham, C and Yau, C and Rosenbluth, JM and Hirst, GL and Campbell, MJ and Borowsky, A and Hylton, N and Esserman, LJ and Basu, A}, title = {Magnetic resonance imaging insights from active surveillance of women with ductal carcinoma in situ.}, journal = {NPJ breast cancer}, volume = {10}, number = {1}, pages = {71}, pmid = {39098868}, issn = {2374-4677}, support = {T32 CA251070/CA/NCI NIH HHS/United States ; U01 CA196406/CA/NCI NIH HHS/United States ; T32CA251070-01//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U01CA196406//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; }, abstract = {New approaches are needed to determine which ductal carcinoma in situ (DCIS) is at high risk for progression to invasive ductal carcinoma (IDC). We retrospectively studied DCIS patients who declined surgery (2002-2019), and received endocrine therapy (ET) and breast MRI. Baseline MRI and changes at 3 months and 6 months were analyzed by recursive partitioning to stratify IDC risk. Sixty-two patients (63 DCIS; 1 bilateral) with a mean follow-up of 8.5 years were included. Fifty-one percent remained on active surveillance (AS) without evidence of IDC, with a mean duration of 7.6 years. A decision tree based on MRI features of lesion distinctness and background parenchymal enhancement (BPE) at baseline and change after 3 months of ET stratified patients into low, intermediate, and high risk for progression to IDC. MRI imaging features in patients treated with ET and undergoing AS, may help determine which DCIS lesions are at low versus high risk for IDC.}, } @article {pmid39097872, year = {2024}, author = {Gilani, N and Ozaslan, M}, title = {Association of XRCC2 with breast cancer, a multi-omics analysis at genomic, transcriptomic, and epigenomic level.}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {70}, number = {7}, pages = {252-259}, doi = {10.14715/cmb/2024.70.7.36}, pmid = {39097872}, issn = {1165-158X}, mesh = {Adult ; Female ; Humans ; Middle Aged ; *Breast Neoplasms/genetics/pathology ; *DNA Methylation/genetics ; *DNA-Binding Proteins/genetics/metabolism ; Epigenomics/methods ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Genomics/methods ; *Multiomics/methods ; Transcriptome/genetics ; }, abstract = {One of the main causes of cancer-related mortality for women worldwide is breast cancer (BC). The XRCC2 gene, essential for DNA repair, has been implicated in cancer susceptibility. This study aims to evaluate the association between XRCC2 and BC risk. The study was conducted at Zheen International Hospital in Erbil, Iraq, between 2021 and 2024 with a total of 88 samples, including 44 paired normal and cancer tissue samples. Mutation analysis was performed using Next-Generation Sequencing, coupled with in silico tools for variant impact prediction. Expression levels were assessed through RT-PCR, and methylation status was determined using methylation-sensitive restriction enzyme digestion PCR. The study identified seven inherited germline variants in the XRCC2 gene, with five of these mutations being Uncertain Significance, one being Likely Pathogenic, and one being Likely benign. RNA purity was found high with mean A260/280 ratios of 1.986 ± 0.097 in normal (N) and 1.963 ± 0.092 in tumor (T) samples. Tumor samples exhibited a higher RNA concentration (78.56 ± 40.87 ng/µL) than normal samples (71.44 ± 40.79 ng/µL). XRCC2 gene expression was significantly upregulated in tumor tissue, with marked increases in patients aged 40-55 and >56 years and in higher cancer grades (II and III) and invasive ductal carcinoma (p-values ranging from <0.0001 to 0.0392). DNA methylation rates in tumor tissues were low (7%), suggesting limited regulation by methylation. The study suggests that XRCC2 can be classified as an oncogene and that its structural investigation by targeted NGS and expression evaluation can be used as a potential biomarker in BC.}, } @article {pmid39097028, year = {2024}, author = {Pyuskyulyan, K and Pipoyan, D and Hovhannisyan, S and Beglaryan, M and Movsisyan, N and Belyaeva, O}, title = {Assessing radon hazard in drinking water: A comprehensive approach integrating deterministic and probabilistic methods with water consumption routines.}, journal = {The Science of the total environment}, volume = {949}, number = {}, pages = {175217}, doi = {10.1016/j.scitotenv.2024.175217}, pmid = {39097028}, issn = {1879-1026}, mesh = {*Radon/analysis ; *Drinking Water/chemistry/analysis ; *Water Pollutants, Radioactive/analysis ; *Radiation Monitoring/methods ; Humans ; Risk Assessment ; }, abstract = {The research aimed to determine the spatiotemporal distribution patterns of radon activity concentrations in tap water of Yerevan city and assess radon-associated hazards using both deterministic and probabilistic approaches. This was accomplished by integrating one-year monitoring data of radon in water with water consumption habits among adult population clusters, which were identified through food frequency questionnaire in Yerevan. The study findings indicated variations in radon activity levels across administrative districts. The highest average activity concentrations were detected in Davtashen (7.07 Bq/L), while the lowest average was observed in Kanaker-Zeytun (1.57 Bq/L). The overall pattern of spatiotemporal variation during monitoring period revealed higher prevalence of radon in water in the northern and western parts of the city compared to the east and south, indicating different sources of drinking water. The radon-associated hazard assessment from water, using a deterministic approach (e.g., inhalation, ingestion, radon dissolution in blood, total effective dose), revealed values below the individual dose criterion (IDC) of 0.1 mSv/y. Monte Carlo simulation revealed a probability of exceeding IDC in specific water consumption-based groups. Residents of Yerevan who drink more than 3 L water daily with the highest observed activity concentration of 11.4 Bq/L, have an 86.26 % chance of exceeding IDC. Residents consuming 2.1 L water daily have a 7.02 % chance of exceeding IDC. The study highlights the importance of applied principles and methodologies for radon monitoring, particularly considering actual water consumption data and different risk assessment approaches. Considering the worst-case scenario results, it is recommended to keep tap water consumption up to 3 L per day, keeping the tap open longer to reduce radon levels. It also emphasizes the need for continued monitoring, given the variations in radon activity. The study provides valuable insights into radon exposure assessment, mitigation, and action plans in terms of water safety and public health.}, } @article {pmid39091563, year = {2024}, author = {Khan, N and de la Torre, M and Moghaddas, H and Fromer, N and Melnikau, S}, title = {A case report of synchronous breast and lung cancer with three different pathologic diagnoses.}, journal = {AME case reports}, volume = {8}, number = {}, pages = {68}, pmid = {39091563}, issn = {2523-1995}, abstract = {BACKGROUND: Multiple primary malignant tumors (MPMTs) pose a significant clinical challenge, denoting the occurrence of two or more distinct malignant tumors with differing histological characteristics, all diagnosed within a 6-month timeframe. MPMT is a rare condition and due to the unique treatment requirements for each specific cancer type, it is crucial for healthcare professionals to accurately differentiate between metastatic growth and distinct primary tumors.

CASE DESCRIPTION: In this case report, we present a 41-year-old female patient who received diagnoses of three separate synchronous primary tumors. The patient presented for evaluation of a right breast mass that had been present for 1 year. Initial diagnostic tests, including mammography and ultrasound, did not provide any conclusive results. Subsequent magnetic resonance imaging (MRI) of the breast prompted an ultrasound-guided biopsy which confirmed moderately differentiated invasive ductal carcinoma (IDC). During pre-surgical testing, a suspicious opacity was detected on a chest X-ray, prompting further investigation with a computed tomography (CT) scan of the chest to distinguish between metastatic disease and a potential new primary tumor. Clinical and pathological examinations revealed the presence of bilateral masses originating from two different origins: invasive mucinous pulmonary adenocarcinoma in the left lower lobe and a neuroendocrine carcinoma in the right middle lobe of the lung.

CONCLUSIONS: Cases of this nature present a complex challenge to physicians and underscore the critical importance of maintaining a high level of clinical suspicion to ensure the delivery of high-quality care. Effective management of such patients requires a multidisciplinary collaboration among breast surgeons, thoracic surgeons, and medical and radiation oncologists.}, } @article {pmid39091410, year = {2024}, author = {Wang, Y and Wang, S and Liu, X and Hu, J and Ma, J}, title = {Volume replacement in tumor plastic surgery and breast-conserving surgery using 3D grid and strip‑shaped acellular dermal matrix: Two case reports.}, journal = {Experimental and therapeutic medicine}, volume = {28}, number = {3}, pages = {366}, pmid = {39091410}, issn = {1792-1015}, abstract = {The present study was driven by the scarcity of suitable materials for mending partial breast defects and the imperative considerations of safety and durability. The current study presents findings from two female patients, aged 59 and 40, who underwent breast cancer treatment. Patient 1 underwent a mastectomy with a sentinel lymph node biopsy, while patient 2 underwent a partial mastectomy with axillary lymph node dissection. Core needle biopsy confirmed invasive ductal carcinoma in both cases. Breast ultrasound revealed hypoechoic lesions with smooth edges. The reconstruction of the breast defect employed an acellular dermal matrix, and the safety and cosmetic outcomes for each patient were analyzed. At 3 months post-radiotherapy, neither patient experienced significant complications. The preservation of breast contour and volume was satisfactory, with no postoperative tumor recurrences detected. In summary, utilizing an acellular dermal matrix with a three-dimensional grid design for partial breast defect reconstruction offers a viable alternative that aligns with oncological safety standards and provides good cosmetic results.}, } @article {pmid39090623, year = {2024}, author = {Phongpreecha, T and Mathi, K and Cholerton, B and Fox, EJ and Sigal, N and Espinosa, C and Reincke, M and Chung, P and Hwang, LJ and Gajera, CR and Berson, E and Perna, A and Xie, F and Shu, CH and Hazra, D and Channappa, D and Dunn, JE and Kipp, LB and Poston, KL and Montine, KS and Maecker, HT and Aghaeepour, N and Montine, TJ}, title = {Single-cell peripheral immunoprofiling of lewy body and Parkinson's disease in a multi-site cohort.}, journal = {Molecular neurodegeneration}, volume = {19}, number = {1}, pages = {59}, pmid = {39090623}, issn = {1750-1326}, support = {T32 GM089626/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Parkinson Disease/immunology/metabolism ; *Lewy Body Disease/immunology ; Male ; Female ; Aged ; Case-Control Studies ; *Leukocytes, Mononuclear/metabolism/immunology ; Biomarkers/metabolism ; Middle Aged ; Cohort Studies ; Aged, 80 and over ; Lewy Bodies/pathology/metabolism ; Single-Cell Analysis/methods ; }, abstract = {BACKGROUND: Multiple lines of evidence support peripheral organs in the initiation or progression of Lewy body disease (LBD), a spectrum of neurodegenerative diagnoses that include Parkinson's Disease (PD) without or with dementia (PDD) and dementia with Lewy bodies (DLB). However, the potential contribution of the peripheral immune response to LBD remains unclear. This study aims to characterize peripheral immune responses unique to participants with LBD at single-cell resolution to highlight potential biomarkers and increase mechanistic understanding of LBD pathogenesis in humans.

METHODS: In a case-control study, peripheral mononuclear cell (PBMC) samples from research participants were randomly sampled from multiple sites across the United States. The diagnosis groups comprise healthy controls (HC, n = 159), LBD (n = 110), Alzheimer's disease dementia (ADD, n = 97), other neurodegenerative disease controls (NDC, n = 19), and immune disease controls (IDC, n = 14). PBMCs were activated with three stimulants (LPS, IL-6, and IFNa) or remained at basal state, stained by 13 surface markers and 7 intracellular signal markers, and analyzed by flow cytometry, which generated 1,184 immune features after gating.

RESULTS: The model classified LBD from HC with an AUROC of 0.87 ± 0.06 and AUPRC of 0.80 ± 0.06. Without retraining, the same model was able to distinguish LBD from ADD, NDC, and IDC. Model predictions were driven by pPLCγ2, p38, and pSTAT5 signals from specific cell populations under specific activation. The immune responses characteristic for LBD were not associated with other common medical conditions related to the risk of LBD or dementia, such as sleep disorders, hypertension, or diabetes.

CONCLUSIONS AND RELEVANCE: Quantification of PBMC immune response from multisite research participants yielded a unique pattern for LBD compared to HC, multiple related neurodegenerative diseases, and autoimmune diseases thereby highlighting potential biomarkers and mechanisms of disease.}, } @article {pmid39090553, year = {2024}, author = {Saito, M and Banno, H and Ito, Y and Ido, M and Goto, M and Ando, T and Mouri, Y and Kousaka, J and Fujii, K and Imai, T and Nakano, S and Suzuki, K}, title = {Evaluation of the intramammary distribution of breast lesions detected by MRI but not conventional second-look B-mode ultrasound using an MRI/ultrasound fusion technique.}, journal = {BMC medical imaging}, volume = {24}, number = {1}, pages = {200}, pmid = {39090553}, issn = {1471-2342}, mesh = {Humans ; Female ; *Magnetic Resonance Imaging/methods ; *Breast Neoplasms/diagnostic imaging/pathology ; Middle Aged ; Adult ; *Ultrasonography, Mammary/methods ; Aged ; Multimodal Imaging/methods ; Breast/diagnostic imaging ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; }, abstract = {The objective of this study was to evaluate the intramammary distribution of MRI-detected mass and focus lesions that were difficult to identify with conventional B-mode ultrasound (US) alone. Consecutive patients with lesions detected with MRI but not second-look conventional B-mode US were enrolled between May 2015 and June 2023. Following an additional supine MRI examination, we performed third-look US using real-time virtual sonography (RVS), an MRI/US image fusion technique. We divided the distribution of MRI-detected mammary gland lesions as follows: center of the mammary gland versus other (superficial fascia, deep fascia, and atrophic mammary gland). We were able to detect 27 (84%) of 32 MRI-detected lesions using third-look US with RVS. Of these 27 lesions, 5 (19%) were in the center of the mammary gland and 22 (81%) were located in other areas. We were able to biopsy all 27 lesions; 8 (30%) were malignant and 19 (70%) were benign. Histopathologically, three malignant lesions were invasive ductal carcinoma (IDC; luminal A), one was IDC (luminal B), and four were ductal carcinoma in situ (low-grade). Malignant lesions were found in all areas. During this study period, 132 MRI-detected lesions were identified and 43 (33%) were located in the center of the mammary gland and 87 (64%) were in other areas. Also, we were able to detect 105 of 137 MRI-detected lesions by second-look conventional-B mode US and 38 (36%) were located in the center of the mammary gland and 67 (64%) were in other areas. In this study, 81% of the lesions identified using third-look US with RVS and 64% lesions detected by second-look conventional-B mode US were located outside the center of the mammary gland. We consider that adequate attention should be paid to the whole mammary gland when we perform third-look US using MRI/US fusion technique.}, } @article {pmid39080302, year = {2024}, author = {Żemojtel-Piotrowska, M and Sawicki, A and Piotrowski, J and Lifshin, U and Kretchner, M and Skowronski, JJ and Sedikides, C and Jonason, PK and Adamovic, M and Ahmed, O and Atitsogbe, KA and Al-Shawaf, L and Appiah, SCY and Ardi, R and Azam, U and Babakr, ZH and Baldursson, EB and Bălțătescu, S and Bochaver, K and Bolatov, A and Bonato, M and Bundhoo, HY and Chaleeraktrakoon, T and Chobthamkit, P and Cowden, RG and Counted, V and de Clunie, G and Dragova-Koleva, S and Esteves, CS and Gouveia, VV and Gundolf, K and Hamouda, S and Haretche, C and Jeong, EHK and Iliško, D and Malik, NI and Aruta, JJB and Jia, F and Jovanović, V and Jukić, T and Jukić, DP and Kamble, SV and Khachatryan, N and Klicperova-Baker, M and Kogler, C and Knezović, E and Koralov, M and Kovacs, M and Eldesoki, WLM and Fernandez, AL and Liik, K and Malik, S and Maltby, J and Malysheva, K and Mamuti, A and Mangafic, J and Moon, C and Milfont, TL and Muehlbacher, S and Najafi, R and Özsoy, E and Park, J and de León, PP and Solcova, IP and Ramos-Diaz, J and Ridic, G and Riđić, O and Samekin, A and Spoto, A and Starc, A and Stefenel, D and Trà, KTT and Tiliouine, H and Tomšik, R and Torres-Marín, J and Umeh, CS and Wills-Herrera, E and Wlodarczyk, A and Vally, Z and Vauclair, CM and Yahiiaiev, I and Zand, S}, title = {Grandiose narcissism, unfounded beliefs, and behavioral reactions during the COVID-19 pandemic.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {17503}, pmid = {39080302}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; *Narcissism ; Male ; Female ; Adult ; Pandemics ; SARS-CoV-2 ; Middle Aged ; Young Adult ; }, abstract = {A theoretical perspective on grandiose narcissism suggests four forms of it (sanctity, admiration, heroism, rivalry) and states that these forms conduce to different ways of thinking and acting. Guided by this perspective, we examined in a multinational and multicultural study (61 countries; N = 15,039) how narcissism forms are linked to cognitions and behaviors prompted by the COVID-19 pandemic. As expected, differences in cognitions and behaviors across narcissism forms emerged. For example, higher narcissistic rivalry predicted lower likelihood of enactment of COVID-19 prevention behaviors, but higher narcissistic sanctity predicted higher likelihood of enactment of COVID-19 prevention behaviors. Further, whereas the heroism, admiration, and rivalry narcissism forms acted in a typically antisocial manner, with high narcissism predicting greater endorsement of unfounded health beliefs, the sanctity form acted in a prosocial manner, with higher narcissism being linked to lower endorsement of unfounded COVID-19 health beliefs. Thus, the findings (a) support the idea of four narcissism forms acting differently, and (b) show that these differences reflect a double-edged sword, sometimes linking to an anti-social orientation, and sometimes linking to a pro-social orientation.}, } @article {pmid39072314, year = {2024}, author = {Habanjar, O and Nehme, R and Goncalves-Mendes, N and Cueff, G and Blavignac, C and Aoun, J and Decombat, C and Auxenfans, C and Diab-Assaf, M and Caldefie-Chézet, F and Delort, L}, title = {The obese inflammatory microenvironment may promote breast DCIS progression.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1384354}, pmid = {39072314}, issn = {1664-3224}, mesh = {Humans ; Female ; *Obesity/metabolism/pathology ; *Breast Neoplasms/pathology/immunology/metabolism ; *Tumor Microenvironment/immunology ; *Carcinoma, Intraductal, Noninfiltrating/pathology/metabolism/immunology ; *Disease Progression ; *Coculture Techniques ; *Macrophages/immunology/metabolism ; Inflammation/pathology/metabolism ; Adipocytes/metabolism/pathology ; Adipose Tissue/pathology/metabolism ; Cell Line, Tumor ; }, abstract = {INTRODUCTION: Ductal carcinoma in situ (DCIS), characterized by a proliferation of neoplastic cells confined within the mammary ducts, is distinctly isolated from the surrounding stroma by an almost uninterrupted layer of myoepithelial cells (MECs) and by the basement membrane. Heightened interactions within the adipose microenvironment, particularly in obese patients, may play a key role in the transition from DCIS to invasive ductal carcinoma (IDC), which is attracting growing interest in scientific research. Adipose tissue undergoes metabolic changes in obesity, impacting adipokine secretion and promoting chronic inflammation. This study aimed to assess the interactions between DCIS, including in situ cancer cells and MECs, and the various components of its inflammatory adipose microenvironment (adipocytes and macrophages).

METHODS: To this end, a 3D co-culture model was developed using bicellular bi-fluorescent DCIS-like tumoroids, adipose cells, and macrophages to investigate the influence of the inflammatory adipose microenvironment on DCIS progression.

RESULTS: The 3D co-culture model demonstrated an inhibition of the expression of genes involved in apoptosis (BAX, BAG1, BCL2, CASP3, CASP8, and CASP9), and an increase in genes related to cell survival (TP53, JUN, and TGFB1), inflammation (TNF-α, PTGS2, IL-6R), invasion and metastasis (TIMP1 and MMP-9) in cancer cells of the tumoroids under inflammatory conditions versus a non-inflammatory microenvironment. On the contrary, it confirmed the compromised functionality of MECs, resulting in the loss of their protective effects against cancer cells. Adipocytes from obese women showed a significant increase in the expression of all studied myofibroblast-associated genes (myoCAFs), such as FAP and α-SMA. In contrast, adipocytes from normal-weight women expressed markers of inflammatory fibroblast phenotypes (iCAF) characterized by a significant increase in the expression of LIF and inflammatory cytokines such as TNF-α, IL-1β, IL-8, and CXCL-10. These changes also influenced macrophage polarization, leading to a pro-inflammatory M1 phenotype. In contrast, myoCAF-associated adipocytes, and the cancer-promoting microenvironment polarized macrophages towards an M2 phenotype, characterized by high CD163 receptor expression and IL-10 and TGF-β secretion.

DISCUSSION: Reciprocal interactions between the tumoroid and its microenvironment, particularly in obesity, led to transcriptomic changes in adipocytes and macrophages, may participate in breast cancer progression while disrupting the integrity of the MEC layer. These results underlined the importance of adipose tissue in cancer progression.}, } @article {pmid39071188, year = {2024}, author = {Bandi, S and Harshini, C and Harsha, TS and Vishwanath, Y and Mushahid, H and Shaikh, H and Nadeem, A and Sydhom, P}, title = {Carcinoma en cuirasse in a middle-aged woman with a unique spoke-wheel presentation: A case report.}, journal = {SAGE open medical case reports}, volume = {12}, number = {}, pages = {2050313X241266496}, pmid = {39071188}, issn = {2050-313X}, abstract = {Carcinoma en cuirasse is a rare form of cutaneous metastasis characterized by the spread of a primary malignant tumor to the skin, most commonly associated with breast cancer in women. It may present as papulonodular lesions, erysipeloid, sclerodermiform infiltration, or en cuirassed, typically appearing months or years after the initial diagnosis of the primary malignancy. Diagnosis of carcinoma en cuirasse can be challenging, but histology can help distinguish it from other skin conditions. Treatment options for carcinoma en cuirasse are not well-defined due to the limited number of reported cases. Here, we report a case of a 30-year-old female, who presented with invasive ductal carcinoma which presented as carcinoma en cuirasse with a spoke-wheel pattern over the course of 6 months.}, } @article {pmid39070610, year = {2024}, author = {Mello, RM and Ceballos, DG and Sandate, CR and Agudelo, D and Jouffe, C and Uhlenhaut, NH and Thomä, NH and Simon, MC and Lamia, KA}, title = {BMAL1-HIF2α heterodimers contribute to ccRCC.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {39070610}, issn = {2693-5015}, support = {R01 CA211187/CA/NCI NIH HHS/United States ; R01 CA271500/CA/NCI NIH HHS/United States ; }, abstract = {Circadian disruption enhances cancer risk, and many tumors exhibit disordered circadian gene expression. We show rhythmic gene expression is unexpectedly robust in clear cell renal cell carcinoma (ccRCC). Furthermore, the clock gene BMAL1 is higher in ccRCC than in healthy kidneys, unlike in other tumor types. BMAL1 is closely related to ARNT, and we show that BMAL1-HIF2α regulates a subset of HIF2α target genes in ccRCC cells. Depletion of BMAL1 reprograms HIF2α chromatin association and target gene expression and reduces ccRCC growth in culture and in xenografts. Analysis of pre-existing data reveals higher BMAL1 in patient-derived xenografts that are sensitive to growth suppression by a HIF2α antagonist (PT2399). We show that BMAL1-HIF2α is more sensitive than ARNT-HIF2α to suppression by PT2399, and increasing BMAL1 sensitizes 786O cells to growth inhibition by PT2399. Together, these findings indicate that an alternate HIF2α heterodimer containing the circadian partner BMAL1 contributes to HIF2α activity, growth, and sensitivity to HIF2α antagonist drugs in ccRCC cells.}, } @article {pmid39069624, year = {2024}, author = {Imamura, T and Komatsu, S and Nishibeppu, K and Kiuchi, J and Ohashi, T and Konishi, H and Shiozaki, A and Yamamoto, Y and Moriumura, R and Ikoma, H and Ochiai, T and Otsuji, E}, title = {Urinary microRNA-210-3p as a novel and non-invasive biomarker for the detection of pancreatic cancer, including intraductal papillary mucinous carcinoma.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {907}, pmid = {39069624}, issn = {1471-2407}, mesh = {Humans ; *MicroRNAs/urine/blood/genetics ; Female ; Male ; *Biomarkers, Tumor/urine/genetics/blood ; *Pancreatic Neoplasms/urine/genetics/diagnosis/blood ; Middle Aged ; Aged ; Adenocarcinoma, Mucinous/urine/genetics/diagnosis ; ROC Curve ; Case-Control Studies ; Gene Expression Regulation, Neoplastic ; Adult ; Carcinoma, Pancreatic Ductal/urine/genetics/diagnosis/blood ; }, abstract = {BACKGROUND: This study aims to explore novel microRNAs in urine for screening and predicting clinical characteristics in pancreatic cancer (PC) patients using a microRNA array-based approach.

METHODS: We used the Toray[®] 3D-Gene microRNA array-based approach to compare urinary levels between PC patients and healthy volunteers.

RESULTS: (1) Four oncogenic microRNAs (miR-744-5p, miR-572, miR-210-3p, and miR-575) that were highly upregulated in the urine of PC patients compared to healthy individuals were identified by comprehensive microRNA array analysis. (2) Test-scale analysis by quantitative RT-PCR for each group of 20 cases showed that miR-210-3p was significantly upregulated in the urine of PC patients compared to healthy individuals (P = 0.009). (3) Validation analysis (58 PC patients and 35 healthy individuals) confirmed that miR-210-3p was significantly upregulated in the urine of PC patients compared to healthy individuals (P < 0.001, area under the receiver operating characteristic curve = 0.79, sensitivity: 0.828, specificity: 0.743). We differentiated PC patients into invasive ductal carcinoma (IDCa) and intraductal papillary mucinous carcinoma (IPMC) groups. In addition to urinary miR-210-3p levels being upregulated in IDCa over healthy individuals (P = 0.009), urinary miR-210-3p levels were also elevated in IPMC over healthy individuals (P = 0.0018). Urinary miR-210-3p can differentiate IPMC from healthy individuals by a cutoff of 8.02 with an AUC value of 0.762, sensitivity of 94%, and specificity of 63%. (4) To test whether urinary miR210-3p levels reflected plasma miR-210-3p levels, we examined the correlation between urinary and plasma levels. Spearman's correlation analysis showed a moderate positive correlation (ρ = 0.64, P = 0.005) between miR-210-3p expression in plasma and urine.

CONCLUSIONS: Urinary miR-210-3p is a promising, non-invasive diagnostic biomarker of PC, including IPMC.

TRIAL REGISTRATION: Not applicable.}, } @article {pmid39062707, year = {2024}, author = {Corrêa, TS and Asprino, PF and de Oliveira, ESC and Leite, ACR and Weis, L and Achatz, MI and de Oliveira, CP and Sandoval, RL and Barroso-Sousa, R}, title = {TP53 p.R337H Germline Variant among Women at Risk of Hereditary Breast Cancer in a Public Health System of Midwest Brazil.}, journal = {Genes}, volume = {15}, number = {7}, pages = {}, pmid = {39062707}, issn = {2073-4425}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/epidemiology ; Brazil/epidemiology ; *Germ-Line Mutation ; Adult ; *Tumor Suppressor Protein p53/genetics ; Middle Aged ; *Genetic Predisposition to Disease ; Genetic Testing/methods ; Public Health ; Li-Fraumeni Syndrome/genetics/epidemiology ; Aged ; }, abstract = {Despite the high prevalence of TP53 pathogenic variants (PV) carriers in the South and Southeast regions of Brazil, germline genetic testing for hereditary breast cancer (HBC) is not available in the Brazilian public health system, and the prevalence of Li-Fraumeni syndrome (LFS) is not well established in other regions of Brazil. We assessed the occurrence of TP53 p.R337H carriers among women treated for breast cancer (BC) between January 2021 and January 2022 at public hospitals of Brasilia, DF, Brazil. A total of 180 patients who met at least one of the NCCN criteria for HBC underwent germline testing; 44.4% performed out-of-pocket germline multigene panel testing, and 55.6% were tested for the p.R337H variant by allelic discrimination PCR. The median age at BC diagnosis was 43.5 years, 93% had invasive ductal carcinoma, 50% had estrogen receptor-positive/HER2 negative tumors, and 41% and 11% were diagnosed respectively at stage III and IV. Two patients (1.11%) harbored the p.R337H variant, and cascade family testing identified 20 additional carriers. The TP53 p.R337H detection rate was lower than that reported in other studies from south/southeast Brazil. Nonetheless, identifying TP53 PV carriers through genetic testing in the Brazilian public health system could guide cancer treatment and prevention.}, } @article {pmid39060359, year = {2024}, author = {Budin, AJ and Sumithran, P and MacCormick, AD and Caterson, ID and Brown, WA}, title = {Patient and healthcare practitioner evaluation of patient-reported outcomes in bariatric surgery - a modified Delphi study.}, journal = {International journal of obesity (2005)}, volume = {48}, number = {10}, pages = {1489-1497}, pmid = {39060359}, issn = {1476-5497}, mesh = {Humans ; *Bariatric Surgery ; *Patient Reported Outcome Measures ; *Delphi Technique ; Female ; Male ; Adult ; Middle Aged ; Obesity, Morbid/surgery/psychology ; Quality of Life ; Health Personnel/psychology/statistics & numerical data ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Patient-reported outcomes are an important emerging metric increasingly utilised in clinical, research and registry settings. These outcomes, while vital, are underutilised and require refinement for the specific patient population of those undergoing bariatric surgery. This study aimed to investigate and compare how pre-surgical patients, post-surgical patients, and healthcare practitioners evaluate patient-reported outcomes of bariatric surgery to identify outcomes that are considered most important.

METHODS: A modified Delphi survey was distributed to patients pre- and post-surgery, and to a variety of healthcare practitioners involved in bariatric care. Across two rounds, participants were asked to rate a variety of physical and psychosocial outcomes of bariatric surgery from 0 (Not Important) to 10 (Extremely Important). Outcomes rated 8-10 by at least 70% of participants were considered highly important (prioritised). The highest-rated outcomes were compared between the three groups as well as between medical and allied health practitioner subgroups.

RESULTS: 20 pre-surgical patients, 95 post-surgical patients, and 28 healthcare practitioners completed both rounds of the questionnaire. There were 58 outcomes prioritised, with 21 outcomes (out of 90, 23.3%) prioritised by all three groups, 13 (14.4%) by two groups, and 24 (26.7%) prioritised by a single group or subgroup. Unanimously prioritised outcomes included 'Co-morbidities', 'General Physical Health', 'Overall Quality of Life' and 'Overall Mental Health'. Discordant outcomes included 'Fear of Weight Regain', 'Suicidal Thoughts', 'Addictive Behaviours', and 'Experience of Stigma or Discrimination'.

CONCLUSION: While there was considerable agreement between stakeholder groups on many outcomes, there remain several outcomes with discordant importance valuations that must be considered. In particular, healthcare practitioners prioritised 20 outcomes that were not prioritised by patients, emphasising the range of priorities across stakeholder groups. Future work will consider these priorities to ensure resulting measures encompass all important outcomes and are beneficial and valid for end users.}, } @article {pmid39060073, year = {2024}, author = {Tanaka, M and Aoki, M and Masuda, Y and Yoshinaga, Y and Hamasaki, M and Iwasaki, A and Sato, T}, title = {Stromal CD73 Expression in Breast Cancer: Subtype-specific Expression and its Prognostic Significance.}, journal = {Anticancer research}, volume = {44}, number = {8}, pages = {3637-3643}, doi = {10.21873/anticanres.17187}, pmid = {39060073}, issn = {1791-7530}, mesh = {Humans ; *5'-Nucleotidase/metabolism ; Female ; Middle Aged ; Prognosis ; *GPI-Linked Proteins/metabolism ; Aged ; Adult ; Triple Negative Breast Neoplasms/pathology/metabolism/mortality ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/pathology/metabolism/mortality ; Carcinoma, Ductal, Breast/pathology/metabolism/mortality ; Disease-Free Survival ; Stromal Cells/metabolism/pathology ; Aged, 80 and over ; }, abstract = {BACKGROUND/AIM: Invasive ductal carcinoma (IDC) is classified into distinct subtypes with varying prognoses and treatment sensitivities. For instance, triple-negative breast cancer (TNBC) is associated with poorer outcomes than other subtypes. We have previously reported the role of interstitial CD73 in tumor invasion and its correlation with prognosis in other cancers. This study aimed to investigate the expression of stromal CD73 (sCD73) in IDC and its potential prognostic significance.

PATIENTS AND METHODS: We analyzed 61 cases of human epidermal growth factor receptor 2-negative IDC, including TNBC and hormone receptor-positive (luminal-type) cases, treated surgically at our institution from 2005 to 2010. Cases that received preoperative drug therapy were excluded. CD73 expression was evaluated by immunostaining of the tumor stroma.

RESULTS: sCD73 expression was observed in 70% of all cases, with a significantly higher rate in TNBC (93%) compared with luminal breast cancer (48%). High sCD73 expression was associated with poor prognosis in terms of overall survival (OS) and disease-free survival (DFS) across all cases. In patients with luminal breast cancer, high sCD73 expression was also indicative of poor prognosis with respect to both OS and DFS.

CONCLUSION: High expression of sCD73 is associated with poor prognosis in IDC, particularly in luminal breast cancer. Further research is needed to establish sCD73 as an independent prognostic factor.}, } @article {pmid39052945, year = {2024}, author = {Adesunkanmi, AO and Wuraola, FO and Fagbayimu, OM and Calcuttawala, MA and Wahab, T and Adisa, AO}, title = {Oncoplastic Breast-Conserving Surgery in African Women: A Systematic Review.}, journal = {JCO global oncology}, volume = {10}, number = {}, pages = {e2300460}, doi = {10.1200/GO.23.00460}, pmid = {39052945}, issn = {2687-8941}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery/pathology ; *Mastectomy, Segmental/methods ; Mammaplasty/methods ; Middle Aged ; Treatment Outcome ; Africa ; }, abstract = {PURPOSE: Breast cancer is the most frequently diagnosed cancer in women worldwide. Surgery is a major treatment modality for breast cancer, and over the years, breast-conserving surgeries with breast radiation have shown similar outcomes with mastectomy. Not much is known about the frequency and outcome of breast-conserving surgery in Africa. This systematic review provides a comprehensive summary of the evidence evaluating cosmetic and oncologic outcomes after oncoplastic breast-conserving surgery (OBCS) for breast cancer in African women.

METHODS: This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Databases were systematically searched for studies on African women undergoing OBCS. The oncologic and cosmetic outcomes, as well as the localization and reconstruction techniques, were evaluated. Descriptive statistics were used to summarize the frequency and proportions of the extracted variables.

RESULTS: The literature search yielded 266 articles but only 26 of these were included in the review. Majority of the studies were from Egypt and South Africa. These studies collectively evaluated 1,896 patients with a mean age of 48.2 years and a mean follow-up period of 36.9 months. The most common histopathology was T2 (71.4%) invasive ductal carcinoma. Hook wire localization was the most common technique used for nonpalpable lesions in 85.3% of patients. Of the studies reporting oncoplastic technique, the latissimus dorsi volume replacement technique was the most reported (15%). Most patients were satisfied with their cosmetic outcome. Seroma was the most common postoperative complication (44.6%). Among studies that reported oncologic outcome data, the crude overall survival and disease-free survival were 93.1% and 89.4%, respectively.

CONCLUSION: This systematic review revealed that the outcome of OBCS in African women compares with that in developed countries.}, } @article {pmid39051633, year = {2024}, author = {Liu, T and Jin, D and Le, SB and Chen, D and Sebastian, M and Riva, A and Liu, R and Tran, DD}, title = {Machine Learning-Directed Conversion of Glioblastoma Cells to Dendritic Cell-Like Antigen-Presenting Cells as Cancer Immunotherapy.}, journal = {Cancer immunology research}, volume = {12}, number = {10}, pages = {1340-1360}, pmid = {39051633}, issn = {2326-6074}, support = {P30CA014089//USC Norris Comprehensive Cancer Center (USC Norris)/ ; R42 CA228875/CA/NCI NIH HHS/United States ; P30 CA014089/CA/NCI NIH HHS/United States ; F30 CA232641/CA/NCI NIH HHS/United States ; R42CA228875//National Cancer Institute (NCI)/ ; 6BC04//Florida Department of Health (DOH)/ ; F30CA232641//National Cancer Institute (NCI)/ ; K08 CA160824/CA/NCI NIH HHS/United States ; }, mesh = {*Glioblastoma/immunology/therapy/pathology ; Animals ; *Dendritic Cells/immunology ; Humans ; Mice ; *Machine Learning ; *Immunotherapy/methods ; Tumor Microenvironment/immunology ; Brain Neoplasms/immunology/therapy/pathology ; Antigen-Presenting Cells/immunology ; Cell Line, Tumor ; Mice, Inbred C57BL ; }, abstract = {Immunotherapy has limited efficacy in glioblastoma (GBM) due to the blood-brain barrier and the immunosuppressed or "cold" tumor microenvironment (TME) of GBM, which is dominated by immune-inhibitory cells and depleted of CTL and dendritic cells (DC). Here, we report the development and application of a machine learning precision method to identify cell fate determinants (CFD) that specifically reprogram GBM cells into induced antigen-presenting cells with DC-like functions (iDC-APC). In murine GBM models, iDC-APCs acquired DC-like morphology, regulatory gene expression profile, and functions comparable to natural DCs. Among these acquired functions were phagocytosis, direct presentation of endogenous antigens, and cross-presentation of exogenous antigens. The latter endowed the iDC-APCs with the ability to prime naïve CD8+ CTLs, a hallmark DC function critical for antitumor immunity. Intratumor iDC-APCs reduced tumor growth and improved survival only in immunocompetent animals, which coincided with extensive infiltration of CD4+ T cells and activated CD8+ CTLs in the TME. The reactivated TME synergized with an intratumor soluble PD1 decoy immunotherapy and a DC-based GBM vaccine, resulting in robust killing of highly resistant GBM cells by tumor-specific CD8+ CTLs and significantly extended survival. Lastly, we defined a unique CFD combination specifically for the human GBM to iDC-APC conversion of both glioma stem-like cells and non-stem-like cell GBM cells, confirming the clinical utility of a computationally directed, tumor-specific conversion immunotherapy for GBM and potentially other solid tumors.}, } @article {pmid39045562, year = {2024}, author = {Li, W and Song, Y and Qian, X and Zhou, L and Zhu, H and Shen, L and Dai, Y and Dong, F and Li, Y}, title = {Radiomics analysis combining gray-scale ultrasound and mammography for differentiating breast adenosis from invasive ductal carcinoma.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1390342}, pmid = {39045562}, issn = {2234-943X}, abstract = {OBJECTIVES: To explore the utility of gray-scale ultrasound (GSUS) and mammography (MG) for radiomic analysis in distinguishing between breast adenosis and invasive ductal carcinoma (IDC).

METHODS: Data from 147 female patients with pathologically confirmed breast lesions (breast adenosis: 61 patients; IDC: 86 patients) between January 2018 and December 2022 were retrospectively collected. A training cohort of 113 patients (breast adenosis: 50 patients; IDC: 63 patients) diagnosed from January 2018 to December 2021 and a time-independent test cohort of 34 patients (breast adenosis: 11 patients; IDC: 23 patients) diagnosed from January 2022 to December 2022 were included. Radiomic features of lesions were extracted from MG and GSUS images. The least absolute shrinkage and selection operator (LASSO) regression was applied to select the most discriminant features, followed by logistic regression (LR) to construct clinical and radiomic models, as well as a combined model merging radiomic and clinical features. Model performance was assessed using receiver operating characteristic (ROC) analysis.

RESULTS: In the training cohort, the area under the curve (AUC) for radiomic models based on MG features, GSUS features, and their combination were 0.974, 0.936, and 0.991, respectively. In the test cohort, the AUCs were 0.885, 0.876, and 0.949, respectively. The combined model, incorporating clinical and all radiomic features, and the MG plus GSUS radiomics model were found to exhibit significantly higher AUCs than the clinical model in both the training cohort and test cohort (p<0.05). No significant differences were observed between the combined model and the MG plus GSUS radiomics model in the training cohort and test cohort (p>0.05).

CONCLUSION: The effectiveness of radiomic features derived from GSUS and MG in distinguishing between breast adenosis and IDC is demonstrated. Superior discriminatory efficacy is shown by the combined model, integrating both modalities.}, } @article {pmid39044875, year = {2024}, author = {Kocaman, N and Onat, E and Balta, H and Üçer, Ö}, title = {Are Meteorin-Like Peptide and Asprosin Important in the Diagnosis of Breast Tumors?.}, journal = {Cureus}, volume = {16}, number = {6}, pages = {e62979}, pmid = {39044875}, issn = {2168-8184}, abstract = {INTRODUCTION: Breast cancer (BC) is one of the most common and leading causes of death in women. Therefore, early and accurate diagnosis is vital. In this study, meteorin-like (METRNL) peptide and asprosin levels were examined in breast tissue in invasive ductal carcinoma (IDC) of the breast, and the roles of these molecules in the diagnosis of BC were investigated.

METHODS: In this retrospective study, tissues from patients with BC in the Pathology Department Laboratory of Fırat University Faculty of Medicine, Elazığ, Turkey, were used. Samples from 30 patients were used. The control group consisted of healthy breast tissues from the same patients. The pathology group consisted of breast tissues with IDC from the same patients. Breast tissue samples from both groups were evaluated immunohistochemically for METRNL and asprosin.

RESULTS: Statistically significant differences were observed between both groups in terms of METRNL and asprosin. It was observed that METRNL and asprosin immunoreactivities were higher in breast tissues with IDC than in healthy breast tissues (p<0.001).

CONCLUSION: When the study results were evaluated, it was seen that there was a significant relationship between healthy breast tissues and the ones with IDC in terms of METRNL and asprosin. It is thought that both METRNL and asprosin may be really important in the future for the early diagnosis and treatment of BC.}, } @article {pmid39041038, year = {2024}, author = {Yanik, S and Venkatesh, V and Gordy, JT and Gabriel-Alameh, M and Meza, J and Li, Y and Glass, E and Flores-Garcia, Y and Tam, Y and Chaiyawong, N and Sarkar, D and Weissman, D and Markham, R and Srinivasan, P}, title = {Immature dendritic cell-targeting mRNA vaccine expressing PfCSP enhances protective immune responses against Plasmodium liver infection.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {39041038}, issn = {2693-5015}, support = {R01 AI155598/AI/NIAID NIH HHS/United States ; T32 AI138953/AI/NIAID NIH HHS/United States ; }, abstract = {Resurgence in malaria has been noted in 2022 with 249 million clinical cases resulting in 608,000 deaths, mostly in children under five. Two vaccines, RTS, S, and more recently R21, targeting the circumsporozoite protein (CSP) are recommended by the WHO but are not yet widely available. Strong humoral responses to neutralize sporozoites before they can infect the hepatocytes are important for vaccine-mediated protection. Suboptimal protection conferred by these first-generation vaccines highlight the need for approaches to improve vaccine-induced immune responses. With the recent success of mRNA-LNP vaccines against COVID-19, there is growing interest in leveraging this approach to enhance malaria vaccines. Here, we present the development of a novel chemokine fusion mRNA vaccine aimed at boosting immune responses to PfCSP by targeting the immunogen to immature dendritic cells (iDC). Vaccination of mice with mRNA encoding full-length CSP fused to macrophage inflammatory protein 3 alpha (MIP3α) encapsulated within lipid nanoparticles (LNP) elicited robust CD4+ T cell responses and enhanced antibody titers against NANP repeat epitopes compared to a conventional CSP mRNA-LNP vaccine. Importantly, the CSP-MIP3α fusion vaccine provided significantly greater protection against liver infection upon challenge with P. berghei PfCSP transgenic sporozoites. This enhanced protection was associated with multifunctional CD4+ T cells levels and anti-NANP repeat titers. This study highlights the potential to augment immune responses to PfCSP through iDC targeting and bolster protection against malaria liver infection.}, } @article {pmid39039278, year = {2024}, author = {Das, M and Semple, JI and Haemmerli, A and Volodkina, V and Scotton, J and Gitchev, T and Annan, A and Campos, J and Statzer, C and Dakhovnik, A and Ewald, CY and Mozziconacci, J and Meister, P}, title = {Condensin I folds the Caenorhabditis elegans genome.}, journal = {Nature genetics}, volume = {56}, number = {8}, pages = {1737-1749}, pmid = {39039278}, issn = {1546-1718}, support = {31003A_176226/PP00P3_159320//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; }, mesh = {Animals ; *Caenorhabditis elegans/genetics ; *Adenosine Triphosphatases/genetics/metabolism ; *Multiprotein Complexes/genetics/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; *Caenorhabditis elegans Proteins/genetics/metabolism ; *X Chromosome/genetics ; Chromosomal Proteins, Non-Histone/metabolism/genetics ; Cohesins ; Cell Cycle Proteins/metabolism/genetics ; Interphase/genetics ; Genome, Helminth ; Genes, X-Linked ; Chromosomes/genetics ; }, abstract = {The structural maintenance of chromosome (SMC) complexes-cohesin and condensins-are crucial for chromosome separation and compaction during cell division. During the interphase, mammalian cohesins additionally fold the genome into loops and domains. Here we show that, in Caenorhabditis elegans, a species with holocentric chromosomes, condensin I is the primary, long-range loop extruder. The loss of condensin I and its X-specific variant, condensin I[DC], leads to genome-wide decompaction, chromosome mixing and disappearance of X-specific topologically associating domains, while reinforcing fine-scale epigenomic compartments. In addition, condensin I/I[DC] inactivation led to the upregulation of X-linked genes and unveiled nuclear bodies grouping together binding sites for the X-targeting loading complex of condensin I[DC]. C. elegans condensin I/I[DC] thus uniquely organizes holocentric interphase chromosomes, akin to cohesin in mammals, as well as regulates X-chromosome gene expression.}, } @article {pmid39038425, year = {2024}, author = {Bar, Y and Bar, K and Feldman, D and Dror, JB and Shahoha, M and Lerner, S and Shachar, SS and Weiss-Meilik, A and Dershowitz, N and Wolf, I and Sonnenblick, A}, title = {The impact of extensive intraductal component (EIC) on the genomic risk of recurrence in early hormone receptor positive breast cancer.}, journal = {Breast (Edinburgh, Scotland)}, volume = {77}, number = {}, pages = {103777}, pmid = {39038425}, issn = {1532-3080}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/surgery ; Middle Aged ; *Neoplasm Recurrence, Local/genetics ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology/surgery ; Aged ; Adult ; Erb-b2 Receptor Tyrosine Kinases/genetics/metabolism ; Receptors, Estrogen/metabolism/analysis ; Receptors, Progesterone/metabolism ; Risk Assessment ; Retrospective Studies ; Genomics ; Risk Factors ; }, abstract = {BACKGROUND: Early invasive ductal carcinoma (IDC) breast cancer often presents with a coexisting ductal carcinoma in situ (DCIS) component, while about 5 % of cases present with an extensive (>25 %) intraductal component (EIC). The impact of EIC on the genomic risk of recurrence is unclear.

METHODS: Patients with early hormone receptor-positive HER2neu-negative (HR + HER2-) IDC breast cancer and a known OncotypeDX Breast Recurrence Score® (RS) who underwent breast surgery at our institute were included. Using a rule-based text-analysis algorithm, we analyzed pathological reports and categorized patients into three groups: EIC, non-extensive DCIS (DCIS-L), and pure-IDC (NO-DCIS). Genomic risk was determined using OncotypeDX RS.

RESULTS: A total of 33 (4.6 %) EIC cases, 377 (57.2 %) DCIS-L cases and 307 (42.8 %) NO-DCIS cases were identified. Patients in the EIC group were younger and had lower tumor grades than other groups. The distribution of genomic risk varied between the groups, with EIC tumors significantly less likely to have a high RS (>25) compared to DCIS-L and No-DCIS tumors (3 % vs 20 % and 20 %, respectively; p = 0.03). When adjusted to age, tumor size, grade and LNs involvement, both DCIS-L and NO-DCIS groups were significantly correlated with a higher probability of high RS compared to the EIC group (OR 12.3 and OR 13.1, respectively; p < 0.02). Moreover, patients with EIC had a lower likelihood for adjuvant chemotherapy recommendation.

CONCLUSIONS: In early HR + HER2- IDC, an EIC correlates with a reduced genomic recurrence risk. The impact on genomic risk seems to be influenced by the extent, not merely the presence, of DCIS.}, } @article {pmid39036532, year = {2024}, author = {Levine, MN and Kemppainen, J and Rosenberg, M and Pettengell, C and Bogach, J and Whelan, T and Saha, A and Ranisau, J and Petch, J}, title = {Breast cancer learning health system: Patient information from a data and analytics platform characterizes care provided.}, journal = {Learning health systems}, volume = {8}, number = {3}, pages = {e10409}, pmid = {39036532}, issn = {2379-6146}, abstract = {PURPOSE: In a learning health system (LHS), data gathered from clinical practice informs care and scientific investigation. To demonstrate how a novel data and analytics platform can enable an LHS at a regional cancer center by characterizing the care provided to breast cancer patients.

METHODS: Socioeconomic information, tumor characteristics, treatments and outcomes were extracted from the platform and combined to characterize the patient population and their clinical course. Oncologists were asked to identify examples where clinical practice guidelines (CPGs) or policy changes had varying impacts on practice. These constructs were evaluated by extracting the corresponding data.

RESULTS: Breast cancer patients (5768) seen at the Juravinski Cancer Centre between January 2014 and June 2022 were included. The average age was 62.5 years. The commonest histology was invasive ductal carcinoma (74.6%); 77% were estrogen receptor-positive and 15.5% were HER2 Neu positive. Breast-conserving surgery (BCS) occurred in 56%. For the 4294 patients who received systemic therapy, the initial indications were adjuvant (3096), neoadjuvant (828) and palliative (370). Metastases occurred in 531 patients and 495 patients died. Lowest-income patients had a higher mortality rate. For the adoption of CPGs, the uptake for adjuvant bisphosphonate was very low, 8% as predicted, compared to 64% for pertuzumab, a HER2 targeted agent and 40.2% for CD4/6 inhibitors in metastases. During COVID-19, the provincial cancer agency issued a policy to shorten the duration of radiation after BCS. There was a significant reduction in the average number of fractions to the breast by five fractions.

CONCLUSION: Our platform characterized care and the clinical course of breast cancer patients. Practice changes in response to regulatory developments and policy changes were measured. Establishing a data platform is important for an LHS. The next step is for the data to feedback and change practice, that is, close the loop.}, } @article {pmid39034491, year = {2024}, author = {Chakrabarti, D and Ghosh, A and Qayoom, S and Manjunath, S and Khalid, B and Rajan, S and Akhtar, N and Ramakant, P and Verma, M and Srivastava, K and Kumar, V and Gupta, R and Mishra, AK and Bhatt, MLB}, title = {Long-term clinical outcomes of male breast cancer patients treated with curative intent by trimodality therapy at an academic university hospital in India.}, journal = {Journal of medical imaging and radiation oncology}, volume = {68}, number = {5}, pages = {604-609}, doi = {10.1111/1754-9485.13733}, pmid = {39034491}, issn = {1754-9485}, mesh = {Humans ; *Breast Neoplasms, Male/therapy/pathology ; Middle Aged ; Male ; Adult ; India ; Retrospective Studies ; Combined Modality Therapy ; Hospitals, University ; Treatment Outcome ; Neoplasm Staging ; Survival Rate ; Neoadjuvant Therapy ; Mastectomy ; }, abstract = {INTRODUCTION: Male breast cancer is rare and accounts for less than 1% of all breast cancer cases worldwide.

METHODS: This retrospective cohort study included all patients of invasive male breast cancer treated with curative intent by a trimodality approach via a multidisciplinary team at an academic university hospital in India between 2009 and 2023. Records were identified from a prospectively maintained database. Clinicopathological parameters, treatment details and survival were recorded and analysed.

RESULTS: Thirty-four patients were included. The median (IQR) age was 55(44-63) years. Most patients were overall stage III (74%) and node positive (79%) with Scarff-Bloom-Richardson grade II (50%). Twenty-five patients (73%) were oestrogen receptor (ER) positive. Lymphovascular space invasion (LVSI) and perineural invasion (PNI) were present in 62% and 21% of patients, respectively. The most common chemotherapy timing was adjuvant (53%) followed by neoadjuvant (41%), and the most commonly used regimen consisted of a combination of doxorubicin-cyclophosphamide followed by a taxane (53%). Most (85%) patients underwent a mastectomy, five patients underwent breast conservation. All patients received radiotherapy to a dose of 42.6 Gy in 16 fractions, followed by a tumour bed boost for those undergoing breast conservation. At a median follow-up of 70 months (range 10-159 months), the five and ten-year overall survival was 91% and 58%, and the five-year disease-free survival (DFS) was 67%. The median DFS was 72 months. On univariate analysis, the tumour sub-type (Luminal versus TNBC) significantly predicted DFS (P = 0.03 log-rank).

CONCLUSION: Breast cancer in males has a high incidence of node positivity, ER positivity and LVSI. Even with advanced stages at presentation, trimodality therapy in a multidisciplinary setting offers good long-term outcomes.}, } @article {pmid39032239, year = {2024}, author = {Davies, LSC and McDaid, L and Anandadas, C and Amaro, PF and Chuter, R and Woolf, D and Eccles, CL}, title = {Does the presence of Magtrace preclude adaptive breast radiotherapy on an MR-Linac?.}, journal = {Journal of medical imaging and radiation sciences}, volume = {55}, number = {4}, pages = {101716}, doi = {10.1016/j.jmir.2024.101716}, pmid = {39032239}, issn = {1876-7982}, mesh = {Female ; Humans ; Artifacts ; *Breast Neoplasms/radiotherapy/diagnostic imaging ; Carcinoma, Ductal, Breast/radiotherapy/diagnostic imaging ; *Magnetic Resonance Imaging/methods ; Particle Accelerators ; *Radiotherapy, Image-Guided/methods ; }, abstract = {INTRODUCTION: This work reports on an unusual finding observed during image quality assessment in the preparation for the clinical implementation of breast magnetic resonance image-guided radiotherapy (MRIgRT) on a 1.5 Tesla (T) magnetic resonance linear accelerator (MR-Linac) (Elekta AB, Stockholm, Sweden).

CASE AND OUTCOMES: A patient with T2 N0 M0 right breast invasive ductal carcinoma, receiving adjuvant radiotherapy, underwent two imaging sessions on the MR-Linac. The imaging protocol included T1- and T2-weighted (W) turbo spin echo (TSE) sequences, a T1W mDixon, and a T2W TSE navigated sequence acquired on end-expiration. All images were reconstructed in the axial plane. Images were assessed for image quality and appropriateness for use within the treatment pathway using visual grading analysis (VGA). An artefact in the right breast was noted independently by all observers. The patient's skin and medical notes were reviewed for possible explanation. The findings were discussed with the patient's responsible clinician, and subsequent referral to the local multi-disciplinary team (MDT) for radiologist review was made. On further investigation, the patient's images demonstrated a signal void in the subareolar region of the right breast coinciding with the surgical site. This was distal from the tumour bed and deemed unlikely to be related to a Magseed marker or intraoperative clips. The patient reported no history of nipple tattoo or piercing. There was nothing on clothing that this could be attributed to.

DISCUSSION: Following MDT review, where all potential sources of signal void were considered, it was concluded that the cause was Magtrace, a superparamagnetic iron oxide tracer, recommended for sentinel lymph node localisation in patients with breast cancer in the United Kingdom. The artefact was characteristic of a magnetic susceptibility artefact. These can arise from local magnetic field inhomogeneities caused by the presence of the metal compounds in MagTrace. For breast MRIgRT on the MR-Linac, treatment verification and the possibility of real-time replanning is a critical aspect. The magnetic susceptibility artefact significantly inhibited plan adaption and confidence in the online image registration process making the patient ineligible for treatment on the MR-Linac.

CONCLUSION: As part of ongoing work-up for breast MRIgRT, the screening of patients for Magtrace is now included. Optimisation of MR imaging sequences for radiotherapy planning and image review to minimise distortion are being developed.}, } @article {pmid39031014, year = {2024}, author = {Chen, C and Tseng, J and Amersi, F and Silberman, AW}, title = {Second primary malignancies in women with breast cancer.}, journal = {Journal of surgical oncology}, volume = {130}, number = {3}, pages = {355-359}, doi = {10.1002/jso.27785}, pmid = {39031014}, issn = {1096-9098}, support = {//Gottlieb, Buss, and Snyder Endowments in Surgical Oncology/ ; }, mesh = {Humans ; Female ; *Neoplasms, Second Primary/epidemiology/pathology ; Middle Aged ; *Breast Neoplasms/pathology/therapy/genetics ; Adult ; Aged ; Aged, 80 and over ; Retrospective Studies ; Young Adult ; Carcinoma, Ductal, Breast/pathology/therapy/epidemiology/genetics ; Prospective Studies ; Follow-Up Studies ; Risk Factors ; }, abstract = {BACKGROUND: Increased screening and treatment advancements have resulted in improved survival rates in women with breast cancer (BC). However, recent data suggests these women have elevated risk of developing a second primary malignancy (SPM) compared to the general population. Limited data exists on factors associated with BC patients developing a SPM.

METHOD: A retrospective review of a prospective single institution database (1990-2016) identified 782 patients with a history of BC. One hundred and ninety-four BC patients developed a SPM. Clinicopathologic and treatment characteristics were analyzed.

RESULTS: Of the 194 patients (24.8%) who developed a SPM, 56 (28.9%) BC patients were <50 years old (range: 24-87 years). Two-thirds (64.9%) had at least one first or second degree relative with a malignancy (no relatives-35.1%; ≥1 relative-62.9%). Most patients had invasive ductal carcinoma (n = 117, 60.3%) or ductal carcinoma in situ (n = 39, 20.1%). Twenty-two patients (11.3%) had pathogenic genetic mutations. Mean time to developing a SPM was 8.9 years (range: 4 months-50 years). Eighty (47.6%) patients received chemotherapy with 91 (54.5%) completing radiation. The most common SPMs were breast (22%), melanoma (17.8%), gynecologic (14.1%), colorectal (12.6%), hematologic (8.9%), and sarcoma (6.5%). Most breast tumors were estrogen receptor (ER) (n = 99, 78.0%) or progesterone receptor (PR) positive (n = 87, 73.1%) but not HER2-neu positive (n = 13, 14.0%).

CONCLUSION: Most BC patients who developed a SPM had ER/PR positive tumors and a family history of malignancy, with most <50 years old. Although chemotherapy and radiation increase cancer risk, there were an equal number of patients with SPMs who did or did not receive either treatment. Most SPMs were breast, soft tissue, gynecologic, hematologic, or colorectal. BC patients should be followed closely given an elevated propensity for developing SPMs.}, } @article {pmid39028546, year = {2024}, author = {Shenkman, G and Shrira, A and Kornadt, AE and Neupert, SD and Tse, DCK and Can, R and Palgi, Y}, title = {Cultural Differences in Daily Coupling of Subjective Views of Aging and Negative Affect.}, journal = {The journals of gerontology. Series B, Psychological sciences and social sciences}, volume = {79}, number = {9}, pages = {}, doi = {10.1093/geronb/gbae124}, pmid = {39028546}, issn = {1758-5368}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Affect ; Ageism/psychology/ethnology ; *Aging/psychology/ethnology ; *Arabs/psychology ; Attitude/ethnology ; Cross-Cultural Comparison ; Israel/ethnology ; *Jews/psychology ; }, abstract = {OBJECTIVES: The established link between subjective views of aging (VoA) and well-being shows variations across different cultures. Although VoA show daily fluctuations, little is known about cultural differences in such fluctuations and the daily coupling of VoA and well-being. We compared Israeli Arabs to Israeli Jews in the daily coupling of VoA and negative affect (NA).

METHODS: Community-dwelling older adults (N = 76, Mage = 66.71) completed measures of subjective age, subjective accelerated aging, ageist attitudes, and NA over 14 consecutive days.

RESULTS: Respondents reported higher daily NA when they felt older, reported to be aging faster, or had more ageist attitudes. The daily coupling between subjective age/subjective accelerated aging and NA was stronger among Israeli Arabs compared to Israeli Jews. There was no such interaction with ageist attitudes.

DISCUSSION: It is important to adopt a cultural perspective when investigating daily fluctuations in VoA and their correlates. In applied contexts, this might help to identify cultural groups that are particularly sensitive to the effects of VoA.}, } @article {pmid40018221, year = {2024}, author = {Baggaley, RF and Gon, G and Mohammed Ali, S and Abdi Mahmoud, S and Jowhar, F and Vegvari, C}, title = {Do current maternal health staffing and bed occupancy benchmarks work in practice? Results from a simulation model.}, journal = {BMJ public health}, volume = {2}, number = {1}, pages = {e000212}, pmid = {40018221}, issn = {2753-4294}, abstract = {INTRODUCTION: The WHO has issued the global target of reducing maternal mortality rates by two-thirds of 2010 baseline levels by 2030. In low-income settings, high birth rates and a relative lack of medical resources mean that an efficient use of resources and skilled staff is important in ensuring quality of intrapartum and postpartum care.

METHODS: We use a stochastic, individual-based model to explore whether WHO resourcing benchmarks are sufficient to ensure consistent quality of care. We simulate all deliveries occurring in a region over a year, with date and time of presentation of each woman delivering at a facility assigned at random. Each woman stays in the delivery room for an assigned duration before her delivery, then moves to the maternity ward, followed by discharge. We explore the potential impact of seasonality of births on our findings and then apply the model to a real-world setting using 2014 data from Emergency Obstetric Care (EmOC) facilities in Zanzibar, United Republic of Tanzania.

RESULTS: We find that small EmOCs are frequently empty, while larger EmOCs are at risk of temporarily falling below minimum recommended staff-to-patient ratios. Similarly for Zanzibar, capacity of EmOCs in terms of beds is rarely exceeded. Where over-capacity occurs, it is generally smaller, basic EmOCs (BEmOCs) that are affected. In contrast, capacity in terms of staffing (skilled birth attendants:women in labour ratio) is exceeded almost 50% of the time in larger Comprehensive EmOCs (CEmOCs).

CONCLUSIONS: Our findings suggest that increasing staffing levels of CEmOCs while maintaining fewer small BEmOCs may improve quality of care (by increasing the staff-to-patient ratio for the most frequently used facilities), provided that timely access to EmOCs for all women can still be guaranteed. Alternatively, BEmOCs may need to be upgraded to ensure that women trust and choose these facilities for giving birth, thus relieving pressure on CEmOCs.}, } @article {pmid40475302, year = {2024}, author = {Xie, J and Jung, KJ and Allen, C and Chang, Y and Paul, S and Li, Z and Ma, Q and Chung, D}, title = {Analysis of community connectivity in spatial transcriptomics data.}, journal = {Frontiers in applied mathematics and statistics}, volume = {10}, number = {}, pages = {}, pmid = {40475302}, issn = {2297-4687}, support = {R01 GM122078/GM/NIGMS NIH HHS/United States ; R01 GM131399/GM/NIGMS NIH HHS/United States ; R01 GM152585/GM/NIGMS NIH HHS/United States ; U01 DA045300/DA/NIDA NIH HHS/United States ; R21 HG012482/HG/NHGRI NIH HHS/United States ; U54 AG075931/AG/NIA NIH HHS/United States ; }, abstract = {INTRODUCTION: The advent of high throughput spatial transcriptomics (HST) has allowed for unprecedented characterization of spatially distinct cell communities within a tissue sample. While a wide range of computational tools exist for detecting cell communities in HST data, none allow for the characterization of community connectivity, i.e., the relative similarity of cells within and between found communities-an analysis task that can elucidate cellular dynamics in important settings such as the tumor microenvironment.

METHODS: To address this gap, we introduce the analysis of community connectivity (ACC), which facilitates understanding of the relative similarity of cells within and between communities. We develop a Bayesian multi-layer network model called BANYAN for the integration of spatial and gene expression information to achieve ACC.

RESULTS: We demonstrate BANYAN's ability to recover community connectivity structure via a simulation study based on real sagittal mouse brain HST data. Next, we use BANYAN to implement ACC across a wide range of real data scenarios, including 10× Visium data of melanoma brain metastases and invasive ductal carcinoma, and NanoString CosMx data of human-small-cell lung cancer, each of which reveals distinct cliques of interacting cell sub-populations. An R package banyan is available at https://github.com/dongjunchung/banyan.}, } @article {pmid40129601, year = {2024}, author = {Harryman, WL and Hinton, JP and Sainz, R and Gard, JMC and Ryniawec, JM and Rogers, GC and Warfel, NA and Knudsen, BS and Nagle, RB and Chipollini, JJ and Lee, BR and Sun, BL and Cress, AE}, title = {Intermediate risk prostate tumors contain lethal subtypes.}, journal = {Frontiers in urology}, volume = {4}, number = {}, pages = {}, pmid = {40129601}, issn = {2673-9828}, support = {P30 CA023074/CA/NCI NIH HHS/United States ; R01 CA242226/CA/NCI NIH HHS/United States ; }, abstract = {In 2024, prostate cancer (PCa) remains the most common non-skin cancer in males within the United States, with an estimated 299,010 new cases, the highest increase incident trend rate (3.8%) of all cancers, and one of the eight deadliest. PCa cases are projected to double from 1.8 million to 2.9 million per year between 2020 and 2040. According to the National Comprehensive Cancer Network (NCCN) treatment guidelines, most cases (65%) are intermediate risk (Gleason sum score <7 [3 + 4, 4 + 3], prostate organ-confined, and PSA < 20) with treatment options limited to active surveillance, external beam radiation, and/or surgery to prevent metastasis in the long term (>10 years). It is increasingly recognized that the two most common subtypes of intermediate risk PCa are cribriform architecture (CA) and intraductal carcinoma of the prostate (IDC-P), which can occur together, and both are associated with increased metastatic risk, biochemical recurrence, and disease-specific mortality. Both subtypes display hypoxia, genomic instability, and are identified as Gleason 4 in pathology reports. However, since false negatives are common (up to 50%) in these subtypes on biopsy, more research is needed to reliably detect these subtypes that have an increased risk for invasive disease. We note that even with mpMRI-guided biopsies, the sensitivity is 54% for cribriform architecture and only 37% for IDC-P. The presence of these PCa subtypes in biopsy or radical prostatectomy (RP) tissue can exclude patients from active surveillance and from designation as intermediate risk disease, further underscoring the need for increased molecular understanding of these subtypes for diagnostic purposes. Understanding the heterogeneity of intermediate risk primary PCa phenotypes, using computational pathology approaches to evaluate the fixed biopsy specimen, or video microscopy of the surgical specimen with AI-driven analysis is now achievable. New research associating the resulting phenotypes with the different therapeutic choices and vulnerabilities will likely prevent extracapsular extension, the definition of high-risk disease, and upstaging of the final pathologic stage.}, } @article {pmid40103629, year = {2024}, author = {Vani, P and Patel, A and Abhishek, K and Goyal, K}, title = {Clinical performance and safety of the Vector® percutaneous transluminal coronary angioplasty balloon catheter: A single-arm, multicenter, retrospective post-marketing clinical study.}, journal = {ARYA atherosclerosis}, volume = {20}, number = {6}, pages = {17-26}, pmid = {40103629}, issn = {1735-3955}, abstract = {BACKGROUND: The present post-marketing clinical study was conducted over a 12-month follow-up period to monitor the clinical outcomes of patients treated with the Vector® Percutaneous Transluminal Coronary Angioplasty (PTCA) Balloon Catheter for the dilatation of coronary lesions. The semi-compliant balloon improves balloon-to-vessel wall apposition and minimizes balloon slippage during PTCA, which could reduce complications and improve clinical outcomes. This investigation aimed to assess the safety and effectiveness of the Vector® PTCA Balloon Catheter in real-world settings.

METHODS: A retrospective study was conducted to investigate the safety and efficacy of the Vector® PTCA Balloon Catheter in 125 patients who underwent pre-dilatation and post-dilatation. The primary outcome of the study was major adverse cardiac events (MACE), a composite endpoint encompassing target-lesion revascularization (TLR), cardiac death, and myocardial infarction (MI).

RESULTS: The Vector® PTCA Balloon Catheter has shown promising results in a small group of patients undergoing dilatation of normal and intricate coronary artery lesions, reflecting a 100% procedural success rate. The successful delivery to the target lesion, deployment, and subsequent retrieval of the device during the index procedure led to a 100% device success rate without any technical issues. A total of 3.2% (4) patients experienced MACE during the 12-month follow-up, with 1.6% (2) MI, 1.6% (2) TLR, and no cardiovascular deaths..

CONCLUSION: This study demonstrated the favorable safety and reliability of the Vector® PTCA Balloon Catheter in patients with angina, MI, and a history of coronary artery disease in a real-world setting.}, } @article {pmid39935756, year = {2024}, author = {Sołek, JM and Nowicka, Z and Fendler, W and Sadej, R and Romanska, H and Braun, M}, title = {Prognostic value of FGFR2 in ER-positive breast cancer is influenced by the profile of stromal gene expression: an in silico analysis based on TCGA data.}, journal = {Contemporary oncology (Poznan, Poland)}, volume = {28}, number = {4}, pages = {341-349}, pmid = {39935756}, issn = {1428-2526}, abstract = {INTRODUCTION: Fibroblast growth factor receptor 2 (FGFR2) activation is associated with endocrine therapy resistance in luminal breast cancer (BC) in vitro, but clinical evidence remains inconsistent. Given the role of FGFRs in mediating tumour microenvironment (TME) interactions, the prognostic value of FGFR2 may depend on the stromal component. This study aimed to validate the association between FGFR-related profile of the stroma and FGFR2 prognostic value in oestrogen receptor-positive invasive ductal carcinoma (IDC).

MATERIAL AND METHODS: An in silico gene expression analysis identified 12 stromal factors (FAP, CXCL12, PDGFRA, COL1A1, HSPG2, CCL2, MMP14, S100A4, MMP9, PDGFA, MCAM, IL6) forming an "FGFR-related profile of the stroma". A cohort of 257 ER+ IDC patients from The Cancer Genome Atlas (TCGA) was analysed. Tumours were clustered using k-means based on stromal gene expression, and Cox proportional hazards regression models were used to assess the association between FGFR2 and overall survival (OS).

RESULTS: Two clusters of ER+ IDC tumours were identified based on the stromal gene expression profile. While both clusters had similar tumour stages and hormone receptor statuses, multivariable analysis adjusted for clinical factors revealed a significant association between FGFR2 expression and cluster assignment. In Cluster I (high expression of stromal genes), high FGFR2 was linked to poor prognosis, whereas in Cluster II (low expression), high FGFR2 indicated favourable prognosis. FGFR1, FGFR3, and FGFR4 showed no significant prognostic value.

CONCLUSIONS: Stromal profiles modulate the prognostic significance of FGFR2 in luminal breast carcinoma, highlighting the importance of TME profiling for biomarker assessment and explaining inconsistencies in FGFR2 studies.}, } @article {pmid39425987, year = {2023}, author = {Chen, SZ and Nguyen, J}, title = {Detection of Primary Malignancy With Contrast-Enhanced Mammography.}, journal = {Journal of breast imaging}, volume = {5}, number = {1}, pages = {96-98}, doi = {10.1093/jbi/wbac054}, pmid = {39425987}, issn = {2631-6129}, } @article {pmid39901391, year = {2022}, author = {Pastorello, J and da Silva, NAL and Schuch, NB and Lando, E}, title = {Gross hematuria secondary to use of carboplatin in neoadjuvant treatment of breast cancer with HER2 overexpression.}, journal = {BMJ case reports}, volume = {15}, number = {9}, pages = {}, pmid = {39901391}, issn = {1757-790X}, abstract = {Breast cancer is a high prevalent neoplasia in women worldwide, and platinum compounds are widely used to treat it. On rare occasions, macroscopic hematuria associated with carboplatin has been identified. Thus, the present study aims to report a rare case of a female patient diagnosed with invasive ductal carcinoma, which presented hematuria secondary to carboplatin, showing improvement of the condition after 4 days of expectant treatment with clot lavage. Due to the scant description of hematuria secondary to carboplatin in the scientific literature, it is essential to report such case in order to assist and enrich the understanding of this event.}, } @article {pmid39845069, year = {2022}, author = {Xavier, J and Pham, CT and Cheah, H and Wong, K and Di Lernia, S}, title = {Bladder injury during laparoscopic appendectomy: Detection, management, and learning point for surgical trainees.}, journal = {Surgery in practice and science}, volume = {9}, number = {}, pages = {100075}, pmid = {39845069}, issn = {2666-2620}, abstract = {BACKGROUND: Laparoscopic appendectomy is one of the most common emergency surgeries. There is a paucity in the literature regarding the incidence and management of iatrogenic bladder injuries. We reviewed a series of iatrogenic bladder injuries during laparoscopic appendectomy to determine incidence, preventable risk factors and management.

METHODS: We performed a retrospective review of laparoscopic appendectomy at two large regional teaching hospitals over a five-year period from February 2014 to February 2019. The outcomes measured included intra-operative data, such as type of port used and surgeon experience, incidence of iatrogenic bladder injury, mechanism and time of bladder injury recognition, management and clinical outcome.

RESULTS: A total of 1147 patients underwent laparoscopic appendectomy. Two iatrogenic bladder injuries secondary to port placement were identified (0.17%). Both procedures were performed after-hours by surgical trainees. There was no previous history of abdominal surgery. Neither patient had an indwelling catheter (IDC) during the procedure. There were no other visceral or major vascular injuries. Both bladder injuries were identified in the early post-operative period. One case was managed conservatively, whilst the other required laparoscopic repair of the bladder perforation.

CONCLUSION: Bladder injury should be suspected in patients with abdominal pain, elevated creatinine and anuria following laparoscopic surgery. Although iatrogenic bladder injury during laparoscopic appendectomy is rare, it has the potential for considerable patient morbidity. Therefore, adequate laparoscopic supervision and specific counselling on port access injuries for surgical trainees, adequate bladder decompression with an IDC, and early detection and management guided by the location of injury are essential.}, } @article {pmid39022491, year = {2024}, author = {Boudagh, G and Kieft, A and Choudhury, MSR and Jacques, SM and Miller, S}, title = {Invasive Ductal Breast Carcinoma Metastasis to the Uterine Cervix Presenting As Heavy Vaginal Bleeding: A Case Report and a Literature Review.}, journal = {Cureus}, volume = {16}, number = {6}, pages = {e62523}, pmid = {39022491}, issn = {2168-8184}, abstract = {Breast carcinoma metastasis to the uterine cervix is a rare occurrence with diagnostic intricacies. We present a case of a 38-year-old woman diagnosed with bilateral stages IIIA and IIIB invasive ductal carcinoma of the breast who developed heavy vaginal bleeding post-treatment, revealing metastatic involvement of the cervix, confirmed by CT imaging and pathological examination, as the presenting sign of widely metastatic disease. This case underscores the importance of a thorough review of systems and physical exams as well as considering uncommon metastatic sites in breast cancer patients.}, } @article {pmid39013683, year = {2024}, author = {Cha, E and Oluyemi, ET and Ambinder, EB and Myers, KS}, title = {Clinical Outcomes of Benign Concordant MRI-Guided Breast Biopsies.}, journal = {Clinical breast cancer}, volume = {24}, number = {7}, pages = {597-603}, doi = {10.1016/j.clbc.2024.06.009}, pmid = {39013683}, issn = {1938-0666}, mesh = {Humans ; Female ; Retrospective Studies ; *Image-Guided Biopsy/methods ; *Breast Neoplasms/pathology/diagnostic imaging ; Middle Aged ; Adult ; Aged ; *Magnetic Resonance Imaging/methods ; Breast/pathology/diagnostic imaging/surgery ; Magnetic Resonance Imaging, Interventional/methods ; Follow-Up Studies ; Aged, 80 and over ; Young Adult ; False Negative Reactions ; }, abstract = {INTRODUCTION: MRI-guided biopsy is the standard of care for breast imaging findings seen only by MRI. Although a non-zero false-negative rate of MRI-guided breast biopsy has been reported by multiple studies, there are varied practice patterns for imaging follow-up after a benign concordant MRI guided biopsy. This study assessed the outcomes of benign concordant MRI-guided biopsies at a single institution.

PATIENTS AND METHODS: This IRB-approved, retrospective study included patients with MRI-guided biopsies of breast lesions from November 1, 2014, to August 31, 2020. Only image-concordant breast lesions with benign histopathology and those follow up with MRI imaging or excision were included in the study.

RESULTS: Out of 275 lesions in 216 patients that met the inclusion criteria, 274 lesions were followed with MRI (range, 5-79 months; average, 25.5 months) and showed benign or stable features upon follow-up. One out of 275 lesions (0.4%), a 6 mm focal nonmass enhancement, was ultimately found to represent malignancy after initial MRI-guided biopsy yielded fibrocystic changes. The lesion was stable at a 6-month follow-up MRI but increased in size at 18 months. Repeat biopsy by ultrasound guidance yielded invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS).

CONCLUSION: Breast MRI-guided biopsy has a low false-negative rate. Our single malignancy from a total of 275 lesions gives a false negative rate of 0.4%. This data also supports a longer follow-up interval than the commonly performed 6-month follow-up, in order to assess for interval change.}, } @article {pmid39012819, year = {2024}, author = {Zin, I and China, A and Khan, K and Nag, JK and Vasu, K and Deshpande, GM and Ghosh, PK and Khan, D and Ramachandiran, I and Ganguly, S and Tamagno, I and Willard, B and Gogonea, V and Fox, PL}, title = {AKT-dependent nuclear localization of EPRS1 activates PARP1 in breast cancer cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {30}, pages = {e2303642121}, pmid = {39012819}, issn = {1091-6490}, support = {R01 AG067146/AG/NIA NIH HHS/United States ; R01 NS124547/NS/NINDS NIH HHS/United States ; R01 DK123236/DK/NIDDK NIH HHS/United States ; R01 DK124203/DK/NIDDK NIH HHS/United States ; R01 NS124581/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Breast Neoplasms/metabolism/genetics/pathology ; Female ; *Poly (ADP-Ribose) Polymerase-1/metabolism/genetics ; *Cell Nucleus/metabolism ; *Proto-Oncogene Proteins c-akt/metabolism/genetics ; Cell Line, Tumor ; PTEN Phosphohydrolase/metabolism/genetics ; Amino Acyl-tRNA Synthetases/metabolism/genetics ; Active Transport, Cell Nucleus ; Nuclear Localization Signals/metabolism ; }, abstract = {Glutamyl-prolyl-tRNA synthetase (EPRS1) is a bifunctional aminoacyl-tRNA-synthetase (aaRS) essential for decoding the genetic code. EPRS1 resides, with seven other aaRSs and three noncatalytic proteins, in the cytoplasmic multi-tRNA synthetase complex (MSC). Multiple MSC-resident aaRSs, including EPRS1, exhibit stimulus-dependent release from the MSC to perform noncanonical activities distinct from their primary function in protein synthesis. Here, we show EPRS1 is present in both cytoplasm and nucleus of breast cancer cells with constitutively low phosphatase and tensin homolog (PTEN) expression. EPRS1 is primarily cytosolic in PTEN-expressing cells, but chemical or genetic inhibition of PTEN, or chemical or stress-mediated activation of its target, AKT, induces EPRS1 nuclear localization. Likewise, preferential nuclear localization of EPRS1 was observed in invasive ductal carcinoma that were also P-Ser[473]-AKT[+]. EPRS1 nuclear transport requires a nuclear localization signal (NLS) within the linker region that joins the catalytic glutamyl-tRNA synthetase and prolyl-tRNA synthetase domains. Nuclear EPRS1 interacts with poly(ADP-ribose) polymerase 1 (PARP1), a DNA-damage sensor that directs poly(ADP-ribosyl)ation (PARylation) of proteins. EPRS1 is a critical regulator of PARP1 activity as shown by markedly reduced ADP-ribosylation in EPRS1 knockdown cells. Moreover, EPRS1 and PARP1 knockdown comparably alter the expression of multiple tumor-related genes, inhibit DNA-damage repair, reduce tumor cell survival, and diminish tumor sphere formation by breast cancer cells. EPRS1-mediated regulation of PARP1 activity provides a mechanistic link between PTEN loss in breast cancer cells, PARP1 activation, and cell survival and tumor growth. Targeting the noncanonical activity of EPRS1, without inhibiting canonical tRNA ligase activity, provides a therapeutic approach potentially supplementing existing PARP1 inhibitors.}, } @article {pmid39012252, year = {2024}, author = {Ghai, S and Klotz, L and Pond, GR and Kebabdjian, M and Downes, MR and Belanger, EC and Moussa, M and van der Kwast, TH}, title = {Comparison of Multiparametric MRI-targeted and Systematic Biopsies for Detection of Cribriform and Intraductal Carcinoma Prostate Cancer.}, journal = {Radiology}, volume = {312}, number = {1}, pages = {e231948}, doi = {10.1148/radiol.231948}, pmid = {39012252}, issn = {1527-1315}, mesh = {Humans ; Male ; *Prostatic Neoplasms/diagnostic imaging/pathology/surgery ; *Multiparametric Magnetic Resonance Imaging/methods ; Aged ; *Image-Guided Biopsy/methods ; Prospective Studies ; Middle Aged ; Prostate/diagnostic imaging/pathology ; }, abstract = {Background Intraductal carcinoma (IDC) and invasive cribriform (Cr) subtypes of prostate cancer (PCa) are an indication of aggressiveness, but the evidence regarding whether MRI can be used to detect Cr/IDC-pattern PCa is contradictory. Purpose To compare the detection of Cr/IDC-pattern PCa at multiparametric MRI (mpMRI)-targeted biopsy versus systematic biopsy in biopsy-naive men at risk for PCa. Materials and Methods This study was a secondary analysis of a prospective randomized controlled trial that recruited participants with a clinical suspicion of PCa between April 2017 and November 2019 at five centers. Participants were randomized 1:1 to either the MRI arm or the systematic biopsy arm. Targeted biopsy was performed in participants with a Prostate Imaging Reporting and Data System score of at least 3. MRI features were recorded, and biopsy slides and prostatectomy specimens were reviewed for the presence or absence of Cr/IDC histologic patterns. Comparison of Cr/IDC patterns was performed using generalized linear mixed modeling. Results A total of 453 participants were enrolled, with 226 in the systematic biopsy arm (median age, 65 years [IQR, 59-70 years]; 196 biopsies available for assessment) and 227 in the mpMRI-targeted biopsy arm (median age, 67 years [IQR, 60-72 years]; 132 biopsies available for assessment). Identification of Cr/IDC PCa was lower in the systematic biopsy arm compared with the mpMRI arm (31 of 196 biopsies [16%] vs 33 of 132 biopsies [25%]; P = .01). No evidence of a difference in mean cancer core length (CCL) (11.3 mm ± 4.4 vs 9.7 mm ± 4.5; P = .09), apparent diffusion coefficient (685 µm[2]/sec ± 178 vs 746 µm[2]/sec ± 245; P = .52), or dynamic contrast-enhanced positivity (27 [82%] vs 37 [90%]; P = .33) for clinically significant PCa (csPCa) was observed between participants with or without Cr/IDC disease in the MRI arm. Cr/IDC-positive histologic patterns overall had a higher mean CCL compared with Cr/IDC-negative csPCa (11.1 mm ± 4.4 vs 9.2 mm ± 4.1; P = .009). Conclusion MRI-targeted biopsy showed increased detection of Cr/IDC histologic patterns compared with systematic biopsy. Clinical trial registration no. NCT02936258 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Scialpi and Martorana in this issue.}, } @article {pmid39011435, year = {2024}, author = {Akbari, ME and Akbari, A and Ebrahimian, S}, title = {Pathological characteristics predicting sentinel lymph node metastasis in early breast cancer patients.}, journal = {Caspian journal of internal medicine}, volume = {15}, number = {3}, pages = {472-477}, pmid = {39011435}, issn = {2008-6164}, abstract = {BACKGROUND: In this study, we aimed to identify the predicting pathological factors affecting sentinel lymph node biopsy (SLNB) in patients with clinically node-negative breast cancer.

METHODS: Our single institution retrospective study was conducted at the Cancer Research Center of Shahid Beheshti University of Medical Sciences from 2018 to 2021. Data were imported into and analyzed using SPSS Version 28 for Windows (IBM Corp., Armonk, NY, USA).

RESULTS: Of the 76 patients who underwent SLNB, 43 (56.6%) had negative SLNB and 33 (43.4%) had positive SLNB which led to axillary lymph node dissection (ALND). The relationship between hormone receptor status (ER/PR/Her2), pathology type (IDC, ILC, DCIS, LCIS), tumor size, and Ki67 expression was assessed. According to the results, axillary lymph node involvement can be predicted based on the scores and results of the three variables: IDC tumor type, lympho vascular invasion (LVI), and Ki67 expression. The positive relationship between IDC tumor type and LVI with SLNB indicates that with positive IDC tumor type and LVI, there is a higher probability of positive axillary lymph nodes (3.88 times higher probability for IDC tumor type and 6.75 times higher probability for the LVI factor). However, when the Ki67 expression is lower, the probability of positive axillary lymph nodes is higher (3.58 times higher probability).

CONCLUSION: IDC tumor type, LVI, and lower Ki67 expression are independent predictive factors of positive SLNB.}, } @article {pmid39006626, year = {2024}, author = {Jiang, H and Cartwright, S and Wagner, DG and Krishnamurthy, J and Santamaria-Barria, JA}, title = {Pathologic Complete Response to Neoadjuvant Chemotherapy and Pembrolizumab in Postpartum High-Risk Basal-Type Breast Cancer.}, journal = {Cureus}, volume = {16}, number = {6}, pages = {e62338}, pmid = {39006626}, issn = {2168-8184}, abstract = {Neoadjuvant chemoimmunotherapy with pembrolizumab now defines the standard of care for early high-risk triple-negative breast cancer (TNBC). However, the role of pembrolizumab in neoadjuvant therapy (NAT) for estrogen receptor-positive (ER+) breast cancer remains uncertain. A 39-year-old G2P2 female discovered a palpable mass in the right breast while breastfeeding her 7-month-old child, leading to the diagnosis of a high-grade ER+ (80% moderate staining), human epidermal growth factor receptor 2-negative (ErbB2-) invasive ductal carcinoma with axillary nodal involvement. Gene expression profiling with the MammaPrint 70-gene signature and BluePrint 80-gene signature revealed a tumor with high-risk, basal-type biology. The multidisciplinary breast cancer team recommended NAT with pembrolizumab, carboplatin, paclitaxel, doxorubicin, and cyclophosphamide. Within six weeks, the patient exhibited a remarkable response, with no palpable mass or lymph node, and post-treatment examinations confirmed a complete clinical and radiologic response. The patient underwent lumpectomy and sentinel lymph node biopsy, revealing a pathological complete response with minimal ductal carcinoma in situ and negative axillary nodes. Adjuvant radiation therapy was administered, and the patient completed adjuvant pembrolizumab, currently showing no evidence of recurrence. This case underscores the potential benefits of neoadjuvant chemoimmunotherapy for patients with ER+ErbB2- high-risk, basal-type breast cancer. The use of immunotherapy in patients with pregnancy-associated breast cancer remains to be further investigated.}, } @article {pmid39006260, year = {2024}, author = {Duan, W and Wu, Z and Zhu, H and Zhu, Z and Liu, X and Shu, Y and Zhu, X and Wu, J and Peng, D}, title = {Deep learning modeling using mammography images for predicting estrogen receptor status in breast cancer.}, journal = {American journal of translational research}, volume = {16}, number = {6}, pages = {2411-2422}, pmid = {39006260}, issn = {1943-8141}, abstract = {BACKGROUND: The estrogen receptor (ER) serves as a pivotal indicator for assessing endocrine therapy efficacy and breast cancer prognosis. Invasive biopsy is a conventional approach for appraising ER expression levels, but it bears disadvantages due to tumor heterogeneity. To address the issue, a deep learning model leveraging mammography images was developed in this study for accurate evaluation of ER status in patients with breast cancer.

OBJECTIVES: To predict the ER status in breast cancer patients with a newly developed deep learning model leveraging mammography images.

MATERIALS AND METHODS: Datasets comprising preoperative mammography images, ER expression levels, and clinical data spanning from October 2016 to October 2021 were retrospectively collected from 358 patients diagnosed with invasive ductal carcinoma. Following collection, these datasets were divided into a training dataset (n = 257) and a testing dataset (n = 101). Subsequently, a deep learning prediction model, referred to as IP-SE-DResNet model, was developed utilizing two deep residual networks along with the Squeeze-and-Excitation attention mechanism. This model was tailored to forecast the ER status in breast cancer patients utilizing mammography images from both craniocaudal view and mediolateral oblique view. Performance measurements including prediction accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curves (AUCs) were employed to assess the effectiveness of the model.

RESULTS: In the training dataset, the AUCs for the IP-SE-DResNet model utilizing mammography images from the craniocaudal view, mediolateral oblique view, and the combined images from both views, were 0.849 (95% CIs: 0.809-0.868), 0.858 (95% CIs: 0.813-0.872), and 0.895 (95% CIs: 0.866-0.913), respectively. Correspondingly, the AUCs for these three image categories in the testing dataset were 0.835 (95% CIs: 0.790-0.887), 0.746 (95% CIs: 0.793-0.889), and 0.886 (95% CIs: 0.809-0.934), respectively. A comprehensive comparison between performance measurements underscored a substantial enhancement achieved by the proposed IP-SE-DResNet model in contrast to a traditional radiomics model employing the naive Bayesian classifier. For the latter, the AUCs stood at only 0.614 (95% CIs: 0.594-0.638) in the training dataset and 0.613 (95% CIs: 0.587-0.654) in the testing dataset, both utilizing a combination of mammography images from the craniocaudal and mediolateral oblique views.

CONCLUSIONS: The proposed IP-SE-DResNet model presents a potent and non-invasive approach for predicting ER status in breast cancer patients, potentially enhancing the efficiency and diagnostic precision of radiologists.}, } @article {pmid39005669, year = {2024}, author = {Olbromski, M and Mrozowska, M and Piotrowska, A and Kmiecik, A and Smolarz, B and Romanowicz, H and Blasiak, P and Maciejczyk, A and Wojnar, A and Dziegiel, P}, title = {Prognostic significance of alpha-2-macrglobulin and low-density lipoprotein receptor-related protein-1 in various cancers.}, journal = {American journal of cancer research}, volume = {14}, number = {6}, pages = {3036-3058}, pmid = {39005669}, issn = {2156-6976}, abstract = {Cancer is the leading cause of death worldwide. The World Health Organization (WHO) estimates that 10 million fatalities occurred in 2023. Breast cancer (BC) ranked first among malignancies with 2.26 million cases, lung cancer (LC) second with 2.21 million cases, and colon and rectum cancers (CC, CRC) third with 1.93 million cases. These results highlight the importance of investigating novel cancer prognoses and anti-cancer markers. In this study, we investigated the potential effects of alpha-2 macroglobulin and its receptor, LRP1, on the outcomes of breast, lung, and colorectal malignancies. Immunohistochemical staining was used to analyze the expression patterns of A2M and LRP1 in 545 cases of invasive ductal breast carcinoma (IDC) and 51 cases of mastopathies/fibrocystic breast disease (FBD); 256 cases of non-small cell lung carcinomas (NSCLCs) and 45 cases of non-malignant lung tissue (NMLT); and 108 cases of CRC and 25 cases of non-malignant colorectal tissue (NMCT). A2M and LRP1 expression levels were also investigated in breast (MCF-7, BT-474, SK-BR-3, T47D, MDA-MB-231, and MDA-MB-231/BO2), lung (NCI-H1703, NCI-H522, and A549), and colon (LS 180, Caco-2, HT-29, and LoVo) cancer cell lines. Based on our findings, A2M and LRP1 exhibited various expression patterns in the examined malignancies, which were related to one another. Additionally, the stroma of lung and colorectal cancer has increased levels of A2M/LRP1 areas, which explains the significance of the stroma in the development and maintenance of tumor homeostasis. A2M expression was shown to be downregulated in all types of malignancies under study and was positively linked with an increase in cell line aggressiveness. Although more invasive cells had higher levels of A2M expression, an IHC analysis showed the opposite results. This might be because exogenous alpha-2-macroglobulin is present, which has an inhibitory effect on several cancerous enzymes and receptor-dependent signaling pathways. Additionally, siRNA-induced suppression of the transcripts for A2M and LRPP1 revealed their connection, which provides fresh information on the function of the LRP1 receptor in A2M recurrence in cancer. Further studies on different forms of cancer may corroborate the fact that both A2M and LRP1 have high potential as innovative therapeutic agents.}, } @article {pmid39004788, year = {2024}, author = {Taitelbaum-Swead, R and Ben-David, BM}, title = {The Role of Early Intact Auditory Experience on the Perception of Spoken Emotions, Comparing Prelingual to Postlingual Cochlear Implant Users.}, journal = {Ear and hearing}, volume = {45}, number = {6}, pages = {1585-1599}, pmid = {39004788}, issn = {1538-4667}, mesh = {Humans ; Adult ; Male ; *Cochlear Implants ; Female ; Middle Aged ; *Deafness/rehabilitation/psychology ; *Emotions ; *Speech Perception ; Young Adult ; *Cochlear Implantation ; Case-Control Studies ; Aged ; Semantics ; }, abstract = {OBJECTIVES: Cochlear implants (CI) are remarkably effective, but have limitations regarding the transformation of the spectro-temporal fine structures of speech. This may impair processing of spoken emotions, which involves the identification and integration of semantic and prosodic cues. Our previous study found spoken-emotions-processing differences between CI users with postlingual deafness (postlingual CI) and normal hearing (NH) matched controls (age range, 19 to 65 years). Postlingual CI users over-relied on semantic information in incongruent trials (prosody and semantics present different emotions), but rated congruent trials (same emotion) similarly to controls. Postlingual CI's intact early auditory experience may explain this pattern of results. The present study examined whether CI users without intact early auditory experience (prelingual CI) would generally perform worse on spoken emotion processing than NH and postlingual CI users, and whether CI use would affect prosodic processing in both CI groups. First, we compared prelingual CI users with their NH controls. Second, we compared the results of the present study to our previous study (Taitlebaum-Swead et al. 2022 ; postlingual CI).

DESIGN: Fifteen prelingual CI users and 15 NH controls (age range, 18 to 31 years) listened to spoken sentences composed of different combinations (congruent and incongruent) of three discrete emotions (anger, happiness, sadness) and neutrality (performance baseline), presented in prosodic and semantic channels (Test for Rating of Emotions in Speech paradigm). Listeners were asked to rate (six-point scale) the extent to which each of the predefined emotions was conveyed by the sentence as a whole (integration of prosody and semantics), or to focus only on one channel (rating the target emotion [RTE]) and ignore the other (selective attention). In addition, all participants performed standard tests of speech perception. Performance on the Test for Rating of Emotions in Speech was compared with the previous study (postlingual CI).

RESULTS: When asked to focus on one channel, semantics or prosody, both CI groups showed a decrease in prosodic RTE (compared with controls), but only the prelingual CI group showed a decrease in semantic RTE. When the task called for channel integration, both groups of CI users used semantic emotional information to a greater extent than their NH controls. Both groups of CI users rated sentences that did not present the target emotion higher than their NH controls, indicating some degree of confusion. However, only the prelingual CI group rated congruent sentences lower than their NH controls, suggesting reduced accumulation of information across channels. For prelingual CI users, individual differences in identification of monosyllabic words were significantly related to semantic identification and semantic-prosodic integration.

CONCLUSIONS: Taken together with our previous study, we found that the degradation of acoustic information by the CI impairs the processing of prosodic emotions, in both CI user groups. This distortion appears to lead CI users to over-rely on the semantic information when asked to integrate across channels. Early intact auditory exposure among CI users was found to be necessary for the effective identification of semantic emotions, as well as the accumulation of emotional information across the two channels. Results suggest that interventions for spoken-emotion processing should not ignore the onset of hearing loss.}, } @article {pmid38994984, year = {2024}, author = {Nascimento, KCG and São Marcos, BF and Fontes, PHB and Isídio, BEO and Leão, SL and da Silva, GRP and Lussón, DB and Dos Santos, DL and Leal, LRS and Espinoza, BCF and de Macêdo, LS and de França Neto, PL and Silva, AJD and Silva Neto, JC and Santos, VEP and de Freitas, AC}, title = {HPV Detection in Breast Tumors and Associated Risk Factors in Northeastern Brazil.}, journal = {Cells}, volume = {13}, number = {13}, pages = {}, pmid = {38994984}, issn = {2073-4409}, support = {444606/2023-8//National Council for Scientific and Technological Development/ ; 444156/2023-2//National Council for Scientific and Technological Development/ ; 308684/2023-0//National Council for Scientific and Technological Development/ ; }, mesh = {Humans ; Brazil/epidemiology ; Female ; Middle Aged ; Risk Factors ; *Breast Neoplasms/virology ; *Papillomavirus Infections/virology/complications/epidemiology ; Adult ; Aged ; Papillomaviridae ; Viral Load ; }, abstract = {Breast cancer risk factors include lifestyle, genetic-hormonal influences, and viral infections. Human papillomavirus (HPV), known primarily as the etiological agent of cervical cancer, also appears active in breast carcinogenesis, as evidenced in our study of 56 patients from northeastern Brazil. We assessed the clinical and sociodemographic characteristics, correlating them with various breast cancer tumor types. HPV detection involved amplifying the L1 region, with viral load measured using the E2/E6 ratio and viral activity indicated by E5 oncogene expression. Predominantly, patients over 56 years of age with healthy lifestyles showed a high incidence of invasive ductal carcinoma and triple-negative breast cancer. HPV was detected in 35.7% of cases, mostly HPV16, which is associated with high viral loads (80 copies per cell) and significant E5 expression. These results hint at a possible link between HPV and breast carcinogenesis, necessitating further studies to explore this association and the underlying viral mechanisms.}, } @article {pmid38992932, year = {2024}, author = {Jamjoum, G and Arab, FS and Tayeb, R and Samkari, A and Johari, AA and Ashkar, L and Akbar, J}, title = {Cutaneous Metastasis in Breast Cancer: A Case Report.}, journal = {The American journal of case reports}, volume = {25}, number = {}, pages = {e943999}, pmid = {38992932}, issn = {1941-5923}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Adult ; *Skin Neoplasms/secondary/pathology ; Carcinoma, Ductal, Breast/secondary ; Lung Neoplasms/secondary/pathology ; }, abstract = {BACKGROUND Breast cancer (BC) is the most common malignant disease in females and one of the leading causes of death worldwide. Its treatment plan includes a long-term follow-up and close surveillance, as recurrence is a well-acknowledged concern. BC can recur either locally or as a metastasis, and skin metastasis is a common complication in advanced breast cancer patients. It can present as a skin nodule, plaque, or erythematous lesion, and can be difficult to distinguish from benign skin conditions. The risk of skin metastasis is higher in patients with inflammatory BC. Treatment of such a complex condition is even more challenging, with poor prognosis. Here, we report a case of a 42-year-old woman with stage 4 luminal A BC who had soft tissue recurrence. CASE REPORT A 42-year-old woman with a history of left-sided BC diagnosed and treated 10 years ago presented with multiple soft tissue masses mimicking abscesses at the right lower middle of the back, bilateral thighs, and back of the neck, in the last 6 months, the largest measuring 8×10 cm. The masses were found to be metastatic BC that had spread to the skin and lungs. Because it was invasive ductal carcinoma with positive ER and PR receptors, she was started on hormonal treatment and chemotherapy. CONCLUSIONS This case report highlights the importance of follow-up in patients with a history of BC, as the cancer can recur and spread many years after treatment.}, } @article {pmid38990246, year = {2024}, author = {Wang, X and Qi, L and Chen, M and Zhang, Y and Gao, X and Cai, Y}, title = {Feasibility study of ADCs targeting TROP-2, HER2, and CD46 in Ductal Adenocarcinoma and Intraductal Carcinoma of the prostate.}, journal = {World journal of urology}, volume = {42}, number = {1}, pages = {404}, pmid = {38990246}, issn = {1433-8726}, support = {2021SK2014//Key Research and Development Program of Hunan Province of China/ ; 82272907//National Natural Science Foundation of China/ ; 81974397//National Natural Science Foundation of China/ ; XIANGYA; 2022LNJJ13//Clinical Research Foundation of the National Clinical Research Center for Geriatric Diseases/ ; 2024JJ2090//Outstanding Youth Fund Project of Hunan Province/ ; }, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/metabolism/drug therapy ; *Feasibility Studies ; *Cell Adhesion Molecules/metabolism ; Retrospective Studies ; *Erb-b2 Receptor Tyrosine Kinases/metabolism ; Aged ; *Immunoconjugates/therapeutic use ; Middle Aged ; *Antigens, Neoplasm/metabolism ; *Membrane Cofactor Protein/metabolism ; Carcinoma, Ductal/metabolism/pathology/drug therapy ; Aged, 80 and over ; }, abstract = {BACKGROUND: Ductal Adenocarcinoma (DAC) and Intraductal Carcinoma of the Prostate (IDC-P) respond poorly to all the currently available conventional therapies. Given their accurate and efficient elimination of cancer cells, Antibody-Drug Conjugates (ADCs) have become one of the most promising anticancer treatments. However, no ADCs have so far been approved for Prostate Cancer (PCa) treatment. This study investigated TROP-2, HER2, and CD46 expression in DAC/IDC-P samples, indirectly analyzing their preliminary feasibility as therapeutic targets for future treatment of the two conditions.

PATIENTS AND METHODS: We conducted a retrospective study involving 184 participants (87 DAC/IDC-P patients and 97 Prostatic Acinar Adenocarcinoma (PAC) patients with a Gleason score ≥ 8) without prior treatment between August 2017 and August 2022. Immunohistochemical staining was employed to detect the differential protein expressions of TROP-2, HER2, and CD46 in DAC/IDC-P, PAC, and normal prostate tissues.

RESULTS: Compared to pure PAC tissues, TROP-2 expression was significantly higher in DAC/IDC-P and DAC/IDC-P-adjacent PAC tissues (H-score 68.8 vs. 43.8, p < 0.001, and 59.8 vs. 43.8, p = 0.022, respectively). No significant differences in HER2 expression were observed across different cancer tissues. Compared to both DAC/IDC-P-adjacent PAC and pure PAC tissues, CD46 expression was significantly higher in DAC/IDC-P tissues (42.3 vs. 28.6, p = 0.041, and 42.3 vs. 24.3, p = 0.0035, respectively).

CONCLUSIONS: Herein, TROP-2 and CD46 expression was higher in DAC/IDC-P tissues than in pure PAC and normal prostate tissues. This finding implies that ADCs targeting the two proteins hold significant promise as potential future treatments for DAC/IDC-P.}, } @article {pmid38988018, year = {2024}, author = {Kim, KE and Lee, HW and Bae, SU}, title = {Rectal metastasis arising from breast cancer: a case report.}, journal = {Korean journal of clinical oncology}, volume = {20}, number = {1}, pages = {41-45}, pmid = {38988018}, issn = {2288-4084}, abstract = {Breast cancer is the most common cancer among women worldwide. Breast cancer often metastasizes to the regional lymph nodes, bone, brain, liver, and lungs, whereas gastrointestinal tract metastases are rare. Herein, we present a rare case of rectal metastasis from breast cancer that occurred during palliative chemotherapy. A 69-year-old female with a history of invasive ductal carcinoma, negative for hormonal receptors and positive for human epidermal growth factor receptor 2 (HER2) receptor, underwent various treatments, including neoadjuvant chemotherapy, breast-conserving surgery, and adjuvant therapy. Eight months postoperatively, the patient experienced axillary lymph node recurrence, requiring palliative chemotherapy. Despite ongoing treatment, metastatic lesions were confirmed in the lungs and pleura. During palliative chemotherapy, the patient developed anal pain, and subsequent examination revealed an infiltrating rectal lesion. Despite histological confirmation of metastatic breast carcinoma and tubular adenoma, a multidisciplinary decision was made regarding palliative chemotherapy over surgical intervention. Eribulin was administered, but due to the patient's inability to tolerate the treatment, she passed away 3 months after rectal lesion diagnosis. Although breast cancer metastasis to the rectum is rare, clinicians should consider the possibility of rectal involvement and perform a digital rectal examination if anal symptoms are present.}, } @article {pmid38985255, year = {2025}, author = {Long, M and Calude, A and Burnette, J}, title = {"This was never about a virus": Perceptions of Vaccination Hazards and Pandemic Risk in #Covid19NZ Tweets.}, journal = {The Journal of medical humanities}, volume = {46}, number = {1}, pages = {115-140}, pmid = {38985255}, issn = {1573-3645}, support = {MFP-UOW2011//Marsden Fund/ ; 109277 ALPSS IDC Long//University of Waikato/ ; }, mesh = {Humans ; *COVID-19/prevention & control/epidemiology ; *Social Media ; *Pandemics ; *Vaccination ; *COVID-19 Vaccines ; SARS-CoV-2 ; }, abstract = {In this paper, we draw on qualitative methods from the medical humanities and quantitative approaches from corpus linguistics to assess the different mappings of pandemic risks by Twitter (X) users employing the #Covid19nz hashtag. We look specifically at their responses to government measures around vaccines between August and November 2021. Risk, we reveal, was a major discursive thread in tweets during this period, but within our tweets, it was the vaccine rather than the virus around which hazard perception and response were grouped. We find that the discursive stance of those opposed to the vaccine evoked entangled medical and political hazards, untrustworthy experts, obscure information, restrictions on sovereignty, threats to children, and uncertain future dangers, all of which positioned them within what Ulrich Beck termed the world risk society. We also found that these narratives of risk manifested in specific Twitter styles, which employed a consistently larger number of hashtags. The lack of conjunctions between the hashtags, we argue, encouraged a disordered reading of doubt and precaution, as the hashtags presented triggering phrases whose interconnections were hinted at rather than specified. By contrast, those who tweeted in support of government measures were rhetorically led by solutions rather than risks, with one exception: their perception of those who were vaccine opposed. We use scholarship on risk and precautionary logic to map out the contrasting positions in tweets addressing Aotearoa New Zealand's pandemic experience during the closing months of 2021.}, } @article {pmid38985057, year = {2024}, author = {Uppal, R and Saeed, U and Uppal, MR and Khan, AA and Ahmad, M and Piracha, ZZ}, title = {SARS-CoV-2 clearance in term of Cycle Threshold (Ct) during first two waves of COVID-19 in Pakistan: a phenomenon of delayed viral clearance post-corticosteroid treatment.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {84}, number = {}, pages = {e271452}, doi = {10.1590/1519-6984.271452}, pmid = {38985057}, issn = {1678-4375}, mesh = {Humans ; *COVID-19 ; Pakistan/epidemiology ; *Viral Load/drug effects ; *SARS-CoV-2 ; Male ; Female ; COVID-19 Drug Treatment ; Adult ; RNA, Viral/analysis ; Middle Aged ; Time Factors ; Adrenal Cortex Hormones/therapeutic use ; Young Adult ; Pandemics ; Adolescent ; Real-Time Polymerase Chain Reaction ; COVID-19 Nucleic Acid Testing ; }, abstract = {SARS-CoV-2 is recently emerged virus, which caused millions of deaths, all over the world. To tackle COVID-19 pandemic, there is an utmost need for in-depth analysis of viral replication. We aimed to examine viral load in SARS-CoV-2 patients during first two waves of COVID-19 in Pakistan. 225,615 suspected subjects from 75 different regions of Pakistan were selected in the study. SARS-CoV-2 RNAs were detected via real time PCR. During first wave (period of June-July, 2020) of COVID-19 the prevalence of SARS-CoV-2 was 20.38%. However, during second wave (period of November-December, 2020) of COVID-19, the rate of prevalence was 9.41%. During first wave of COVID-19 96.31% of participants remained PCR positive for 14 to 21 days, 3.39% of subjects showed positive results for 22 to 35 days, while delayed Ct values were observed among 0.26% of participants for 36 to 49 days. However, during second wave of COVID-19 89.31% of the subjects exhibited symptoms and showed real-time PCR positive results for 14 to 21 days, 9.42% showed positive results for 22 to 35 days, while significantly delayed Ct value results were observed among 1.026% of participants for 36 to 63 days (3.95 times higher than first wave). In contrast to first wave of COVID-19, the factors that were different in second wave were neither viral (different strains) nor host (same population). But treatment factors changed significantly. As during second wave besides azithromycin, corticosteroid dexamethasone consumption was increased consequently causing delayed Ct value negativity. This suggests that corticosteroid treatment might be linked with delayed Ct value or viral clearance. This study is crucial for re-considering effective therapeutic options against COVID-19.}, } @article {pmid38984194, year = {2024}, author = {Aldarayseh, M and Sodhi, SS and Musleh, G and Kumar, D and Cholankeril, M}, title = {Unforeseen Complications of Pembrolizumab in Breast Reconstruction Post-Mastectomy.}, journal = {European journal of case reports in internal medicine}, volume = {11}, number = {7}, pages = {004675}, pmid = {38984194}, issn = {2284-2594}, abstract = {UNLABELLED: A 53-year-old post-menopausal Indian female presented with invasive ductal carcinoma, treated with neoadjuvant chemotherapy and pembrolizumab due to a PD-L1 combined positive score of 5. Following a right mastectomy and axillary dissection, she received a breast expander and AlloDerm™ graft. After resuming pembrolizumab and paclitaxel postoperatively, she developed severe breast redness and high-grade fever, necessitating expander removal due to suspected pembrolizumab-induced complications. This case underscores the unique and severe adverse effects of pembrolizumab on breast reconstruction, highlighting the need for careful monitoring and management in patients undergoing similar treatments.

LEARNING POINTS: Among patients with early triple-negative breast cancer, the combination of pembrolizumab with neoadjuvant chemotherapy enhances outcomes compared to chemotherapy alone.Early recognition is essential for managing pembrolizumab-induced complications, as demonstrated by the need for expander removal and debridement in this case.The unique adverse effects observed in this case underscore the importance of tailoring cancer treatment plans to individual patients, taking into account the potential risks associated with immunotherapy in the context of reconstructive surgery.}, } @article {pmid38983285, year = {2024}, author = {Balbino, M and Montatore, M and Masino, F and Carpagnano, FA and Guglielmi, G}, title = {Cat scratch disease unveils hidden breast carcinoma: A diagnostic twist.}, journal = {Radiology case reports}, volume = {19}, number = {9}, pages = {3770-3775}, pmid = {38983285}, issn = {1930-0433}, abstract = {Cat scratch disease is a rare condition that can present with different clinical manifestations, including axillary lymphadenopathy. Here, we report the case of a 45-year-old female who presented with axillary lymphadenopathy attributable to a process of differential diagnosis to cat scratch disease. During the thorough investigation of her condition, a routine mammogram was performed, due to the unilateral axillary lymphadenopathy, revealing the presence of previously undiagnosed breast carcinoma in situ; in fact, a DCIS (invasive ductal carcinoma with spread to the ipsilateral axillary nodes) was incidentally found. This case highlights the importance of comprehensive differential diagnosis and a multidisciplinary approach in managing patients with atypical presentations of common diseases, given that other alarming but unrelated findings are visible.}, } @article {pmid38979936, year = {2025}, author = {Hofmann, LC and Strauss, S and Shpigel, M and Guttman, L and Stengel, DB and Rebours, C and Gjorgovska, N and Turan, G and Balina, K and Zammit, G and Adams, JMM and Ahsan, U and Bartolo, AG and Bolton, JJ and Domingues, R and Dürrani, Ö and Eroldogan, OT and Freitas, A and Golberg, A and Kremer, KI and Marques, F and Milia, M and Steinhagen, S and Sucu, E and Vargas-Murga, L and Zemah-Shamir, S and Zemah-Shamir, Z and Meléndez-Martínez, AJ}, title = {The green seaweed Ulva: tomorrow's "wheat of the sea" in foods, feeds, nutrition, and biomaterials.}, journal = {Critical reviews in food science and nutrition}, volume = {65}, number = {19}, pages = {3728-3763}, doi = {10.1080/10408398.2024.2370489}, pmid = {38979936}, issn = {1549-7852}, mesh = {*Ulva/chemistry ; *Seaweed/chemistry ; Nutritive Value ; Humans ; *Biocompatible Materials ; *Animal Feed/analysis ; Aquaculture ; Animals ; }, abstract = {Ulva, a genus of green macroalgae commonly known as sea lettuce, has long been recognized for its nutritional benefits for food and feed. As the demand for sustainable food and feed sources continues to grow, so does the interest in alternative, plant-based protein sources. With its abundance along coastal waters and high protein content, Ulva spp. have emerged as promising candidates. While the use of Ulva in food and feed has its challenges, the utilization of Ulva in other industries, including in biomaterials, biostimulants, and biorefineries, has been growing. This review aims to provide a comprehensive overview of the current status, challenges and opportunities associated with using Ulva in food, feed, and beyond. Drawing on the expertise of leading researchers and industry professionals, it explores the latest knowledge on Ulva's nutritional value, processing methods, and potential benefits for human nutrition, aquaculture feeds, terrestrial feeds, biomaterials, biostimulants and biorefineries. In addition, it examines the economic feasibility of incorporating Ulva into aquafeed. Through its comprehensive and insightful analysis, including a critical review of the challenges and future research needs, this review will be a valuable resource for anyone interested in sustainable aquaculture and Ulva's role in food, feed, biomaterials, biostimulants and beyond.}, } @article {pmid38977727, year = {2024}, author = {Thakur, AS and Srivatava, V and Park, HKB and Kebaili, I and Boukhris, I and Joo, YH and Sung, TH and Kumar, A and Vaish, R}, title = {Calligraphic interdigitated capacitive sensors for green electronics.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {15685}, pmid = {38977727}, issn = {2045-2322}, abstract = {This study presents a novel approach to fabricating interdigitated capacitive (IDC) touch sensors using graphite-based pencils on a wood substrate. The sensors were designed to detect touches and pressure variations, offering a cost-effective and environmentally friendly solution for sensor fabrication. The fabrication process involved abrasion of graphite pencils on a wooden substrate to create conductive traces, followed by the integration of interdigitated electrode structures. Capacitance variations resulting from touch interactions were investigated to calibrate sensor responses for tailored tasks. The sensitivity of the sensor was found to be 1.2 pF/kPa, highlighting its responsiveness to pressure variations. Additionally, the sensors were interfaced with an Arduino Uno microcontroller board to demonstrate practical applications, such as replicating arrow key functionality. Additionally, the sensors exhibit sensitivity to environmental factors, with the relative change in capacitance increasing from 0.1 to 0.65 as relative humidity ranges from 30 to 90%. Furthermore, variations in temperature from 30 to 60ºC result in a relative change in capacitance increasing to approximately 0.5. The results indicate the feasibility and versatility of using wood-based substrates and graphite-based pencils for fabricating IDC touch sensors, offering promising prospects for sustainable and accessible sensor technology.}, } @article {pmid38977630, year = {2024}, author = {Huang, Y and Dai, D and Zhu, L and Qi, X}, title = {Novel associations between MTDH gene polymorphisms and invasive ductal breast cancer: a case-control study.}, journal = {Discover oncology}, volume = {15}, number = {1}, pages = {273}, pmid = {38977630}, issn = {2730-6011}, support = {2019ZY-A101//Clinical Science and Research Funding of Zhejiang Medical Association/ ; }, abstract = {OBJECTIVE: To reveal the contributing effects of MTDH gene SNPs in the risk of invasive ductal breast cancer (IDC).

PATIENTS AND METHODS: A case-control study was conducted, recruiting a total of 300 cases of IDC and 565 cancer-free controls from East China. Genotyping of three single-nucleotide polymorphisms (SNPs) in the MTDH gene was performed. Genomic DNA was extracted from peripheral blood samples of patients. The three SNPs (rs1311 T > C, rs16896059 G > A, rs2449512 A > G) in the MTDH gene were selected for detection using a TaqMan real-time polymerase chain reaction assay. The association between MTDH and the risk of IDC was analyzed employing an epidemiology case-control study and a multinomial logistic regression model.

RESULTS: Among the three evaluated SNPs, rs1311 T > C, rs16896059 G > A, and rs2449512 A > G demonstrated a significant association with an increased risk of IDC. Furthermore, stratified analysis revealed that individuals carrying the rs1311 CC genotype, rs16896059 GA/AA genotypes, and rs2449512 GG genotype were more susceptible to developing IDC in subgroups of patients younger than 53 years, without family history of IDC, pre-menopause status, clinical stage 2, high grade, with no distant metastasis or invasion, Her2-positive type, ER positive, PR positive, and Ki67 cells less than 10%. However, carriers of the rs16896059 GA/AA genotypes and rs2449512 GG genotype had an elevate the risk of IDC in patients with tumor size larger than 2 cm, post-menopause status, clinical stage 3, with invasion, lymph node infiltration, ER negative, PR negative, Her2 negative, and Ki67 cells exceeding 10%. Compared to the reference haplotype TGA, haplotypes TAA, TAG, and TGG were significantly associated with an increased IDC risk.

CONCLUSION: In this study, we demonstrated a significant association between MTDH gene polymorphisms and an increased risk of IDC. Moreover, our findings suggested that MTDH gene polymorphisms could serve as a potential biomarker for IDC subtyping and therapeutic selection.}, } @article {pmid38977136, year = {2025}, author = {Kwon, Y and Gottmann, P and Wang, S and Tissink, J and Motzler, K and Sekar, R and Albrecht, W and Cadenas, C and Hengstler, JG and Schürmann, A and Zeigerer, A}, title = {Induction of steatosis in primary human hepatocytes recapitulates key pathophysiological aspects of metabolic dysfunction-associated steatotic liver disease.}, journal = {Journal of hepatology}, volume = {82}, number = {1}, pages = {18-27}, doi = {10.1016/j.jhep.2024.06.040}, pmid = {38977136}, issn = {1600-0641}, mesh = {Humans ; *Hepatocytes/metabolism/pathology ; *Fatty Liver/metabolism/pathology/etiology ; Male ; Female ; Insulin Resistance ; Cells, Cultured ; }, abstract = {BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease. Owing to limited available treatment options, novel pre-clinical models for target selection and drug validation are warranted. We have established and extensively characterized a primary human steatotic hepatocyte in vitro model system that could guide the development of treatment strategies for MASLD.

METHODS: Cryopreserved primary human hepatocytes from five donors varying in sex and ethnicity were cultured with free fatty acids in a 3D collagen sandwich for 7 days and the development of MASLD was followed by assessing classical hepatocellular functions. As proof of concept, the effects of the drug firsocostat (GS-0976) on in vitro MASLD phenotypes were evaluated.

RESULTS: Incubation with free fatty acids induced steatosis, insulin resistance, mitochondrial dysfunction, inflammation, and alterations in prominent human gene signatures similar to patients with MASLD, indicating the recapitulation of human MASLD in this system. The application of firsocostat rescued clinically observed fatty liver disease pathologies, highlighting the ability of the in vitro system to test the efficacy and potentially characterize the mode of action of drug candidates.

CONCLUSIONS: Altogether, our human MASLD in vitro model system could guide the development and validation of novel targets and drugs for the treatment of MASLD.

IMPACT AND IMPLICATIONS: Due to low drug efficacy and high toxicity, clinical treatment options for metabolic dysfunction-associated steatotic liver disease (MASLD) are currently limited. To facilitate earlier stop-go decisions in drug development, we have established a primary human steatotic hepatocyte in vitro model. As the model recapitulates clinically relevant MASLD characteristics at high phenotypic resolution, it can serve as a pre-screening platform and guide target identification and validation in MASLD therapy.}, } @article {pmid38973399, year = {2024}, author = {Batra, H and Bose, PSC and Ding, Y and Dai, A and Chen, H and Albarracin, CT and Sun, H and Sahin, AA and Yang, F and Wistuba, II and Raso, MG}, title = {MYB expression by immunohistochemistry is highly specific and sensitive for detection of solid variant of adenoid cystic carcinoma of the breast among all triple-negative breast cancers.}, journal = {Histopathology}, volume = {85}, number = {3}, pages = {503-509}, doi = {10.1111/his.15276}, pmid = {38973399}, issn = {1365-2559}, mesh = {Humans ; *Carcinoma, Adenoid Cystic/metabolism/diagnosis/pathology ; *Triple Negative Breast Neoplasms/pathology/metabolism/diagnosis ; Female ; *Immunohistochemistry ; *Proto-Oncogene Proteins c-myb/metabolism ; *Biomarkers, Tumor/analysis/metabolism ; Middle Aged ; Aged ; Adult ; Sensitivity and Specificity ; Aged, 80 and over ; }, abstract = {BACKGROUND: Adenoid cystic carcinoma is a rare subtype of triple-negative breast carcinoma. These low-grade tumours, which are treated by simple mastectomy and have an excellent prognosis compared to other triple-negative breast carcinomas. Solid-variant adenoid cystic carcinomas have basaloid features and are difficult to distinguish morphologically from other triple-negative breast cancers. Breast adenoid cystic carcinoma exhibits MYB protein overexpression, which can be detected by immunohistochemistry (IHC).

AIM: We compared the IHC expression of MYB in solid-variant adenoid cystic carcinoma with that in other triple-negative breast cancers.

METHODS: We conducted IHC staining of 210 samples of triple-negative breast cancers, including solid-variant adenoid cystic carcinoma (n = 17), metaplastic breast carcinoma (n = 44), basaloid triple-negative breast cancer (n = 21), and other triple-negative invasive ductal carcinoma (n = 128). We classified nuclear staining of MYB as diffuse/strong (3+), focal moderate (2+), focal weak (1+), or none (0).

RESULTS: All 17 solid/basaloid adenoid cystic carcinoma cases exhibited 3+ MYB expression. Of the 21 solid/basaloid triple-negative breast cancers, one (5%) had 2+ expression, seven (33%) 1+ expression, and 13 (62%) 0 expression. Of the 44 metaplastic carcinoma cases, 39 cases (89%) had no (0) staining, and the other five cases had focal weak (1+) or moderate (2+) staining. Among the 128 triple-negative invasive ductal carcinoma cases, 92 cases (72%) had no (0) staining, 36 cases (28%) exhibited focal weak (1+) or moderate (2+) staining.

CONCLUSIONS: Our study revealed diffuse/strong MYB staining (3+) only in solid/basaloid adenoid cystic carcinomas. Thus, we recommend routine MYB IHC staining in triple-negative breast carcinoma with solid/basaloid morphology to improve diagnostic accuracy.}, } @article {pmid38968480, year = {2024}, author = {Zhang, Z and Huang, C and Wu, J and Cheng, Q and Wang, S}, title = {TICRR as a potential prognostic biomarker for lung adenocarcinoma: A comprehensive analysis using TCGA database.}, journal = {Medicine}, volume = {103}, number = {27}, pages = {e38660}, pmid = {38968480}, issn = {1536-5964}, mesh = {Humans ; *Adenocarcinoma of Lung/genetics/mortality/pathology ; Male ; *Biomarkers, Tumor/genetics/metabolism ; Female ; Prognosis ; *Lung Neoplasms/genetics/mortality/pathology ; Middle Aged ; Nomograms ; Kaplan-Meier Estimate ; Aged ; ROC Curve ; Neoplasm Staging ; Databases, Genetic ; }, abstract = {To investigate the role of TopBP1-interacting checkpoint and replication regulator (TICRR) in the tumorigenesis and prognosis of lung adenocarcinoma (LUAD) patients. Wilcoxon signed-rank test and logistic regression were utilized to analyze the relationship between clinical characteristics and TICRR expression in LUAD from TCGA dataset. Kaplan-Meier plots and Cox regressions were used to assess the impact of TICRR impact on prognosis. ROC curves and nomograms were generated to further evaluate the relationship between TICRR expression and the risk of LUAD. Gene set enrichment analysis (GSEA) was conducted on TCGA dataset, and ssGSEA was employed to investigate the association between TICRR and immune infiltrates. The results showed that high TICRR expression was significantly associated with various clinical factors including gender, age, pathological stage, T stage, N stage, M stage, outcome of primary therapy and smoking status. ROC curves also demonstrated that TICRR was a promising biomarker for molecular pathology diagnosis in LUAD patients (AUC = 0.952). Further analysis using gene ontology (GO) term enrichment and GSEA revealed an abnormal correlation between TICRR expression and cell division. Interestingly, ssGSEA analysis showed that TICRR expression correlated with multiple immune cell types, such as Th2 cell, TFH cell, mast cell, iDC, eosinophils, and dendritic cell. Lastly, the KM-plotters indicated that LUAD patients with high TICRR expression obtained worse life expectancy (P < .001). TICRR has proven to be a valuable tool in predicting disease progression and prognosis in patients with LUAD, thereby establishing itself as a fitting biomarker for forecasting overall survival (OS) of LUAD patients.}, } @article {pmid38966846, year = {2024}, author = {Zaldarriaga, JMH and Aw, AMN and Vega, GP and Gaerlan-Tagle, A and Pena-Camacho, A and Magsanoc, JMJ}, title = {Breast Cancer in a Filipino Male: A Case Report and Brief Literature Review.}, journal = {Acta medica Philippina}, volume = {58}, number = {3}, pages = {70-75}, pmid = {38966846}, issn = {2094-9278}, abstract = {This is a case report of a 76-year-old Filipino male who presented with a six-year history of a steadily growing left breast mass. The mass was eventually diagnosed to be Invasive Ductal Carcinoma, Anatomic and Prognostic Stage IIIB (T4b cN0 M0), Grade 3, Luminal A. Subsequently, the patient underwent neoadjuvant chemotherapy of doxorubicin/cyclophosphamide and paclitaxel, followed by modified radical mastectomy with axillary lymph node dissection, concluded by post-mastectomy radiation therapy. The patient had complete clinical response to this trimodality therapy. The rarity of this case is juxtaposed and integrated with the present literature on male breast cancer.}, } @article {pmid38964999, year = {2024}, author = {Yan, X and Yang, L and Ye, X and Chen, J and Wang, T and Du, M}, title = {Unpacking the hazards: An analytic study of injury patterns and risk factors in urban instant delivery.}, journal = {Injury}, volume = {55}, number = {9}, pages = {111706}, doi = {10.1016/j.injury.2024.111706}, pmid = {38964999}, issn = {1879-0267}, mesh = {Humans ; Female ; Risk Factors ; Male ; China/epidemiology ; *Accidents, Traffic/statistics & numerical data ; *Wounds and Injuries/epidemiology ; Middle Aged ; Adult ; Risk-Taking ; Urban Population/statistics & numerical data ; Young Adult ; }, abstract = {The rapid growth of urban instant delivery, facilitated by digital platforms and characterized by on-demand, short-term, task-based labor, has raised concerns about safety, particularly with the increasing frequency of instant delivery crashes (IDCs). This study addresses knowledge gaps in understanding injury patterns and risk factors associated with IDCs. Utilizing data extracted from judicial verdicts on IDC disputes in China, encompassing demographic, contextual, crash, and injury information, the research employs ordered logit regression to identify significant factors affecting injury patterns, the number of injuries per person (IPP), and injury severity. Overall, traffic injuries related to instant delivery services have gradually improved since 2020, as evidenced by the severity of individual accidents, the number of injuries, and the economic losses. Analysis of 648 injuries among 448 non-fatal victims reveals a prevalence of lower extremity injuries, followed by external, upper extremity, and head injuries. While the majority of victims suffered a single injury, approximately 22 % experienced major injuries. Female delivery riders exhibited higher injury ratios across various body regions. Rider risk behavior, type of delivery vehicles, and the mode of transport of non-delivery travelers emerged as significant influencers of injury patterns. Notably, functional and physical intersection areas exhibited the highest injury ratios among facility types. Contrary to conventional wisdom, older riders and travelers aged above 50 were associated with higher injury severity, challenging the perception of young age as the primary risk factor. The prominence of lower extremity injuries underscores the necessity for heightened protective measures for delivery riders. Major injuries among victims emphasize potential long-term consequences and associated costs. The significance of gender, age, and risk behavior as determining factors highlights the need for targeted safety interventions. These findings offer crucial insights for stakeholders, guiding the formulation of precise safety measures and informed policy initiatives within the dynamic landscape of instant delivery safety.}, } @article {pmid38964363, year = {2024}, author = {Moore, KA and Ostrowsky, JT and Mehr, AJ and Johnson, RA and Ulrich, AK and Moua, NM and Fay, PC and Hart, PJ and Golding, JP and Benassi, V and Preziosi, MP and Adetifa, IM and Akpede, GO and Ampofo, WK and Asogun, DA and Barrett, ADT and Bausch, DG and de Coster, I and Emperador, DM and Feldmann, H and Fichet-Calvet, E and Formenty, PBH and Garry, RF and Grant, DS and Günther, S and Gupta, SB and Jaspard, M and Mazzola, LT and Okogbenin, SA and Roth, C and Schmaljohn, CS and Osterholm, MT}, title = {Lassa fever research priorities: towards effective medical countermeasures by the end of the decade.}, journal = {The Lancet. Infectious diseases}, volume = {24}, number = {11}, pages = {e696-e706}, doi = {10.1016/S1473-3099(24)00229-9}, pmid = {38964363}, issn = {1474-4457}, support = {001/WHO_/World Health Organization/International ; }, mesh = {*Lassa Fever/prevention & control/diagnosis/epidemiology ; Humans ; Lassa virus ; Medical Countermeasures ; Research ; Antiviral Agents/therapeutic use ; Biomedical Research/trends ; World Health Organization ; }, abstract = {In 2016, WHO designated Lassa fever a priority disease for epidemic preparedness as part of the WHO Blueprint for Action to Prevent Epidemics. One aspect of preparedness is to promote development of effective medical countermeasures (ie, diagnostics, therapeutics, and vaccines) against Lassa fever. Diagnostic testing for Lassa fever has important limitations and key advancements are needed to ensure rapid and accurate diagnosis. Additionally, the only treatment available for Lassa fever is ribavirin, but controversy exists regarding its effectiveness. Finally, no licensed vaccines are available for the prevention and control of Lassa fever. Ongoing epidemiological and behavioural studies are also crucial in providing actionable information for medical countermeasure development, use, and effectiveness in preventing and treating Lassa fever. This Personal View provides current research priorities for development of Lassa fever medical countermeasures based on literature published primarily in the last 5 years and consensus opinion of 20 subject matter experts with broad experience in public health or the development of diagnostics, therapeutics, and vaccines for Lassa fever. These priorities provide an important framework to ensure that Lassa fever medical countermeasures are developed and readily available for use in endemic and at-risk areas by the end of the decade.}, } @article {pmid38963526, year = {2024}, author = {Magnoni, F and Bianchi, B and Pagan, E and Corso, G and Sala, I and Bagnardi, V and Claudia, S and Brancaccio, R and Bottazzoli, E and Boato, A and Munzone, E and Dellapasqua, S and Fusco, N and Viviana, G and Veronesi, P}, title = {Long-term outcome of invasive pure micropapillary breast cancer compared with invasive mixed micropapillary and invasive ductal breast cancer: a matched retrospective study.}, journal = {Breast cancer research and treatment}, volume = {208}, number = {2}, pages = {333-347}, pmid = {38963526}, issn = {1573-7217}, mesh = {Humans ; Female ; Retrospective Studies ; *Breast Neoplasms/pathology/mortality ; Middle Aged ; *Carcinoma, Ductal, Breast/pathology/mortality ; Aged ; Prognosis ; Adult ; Carcinoma, Papillary/pathology/mortality/surgery ; Neoplasm Invasiveness ; Disease-Free Survival ; }, abstract = {PURPOSE: Data on the prognostic impact of the micropapillary component in breast cancer are limited. The purpose of this study was to investigate the clinicopathological characteristics and long-term outcomes of pure and mixed invasive micropapillary breast cancer (IMPC) patients compared to invasive ductal cancer (IDC) patients.

METHODS: This retrospective study analysed all IMPC and IDC patients treated at the European Institute of Oncology (IEO) between 1997 and 2019. The overall cohort of IMPC patients was divided in two groups, pure and mixed IMPC. Each patient with mixed or pure IMPC was matched with one patient with IDC, based on year of surgery, age, pT, pN, and molecular subtype.

RESULTS: A total of 30,115 IDC, 120 pure IMPC and 150 mixed IMPC patients were considered eligible. Compared to IDC, pure and mixed IMPC patients presented a higher rate of locally advanced disease (pT2-T3, pN2-N3), vascular invasion, and Luminal B subtype. After matching, pure and mixed IMPC showed a significant higher rate of vascular invasion compared to IDC patients (p < 0.001). Invasive disease-free survival was better in IDC compared to pure IMPC patients (p = 0.11). Long-term overall survival was significantly worse in pure IMPC group compared to IDC group (p = 0.004), being instead similar between mixed IMPC vs matched IDC (p = 0.07).

CONCLUSION: These real-world data reported the worse prognosis of pure IMPC compared to IDC, highlighting the peculiar prognostic value of the micropapillary subtype itself in the decision-making process of IMPC management. An accurate pre-surgical diagnostic evaluation and a multidisciplinary approach are pivotal to best personalize its treatment.}, } @article {pmid38955387, year = {2024}, author = {Wu, F and Andaleeb, U and Ahmed, I}, title = {Extramammary breast cancer of the vulva.}, journal = {BMJ case reports}, volume = {17}, number = {7}, pages = {}, doi = {10.1136/bcr-2023-259567}, pmid = {38955387}, issn = {1757-790X}, mesh = {Humans ; Female ; *Vulvar Neoplasms/pathology/surgery/diagnosis ; Aged ; *Breast Neoplasms/pathology/surgery ; Sentinel Lymph Node Biopsy ; Vulva/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/diagnosis/surgery ; }, abstract = {A woman in her 70s was seen in the gynaecology outpatient clinic with a swelling on the right side of the vulva. Surgical excision of the lesion revealed unexpectedly an extensive ductal carcinoma in situ with a focus of a grade 2 invasive ductal carcinoma arising in extramammary breast tissue of the vulva. Postoperative staging studies showed normal breasts, with no evidence of disease elsewhere. The patient underwent a wider excision of the right vulva and sentinel node biopsy of the right inguinal region, which revealed no further disease. The patient is currently taking adjuvant hormonal therapy and has remained disease free at 2-year follow-up. This case underscores the importance of considering rare presentations of vulvar malignancies and the necessity for a multidisciplinary approach in managing such cases.}, } @article {pmid38955134, year = {2024}, author = {Setyawan, G and Sejati, PA and Ogawa, R and Ibrahim, KA and Fujimoto, H and Yamamoto, H and Takei, M}, title = {Detection of invasive ductal carcinoma in quadrant breast areas by electrical impedance tomography implemented with gaussian relaxation-time distribution (EIT-GRTD).}, journal = {Biomedical physics & engineering express}, volume = {10}, number = {5}, pages = {}, doi = {10.1088/2057-1976/ad5db1}, pmid = {38955134}, issn = {2057-1976}, mesh = {Humans ; *Electric Impedance ; Female ; *Breast Neoplasms/diagnostic imaging ; *Tomography/methods ; *Carcinoma, Ductal, Breast/diagnostic imaging ; Normal Distribution ; Breast/diagnostic imaging ; Computer Simulation ; Algorithms ; Image Processing, Computer-Assisted/methods ; }, abstract = {Invasive ductal carcinoma (IDC) in breast specimens has been detected in the quadrant breast area: (I) upper outer, (II) upper inner, (III) lower inner, and (IV) lower outer areas by electrical impedance tomography implemented with Gaussian relaxation-time distribution (EIT-GRTD). The EIT-GRTD consists of two steps which are (1) the optimum frequencyfoptselection and (2) the time constant enhancement of breast imaging reconstruction.foptis characterized by a peak in the majority measurement pair of the relaxation-time distribution functionγ,which indicates the presence of IDC.γrepresents the inverse of conductivity and indicates the response of breast tissues to electrical currents across varying frequencies based on the Voigt circuit model. The EIT-GRTD is quantitatively evaluated by multi-physics simulations using a hemisphere container of mimic breast, consisting of IDC and adipose tissues as normal breast tissue under one condition with known IDC in quadrant breast area II. The simulation results show that EIT-GRTD is able to detect the IDC in four layers atfopt= 30, 170 Hz. EIT-GRTD is applied in the real breast by employed six mastectomy specimens from IDC patients. The placement of the mastectomy specimens in a hemisphere container is an important factor in the success of quadrant breast area reconstruction. In order to perform the evaluation, EIT-GRTD reconstruction images are compared to the CT scan images. The experimental results demonstrate that EIS-GRTD exhibits proficiency in the detection of the IDC in quadrant breast areas while compared qualitatively to CT scan images.}, } @article {pmid38952531, year = {2024}, author = {Majeed, AI and Zinan, S and Faryal, R}, title = {Unraveling the Role of BRCA1 variants in Dysregulation of Transcriptional and Post-Transcriptional Mechanisms in Breast Cancer.}, journal = {Pakistan journal of medical sciences}, volume = {40}, number = {6}, pages = {1093-1098}, pmid = {38952531}, issn = {1682-024X}, abstract = {OBJECTIVE: To screen BRCA1 gene variants and predict potential role of the identified variants in breast cancer.

METHOD: This case-control study included two hundred and fifty breast cancer patients and equal healthy individuals from the Federal Breast Cancer Screening Centre, Pakistan Institute of Medical Sciences, Islamabad from March 2021- January 2023. Demographic data was collected through questionnaires and clinical data was assessed using mammograms, ultrasound, histopathology and immunohistochemistry reports. Polymerase chain reaction and Sanger sequencing approach were used to detect variants in BRCA1 gene. In-silico analyses were carried out to predict mutation effect, miRNA binding site alterations and change in mRNA structure and stability.

RESULTS: Invasive ductal carcinoma was the most prevalent type of breast cancer. Old age [OR: 2.8149 (1.5995 to 4.9538) p value = 0.0003] and family history [OR: 4.3186 (1.7336 to 10.7581) p value = 0.001] were significant breast cancer risk. Six variants were identified. Two novel missense variants, Chr17:43082553A>T and Chr17:43093710A>T were predicted deleterious as these disrupted interaction with PALB2 and importin alpha's NLS2 site, respectively. In silico analysis predicted the loss of hsa-miR-1179 binding site due to variant Chr17:43093220T>C. Moreover, four variants were predicted to affect the mRNA structure and stability.

CONCLUSION: Two novel variants were predicted to be pathogenic. In-silico analysis predicted the loss of miRNA binding site along with change in mRNA secondary structure plus stability, possible mechanisms for oncogenesis. Further, expressional studies are required to confirm BRCA1 gene dysregulation in breast cancer due to these variants.}, } @article {pmid38951766, year = {2024}, author = {Nisar, MI and Kabole, I and Khanam, R and Shahid, S and Bakari, BA and Chowdhury, NH and Qazi, MF and Dutta, A and Rahman, S and Khalid, J and Dhingra, U and Hasan, T and Ansari, N and Deb, S and Mitra, DK and Mehmood, U and Aftab, F and Ahmed, S and Khan, S and Ali, SM and Ahmed, S and Manu, A and Yoshida, S and Bahl, R and Baqui, AH and Sazawal, S and Jehan, F}, title = {Does the implementation of revised American College of Cardiology and American Heart Association (ACC/AHA) guidelines improve the identification of stillbirths and preterm births in hypertensive pregnancies: a population-based cohort study from South Asia and sub-Saharan Africa.}, journal = {BMC pregnancy and childbirth}, volume = {24}, number = {1}, pages = {451}, pmid = {38951766}, issn = {1471-2393}, support = {001/WHO_/World Health Organization/International ; I64438//Bill and Melinda Gates Foundation/ ; }, mesh = {Humans ; Female ; Pregnancy ; *Premature Birth/epidemiology ; *Stillbirth/epidemiology ; Adult ; *Hypertension, Pregnancy-Induced/diagnosis/epidemiology ; *Practice Guidelines as Topic ; United States/epidemiology ; Pakistan/epidemiology ; Cohort Studies ; American Heart Association ; Bangladesh/epidemiology ; Tanzania/epidemiology ; Young Adult ; Blood Pressure ; Infant, Newborn ; Asia, Southern ; }, abstract = {BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a significant cause of maternal mortality worldwide. The classification and treatment of hypertension in pregnancy remain debated. We aim to compare the effectiveness of the revised 2017 ACC/AHA blood pressure threshold in predicting adverse pregnancy outcomes.

METHODS: We conducted a secondary data analysis of the Alliance for Maternal and Newborn Health Improvement (AMANHI) biorepository study, including 10,001 pregnant women from Bangladesh, Pakistan, and Tanzania. Blood pressure was measured using validated devices at different antenatal care visits. The blood pressure readings were categorized as: normal blood pressure (systolic blood pressure (sBP) < 120 mm Hg and diastolic blood pressure (dBP) < 80 mm Hg), elevated blood pressure (sBP 120-129 and dBP < 80), stage 1 hypertension (sBP 130-139 or dBP 80-89, or both), and stage 2 hypertension (sBP ≥ 140 or dBP ≥ 90, or both). We estimated risk ratios for stillbirths and preterm births, as well as diagnostic test properties of both the pre-existing JNC7 (≥ 140/90) and revised ACC/AHA (≥ 130/80) thresholds using normal blood pressure as reference group.

RESULTS: From May 2014 to June 2018, blood pressure readings were available for 9,448 women (2,894 in Bangladesh, 2,303 in Pakistan, and 4,251 in Tanzania). We observed normal blood pressure in 70%, elevated blood pressure in 12.4%, stage 1 hypertension in 15.2%, and stage 2 hypertension in 2.5% of the pregnant women respectively. Out of these, 310 stillbirths and 9,109 live births were recorded, with 887 preterm births. Using the ACC/AHA criteria, the stage 1 hypertension cut-off revealed 15.3% additional hypertension diagnoses as compared to JNC7 criteria. ACC/AHA defined hypertension was significantly associated with stillbirths (RR 1.8, 95% CI 1.4, 2.3). The JNC 7 hypertension cut-off of ≥ 140/90 was significantly associated with a higher risk of preterm births (RR 1.6, 95% CI 1.2, 2.2) and stillbirths (RR 3.6, 95% CI 2.5, 5.3). Both criteria demonstrated low sensitivities (8.4 for JNC-7 and 28.1 for ACC/AHA) and positive predictive values (11.0 for JNC7 and 5.2 for ACC/AHA) in predicting adverse outcomes.

CONCLUSION: The ACC/AHA criteria (≥ 130/80) identified additional cases of hypertension but had limited predictive accuracy for stillbirths and preterm births, highlighting the ongoing need for improved criteria in managing pregnancy-related hypertension.}, } @article {pmid38951111, year = {2024}, author = {Kim, JM and Cho, EY}, title = {Prediction of Oncotype DX Recurrence Score Based on Systematic Evaluation of Ki-67 Scores in Hormone Receptor-Positive Early Breast Cancer.}, journal = {Journal of breast cancer}, volume = {27}, number = {3}, pages = {201-214}, pmid = {38951111}, issn = {1738-6756}, abstract = {PURPOSE: Oncotype DX (ODX) predicts the risk of recurrence and benefits of adding chemotherapy for patients with estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer. We aimed to develop a simplified scoring system using readily available clinicopathological parameters to predict a high-risk ODX recurrence score (RS) while minimizing reproducibility issues regarding Ki-67 index evaluation methods.

METHODS: We enrolled 300 patients with ER+/HER2- early breast cancer, for whom ODX RS data were available in the test set. Using the QuPath image analysis platform, we systematically evaluated the average, hotspot, and hottest spot Ki-67 scores in the test set. Logistic regression analyses were conducted to establish a predictive scoring system for high-risk ODX RS. An independent validation set comprising 117 patients over different periods was established.

RESULTS: Factors such as age ≤ 50 years, invasive ductal carcinoma tumor type, histologic grade 2 or 3, tumor necrosis, progesterone receptor negativity, and a high Roche-analyzed Ki-67 score (> 20) were associated with high-risk ODX RS. These variables were incorporated into our scoring system. The area under the curve of the scoring system was 0.8057. When applied to both the test and validation sets with a cutoff value of 3, the sensitivity of our scoring system was 92%.

CONCLUSION: We successfully developed a scoring system based on the systematic evaluation of Ki-67 scoring methods. We believe that our user-friendly predictive scoring system for high risk ODX RS could help clinicians in identifying patients who may or may require additional ODX testing.}, } @article {pmid38949561, year = {2024}, author = {Alan Selçuk, N and Akçay, K and Beydağı, G and Sönmez, Ö and Çelik, S and Öven, BB and Kabasakal, L}, title = {Revision of the Histopathological Examination Following [68]Ga-DOTA-FAPI-04 PET/CT of a Breast Tumor Diagnosed as Invasive Ductal Carcinomatosis.}, journal = {Molecular imaging and radionuclide therapy}, volume = {33}, number = {2}, pages = {134-137}, pmid = {38949561}, issn = {2146-1414}, abstract = {Neuroendocrine tumors (NETs) of the breast represent 1% of breast carcinomas. Histopathological misinterpretation of breast NET is common. We present the case of a female patient who had a breast mass diagnosed as invasive ductal carcinoma initially by histopathological examination. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) revealed 2 ametabolic hypodense liver lesions. Subsequently, the patient underwent fibroblast activation protein inhibitor (FAPI)-PET/CT, which did not reveal any FAP expression in the liver lesions, but increased FAP expression was observed in the soft tissue mass of the mesenteric root. Consequently, the pathology of the biopsy taken from the nodule in the right breast was revised, and a diagnosis of grade 2 NET was established. The benefit of FAPI-PET/CT on NETs has been previously investigated. Further prospective studies are required to establish the role of FAPI-PET/CT in NET management.}, } @article {pmid38946749, year = {2024}, author = {Dhone, K and Aurangabadkar, G}, title = {Invasive ductal carcinoma of the breast presenting as a cauliflower-like growth.}, journal = {The Pan African medical journal}, volume = {48}, number = {}, pages = {4}, doi = {10.11604/pamj.2024.48.4.43431}, pmid = {38946749}, issn = {1937-8688}, mesh = {Humans ; *Breast Neoplasms/pathology/diagnosis ; Female ; *Carcinoma, Ductal, Breast/diagnosis/pathology ; Middle Aged ; }, } @article {pmid38944914, year = {2024}, author = {Bogaard, M and Strømme, JM and Kidd, SG and Johannessen, B and Bakken, AC and Lothe, RA and Axcrona, K and Skotheim, RI and Axcrona, U}, title = {GRIN3A: A biomarker associated with a cribriform pattern and poor prognosis in prostate cancer.}, journal = {Neoplasia (New York, N.Y.)}, volume = {55}, number = {}, pages = {101023}, pmid = {38944914}, issn = {1476-5586}, mesh = {Humans ; Male ; *Prostatic Neoplasms/genetics/pathology/metabolism/surgery ; *Biomarkers, Tumor/genetics/metabolism ; Prognosis ; *Neoplasm Grading ; Middle Aged ; Aged ; Gene Expression Regulation, Neoplastic ; Prostatectomy ; Gene Expression Profiling ; }, abstract = {Prostate cancer with a cribriform pattern, including invasive cribriform carcinoma (ICC) and/or intraductal carcinoma (IDC) is associated with a poor prognosis, and the underlying mechanisms are unclear. Therefore, we aimed to identify biomarkers for this feature. Using a radical prostatectomy cohort, we performed within-patient differential expression analyses with RNA sequencing data to compare samples with a cribriform pattern to those with non-cribriform Gleason pattern 4 (NcGP4; n=13). ACSM1, GRIN3A, PCDHB2, and REG4 were identified as differentially expressed, and validation was performed using real-time reverse transcription polymerase chain reaction (n=99; 321 RNA samples) and RNA in situ hybridization on tissue microarrays (n=479; 2047 tissue cores). GRIN3A was significantly higher expressed in cribriform pattern vs. NcGP4, when assessed within the same patient (n=27; p=0.005) and between different patients (n=83; p=0.001). Tissue cores with IDC more often expressed GRIN3A compared to ICC, NcGP4, and benign tissue (52 % vs. ≤ 32 %). When IDC and NcGP4 was compared within the same patient (173 pairs of tissue cores; 54 patients), 38 (22 %) of the tissue microarray core pairs had GRIN3A expression in only IDC, 33 (19 %) had expression in both IDC and NcGP4, 14 (8 %) in only NcGP4 and 88 (51 %) were negative in both entities (p=0.001). GRIN3A was as well associated with biochemical recurrence (log-rank, p=0.002). In conclusion, ectopic GRIN3A expression is an RNA-based biomarker for the presence of cribriform prostate cancer, particularly for IDC.}, } @article {pmid38944574, year = {2024}, author = {González-López, MM and Esquinas-López, C and Romero-García, M and Benito-Aracil, L and Martínez-Momblan, MA and Villanueva-Cendán, M and Jaume-Literas, M and Hospital-Vidal, MT and Delgado-Hito, P}, title = {Intensity of Interprofessional Collaboration and related factors in Intensive Care Units. A descriptive cross-sectional study with an analytical approach.}, journal = {Enfermeria intensiva}, volume = {35}, number = {3}, pages = {188-200}, doi = {10.1016/j.enfie.2023.10.002}, pmid = {38944574}, issn = {2529-9840}, mesh = {Cross-Sectional Studies ; Humans ; Male ; Adult ; Female ; *Intensive Care Units ; *Interprofessional Relations ; *Cooperative Behavior ; Middle Aged ; }, abstract = {OBJECTIVE: To determine the Intensity of Collaboration between the intensive care professionals of a third level hospital.

METHOD: Descriptive cross-sectional study with an analytical approach.

SETTING: 6 intensive care units of a third level hospital.

SAMPLE: nurses and doctors. Consecutive type non-probabilistic sampling.

DATA COLLECTION: sociodemographic, economic, motivation and professional satisfaction variables, and the intensity of collaboration using the "Scale of Intensity of Interprofessional Collaboration in Health."

RESULTS: A total of 102 health professionals (91 nurses and 11 doctors) were included. The mean overall Intensity of Collaboration (IoC) was moderate. Men showed higher scores in all factors (p<.05). The IoC global score was higher in the group of professionals with ≤10 years of experience (p=.043) and those who were highly satisfied with the profession (p=.037). Physicians presented higher scores in the global IdC (p=.037) and in the Collaboration mean (p=.020) independently in the multivariate models. A negative linear relationship (rho: -0,202, p=.042) was observed between age and the overall IoC score. Professionals aged ≤30years reported a higher perception of Shared Activities (p=.031). Negative linear relationships were observed between years of experience and total IoC score (rho: -0,202, p=.042) and patients' Perception score (rho: -0.241, p=0.015). The research activity also showed to be a variable related to a greater degree of Collaboration at a global level and in some of the factors (p<.05). The scale of IoC obtained a Cronbach's α of 0,9.

CONCLUSIONS: The intensity of interprofessional collaboration in ICUs is moderate. Professionals with experience of ≤10 years, a higher level of satisfaction and participation in research activities show a greater intensity of collaboration. Doctors perceive collaboration more intensely than nurses. All factors contribute equally to the internal consistency of the questionnaire.}, } @article {pmid38942922, year = {2024}, author = {Pantazi, V and Miklós, V and Smith, P and Oláh-Németh, O and Pankotai-Bodó, G and Teja Dondapati, D and Ayaydin, F and D'Angiolella, V and Pankotai, T}, title = {Prognostic potential of CUL3 ligase with differential roles in luminal A and basal type breast cancer tumors.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {14912}, pmid = {38942922}, issn = {2045-2322}, support = {MR/X006980/1/MRC_/Medical Research Council/United Kingdom ; National Research, Development and Innovation Office under NKFI-FK 13208//Tibor Pankotai/ ; Medical Research Council (MRC) grant MR/X006980/1//Vincenzo D'Angiolella/ ; }, mesh = {Humans ; *Cullin Proteins/metabolism/genetics ; Female ; Prognosis ; *Breast Neoplasms/pathology/genetics/metabolism ; *Biomarkers, Tumor/metabolism/genetics ; *Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; Gene Expression Profiling ; MCF-7 Cells ; Triple Negative Breast Neoplasms/genetics/pathology/metabolism ; }, abstract = {Breast cancer is a prevalent and significant cause of mortality in women, and manifests as six molecular subtypes. Its further histologic classification into non-invasive ductal or lobular carcinoma (DCIS) and invasive carcinoma (ILC or IDC) underscores its heterogeneity. The ubiquitin-proteasome system plays a crucial role in breast cancer, with inhibitors targeting the 26S proteasome showing promise in clinical treatment. The Cullin-RING ubiquitin ligases, including CUL3, have direct links to breast cancer. This study focuses on CUL3 as a potential biomarker, leveraging high-throughput sequencing, gene expression profiling, experimental and data analysis tools. Through comprehensive analysis using databases like GEPIA2 and UALCAN, as well as TCGA datasets, CUL3's expression and its association with prognostic values were assessed. Additionally, the impact of CUL3 overexpression was explored in MCF-7 and MDA-MB-231 breast cancer cell lines, revealing distinct differences in molecular and phenotypic characteristics. We further profiled its expression and localization in breast cancer tissues identifying prominent differences between luminal A and TNBC tumors. Conclusively, CUL3 was found to be associated with cell cycle progression, and DNA damage response, exhibiting diverse roles depending on the tumor's molecular type. It exhibits a tendency to act as an oncogene in triple-negative tumors and as a tumor suppressor in luminal A types, suggesting a potential significance in breast cancer progression and therapeutic directions.}, } @article {pmid38939257, year = {2024}, author = {Shrivastava, N}, title = {A Retrospective Analysis of Breast Cancer Presentation Among Young and Older Women in an Indian Cohort of 70 Patients.}, journal = {Cureus}, volume = {16}, number = {5}, pages = {e61239}, pmid = {38939257}, issn = {2168-8184}, abstract = {Introduction In females, carcinoma of the breast is a common malignancy. Disease management can be challenging for the treating clinician if the condition is presented in a locally advanced stage. Clinical presentation of a disease in a defined area provides a comprehensive map to target the at-risk population efficiently and select the appropriate intervention accordingly. In this retrospective study, we analyzed different factors that can affect breast carcinoma outcomes by assessing patients for a specific period of one year. Methods This is a retrospective study of carcinoma of breast patients and was conducted between 2017 and 2018. Results We reported a 25.83% incidence of breast cancer during the study period. A painful breast lump was present in 54.2% of patients, axillary nodes were present in 50% of patients, ulcers were present in 10% of patients, and nipple discharge was present in 8.5% of patients. According to the side and quadrant of involvement, the right side was the most common site of involvement in 55.7% of patients, and the upper outer quadrant was the most common quadrant involved in 61.4% of patients. The most familiar stage of the presentation was stage II, presented in 45.7% of patients. The most common histology was infiltrating ductal carcinoma, presented in 85.7% of patients. Conclusions This retrospective cohort study shows that carcinoma of the breast is a predominant malignancy among middle-aged females in developing countries such as India. This predominance is due to unawareness regarding disease symptoms and the fear of diagnosed malignancy during the investigation of symptoms. Early detection by screening and intervention at an early stage is the core of treatment success in this malignant disease. However, it is still challenging to apply screening as a tool to pick up early malignant disease in developing countries like India.}, } @article {pmid38937563, year = {2024}, author = {Kurokawa, K and Yamada, Y and Sakamoto, S and Horikoshi, T and Sato, K and Nanba, S and Kubota, Y and Kanesaka, M and Fujimoto, A and Takeuchi, N and Shibata, H and Sazuka, T and Imamura, Y and Tsuzuki, T and Uno, T and Ichikawa, T}, title = {Implications of unconventional histological subtypes on magnetic resonance imaging and oncological outcomes in patients who have undergone radical prostatectomy.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {14868}, pmid = {38937563}, issn = {2045-2322}, support = {23K19497//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; Male ; *Prostatectomy/methods ; *Prostatic Neoplasms/surgery/pathology/diagnostic imaging ; *Magnetic Resonance Imaging/methods ; Aged ; Middle Aged ; Neoplasm Grading ; Prognosis ; Retrospective Studies ; Prostate/pathology/surgery/diagnostic imaging ; Robotic Surgical Procedures/methods ; }, abstract = {The prognostic significance of unconventional histology (UH) subtypes including intraductal carcinoma of the prostate (IDC-P), ductal adenocarcinoma, and cribriform pattern has been investigated for prostate cancer (PCa). However, little is known about magnetic resonance imaging (MRI) features and the oncological impact of tumor localization in localized PCa with UH. Clinical data of 211 patients with acinar adenocarcinoma (conventional histology [CH]) and 82 patients with UH who underwent robotic-assisted radical prostatectomy (RARP) were reviewed. Patients with UH are more likely to be older and have higher Gleason grade group, higher Prostate Imaging-Reporting and Data System (PI-RADS) v2.1 score, and larger tumor volume (TV) than those with CH. Multivariate analysis identified the presence of UH as an independent prognostic factor for progression-free survival (PFS) (hazard ration (HR) 2.41, 95% confidence interval (CI) 0.22-0.79, P = 0.0073). No significant difference in PFS was seen regarding tumor localization (transition zone [TZ] or peripheral zone [PZ]) in patients with UH (P = 0.8949), whereas PZ cancer showed shorter PFS in patients with CH (P = 0.0174). PCa with UH was associated with higher progression than PCa with CH among resection margin (RM)-negative cases (P < 0.0001). Further, increased PI-RADS v2.1 score did not correlate with larger TV in UH (P = 0.991), whereas a significant difference in TV was observed in CH (P < 0.0001). The prognostic significance of UH tumor was independent of tumor localization, and shorter PFS was observed even in RM-negative cases, indicating an aggressive subtype with micro-metastatic potential. Furthermore, UH tumors are more likely to harbor a large TV despite PI-RADS v2.1 score ≤ 3. These findings will help optimal perioperative management for PCa with UH.}, } @article {pmid38935197, year = {2024}, author = {Delfin, L and Doff, JJ and Gagan, J and Flack, A and Krane, JF and Jo, VY and Torell, AG and Palsgrove, D and Bishop, JA}, title = {Pure Apocrine Intraductal Carcinoma of Salivary Glands: Reassessment of Molecular Underpinnings and Behavior.}, journal = {Head and neck pathology}, volume = {18}, number = {1}, pages = {58}, pmid = {38935197}, issn = {1936-0568}, mesh = {Humans ; Male ; Middle Aged ; Aged ; Female ; *Salivary Gland Neoplasms/pathology/genetics ; Aged, 80 and over ; Carcinoma, Intraductal, Noninfiltrating/pathology/genetics ; Biomarkers, Tumor/analysis/genetics ; Adult ; Carcinoma, Ductal/pathology/genetics ; }, abstract = {BACKGROUND: Intraductal carcinoma (IDC) of the salivary glands is a confounding entity, our understanding of which continues to evolve. At least four forms have been elucidated based on histomorphology, immunophenotype, and molecular profile: (1) intercalated duct-like, S100/SOX10+ with frequent NCOA4::RET fusions; (2) oncocytic, S100/SOX10+ with TRIM33::RET, NCOA4::RET, and BRAF V600E; (3) apocrine, AR+ with PI3 kinase pathway mutations; and (4) mixed/hybrid intercalated duct-like/apocrine, with S100/SOX10+ and AR+ areas and frequent TRIM27::RET. The revelation that myoepithelial cells harbor the same fusion as luminal cells suggested that fusion-positive cases are not in situ carcinomas as previously believed. To this point, purely apocrine IDC with entirely intraductal growth has not been found to harbor fusions, but very few cases have been tested.

METHODS: IDCs with pure apocrine morphology, entirely intraductal growth, and no precursor lesion (pleomorphic adenoma or sclerosing polycystic adenoma) were retrieved from the authors' archives. Several immunostains (S100, SOX10, GCDFP-15, AR, p40/SMA) and targeted next generation sequencing (NGS) panel including 1425 cancer-related genes were performed.

RESULTS: Seven entirely IDC with pure apocrine type were collected. The cases arose in the parotid glands (mean, 1.9 cm) of 5 men and 2 women ranging from 51 to 84 years (mean, 69.7 years). Histologically, tumors consisted of rounded to angulated ductal cysts lined by epithelial cells with abundant finely granular eosinophilic cytoplasm and large nuclei with prominent nucleoli. Pleomorphism was mild to moderate, the mitotic rate was low, and necrosis was absent. Conventionally invasive foci or areas of intercalated duct-like morphology were not identified. In all cases, luminal cells were diffusely positive for AR and GCDFP-15 while negative for S100/SOX10, and the ducts were completely surrounded by myoepithelial cells highlighted by p40 and SMA. Molecular analysis was successful in 6 cases. Three harbored fusions: one with NCOA4::RET, another with STRN::ALK and one with both CDKN2A::CNTRL and TANC1::YY1AP1. The three fusion-negative cases all harbored HRAS mutations; additional mutations (PIK3CA, SPEN, ATM) were found in 2 of 3 cases. All patients were treated by surgery alone. Six of them are currently free of disease (follow up 12-190 months), but the case harboring NCOA4::RET developed lymph nodes metastasis in the form of a fusion-positive invasive salivary duct carcinoma.

CONCLUSIONS: Purely apocrine IDC is a heterogeneous disease. A subset seems to be genetically similar to salivary duct carcinoma and may indeed represent carcinoma in situ. The other group harbors fusions, similar to other forms of IDC. Moreover, the occurrence of lymph node metastasis discredits the idea that any fusion-positive IDC with a complete myoepithelial cell layer has no metastatic potential. With the wide use of RET-and ALK-based targeted therapies, our findings further underscore the importance of fusion analysis for IDC.}, } @article {pmid38929597, year = {2024}, author = {Yoo, KC and Kim, DH and Park, S and Yun, H and Ryu, DH and Lee, J and Son, SM}, title = {Gastric Metastasis Mimicking Early Gastric Cancer from Invasive Ductal Carcinoma of the Breast: Case Report and Literature Review.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {6}, pages = {}, pmid = {38929597}, issn = {1648-9144}, mesh = {Humans ; Female ; *Stomach Neoplasms/pathology/diagnosis ; Aged ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/secondary/diagnosis ; *Gastrectomy/methods ; Diagnosis, Differential ; Lymphatic Metastasis ; }, abstract = {Backgound and Objectives: Gastric metastasis from invasive ductal breast cancer (BC) is rare. It mainly occurs in patients with lobular BC. The occurrence of multiple metastases is typically observed several years after the primary diagnosis. Endoscopic findings of gastric metastasis of the BC were usually the linitis plastic type. Case presentation: A 72-year-old women who underwent right modified radical mastectomy (MRM) 10 month ago was referred after being diagnosed with early gastric cancer (EGC) during systemic chemotherapy. EGC type I was found at gastric fundus, and pathologic finding showed poorly differentiated adenocarcinoma. Metachronous double primary tumor EGC was considered. Management and Outcome: A laparoscopic total gastrectomy was performed, and postoperative pathology revealed submucosa invasion and two lymph node metastases. A pathologic review that focused on immunohistochemical studies of selected antibodies such as GATA binding protein 3 (GATA3), gross cystic disease fluid protein-15 (GCDFP-15), cytokeratin 7 (CK7) was performed again, comparing previous results. As a result, gastric metastasis from BC was diagnosed. After totally laparoscopic total gastrectomy, palliative first-line chemotherapy with paclitaxel/CDDP was performed. Two months after gastrectomy, she was diagnosed with para-aortic lymph node metastasis and multiple bone metastases. She expired six months after gastrectomy. Conclusions: Gastric metastasis from invasive ductal carcinoma of the breast, which is clinically manifested as EGC, is a very rare condition. If there is a history of BC, careful pathological review will be required.}, } @article {pmid38928454, year = {2024}, author = {Hulahan, TS and Spruill, L and Wallace, EN and Park, Y and West, RB and Marks, JR and Hwang, ES and Drake, RR and Angel, PM}, title = {Extracellular Microenvironment Alterations in Ductal Carcinoma In Situ and Invasive Breast Cancer Pathologies by Multiplexed Spatial Proteomics.}, journal = {International journal of molecular sciences}, volume = {25}, number = {12}, pages = {}, pmid = {38928454}, issn = {1422-0067}, support = {RO1CA253460//NIH/NCI/ ; S10OD010731//NIH/OD/ ; 5T32 GM008716-24/GF/NIH HHS/United States ; 5TL1TR001451-09/GF/NIH HHS/United States ; S10OD025126//NIH/OD/ ; S100D030212//NIH/OD/ ; P30 CA138313/GF/NIH HHS/United States ; }, mesh = {Humans ; Female ; *Breast Neoplasms/metabolism/pathology ; *Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; *Tumor Microenvironment ; *Proteomics/methods ; *Extracellular Matrix/metabolism/pathology ; Proteome/metabolism/analysis ; Neoplasm Invasiveness ; Carcinoma, Ductal, Breast/metabolism/pathology ; Middle Aged ; }, abstract = {Ductal carcinoma in situ (DCIS) is a heterogeneous breast disease that remains challenging to treat due to its unpredictable progression to invasive breast cancer (IBC). Contemporary literature has become increasingly focused on extracellular matrix (ECM) alterations with breast cancer progression. However, the spatial regulation of the ECM proteome in DCIS has yet to be investigated in relation to IBC. We hypothesized that DCIS and IBC present distinct ECM proteomes that could discriminate between these pathologies. Tissue sections of pure DCIS, mixed DCIS-IBC, or pure IBC (n = 22) with detailed pathological annotations were investigated by multiplexed spatial proteomics. Across tissues, 1,005 ECM peptides were detected in pathologically annotated regions and their surrounding extracellular microenvironments. A comparison of DCIS to IBC pathologies demonstrated 43 significantly altered ECM peptides. Notably, eight fibrillar collagen peptides could distinguish with high specificity and sensitivity between DCIS and IBC. Lesion-targeted proteomic imaging revealed heterogeneity of the ECM proteome surrounding individual DCIS lesions. Multiplexed spatial proteomics reported an invasive cancer field effect, in which DCIS lesions in closer proximity to IBC shared a more similar ECM profile to IBC than distal counterparts. Defining the ECM proteomic microenvironment provides novel molecular insights relating to DCIS and IBC.}, } @article {pmid38927753, year = {2024}, author = {Markalunas, EG and Arnold, DH and Funkhouser, AT and Martin, JC and Shtutman, M and Edenfield, WJ and Blenda, AV}, title = {Correlation Analysis of Genetic Mutations and Galectin Levels in Breast Cancer Patients.}, journal = {Genes}, volume = {15}, number = {6}, pages = {}, pmid = {38927753}, issn = {2073-4425}, support = {P20 GM109091/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Breast Neoplasms/genetics/blood/pathology ; Female ; *Galectins/genetics/blood ; *Mutation ; *Biomarkers, Tumor/genetics/blood ; Galectin 1/genetics/blood ; Middle Aged ; Galectin 3/genetics/blood ; Adult ; Blood Proteins ; }, abstract = {Galectins are innate immune system regulators associated with disease progression in cancer. This paper aims to investigate the correlation between mutated cancer-critical genes and galectin levels in breast cancer patients to determine whether galectins and genetic profiles can be used as biomarkers for disease and potential therapy targets. Prisma Health Cancer Institute's Biorepository provided seventy-one breast cancer samples, including all four stages spanning the major molecular subtypes and histologies. Hotspot mutation statuses of cancer-critical genes were determined using multiplex PCR in tumor samples from the same patients by Precision Genetics and the University of South Carolina Functional Genomics Core Facility. The galectin-1, -3, and -9 levels in patients' sera were analyzed using Enzyme-linked Immunosorbent Assay (ELISA). An analysis was performed using JMP software to compare mean and median serum galectin levels between samples with and without specific cancer-critical genes, including pooled t-test, Wilcoxon Rank Sum Test, ANOVA, and Steel Dwass Test (α=0.05). Our analysis indicates that KIT mutations correlate with elevated serum levels of galectin-9 in patients with breast cancer. In patients with Luminal A subtype, FLT3 mutation correlates with lower serum galectin-1 and -9 levels and TP53 mutations correlate with higher serum galectin-3 levels. Patients with invasive ductal carcinoma had significantly higher serum galectin-3 levels than patients with ductal carcinoma in situ. Patients with both TP53 and PIK3CA mutations exhibit elevated serum galectin-3 levels, while patients with one or neither mutation show no significant difference in serum galectin-3 levels. In addition, metastatic breast cancer samples were more likely to have a KIT or PIK3CA mutation compared to primary breast cancer samples. The relationship between genetic mutations and galectin levels has the potential to identify appropriate candidates for combined therapy, targeting genetic mutations and galectins. Further understanding of the effect of genetic mutations and galectin levels on cancer progression and metastasis could aid in the search for biomarkers for breast cancer diagnosis, disease progression, and prognosis.}, } @article {pmid38926485, year = {2024}, author = {Baranová, I and Samec, M and Dvorská, D and Šťastný, I and Janíková, K and Kašubová, I and Hornáková, A and Lukáčová, E and Kapinová, A and Biringer, K and Halašová, E and Danková, Z}, title = {Droplet digital PCR analysis of CDH13 methylation status in Slovak women with invasive ductal breast cancer.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {14700}, pmid = {38926485}, issn = {2045-2322}, support = {1/0286/22//Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences/ ; }, mesh = {Humans ; *Cadherins/genetics ; Female ; *DNA Methylation ; *Breast Neoplasms/genetics/pathology ; Middle Aged ; *Carcinoma, Ductal, Breast/genetics/pathology/metabolism ; Aged ; *Promoter Regions, Genetic ; Slovakia ; Biomarkers, Tumor/genetics ; Adult ; Polymerase Chain Reaction/methods ; }, abstract = {Identifying novel epigenetic biomarkers is a promising way to improve the clinical management of patients with breast cancer. Our study aimed to determine the methylation pattern of 25 tumor suppressor genes (TSG) and select the best methylation biomarker associated with clinicopathological features in the cohort of Slovak patients diagnosed with invasive ductal carcinoma (IDC). Overall, 166 formalin-fixed, paraffin-embedded (FFPE) tissues obtained from patients with IDC were included in the study. The methylation status of the promoter regions of 25 TSG was analyzed using semiquantitative methylation-specific MLPA (MS-MLPA). We identified CDH13 as the most frequently methylated gene in our cohort of patients. Further analysis by ddPCR confirmed an increased level of methylation in the promoter region of CDH13. A significant difference in CDH13 methylation levels was observed between IDC molecular subtypes LUM A versus HER2 (P = 0.0116) and HER2 versus TNBC (P = 0.0234). In addition, significantly higher methylation was detected in HER2+ versus HER2- tumors (P = 0.0004) and PR- versus PR+ tumors (P = 0.0421). Our results provide evidence that alteration in CDH13 methylation is associated with clinicopathological features in the cohort of Slovak patients with IDC. In addition, using ddPCR as a methylation-sensitive method represents a promising approach characterized by higher precision and technical simplicity to measure the methylation of target CpGs in CDH13 compared to other conventional methods such as MS-MLPA.}, } @article {pmid38923054, year = {2024}, author = {Sendag, S and Koca, D and Arslan, T and Schuler, G and Wehrend, A}, title = {Oestrogen and progesterone concentrations in intrapartum cows with insufficient cervix dilation.}, journal = {Reproduction in domestic animals = Zuchthygiene}, volume = {59}, number = {6}, pages = {e14656}, doi = {10.1111/rda.14656}, pmid = {38923054}, issn = {1439-0531}, mesh = {Animals ; Female ; Cattle ; *Progesterone/blood ; Pregnancy ; *Cervix Uteri ; *Estrogens/blood ; Dystocia/veterinary ; Estradiol/blood ; Cattle Diseases/blood ; }, abstract = {The cervix is an important organ that has to dilate sufficiently at delivery to allow the foetus to transition to extrauterine life. Insufficient dilatation of the cervix (IDC) is a frequent cause of dystocia in cattle. The mechanisms underlying cervical opening and the pathogenesis of IDC are still widely unclear. Systematic studies on the relationship between IDC and steroid hormones have been limited and have yielded inconsistent findings. This study aimed to measure oestrogen and progesterone (P4) concentrations in intrapartum cows presented with dystocia due to IDC and in a comparison (C) group of cows with eutocic delivery. Before any obstetrical procedures, and right after the initial evaluation, blood samples were taken from IDC and C animals. Concentrations of P4, oestradiol-17β (E2), free total oestrogens (FTE) and conjugated total oestrogens (CTE) were measured by established radioimmunoassays. Concentrations of P4 (p = .538), FTE (p = .065) and CTE (p = .605) were not statistically different between C and IDC groups. However, E2 levels in group C were significantly lower when compared to those in the IDC group (p = .013), which is inconsistent with the function of oestrogens in cervical dilatation. The correlation analysis demonstrated significant positive correlations between the pairs P4 versus FTE, P4 versus E2 and FTE versus E2 in group C and between the pair FTE versus E2 in group IDC. In conclusion, the results suggest that local activities of steroids relevant to the aetiology of IDC are not reflected by concentrations in the systemic circulation or that other factors are clearly more important.}, } @article {pmid38919804, year = {2024}, author = {Wang, A and Quint, E and Kukeev, I and Agassi, R and Belochitski, O and Barski, G and Vaynshtein, J}, title = {Application of Intraoperative Radiotherapy in Early-Stage Breast Cancer Patients in a Clinical Setting.}, journal = {International journal of breast cancer}, volume = {2024}, number = {}, pages = {5551907}, pmid = {38919804}, issn = {2090-3170}, abstract = {Background: Intraoperative radiation therapy (IORT) has gained popularity in recent years as an alternative to external beam whole breast radiation therapy (WBRT) for early-stage breast cancer. Here, we report 43-month recurrence and survival outcomes in a multiethnic cohort treated with IORT in a clinical context. Method: Two hundred and eleven patients with low-risk features were treated with IORT for early-stage breast cancer from 2014 to 2021. Selection criteria were based on Group Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) guidelines: preferably unifocal intraductal carcinoma (IDC), aged > 50, tumor size ≤ 2.0 cm, and without lymph node involvement. All patients received 20 Gy of radiation dose during the lumpectomy. Information on patient and tumor characteristics was collected. Results: The mean age of this cohort was 67.5 years; 95.2% of patients are Jewish, and the rest are Bedouins (4.7%). Most tumors were intraductal carcinoma (97.2%) and stage 1 (94.8%). The mean follow-up time was 43.4 months. Bedouins had larger tumor sizes (mean 1.21 vs. 1.13 cm) and were younger at diagnosis than Jewish patients (mean 65.4 vs. 67.6 years), although the differences are not significant. The overall recurrence rate was 1.4%. One case of local recurrence (0.5%) and two cases of metastasis (0.9%) were observed during the study period. One patient died from metastasis. Conclusion: Our findings suggest that IORT in selected low-risk patients can achieve an excellent prognosis with low rates of recurrence and metastasis.}, } @article {pmid38911548, year = {2024}, author = {Zhou, YT and Zhang, PJ and Wang, SP and Li, CH and Zhang, JQ and Zhang, WX and Zhao, YD and Cao, YC and Fan, JX}, title = {Biosafety assessments of hexafluoropropylene trimer derivative as a fluorinated cooling fluid for electronics.}, journal = {Toxicological research}, volume = {40}, number = {3}, pages = {431-440}, pmid = {38911548}, issn = {1976-8257}, abstract = {UNLABELLED: The Internet Data Center (IDC) is one of the most important infrastructures in the field of information technology. The cooling system for heat dissipation of IDC is indispensable due to it generates a large amount of heat during its calculation process, which may potentially harm its normal operation. Electronic fluorinated fluids have been widely used in cooling systems of IDC with stable physical and chemical properties. However, the biological toxicity of electronic fluorinated fluids has not been fully evaluated and there is a lack of unified safety standards, which may pose potential risks to the environment and human health. Here, hexafluoropropylene terpolymer (HFPT) as an example has been systematically studied, fully considering the application scenarios of data centers. Also, the emergency effects of fluorinated coolants in mammalian models from the perspectives of inhalation, skin contact, accidental entry into eyes, accidental ingestion, and chronic toxicity, are evaluated. Multiple in vivo experiments have proven that HFPT not only has stable physical and chemical properties, that can maintain the safe operation of IDC, but also has low physiological toxicity to mammals and can provide health benefits to data center staff and the assurance of surrounding environment. This study proves the good biological safety of electronic fluorinated fluids and provides a reference for environmental assessment and risk management of liquid cooling technology in IDC.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43188-024-00234-3.}, } @article {pmid38908072, year = {2024}, author = {Berndt, C and Alborzinia, H and Amen, VS and Ayton, S and Barayeu, U and Bartelt, A and Bayir, H and Bebber, CM and Birsoy, K and Böttcher, JP and Brabletz, S and Brabletz, T and Brown, AR and Brüne, B and Bulli, G and Bruneau, A and Chen, Q and DeNicola, GM and Dick, TP and Distéfano, A and Dixon, SJ and Engler, JB and Esser-von Bieren, J and Fedorova, M and Friedmann Angeli, JP and Friese, MA and Fuhrmann, DC and García-Sáez, AJ and Garbowicz, K and Götz, M and Gu, W and Hammerich, L and Hassannia, B and Jiang, X and Jeridi, A and Kang, YP and Kagan, VE and Konrad, DB and Kotschi, S and Lei, P and Le Tertre, M and Lev, S and Liang, D and Linkermann, A and Lohr, C and Lorenz, S and Luedde, T and Methner, A and Michalke, B and Milton, AV and Min, J and Mishima, E and Müller, S and Motohashi, H and Muckenthaler, MU and Murakami, S and Olzmann, JA and Pagnussat, G and Pan, Z and Papagiannakopoulos, T and Pedrera Puentes, L and Pratt, DA and Proneth, B and Ramsauer, L and Rodriguez, R and Saito, Y and Schmidt, F and Schmitt, C and Schulze, A and Schwab, A and Schwantes, A and Soula, M and Spitzlberger, B and Stockwell, BR and Thewes, L and Thorn-Seshold, O and Toyokuni, S and Tonnus, W and Trumpp, A and Vandenabeele, P and Vanden Berghe, T and Venkataramani, V and Vogel, FCE and von Karstedt, S and Wang, F and Westermann, F and Wientjens, C and Wilhelm, C and Wölk, M and Wu, K and Yang, X and Yu, F and Zou, Y and Conrad, M}, title = {Ferroptosis in health and disease.}, journal = {Redox biology}, volume = {75}, number = {}, pages = {103211}, pmid = {38908072}, issn = {2213-2317}, support = {R01 CA165065/CA/NCI NIH HHS/United States ; R01 CA254970/CA/NCI NIH HHS/United States ; U01 AI156924/AI/NIAID NIH HHS/United States ; R01 NS076511/NS/NINDS NIH HHS/United States ; R01 AI145406/AI/NIAID NIH HHS/United States ; R01 NS061817/NS/NINDS NIH HHS/United States ; R01 CA243142/CA/NCI NIH HHS/United States ; P01 HL114453/HL/NHLBI NIH HHS/United States ; R35 CA253059/CA/NCI NIH HHS/United States ; R01 GM112948/GM/NIGMS NIH HHS/United States ; R01 CA258390/CA/NCI NIH HHS/United States ; R37 NS061817/NS/NINDS NIH HHS/United States ; R01 CA266342/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; U01 AI156923/AI/NIAID NIH HHS/United States ; }, mesh = {*Ferroptosis ; Humans ; Animals ; Iron/metabolism ; Neoplasms/metabolism/drug therapy/pathology ; Lipid Peroxidation ; Oxidation-Reduction ; Disease Susceptibility ; }, abstract = {Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark of ferroptosis is uncontrolled and overwhelming peroxidation of polyunsaturated fatty acids contained in membrane phospholipids, which eventually leads to rupture of the plasma membrane. Ferroptosis is unique in that it is essentially a spontaneous, uncatalyzed chemical process based on perturbed iron and redox homeostasis contributing to the cell death process, but that it is nonetheless modulated by many metabolic nodes that impinge on the cells' susceptibility to ferroptosis. Among the various nodes affecting ferroptosis sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets for the treatment of numerous currently incurable diseases. Herein, the current members of a Germany-wide research consortium focusing on ferroptosis research, as well as key external experts in ferroptosis who have made seminal contributions to this rapidly growing and exciting field of research, have gathered to provide a comprehensive, state-of-the-art review on ferroptosis. Specific topics include: basic mechanisms, in vivo relevance, specialized methodologies, chemical and pharmacological tools, and the potential contribution of ferroptosis to disease etiopathology and progression. We hope that this article will not only provide established scientists and newcomers to the field with an overview of the multiple facets of ferroptosis, but also encourage additional efforts to characterize further molecular pathways modulating ferroptosis, with the ultimate goal to develop novel pharmacotherapies to tackle the various diseases associated with - or caused by - ferroptosis.}, } @article {pmid38907536, year = {2024}, author = {Shenkman, G and Ifrah, K and Shmotkin, D}, title = {Evil-related threats and mental health concomitants among offspring of Holocaust survivors gay men.}, journal = {Aging & mental health}, volume = {28}, number = {11}, pages = {1522-1531}, doi = {10.1080/13607863.2024.2363342}, pmid = {38907536}, issn = {1364-6915}, mesh = {Humans ; Male ; *Holocaust/psychology ; Aged ; Middle Aged ; *Survivors/psychology ; Israel/epidemiology ; *Depression/psychology/epidemiology ; Aged, 80 and over ; *Personal Satisfaction ; Homosexuality, Male/psychology/statistics & numerical data ; Mental Health ; Sexual and Gender Minorities/psychology/statistics & numerical data ; }, abstract = {OBJECTIVES: In view of the accumulated stress associated with the combination of intergenerational trauma and minority stress, we aimed to examine whether offspring of Holocaust survivors (OHS) reported stronger evil-related threats compared to non-OHS individuals and whether OHS gay men experienced stronger threats. We also examined whether sexual orientation moderated the hypothesized indirect effect of Holocaust background on mental health through evil-related threats.

METHOD: Participants were 346 middle-aged and older Israeli men (mean age = 60.56, SD = 8.42, range 50-86). Among them, 173 identified as gay men, and 81 identified as OHS. Participants completed measures of evil-related threats, depression, and life satisfaction.

RESULTS: Analysis of covariance revealed that OHS men reported stronger evil-related threats compared to non-OHS men. Yet, an interaction between Holocaust background and sexual orientation indicated that OHS gay men reported stronger evil-related threats compared to non-OHS gay men, while no such difference existed among heterosexual counterparts. Conditional indirect effect analysis showed a significant indirect effect, in which Holocaust background related to higher depressive symptoms and lower life satisfaction through evil-related threats among gay men, but not among heterosexual men.

CONCLUSION: This study sheds light on the particular experience of evil-related threats, focusing on older OHS gay men and the mental health vulnerability associated with it. In applied contexts, this might help identify a sexual minority group that is particularly sensitive to adverse mental health and offer it supporting interventions.}, } @article {pmid38905209, year = {2024}, author = {von Rauchhaupt, E and Rodemer, C and Kliemank, E and Bulkescher, R and Campos, M and Kopf, S and Fleming, T and Herzig, S and Nawroth, PP and Szendroedi, J and Zemva, J and Sulaj, A}, title = {Glucose Load Following Prolonged Fasting Increases Oxidative Stress- Linked Response in Individuals With Diabetic Complications.}, journal = {Diabetes care}, volume = {47}, number = {9}, pages = {1584-1592}, pmid = {38905209}, issn = {1935-5548}, support = {82DZD07C2G//German Center for Diabetes Research (DZD)/ ; 236360313â€"SFB 1118//Deutsche Forschungsgemeinschaft (DFG)/ ; //Deutsche Diabetes Gesellschaft (DDG)/ ; Friedrich-Fischer-Estate//Medizinischen Fakultät Heidelberg, Universität Heidelberg/ ; }, mesh = {Humans ; *Oxidative Stress/physiology ; *Fasting/physiology ; *Diabetes Mellitus, Type 2/metabolism ; Male ; Middle Aged ; Female ; Diabetes Complications/metabolism ; Glucose/metabolism ; Glucose Tolerance Test ; Adult ; Leukocytes, Mononuclear/metabolism ; Blood Glucose/metabolism ; Aged ; }, abstract = {OBJECTIVE: Prolonged catabolic states in type 2 diabetes (T2D), exacerbated by excess substrate flux and hyperglycemia, can challenge metabolic flexibility and antioxidative capacity. We investigated cellular responses to glucose load after prolonged fasting in T2D.

RESEARCH DESIGN AND METHODS: Glucose-tolerant individuals (CON, n = 10) and individuals with T2D with (T2D+, n = 10) and without (T2D-, n = 10) diabetes complications underwent oral glucose tolerance test before and after a 5-day fasting-mimicking diet. Peripheral blood mononuclear cell (PBMC) resistance to ex vivo dicarbonyl methylglyoxal (MG) exposure after glucose load was assessed. Markers of dicarbonyl detoxification, oxidative stress, and mitochondrial biogenesis were analyzed by quantitative PCR, with mitochondrial complex protein expression assessed by Western blotting.

RESULTS: T2D+ exhibited decreased PBMC resistance against MG, while T2D- resistance remained unchanged, and CON improved postglucose load and fasting (-19.0% vs. -1.7% vs. 12.6%; all P = 0.017). T2D+ showed increased expression in dicarbonyl detoxification (mRNA glyoxalase-1, all P = 0.039), oxidative stress (mRNA glutathione-disulfide-reductase, all P = 0.006), and mitochondrial complex V protein (all P = 0.004) compared with T2D- and CON postglucose load and fasting. Citrate synthase activity remained unchanged, indicating no change in mitochondrial number. Mitochondrial biogenesis increased in T2D- compared with CON postglucose load and fasting (mRNA HspA9, P = 0.032). T2D-, compared with CON, exhibited increased oxidative stress postfasting, but not postglucose load, with increased mRNA expression in antioxidant defenses (mRNA forkhead box O4, P = 0.036, and glutathione-peroxidase-2, P = 0.034), and compared with T2D+ (glutathione-peroxidase-2, P = 0.04).

CONCLUSIONS: These findings suggest increased susceptibility to glucose-induced oxidative stress in individuals with diabetes complications after prolonged fasting and might help in diet interventions for diabetes management.}, } @article {pmid38900042, year = {2024}, author = {Mayfield, JD and Ataya, D and Abdalah, M and Stringfield, O and Bui, MM and Raghunand, N and Niell, B and El Naqa, I}, title = {Presurgical Upgrade Prediction of DCIS to Invasive Ductal Carcinoma Using Time-dependent Deep Learning Models with DCE MRI.}, journal = {Radiology. Artificial intelligence}, volume = {6}, number = {5}, pages = {e230348}, pmid = {38900042}, issn = {2638-6100}, support = {P30 CA076292/CA/NCI NIH HHS/United States ; R01 CA249016/CA/NCI NIH HHS/United States ; U01 CA261841/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology/surgery ; *Deep Learning ; Middle Aged ; *Magnetic Resonance Imaging/methods ; Retrospective Studies ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology/surgery ; *Contrast Media ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology/surgery ; Aged ; Adult ; Predictive Value of Tests ; Image Interpretation, Computer-Assisted/methods ; Breast/diagnostic imaging/pathology/surgery ; }, abstract = {Purpose To determine whether time-dependent deep learning models can outperform single time point models in predicting preoperative upgrade of ductal carcinoma in situ (DCIS) to invasive malignancy at dynamic contrast-enhanced (DCE) breast MRI without a lesion segmentation prerequisite. Materials and Methods In this exploratory study, 154 cases of biopsy-proven DCIS (25 upgraded at surgery and 129 not upgraded) were selected consecutively from a retrospective cohort of preoperative DCE MRI in women with a mean age of 59 years at time of diagnosis from 2012 to 2022. Binary classification was implemented with convolutional neural network (CNN)-long short-term memory (LSTM) architectures benchmarked against traditional CNNs without manual segmentation of the lesions. Combinatorial performance analysis of ResNet50 versus VGG16-based models was performed with each contrast phase. Binary classification area under the receiver operating characteristic curve (AUC) was reported. Results VGG16-based models consistently provided better holdout test AUCs than did ResNet50 in CNN and CNN-LSTM studies (multiphase test AUC, 0.67 vs 0.59, respectively, for CNN models [P = .04] and 0.73 vs 0.62 for CNN-LSTM models [P = .008]). The time-dependent model (CNN-LSTM) provided a better multiphase test AUC over single time point (CNN) models (0.73 vs 0.67; P = .04). Conclusion Compared with single time point architectures, sequential deep learning algorithms using preoperative DCE MRI improved prediction of DCIS lesions upgraded to invasive malignancy without the need for lesion segmentation. Keywords: MRI, Dynamic Contrast-enhanced, Breast, Convolutional Neural Network (CNN) Supplemental material is available for this article. © RSNA, 2024.}, } @article {pmid38897820, year = {2024}, author = {Corso, G and Fusco, N and Guerini-Rocco, E and Leonardi, MC and Criscitiello, C and Zagami, P and Nicolò, E and Mazzarol, G and La Vecchia, C and Pesapane, F and Zanzottera, C and Tarantino, P and Petitto, S and Bianchi, B and Massari, G and Boato, A and Sibilio, A and Polizzi, A and Curigliano, G and De Scalzi, AM and Lauria, F and Bonanni, B and Marabelli, M and Rotili, A and Nicosia, L and Albini, A and Calvello, M and Mukhtar, RA and Robson, ME and Sacchini, V and Rennert, G and Galimberti, V and Veronesi, P and Magnoni, F}, title = {Invasive lobular breast cancer: Focus on prevention, genetics, diagnosis, and treatment.}, journal = {Seminars in oncology}, volume = {51}, number = {3-4}, pages = {106-122}, doi = {10.1053/j.seminoncol.2024.05.001}, pmid = {38897820}, issn = {1532-8708}, mesh = {Humans ; *Breast Neoplasms/diagnosis/genetics/therapy/pathology/prevention & control ; Female ; *Carcinoma, Lobular/diagnosis/therapy/genetics/pathology ; }, abstract = {Invasive lobular cancer (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast malignancies. The distinctive biological features of ILC include the loss of the cell adhesion molecule E-cadherin, which drives the tumor's peculiar discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, such tumors originate in the lobules, are more commonly bilateral compared to invasive ductal cancer (IDC) and require a more accurate diagnostic examination through imaging. They are luminal in molecular subtype, and exhibit estrogen and progesterone receptor positivity and HER2 negativity, thus presenting a more unpredictable response to neoadjuvant therapies. There has been a significant increase in research focused on this distinctive breast cancer subtype, including studies on its pathology, its clinical and surgical management, and the high-resolution definition of its genomic profile, as well as the development of new therapeutic perspectives. This review will summarize the heterogeneous pattern of this unique disease, focusing on challenges in its comprehensive clinical management and on future insights and research objectives.}, } @article {pmid38895649, year = {2024}, author = {Zhang, Z and Lan, H and Zhao, S}, title = {Analysis of the Value of Quantitative Features in Multimodal MRI Images to Construct a Radio-Omics Model for Breast Cancer Diagnosis.}, journal = {Breast cancer (Dove Medical Press)}, volume = {16}, number = {}, pages = {305-318}, pmid = {38895649}, issn = {1179-1314}, abstract = {OBJECTIVE: To analyze the diagnostic value of quantitative features in multimodal magnetic resonance imaging (MRI) images to construct a radio-omics model for breast cancer.

METHODS: Ninety-five patients with breast-related diseases from January 2020 to January 2021 were grouped into the benign group (n=57) and malignant group (n=38) according to the pathological findings. All cases were randomized as the training group (n=66) and validation group (n=29) in a 7:3 ratio based on the examination time. All subjects were examined by T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), dynamic contrast enhancement (DCE), and apparent diffusion coefficient (ADC) multimodality MRI. The MRI findings were analyzed against pathological findings. A diagnostic breast cancer radiomics model was constructed. The diagnostic efficacy of the model in the validation group was analyzed, and the diagnostic efficacy was analyzed via the ROC curve.

RESULTS: Fibroadenoma accounted for 49.12% of benign breast diseases, and invasive ductal carcinoma accounted for 73.68% of malignant breast diseases. The sensitivity of T1WI, T2WI, DWI, ADC, and DCE in diagnosing breast cancer was 61.14%, 66.67%, 73.30%, 78.95%, and 85.96%, using the four-fold table method. The area under the curves (AUCs) of T1WI, T2WI, DWI, ADC, and DCE for diagnosing breast cancer were 0.715, 0.769, 0.785, 0.835, and 0.792, respectively. The AUCs of plain scan, diffuse, enhanced, plain scan + diffuse, plain scan + enhanced, enhanced + diffuse, and plain scan + enhanced + diffuse for diagnosing breast cancer were 0.746, 0.798, 0.816, 0.839, 0.890, 0.906, and 0.927, respectively.

CONCLUSION: The construction of a radio-omics model by quantitative features in multimodal MRI images was valuable in the diagnosis of breast cancer. The value of radio-omics models such as plain scan + enhanced + diffuse was higher than the other models in diagnosing breast cancer and could be widely applied in clinical practice.}, } @article {pmid38895384, year = {2024}, author = {Mello, RM and Ceballos, DG and Sandate, CR and Agudelo, D and Jouffe, C and Uhlenhaut, NH and Thomä, NH and Simon, MC and Lamia, KA}, title = {BMAL1-HIF2α heterodimers contribute to ccRCC.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38895384}, issn = {2692-8205}, support = {R01 CA211187/CA/NCI NIH HHS/United States ; R01 CA271500/CA/NCI NIH HHS/United States ; }, abstract = {Circadian disruption enhances cancer risk, and many tumors exhibit disordered circadian gene expression. We show rhythmic gene expression is unexpectedly robust in clear cell renal cell carcinoma (ccRCC). Furthermore, the clock gene BMAL1 is higher in ccRCC than in healthy kidneys, unlike in other tumor types. BMAL1 is closely related to ARNT, and we show that BMAL1-HIF2α regulates a subset of HIF2α target genes in ccRCC cells. Depletion of BMAL1 reprograms HIF2α chromatin association and target gene expression and reduces ccRCC growth in culture and in xenografts. Analysis of pre-existing data reveals higher BMAL1 in patient-derived xenografts that are sensitive to growth suppression by a HIF2α antagonist (PT2399). We show that BMAL1-HIF2α is more sensitive than ARNT-HIF2α to suppression by PT2399, and increasing BMAL1 sensitizes 786O cells to growth inhibition by PT2399. Together, these findings indicate that an alternate HIF2α heterodimer containing the circadian partner BMAL1 contributes to HIF2α activity, growth, and sensitivity to HIF2α antagonist drugs in ccRCC cells.}, } @article {pmid38894870, year = {2024}, author = {Ramamoorthy, P and Ramakantha Reddy, BR and Askar, SS and Abouhawwash, M}, title = {Histopathology-based breast cancer prediction using deep learning methods for healthcare applications.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1300997}, pmid = {38894870}, issn = {2234-943X}, abstract = {Breast cancer (BC) is the leading cause of female cancer mortality and is a type of cancer that is a major threat to women's health. Deep learning methods have been used extensively in many medical domains recently, especially in detection and classification applications. Studying histological images for the automatic diagnosis of BC is important for patients and their prognosis. Owing to the complication and variety of histology images, manual examination can be difficult and susceptible to errors and thus needs the services of experienced pathologists. Therefore, publicly accessible datasets called BreakHis and invasive ductal carcinoma (IDC) are used in this study to analyze histopathological images of BC. Next, using super-resolution generative adversarial networks (SRGANs), which create high-resolution images from low-quality images, the gathered images from BreakHis and IDC are pre-processed to provide useful results in the prediction stage. The components of conventional generative adversarial network (GAN) loss functions and effective sub-pixel nets were combined to create the concept of SRGAN. Next, the high-quality images are sent to the data augmentation stage, where new data points are created by making small adjustments to the dataset using rotation, random cropping, mirroring, and color-shifting. Next, patch-based feature extraction using Inception V3 and Resnet-50 (PFE-INC-RES) is employed to extract the features from the augmentation. After the features have been extracted, the next step involves processing them and applying transductive long short-term memory (TLSTM) to improve classification accuracy by decreasing the number of false positives. The results of suggested PFE-INC-RES is evaluated using existing methods on the BreakHis dataset, with respect to accuracy (99.84%), specificity (99.71%), sensitivity (99.78%), and F1-score (99.80%), while the suggested PFE-INC-RES performed better in the IDC dataset based on F1-score (99.08%), accuracy (99.79%), specificity (98.97%), and sensitivity (99.17%).}, } @article {pmid38893590, year = {2024}, author = {Cicciarelli, F and Guiducci, E and Galati, F and Moffa, G and Ricci, P and Pediconi, F and Rizzo, V}, title = {Digital Mammography (DM) vs. Dynamic Contrast Enhancement-Magnetic Resonance Imaging (DCE-MRI) in Microcalcifications Assessment: A Radiological-Pathological Comparison.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, pmid = {38893590}, issn = {2075-4418}, abstract = {The aim of this study was to compare the characteristics of breast microcalcification on digital mammography (DM) with the histological and molecular subtypes of breast cancer and to identify the predictive value of DM and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing microcalcifications for radiologic-pathologic correlation. We relied on our prospectively maintained database of suspicious microcalcifications on DM, from which data were retrospectively collected between January 2020 and April 2023. We enrolled 158 patients, all of whom were subjected to biopsy. Additionally, 63 patients underwent breast DCE-MRI. Microcalcifications with a linear branched morphology were correlated with malignancies (p < 0.001), among which an association was highlighted between triple negatives (TNs) and segmental distribution (p < 0.001). Amorphous calcifications were correlated with atypical ductal hyperplasia (ADH) (p = 0.013), coarse heterogeneous (p < 0.001), and fine-pleomorphic (p = 0.008) with atypical lobular hyperplasia (ALH) and fine pleomorphic (p = 0.009) with flat epithelial atypia (FEA). Regarding DCE-MRI, no statistical significance was observed between non-mass lesions and ductal carcinoma in situ (DCIS). Concerning mass lesions, three were identified as DCIS and five as invasive ductal carcinoma (IDC). In conclusion, microcalcifications assessed in DM exhibit promising predictive characteristics concerning breast lesion subtypes, leading to a reduction in diagnostic times and further examination costs, thereby enhancing the clinical management of patients.}, } @article {pmid38889436, year = {2024}, author = {Su, HZ and Hong, LC and Su, YM and Chen, XS and Zhang, ZB and Zhang, XD}, title = {A Nomogram Based on Conventional Ultrasound Radiomics for Differentiating Between Radial Scar and Invasive Ductal Carcinoma of the Breast.}, journal = {Ultrasound quarterly}, volume = {40}, number = {3}, pages = {}, doi = {10.1097/RUQ.0000000000000685}, pmid = {38889436}, issn = {1536-0253}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging ; *Nomograms ; Middle Aged ; Diagnosis, Differential ; *Ultrasonography, Mammary/methods ; *Carcinoma, Ductal, Breast/diagnostic imaging ; Adult ; *Breast/diagnostic imaging ; Cicatrix/diagnostic imaging ; Aged ; Reproducibility of Results ; Retrospective Studies ; Radiomics ; }, abstract = {We aimed to develop and validate a nomogram based on conventional ultrasound (CUS) radiomics model to differentiate radial scar (RS) from invasive ductal carcinoma (IDC) of the breast. In total, 208 patients with histopathologically diagnosed RS or IDC of the breast were enrolled. They were randomly divided in a 7:3 ratio into a training cohort (n = 145) and a validation cohort (n = 63). Overall, 1316 radiomics features were extracted from CUS images. Then a radiomics score was constructed by filtering unstable features and using the maximum relevance minimum redundancy algorithm and the least absolute shrinkage and selection operator logistic regression algorithm. Two models were developed using data from the training cohort: one using clinical and CUS characteristics (Clin + CUS model) and one using clinical information, CUS characteristics, and the radiomics score (radiomics model). The usefulness of nomogram was assessed based on their differentiating ability and clinical utility. Nine features from CUS images were used to build the radiomics score. The radiomics nomogram showed a favorable predictive value for differentiating RS from IDC, with areas under the curve of 0.953 and 0.922 for the training and validation cohorts, respectively. Decision curve analysis indicated that this model outperformed the Clin + CUS model and the radiomics score in terms of clinical usefulness. The results of this study may provide a novel method for noninvasively distinguish RS from IDC.}, } @article {pmid38887513, year = {2024}, author = {Nemerovsky, L and Ghetler, Y and Wiser, A and Levi, M}, title = {Two types of cleavage, from zygote to three cells, result in different clinical outcomes and should be treated differently.}, journal = {Frontiers in cell and developmental biology}, volume = {12}, number = {}, pages = {1398684}, pmid = {38887513}, issn = {2296-634X}, abstract = {RESEARCH QUESTION: What is the utilization rate of embryos that exert inadequate zygote cleavage into three daughter cells?

DESIGN: This study used a retrospective dataset from a single IVF Unit. A total of 3,060 embryos from 1,811 fresh IVF cycles were analyzed. The cleavage pattern, morphokinetics, and outcome were recorded. Only 2pn embryos, fertilized by ejaculated sperm, and cultured in a time-lapse system for at least 5 days were included. We generated three study groups according to the embryo's cleavage pattern: (I) Control, normal cleavage (n = 551); (II) fast cleavage, zygote to three cells within 5 h (n = 1,587); and (III) instant direct tripolar cleavage (IDC) from zygote to three cells (n = 922).

RESULTS: The rate of usable fast cleavage blastocysts was 108/1,587 (6.81%) and usable control blastocysts was 180/551 (32.67%). The time of PN fading and from fading to first cleavage differed significantly between the three groups. Although the pregnancy rate of control and fast cleavage blastocysts were comparable (40.35% and 42.55%, respectively), the amount of instant direct cleavage embryos that reached blastocyst stage was neglectable (only four embryos out of 922 analyzed IDC embryos) and unsuitable for statistical comparison of pregnancy rates.

CONCLUSION: Our results indicate the need to culture instant direct cleavage embryos for 5 days, up to the blastocyst stage, and avoid transfer of embryos that are fated to arrest even when their morphological grade on day 3 is acceptable, whereas fast cleavage embryos could be transferred on day 3 when there is no alternative.}, } @article {pmid38883142, year = {2024}, author = {Ibrahim, EH and Ali, TA and Sharbatti, S and Ismail, MK and Rahamathullah, N and Bylappa, SK and Khalfan, NH and Mohammed, ME and Qasem, AM and Hussein, MA and Ibrahim, SM and Bashir, GA and Alassal, MF and Sobhy, M and Dahy, AA and Abuelsoud, A}, title = {Histopathological Profile of Different Breast Lesions: A Single-Center Observational Study.}, journal = {Cureus}, volume = {16}, number = {5}, pages = {e60408}, pmid = {38883142}, issn = {2168-8184}, abstract = {OBJECTIVE: To describe the histopathological pattern of different breast lesions among tissue specimens sent to our laboratory.

METHOD: A record-based study using a retrospective review of 255 histologically diagnosed breast biopsy reports in the histopathology department of authors from December 2016 to November 2021 was conducted. The specimens were collected from core biopsy, lumpectomy, and mastectomy. All data obtained were analyzed using the Statistical Package for the Social Sciences (SPSS) version 28 (IBM SPSS Statistics, Armonk, NY). Then, the findings were presented using text, tables, and charts.

RESULT: A total of 255 breast lesions were analyzed in this study. Most of the cases were benign (58.8%), followed by inflammatory lesions (21.6%), and malignant (19.6%). Fibroadenoma was the most prevalent benign lesion (36.7%), and most of the patients (70.9%) were in the age group of 20-39 years old. The most common inflammatory lesion was granulomatous mastitis (56.4%), and most of the cases were diagnosed in the age group of 30-39 years old. Invasive ductal carcinoma (IDC) was the most encountered histological type of carcinoma (62%). Of the malignant cases, 52% were diagnosed before the age of 50 years. Among these 50 cases, grade 2 was the most prevalent one (46%).

CONCLUSION: Benign breast lesions are more common than malignant breast lesions, and fibroadenoma is the most common benign subtype. Granulomatous mastitis is the most prevalent inflammatory breast lesion. About two-thirds of malignant cases are non-Arab. Invasive ductal carcinoma with no special type (NST) is the most common malignant subtype.}, } @article {pmid38882784, year = {2024}, author = {Vasudevan, S and Kannan, K and Raghavan, AV and Sulochana, S}, title = {Analyzing Tumor Budding Scores in Invasive Breast Carcinoma: A Tertiary Care Center Study in South India.}, journal = {Journal of pharmacy & bioallied sciences}, volume = {16}, number = {Suppl 2}, pages = {S1850-S1853}, pmid = {38882784}, issn = {0976-4879}, abstract = {INTRODUCTION AND AIM: Tumor budding is a distinctive phenomenon which involves the presence of small clusters or individual cancer cells at the invasive front of tumors. Tumor budding has garnered attention due to its potential implications for prognosis, treatment strategies, and our understanding of cancer progression. Our aim is to study the distribution of tumor buds and its scoring in patients with infiltrating breast carcinoma and to associate with other histopathological parameters like the size of the tumor, its grade, lymphovascular invasion, and lymph node metastasis.

MATERIALS AND METHODS: This was a study analyzing the data of 70 resected specimens of primary breast carcinomas and providing a descriptive overview. Tumor budding was recognized, counted, and graded in hematoxylin and eosin slides. The cases were classified as low (0-4), intermediate (5-9), and high (≥10 buds) based on the count of tumor buds. Tumor budding has significant correlation with tumor grade and tumor size.

RESULTS: Of the 70 cases, 60 cases (85.71%) were diagnosed as invasive ductal carcinoma NOS. The majority [38 (54.28%)] of the cases showed an intermediate tumor budding score of 5-9/10 HPF.

CONCLUSION: Evaluation of tumor budding allows pathologists and oncologists to gather valuable information about the tumor's biological aggressiveness and potential for metastasis. It also helps in better risk stratification of patients, enabling a more personalized and tailored approach to treatment planning. In conclusion, assessing tumor budding in breast carcinoma holds significant clinical importance in the management and prognosis of this disease.}, } @article {pmid38881244, year = {2024}, author = {Rotstein, MS and Zimmerman-Brenner, S and Davidovitch, S and Ben-Haim, Y and Koryto, Y and Sion, R and Rubinstein, E and Djerassi, M and Lubiniaker, N and Peleg, TP and Steinberg, T and Leitner, Y and Raz, G}, title = {Gamified Closed-Loop Intervention Enhances Tic Suppression in Children: A Randomized Trial.}, journal = {Movement disorders : official journal of the Movement Disorder Society}, volume = {39}, number = {8}, pages = {1310-1322}, doi = {10.1002/mds.29875}, pmid = {38881244}, issn = {1531-8257}, support = {//Tourette Association of America/ ; //The Brainboost Innovation Center at the Sagol School of Neuroscience, Tel-Aviv University/ ; }, mesh = {Humans ; Child ; Male ; Female ; Adolescent ; *Tic Disorders/therapy ; Cross-Over Studies ; Video Games ; Behavior Therapy/methods ; Treatment Outcome ; Reward ; Severity of Illness Index ; Tics/therapy ; }, abstract = {BACKGROUND: Gamification of behavioral intervention for tic disorders (TDs) potentially enhances compliance and offers key clinical advantages. By delivering immediate positive feedback upon tic-suppression, games may counteract negative reinforcement, which presumably contribute to tic consolidation by relieving uncomfortable premonitory urges.

OBJECTIVES: We developed a gamified protocol (XTics), which leverages this potential by combining gamified tic-triggering with immediate feedback, and evaluated its clinical value in enhancing tic suppression.

METHODS: XTics encompasses two conditions: Immediate and Contingent Reward (ICR), where game progression is contingent upon successful tic suppression, and Delayed Reward (DR), where game events' outcomes are random. Employing a randomized crossover design, 35 participants (aged 7-15 years) underwent daily gaming sessions over a week per condition. Improvements in our primary measures, including the inter-tic interval (ITI) and tic severity assessment by blinded evaluators (Yale Global Tic Severity-Total Tic Score [YGTSS-TTS], Rush), and parents (Parent Tic Questionnaire [PTQ]), were compared between ICR and DR, and assessed across conditions for the 4-week protocol.

RESULTS: No participant voluntarily left the study before completing its two-phase protocol. As expected, ITI showed significantly larger improvement (Z = 4.19, P = 2.85 × 10-5) after ICR (1442 ± 2250%) versus DR (242 ± 493%) training, increasing at a higher pace (t(67) = 3.15, P = 0.0025). Similarly, Rush tic severity scores reduced more post-ICR versus DR (t(47) = 3.47, P = 0.002). We observed a clinically significant reduction of 25.69 ± 23.39% in YGTSS-TTS following a f4-week protocol including both conditions. Parent-reported tic severity decreased by 42.99 ± 31.69% from baseline to 3 months post-treatment.

CONCLUSIONS: The combination of gamified tic-triggering with immediate and contingent rewards demonstrates a promising approach for enhancing treatment efficacy in TDs, boosting traditional therapeutic methods. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.}, } @article {pmid38877185, year = {2024}, author = {Alabedi, HH and Ahmed, IK and Jamil, ASM}, title = {Incidence of local breast cancer recurrence with delayed radiation therapy.}, journal = {Breast cancer research and treatment}, volume = {207}, number = {3}, pages = {625-631}, pmid = {38877185}, issn = {1573-7217}, mesh = {Humans ; Female ; *Neoplasm Recurrence, Local/epidemiology/pathology ; *Breast Neoplasms/pathology/radiotherapy/epidemiology ; Middle Aged ; Adult ; Aged ; Retrospective Studies ; Incidence ; Mastectomy ; Time-to-Treatment ; Neoplasm Staging ; }, abstract = {BACKGROUND: The purpose of this research was to examine the probability of ipsilateral breast cancer recurrence in individuals whose RT was delayed after the first chemotherapy and surgery.

PURPOSE: To analyze the effect of delaying RT for breast cancer patients (by more than 6 weeks after treatment).

METHODOLOGY: A retrospective analysis comprised 136 female breast cancer patients treated at the Baghdad Centre for Radiation Oncology and Nuclear Medicine from 2021 to May 2022. External beam radiation was started more than 6 weeks after chemotherapy was finished for all patients who also had surgery. Clinical examination and ultrasound were part of the follow-up process.

RESULTS: Patients' ages varied from 28 to 71, and the majority (83%) had a mastectomy. The majority of cases (95.5%) were diagnosed as invasive ductal carcinoma on histopathology, with 49.6% being at stage 2 and 42.6% being at stage 3. Seventy-six percent of patients tested positive for hormones. Although 10 patients (7.35%) acquired distant metastases within 5 years, only 2 (1.47%) had local recurrence because of the delay in RT. Specifically, 91.1% had complete local control with no evidence of disease spread.

CONCLUSION: Delaying RT by more than 6 weeks in patients with breast cancer did not substantially affect local control, according to the results of a new research, the first of its type in Iraq.}, } @article {pmid38864081, year = {2024}, author = {Andrianto, A and Sudiana, IK and Suprabawati, DGA}, title = {α-Smooth Muscle Actin as Predictors of Early Recurrence in Early-Stage Ductal Type Breast Cancer After Mastectomy and Chemotherapy.}, journal = {Iranian journal of pathology}, volume = {19}, number = {1}, pages = {67-74}, pmid = {38864081}, issn = {1735-5303}, abstract = {BACKGROUND & OBJECTIVE: Breast cancer recurrence after surgery was a sign that the progress of the disease was continuing. Early detection of breast cancer patients who are at risk requires development of a marker. Alfa smooth muscle actin (α-SMA) plays a role in the local recurrence process of invasive ductal carcinoma (IDC). Currently, existing tumor markers are used to predict the prognosis of breast cancer in general, not the early stages. Therefore, it was thought that finding α-SMA expression might predict early recurrence in early-stage IDC more accurately than others. This study investigated the potential role of α-SMA expression as a predictor of early recurrence in early-stage IDC and its relationship to clinicopathological factors.

METHODS: The study design was cross-sectional, with data obtained from the medical records of Dr. Koesnadi, General Hospital, Bondowoso, Indonesia. Bivariate and multivariate analysis was performed to analyze data.

RESULTS: We included 50 subjects divided into the local recurrence group (n=25) and the non-local recurrence group (n=25). We found a statistically significant correlation between the incidence of local recurrence in early-stage IDC and the high expression of α-SMA (odd ratio [OR]=23.22, 95% confidence interval [CI]=5.101-105.7, P=0.001). Clinicopathological variables and α-SMA expression did not have a significant correlation.

CONCLUSION: In early-stage IDC, α-SMA expression had the potential to predict and could be an independent prognostic factor for early recurrence.}, } @article {pmid38863962, year = {2024}, author = {Qamar, MA and Rehman, A and Toor, HUR}, title = {Multidisciplinary management of necrotizing fasciitis as a postoperative complication after mastectomy in an adult male in a low- and middle-income country.}, journal = {Journal of surgical case reports}, volume = {2024}, number = {6}, pages = {rjae412}, pmid = {38863962}, issn = {2042-8812}, abstract = {Necrotizing fasciitis, a rare, potentially life-threatening infection, often necessitates urgent medical intervention and surgical excision of the affected tissue. We present a 55-year-old male patient with a progressively enlarging lump in the left breast that was diagnosed as a breast carcinoma. Post-modified radical mastectomy, histopathological examination revealed Grade II invasive ductal carcinoma with neuroendocrine features. Due to financial constraints, the patient missed post-operative follow-ups and did not complete the prescribed radiotherapy sessions. Three months later, the patient returned with fever, swelling alongside sharp pain in the left arm and oozing blood. A clinical diagnosis of necrotizing fasciitis was made, leading to urgent surgical debridement. While the wound progressively healed, a contracture developed restricting elbow movement. An Orthopedic Review and Bone scintigraphy revealed metastasis of breast carcinoma to the sternum. This case report highlights the multi-disciplinary management required in such financially constrained rare cases in low- and middle-income countries.}, } @article {pmid38860104, year = {2024}, author = {Shetty, ND and Dhande, R and Parihar, P and Bora, N}, title = {Magnetic Resonance Imaging of Radiation-Induced Brachial Plexopathy.}, journal = {Cureus}, volume = {16}, number = {5}, pages = {e60067}, pmid = {38860104}, issn = {2168-8184}, abstract = {This report illustrates the case of a 37-year-old woman following chemoradiotherapy for invasive ductal carcinoma of the right breast. The patient underwent surgery and received a radiation dose of 50 gray to the chest wall and 45 gray to the regional lymph nodes in 25 total fractions. She developed motor and sensory weakness in the right upper limb eight years after treatment. Brachial plexus neuropathy in cancer patients may result from either trauma to the plexus during surgery, the spread of cancer, or radiation therapy, and distinguishing between them may be difficult. The case highlights the importance of recognizing the signs, symptoms, and possible differential diagnosis of radiation-induced brachial plexopathy in cancer patients post-radiation therapy. It emphasizes the role of magnetic resonance imaging in the careful assessment and diagnosis of such a case.}, } @article {pmid38850114, year = {2024}, author = {Cheng, L and Wang, J and Tang, L}, title = {Analysis of prognostic factors and construction of prognostic models for invasive lobular carcinoma of the breast.}, journal = {Biomolecules & biomedicine}, volume = {24}, number = {6}, pages = {1692-1702}, pmid = {38850114}, issn = {2831-090X}, mesh = {Humans ; Female ; *Carcinoma, Lobular/therapy/pathology/mortality ; *Breast Neoplasms/pathology/mortality/therapy/diagnosis ; Middle Aged ; Aged ; Prognosis ; Retrospective Studies ; SEER Program ; Carcinoma, Ductal, Breast/mortality/pathology/therapy ; Adult ; Nomograms ; Neoplasm Staging ; }, abstract = {Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) account for most cases of breast cancer. However, there is ongoing debate about any potential variations in overall survival (OS) between ILC and IDC. This study aimed to compare survival between IDC and ILC, identify prognostic factors for ILC patients, and construct a nomogram for predicting OS rates. This retrospective cohort analysis utilized data from the Surveillance, Epidemiology, and End Results (SEER) Cancer Database. Patients diagnosed with ILC and IDC between 2000 and 2019 were enrolled. To minimize baseline differences in clinicopathological characteristics and survival outcomes, a propensity score matching (PSM) method was used. Data from the multivariate Cox regression analyses were used to construct a predictive nomogram for OS at 1, 3, and 5 years, incorporating all independent prognostic factors. Following the PSM procedure, patients with ILC exhibited a better prognosis compared to those with IDC. TNM stage, age >70, radiotherapy, surgery, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HR-/HER2+) subtype were identified as independent factors for OS in ILC patients. Surgery and radiotherapy effectively reduced the risk of death, while chemotherapy did not demonstrate the same benefit. This model could support clinicians in evaluating the prognosis of ILC for decision-making and patient counseling.}, } @article {pmid38847615, year = {2024}, author = {Hunt, KN and Conners, AL and Gray, L and Hruska, CB and O'Connor, MK}, title = {Molecular Breast Imaging Biopsy with a Dual-Detector System.}, journal = {Radiology. Imaging cancer}, volume = {6}, number = {4}, pages = {e230186}, pmid = {38847615}, issn = {2638-616X}, support = {R01 CA239200/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology ; Middle Aged ; Prospective Studies ; *Image-Guided Biopsy/methods/instrumentation ; Adult ; *Technetium Tc 99m Sestamibi ; *Molecular Imaging/methods/instrumentation ; Aged ; Radiopharmaceuticals ; Breast/diagnostic imaging ; }, abstract = {Purpose To develop a molecular breast imaging (MBI)-guided biopsy system using dual-detector MBI and to perform initial testing in participants. Materials and Methods The Stereo Navigator MBI Accessory biopsy system comprises a lower detector, upper fenestrated compression paddle, and upper detector. The upper detector retracts, allowing craniocaudal, oblique, or medial or lateral biopsy approaches. The compression paddle allows insertion of a needle guide and needle. Lesion depth is calculated by triangulation of lesion location on the upper detector at 0° and 15° and relative lesion activity on upper and lower detectors. In a prospective study (July 2022-June 2023), participants with Breast Imaging Reporting and Data System category 2, 3, 4, or 5 breast lesions underwent MBI-guided biopsy. After injection of 740 MBq technetium 99m sestamibi, craniocaudal and mediolateral oblique MBI (2-minute acquisition per view) confirmed lesion visualization. A region of interest over the lesion permitted depth calculation in the system software. Upper detector retraction allowed biopsy device placement. Specimen images were obtained on the retracted upper detector, confirming sampling of the target. Results Of 21 participants enrolled (mean age, 50.6 years ± 10.1 [SD]; 21 [100%] women), 17 underwent MBI-guided biopsy with concordant pathology. No lesion was observed at the time of biopsy in four participants. Average lesion size was 17 mm (range, 6-38 mm). Average procedure time, including preprocedure imaging, was 55 minutes ± 13 (range, 38-90 minutes). Pathology results included invasive ductal carcinoma (n = 1), fibroadenoma (n = 4), pseudoangiomatous stromal hyperplasia (n = 6), and fibrocystic changes (n = 6). Conclusion MBI-guided biopsy using a dual-head system with retractable upper detector head was feasible, well tolerated, and efficient. Keywords: Breast Biopsy, Molecular Breast Imaging, Image-guided Biopsy, Molecular Breast Imaging-guided Biopsy, Breast Cancer Clinical trial registration no. NCT06058650 © RSNA, 2024.}, } @article {pmid38840117, year = {2024}, author = {Pickett, MR and Chen, YI and Kamra, M and Kumar, S and Kalkunte, N and Sugerman, GP and Varodom, K and Rausch, MK and Zoldan, J and Yeh, HC and Parekh, SH}, title = {Assessing the impact of extracellular matrix fiber orientation on breast cancer cellular metabolism.}, journal = {Cancer cell international}, volume = {24}, number = {1}, pages = {199}, pmid = {38840117}, issn = {1475-2867}, support = {SERB-SRG/2021/001886//Science and Engineering Research Board/ ; EY033106/NH/NIH HHS/United States ; Adhoc-ID.2021-9106//Indian Council of Medical Research/ ; R01HL157829/NH/NIH HHS/United States ; F-2008-20220331//Welch Foundation/ ; R21 EY033106/EY/NEI NIH HHS/United States ; 2235856//National Science Foundation/ ; GRFP//National Science Foundation/ ; 2235455//National Science Foundation/ ; 2146549//National Science Foundation/ ; }, abstract = {The extracellular matrix (ECM) is a dynamic and complex microenvironment that modulates cell behavior and cell fate. Changes in ECM composition and architecture have been correlated with development, differentiation, and disease progression in various pathologies, including breast cancer [1]. Studies have shown that aligned fibers drive a pro-metastatic microenvironment, promoting the transformation of mammary epithelial cells into invasive ductal carcinoma via the epithelial-to-mesenchymal transition (EMT) [2]. The impact of ECM orientation on breast cancer metabolism, however, is largely unknown. Here, we employ two non-invasive imaging techniques, fluorescence-lifetime imaging microscopy (FLIM) and intensity-based multiphoton microscopy, to assess the metabolic states of cancer cells cultured on ECM-mimicking nanofibers in a random and aligned orientation. By tracking the changes in the intrinsic fluorescence of nicotinamide adenine dinucleotide and flavin adenine dinucleotide, as well as expression levels of metastatic markers, we reveal how ECM fiber orientation alters cancer metabolism and EMT progression. Our study indicates that aligned cellular microenvironments play a key role in promoting metastatic phenotypes of breast cancer as evidenced by a more glycolytic metabolic signature on nanofiber scaffolds of aligned orientation compared to scaffolds of random orientation. This finding is particularly relevant for subsets of breast cancer marked by high levels of collagen remodeling (e.g. pregnancy associated breast cancer), and may serve as a platform for predicting clinical outcomes within these subsets [3-6].}, } @article {pmid38839260, year = {2025}, author = {Sun, T and Golestani, R and Zhan, H and Krishnamurti, U and Harigopal, M and Zhong, M and Liang, Y}, title = {Clinicopathologic Characteristics of MYC Copy Number Amplification in Breast Cancer.}, journal = {International journal of surgical pathology}, volume = {33}, number = {1}, pages = {59-64}, doi = {10.1177/10668969241256109}, pmid = {38839260}, issn = {1940-2465}, mesh = {Humans ; Female ; Middle Aged ; Gene Amplification ; *Breast Neoplasms/genetics/pathology/mortality ; Adult ; Aged ; *Proto-Oncogene Proteins c-myc/genetics/analysis ; *Biomarkers, Tumor/genetics/analysis ; Gene Dosage ; Prognosis ; Aged, 80 and over ; *Carcinoma, Ductal, Breast/genetics/pathology/mortality ; High-Throughput Nucleotide Sequencing ; Immunohistochemistry ; Breast/pathology ; }, abstract = {INTRODUCTION: MYC overexpression is a known phenomenon in breast cancer. This study investigates the correlation of MYC gene copy number amplification and MYC protein overexpression with coexisting genetic abnormalities and associated clinicopathologic features in breast cancer patients.

METHODS: The study analyzed data from 81 patients with localized or metastatic breast cancers using targeted next-generation sequencing and MYC immunohistochemical studies, along with pathological and clinical data.

RESULTS: Applying the criteria of MYC/chromosome 8 ratio ≥5, MYC copy number amplified tumors (n = 11, 14%) were associated with invasive ductal carcinoma (91% vs 68%, P = .048), poorly differentiated (grade 3, 64% vs 30%, P = .032), mitotically active (Nottingham mitotic score 3, 71% vs 20%, P = .004), estrogen receptor (ER)-negative (45% vs 12%, P = .008), and triple-negative (56% vs 12%, P = .013) compared to MYC non-amplified tumors. Among MYC-amplified breast cancer patients, those with triple-negative status showed significantly shorter disease-free survival time than non-triple negative MYC-amplified patients (median survival month: 25.5 vs 127.6, P = .049). MYC amplification is significantly associated with TP53 mutation (P = .007). The majority (10 of 11; 91%) of MYC-amplified tumors showed positive c-MYC immunostaining.

CONCLUSION: Breast cancers with MYC copy number amplication display distinct clinicopathologic characteristics indicative of more aggressive behavior.}, } @article {pmid38838211, year = {2024}, author = {Wang, Y and Li, G and Chen, B and Shakir, G and Volz, M and van der Vorst, EPC and Maas, SL and Geiger, M and Jethwa, C and Bartelt, A and Li, Z and Wettich, J and Sachs, N and Maegdefessel, L and Nazari Jahantigh, M and Hristov, M and Lacy, M and Lutz, B and Weber, C and Herzig, S and Guillamat Prats, R and Steffens, S}, title = {Myeloid cannabinoid CB1 receptor deletion confers atheroprotection in male mice by reducing macrophage proliferation in a sex-dependent manner.}, journal = {Cardiovascular research}, volume = {120}, number = {12}, pages = {1411-1426}, pmid = {38838211}, issn = {1755-3245}, support = {STE1053/6-1//Deutsche Forschungsgemeinschaft/ ; 81Z0600205//German Ministry of Research and Education/ ; 1061//LMU Medical Faculty FöFoLe program/ ; //Interdisciplinary Center for Clinical Research/ ; //RWTH Aachen University/ ; 10.20.2.043MN//Fritz Thyssen Stiftung/ ; 201908080123//Chinese Scholar Council/ ; }, mesh = {Animals ; Female ; Humans ; Male ; Aortic Diseases/genetics/pathology/prevention & control/metabolism/enzymology ; *Atherosclerosis/genetics/pathology/metabolism/prevention & control/enzymology ; Carotid Artery Diseases/genetics/pathology/metabolism/prevention & control ; *Cell Proliferation ; *Disease Models, Animal ; Estradiol/pharmacology ; Estrogen Receptor alpha/metabolism/genetics/deficiency ; *Macrophages/metabolism/pathology ; Mice, Inbred C57BL ; Mice, Knockout ; Phenotype ; *Plaque, Atherosclerotic ; *Receptor, Cannabinoid, CB1/metabolism/genetics ; Sex Factors ; *Signal Transduction ; Tumor Suppressor Protein p53/metabolism/genetics/deficiency ; }, abstract = {AIMS: Although the cannabinoid CB1 receptor has been implicated in atherosclerosis, its cell-specific effects in this disease are not well understood. To address this, we generated a transgenic mouse model to study the role of myeloid CB1 signalling in atherosclerosis.

METHODS AND RESULTS: Here, we report that male mice with myeloid-specific Cnr1 deficiency on atherogenic background developed smaller lesions and necrotic cores than controls, while only minor genotype differences were observed in females. Male Cnr1-deficient mice showed reduced arterial monocyte recruitment and macrophage proliferation with less inflammatory phenotype. The sex-specific differences in proliferation were dependent on oestrogen receptor (ER)α-oestradiol signalling. Kinase activity profiling identified a CB1-dependent regulation of p53 and cyclin-dependent kinases. Transcriptomic profiling further revealed chromatin modifications, mRNA processing, and mitochondrial respiration among the key processes affected by CB1 signalling, which was supported by metabolic flux assays. Chronic administration of the peripherally restricted CB1 antagonist JD5037 inhibited plaque progression and macrophage proliferation, but only in male mice. Finally, CNR1 expression was detectable in human carotid endarterectomy plaques and inversely correlated with proliferation, oxidative metabolism, and inflammatory markers, suggesting a possible implication of CB1-dependent regulation in human pathophysiology.

CONCLUSION: Impaired macrophage CB1 signalling is atheroprotective by limiting their arterial recruitment, proliferation, and inflammatory reprogramming in male mice. The importance of macrophage CB1 signalling appears to be sex-dependent.}, } @article {pmid38837365, year = {2024}, author = {Voloch, L and Icht, M and Ben-David, BM and Carmel Neiderman, NN and Levenberg, G and Manor, Y and Shpunt, D and Oestreicher-Kedem, Y}, title = {Seven Days of Voice Rest Post-phonosurgery Is Not Better than 3 days: A Prospective Randomized Short-term Outcome Study.}, journal = {The Laryngoscope}, volume = {134}, number = {11}, pages = {4661-4666}, doi = {10.1002/lary.31556}, pmid = {38837365}, issn = {1531-4995}, mesh = {Humans ; Female ; Male ; Prospective Studies ; Adult ; *Vocal Cords/surgery/physiopathology ; *Voice Quality ; Time Factors ; Treatment Outcome ; Middle Aged ; *Laryngeal Diseases/surgery/physiopathology ; Rest/physiology ; Voice Disorders/etiology/surgery/physiopathology ; Phonation/physiology ; Postoperative Period ; Postoperative Care/methods ; }, abstract = {OBJECTIVE: The aim of the study is to compare the short-term effect of 7 versus 3 days of voice rest (VR) on objective vocal (acoustic) parameters following phonosurgery.

METHODS: A prospective randomized study conducted at a tertiary referral medical center. Patients with vocal fold nodules, polyps, or cysts and scheduled for phonosurgery were recruited from the Voice Clinic. They were randomized into groups of 7- or 3-day postoperative VR periods and their voices were recorded preoperatively and at 4-week postoperatively. A mixed linear model statistical analysis (MLMSA) was used to compare pre- and postoperative jitter, shimmer, harmonic-to-noise ratio, and maximum phonation time between the two groups.

RESULTS: Sixty-five patients were recruited, but only 34 fully complied with the study protocol, and their data were included in the final analysis (19 males, 20 females; mean age: 40.6 years; 17 patients in the 7-day VR group and 16 in the 3-day VR group). The groups were comparable in age, sex, and type of vocal lesion distribution. The preoperative MLMSA showed no significant group differences in the tested vocal parameters. Both groups exhibited significant (p < 0.05) and comparable improvement in all vocal parameters at postoperative week 4.

CONCLUSIONS: A VR duration of 7 days showed no greater benefit on the examined vocal parameters than the 3-day protocol 4-week postoperatively. Our results suggest that a 3-day VR regimen can be followed by patients who undergo phonosurgery without compromising the vocal results. Larger-scale and longer-duration studies are needed to confirm our findings.

LEVEL OF EVIDENCE: 2 Laryngoscope, 134:4661-4666, 2024.}, } @article {pmid38837155, year = {2024}, author = {Wang, WE and Ho, CC and Chang, CH}, title = {Taxane-Induced Cutaneous Toxic Effects.}, journal = {JAMA dermatology}, volume = {160}, number = {7}, pages = {771-772}, doi = {10.1001/jamadermatol.2024.1204}, pmid = {38837155}, issn = {2168-6084}, mesh = {Humans ; *Taxoids/adverse effects ; Female ; Drug Eruptions/etiology/pathology ; Antineoplastic Agents/adverse effects ; Middle Aged ; }, } @article {pmid38833720, year = {2025}, author = {Wang, L and Vasudevaraja, V and Tran, I and Sukhadia, P and Reuter, VE and Abu-Rustum, NR and Rubinstein, MM and Gopalan, A and Ross, D and Snuderl, M and Chiang, S}, title = {Novel Androgen Receptor Splice Variant 7 in Gynecologic Tumors.}, journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists}, volume = {44}, number = {1}, pages = {88-93}, doi = {10.1097/PGP.0000000000001029}, pmid = {38833720}, issn = {1538-7151}, mesh = {Female ; Humans ; Middle Aged ; Biomarkers, Tumor/genetics ; DNA Methylation ; Genital Neoplasms, Female/genetics/pathology ; Ovarian Neoplasms/pathology/genetics ; *Receptors, Androgen/genetics ; Uterine Neoplasms/genetics/pathology ; }, abstract = {Androgen receptor splicing variant 7 (AR-V7) is a truncated variant of the AR mRNA that may be a predictive biomarker for AR-targeted therapy. AR-V7 has been described in prostate, breast, salivary duct, and hepatocellular carcinomas as well as mammary and extra-mammary Paget disease. We report 2 gynecologic cancers occurring in the lower uterine segment and ovary and both harboring AR-V7 by targeted RNA sequencing. The uterine tumor was an undifferentiated carcinoma consisting of epithelioid cells and focally spindled cells arranged in sheets, nests, and cords associated with brisk mitotic activity and tumor necrosis. The ovarian tumor consisted of glands with cribriform and solid architecture and uniform cytologic atypia. ER and PR were positive in the ovarian tumor and negative in the uterine tumor. Both were positive for AR and negative for HER2, GATA3, and NKX3.1. DNA methylation profiling showed epigenetic similarity of the AR-V7-positive gynecologic cancers to AR-V7-positive breast cancers rather than to prostate cancers. AR-V7 may underpin rare gynecologic carcinomas with undifferentiated histology or cribriform growth reminiscent of prostatic adenocarcinoma and breast invasive ductal carcinoma.}, } @article {pmid38831458, year = {2024}, author = {Morla-Barcelo, PM and Laguna-Macarrilla, D and Cordoba, O and Matheu, G and Oliver, J and Roca, P and Nadal-Serrano, M and Sastre-Serra, J}, title = {Unraveling malignant phenotype of peritumoral tissue: transcriptomic insights into early-stage breast cancer.}, journal = {Breast cancer research : BCR}, volume = {26}, number = {1}, pages = {89}, pmid = {38831458}, issn = {1465-542X}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/mortality/metabolism ; *Gene Expression Profiling ; *Transcriptome ; *Gene Expression Regulation, Neoplastic ; *Neoplasm Staging ; Prognosis ; *Protein Interaction Maps/genetics ; Middle Aged ; Biomarkers, Tumor/genetics ; Gene Regulatory Networks ; Carcinoma, Ductal, Breast/genetics/pathology/metabolism ; Phenotype ; Neoplasm Recurrence, Local/genetics/pathology ; Aged ; Adult ; }, abstract = {BACKGROUND: Early-stage invasive ductal carcinoma displays high survival rates due to early detection and treatments. However, there is still a chance of relapse of 3-15% after treatment. The aim of this study was to uncover the distinctive transcriptomic characteristics and monitoring prognosis potential of peritumoral tissue in early-stage cases.

METHODS: RNA was isolated from tumoral, peritumoral, and non-tumoral breast tissue from surgical resection of 10 luminal early-stage invasive ductal carcinoma patients. Transcriptome expression profiling for differentially expressed genes (DEGs) identification was carried out through microarray analysis. Gene Ontology and KEGG pathways enrichment analysis were explored for functional characterization of identified DEGs. Protein-Protein Interactions (PPI) networks analysis was performed to identify hub nodes of peritumoral tissue alterations and correlated with Overall Survival and Relapse Free Survival.

RESULTS: DEGs closely related with cell migration, extracellular matrix organization, and cell cycle were upregulated in peritumoral tissue compared to non-tumoral. Analyzing PPI networks, we observed that the proximity to tumor leads to the alteration of gene modules involved in cell proliferation and differentiation signaling pathways. In fact, in the peritumoral area were identified the top ten upregulated hub nodes including CDK1, ESR1, NOP58, PCNA, EZH2, PPP1CA, BUB1, TGFBR1, CXCR4, and CCND1. A signature performed by four of these hub nodes (CDK1, PCNA, EZH2, and BUB1) was associated with relapse events in untreated luminal breast cancer patients.

CONCLUSIONS: In conclusion, our study characterizes in depth breast peritumoral tissue providing clues on the changes that tumor signaling could cause in patients with early-stage breast cancer. We propose that the use of a four gene signature could help to predict local relapse. Overall, our results highlight the value of peritumoral tissue as a potential source of new biomarkers for early detection of relapse and improvement in invasive ductal carcinoma patient's prognosis.}, } @article {pmid38830849, year = {2024}, author = {Wearn, A and Tremblay, SA and Tardif, CL and Leppert, IR and Gauthier, CJ and Baracchini, G and Hughes, C and Hewan, P and Tremblay-Mercier, J and Rosa-Neto, P and Poirier, J and Villeneuve, S and Schmitz, TW and Turner, GR and Spreng, RN and , }, title = {Neuromodulatory subcortical nucleus integrity is associated with white matter microstructure, tauopathy and APOE status.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4706}, pmid = {38830849}, issn = {2041-1723}, support = {R01 AG068563/AG/NIA NIH HHS/United States ; NIA R01 AG068563//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; AARG-22-927100/ALZ/Alzheimer's Association/United States ; }, mesh = {Humans ; *White Matter/diagnostic imaging/pathology/metabolism ; Female ; Male ; Aged ; Middle Aged ; *Alzheimer Disease/genetics/pathology/cerebrospinal fluid/metabolism/diagnostic imaging ; *Tauopathies/diagnostic imaging/metabolism/pathology/genetics/cerebrospinal fluid ; *tau Proteins/metabolism/cerebrospinal fluid ; *Magnetic Resonance Imaging ; Brain/pathology/diagnostic imaging/metabolism ; Apolipoproteins E/genetics/metabolism ; Apolipoprotein E4/genetics/metabolism ; Neurites/metabolism/pathology ; }, abstract = {The neuromodulatory subcortical nuclei within the isodendritic core (IdC) are the earliest sites of tauopathy in Alzheimer's disease (AD). They project broadly throughout the brain's white matter. We investigated the relationship between IdC microstructure and whole-brain white matter microstructure to better understand early neuropathological changes in AD. Using multiparametric quantitative magnetic resonance imaging we observed two covariance patterns between IdC and white matter microstructure in 133 cognitively unimpaired older adults (age 67.9 ± 5.3 years) with familial risk for AD. IdC integrity related to 1) whole-brain neurite density, and 2) neurite orientation dispersion in white matter tracts known to be affected early in AD. Pattern 2 was associated with CSF concentration of phosphorylated-tau, indicating AD specificity. Apolipoprotein-E4 carriers expressed both patterns more strongly than non-carriers. IdC microstructure variation is reflected in white matter, particularly in AD-affected tracts, highlighting an early mechanism of pathological development.}, } @article {pmid38827535, year = {2024}, author = {Sitharthan, D and Sved, P}, title = {A rare case of fatal rectal perforation and sepsis following traumatic urinary catheterization.}, journal = {Urology case reports}, volume = {54}, number = {}, pages = {102706}, pmid = {38827535}, issn = {2214-4420}, abstract = {This case report details a fatal rectal perforation and sepsis in a comorbid 96-year-old male after traumatic urinary catheterization, highlighting the risks of IDC management in elderly patients with complex health backgrounds. Despite maximal medical therapy, including escalated antibiotics and ICU care, the patient died from septic shock linked to improper catheter insertion by a non-specialist nurse in the community. This case emphasizes the urgent need for better catheterization practices, specialized nursing education, and clear guidelines to prevent such outcomes.}, } @article {pmid38817738, year = {2024}, author = {LaRota-Aguilera, MJ and Zapata-Caldas, E and Buitrago-Bermúdez, O and Marull, J}, title = {New criteria for sustainable land use planning of metropolitan green infrastructures in the tropical Andes.}, journal = {Landscape ecology}, volume = {39}, number = {6}, pages = {112}, pmid = {38817738}, issn = {0921-2973}, abstract = {CONTEXT: Urbanization is rapidly increasing worldwide, with about 60% of the global population currently residing in cities and expected to reach 68% by 2050. In Latin America's tropical Andes region, managing these changes poses challenges, including biodiversity loss and vulnerability to climate change.

OBJECTIVES: This study assesses urban growth and agricultural intensification impacts on the ecological functionality of metropolitan green infrastructures and their capacity to provide ecosystem services using a landscape sustainability and sociometabolic approach. Specifically, it aims to identify landscape configurations promoting socio-ecological sustainability amidst rapid urbanization.

METHODS: A landscape-metabolic model (IDC) was applied to evaluate the interactions between land use changes and ecosystem functions in the metropolitan region of Cali.

RESULTS: Agricultural intensification and industrialization, coupled with uncontrolled urban growth, have significantly transformed the landscape, posing threats to its sustainability. The prevailing biocultural landscapes hold a substantial potential to provide essential ecosystem services to the metropolis. The IDC offers an approach that utilizes a land cover map and agricultural production/metabolism data to calculate an indicator closely related to ecosystem services and multifunctionality.

CONCLUSIONS: The IDC model stands out for efficiently capturing landscape dynamics, providing insights into landscape configuration and social metabolism without extensive resource requirements. This research highlights the importance of adopting a landscape-metabolic and green infrastructure framework to guide territorial policies in the tropical Andes and similar regions. It stresses the need for informed land use planning to address challenges and leverage opportunities presented by biocultural landscapes for regional sustainability amidst rapid urbanization and agricultural expansion.}, } @article {pmid38814508, year = {2024}, author = {Roca Navarro, MJ and Oliver Goldaracena, JM and Garrido Alonso, D and Navarro Monforte, Y and Díaz de Bustamante Durbán, T and Córdoba Chicote, MV and García Martínez, F and Martí Álvarez, C and Yébenes Gregorio, L and Montes Botella, JL and Martín Hervás, C and Sánchez Méndez, JI}, title = {Pre-surgical cryoablation in ≤ 2 cm ER + /HER2-tumors. Prognostic factors for the presence of residual invasive carcinoma.}, journal = {Breast cancer research and treatment}, volume = {206}, number = {3}, pages = {561-573}, pmid = {38814508}, issn = {1573-7217}, mesh = {Humans ; Female ; *Cryosurgery/methods ; *Breast Neoplasms/surgery/pathology/diagnostic imaging ; Middle Aged ; Aged ; *Erb-b2 Receptor Tyrosine Kinases/metabolism ; Prospective Studies ; Prognosis ; Neoplasm, Residual ; Adult ; Receptors, Estrogen/metabolism ; Carcinoma, Ductal, Breast/surgery/pathology/diagnostic imaging ; Mastectomy, Segmental/methods ; Aged, 80 and over ; Preoperative Care/methods ; }, abstract = {BACKGROUND: Breast cancer remains the most commonly diagnosed cancer in women. Breast-conserving surgery (BCS) is the standard approach for small low-risk tumors. If the efficacy of cryoablation is demonstrated, it could provide a minimally invasive alternative to surgery.

PURPOSE: To determine the success of ultrasound-guided cryoablation in achieving the absence of Residual Invasive Cancer (RIC) for patients with ER + /HER2- tumors ≤ 2cm and sonographically negative axillary nodes.

MATERIALS AND METHODS: This prospective study was carried out from April 2021 to June 2023, and involved 60 preoperative cryoablation procedures on ultrasound-visible, node-negative (cN0) infiltrating ductal carcinomas (IDC). Standard diagnostic imaging included mammography and tomosynthesis, supplemented by ultrasound-guided biopsy. MRI was performed in patients with associated intraductal carcinoma (DCIS) and an invasive component on core needle biopsy (18 out of 22 cases). All tumors were tagged with ferromagnetic seeds. A triple-phase protocol (freezing-thawing-freezing) with Argon was used, with an average procedure duration of 40 min. A logistic regression model was applied to determine significant correlation between RIC and the study variables.

RESULTS: Fifty-nine women (mean age 63 ± 8 years) with sixty low-risk unifocal IDC underwent cryoablation prior to surgery. Pathological examination of lumpectomy specimens post-cryoablation revealed RIC in only one of 38 patients with pure IDC and in 4 of 22 mixed IDC/DCIS cases. All treated tumors had clear surgical margins, with no significant procedural complications.

CONCLUSIONS: Cryoablation was effective in eradicating 97% of pure infiltrating ER + /HER2-tumors ≤ 2cm, demonstrating its potential as a surgical alternative in selected patients.}, } @article {pmid38804125, year = {2024}, author = {Burns, N and Bourke, A}, title = {Recurrence in lobular carcinoma of the breast: A 14-year review.}, journal = {Journal of medical imaging and radiation oncology}, volume = {68}, number = {5}, pages = {523-529}, doi = {10.1111/1754-9485.13715}, pmid = {38804125}, issn = {1754-9485}, mesh = {Humans ; *Breast Neoplasms/diagnostic imaging/pathology ; Female ; *Carcinoma, Lobular/diagnostic imaging/pathology/therapy ; *Neoplasm Recurrence, Local/diagnostic imaging ; Retrospective Studies ; Middle Aged ; Aged ; Western Australia ; Adult ; Registries ; Aged, 80 and over ; Incidence ; }, abstract = {INTRODUCTION: The two most common types of breast cancer are invasive or infiltrating ductal carcinoma (IDC) and invasive or infiltrating lobular carcinoma (ILC) (Pestalozzi et al., J. Clin. Oncol., 26, 2008, 3006). Between 5% and 15% of invasive breast carcinomas are lobular carcinomas (Pestalozzi et al., J. Clin. Oncol., 26, 2008, 3006; Dossus and Benusiglio, Breast Cancer Res., 17, 2015, 37; Braunstein et al., Breast Cancer Res. Treat., 149, 2015, 555). The paucity of data relating to recurrence rates of lobular cancers prompted this study.

METHODS: A retrospective cohort study of all cases of lobular breast carcinoma reported to the Western Australia Cancer Registry with the clinical and pathological details between 2000 and 2014.

RESULTS: Overall, 2463 subjects with a total of 2526 events of invasive lobular carcinoma of the breast. 11/2463 (0.45%) subjects met criteria for local recurrence of invasive lobular breast cancer, with an incidence of 1 in 224.

CONCLUSION: There are clinical implications for the management and follow-up for patients with a diagnosis of lobular cancer of the breast. Due to the low recurrence rate, now, the standard practice in our institution does not offer magnetic resonance imaging (MRI) as part of the follow-up for ILC patients. Other centres should establish local recurrence rates to aid development of appropriate management protocols.}, } @article {pmid38800403, year = {2024}, author = {Peng, L and Ma, M and Zhao, D and Zhao, J and Sun, Q and Mao, F}, title = {Comparison of clinical characteristics and outcomes in primary neuroendocrine breast carcinoma versus invasive ductal carcinoma.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1291034}, pmid = {38800403}, issn = {2234-943X}, abstract = {BACKGROUND: Neuroendocrine breast carcinoma (NECB) is a rare, special histologic type of breast cancer. There are some small sample studies on the clinical outcomes of NECB patients, which are worthy of further discussion.

METHODS: We conducted a retrospective case-control study of clinical characteristics and outcomes among patients with primary NECB versus invasive carcinoma of no special type (NST) between November 2004 and November 2017 in the Peking Union Medical College Hospital, Beijing. NST patients were strictly matched 1:4 during the same period based on the TNM stage. Statistical comparisons were performed to determine the differences in survival between NST and NECB patients and to identify clinical factors that correlate with prognosis.

RESULTS: A total of 121 participants affected by primary NECB were included in our analysis from November 2004 to November 2017. Elderly persons (>60 years of age) were more likely to have primary NECB than young persons (p=0.001). In addition, primary NECB patients had significantly higher odds of having tumors 2-5 cm (36.5%) and >5 cm (6.1%) in size than NST patients. Despite a significant difference in tumor size, the proportion of patients with lymph node metastases showed no difference between the two groups (p=0.021). In addition, the rate of patients with ER-negative tumors in the NECB group (4.2%) was significantly lower than that in the primary NST group (29.8%). Significant differences were noted in the PR-negative (13.3% versus 36.6%, P<0.001) and HER2-negative (90.5% versus 76.4%, P=0.001) expression statuses among these patients. Of 121 primary NECB patients, 11 (9.1%) experienced relapses during the follow-up period. We found that tumor size was an independent risk factor for relapse. For hormone receptors on tumor cells, ER-positive breast cancer patients had significantly lower odds of relapse than receptor-negative patients.

CONCLUSIONS: Our data demonstrate no significant difference in mortality and relapse between the primary NECB and NST groups. The tumor size in the primary NECB group was significantly larger than that in the NST group. In addition, the absence of ER independently increased the relapse rate for breast carcinoma patients.}, } @article {pmid38795111, year = {2024}, author = {Voß, F and Zweck, E and Ipek, R and Schultheiss, HP and Roden, M and Kelm, M and Szendroedi, J and Polzin, A and Westenfeld, R and Scheiber, D}, title = {Myocardial Mitochondrial Function Is Impaired in Cardiac Light-Chain Amyloidosis Compared to Transthyretin Amyloidosis.}, journal = {JACC. Heart failure}, volume = {12}, number = {10}, pages = {1778-1780}, doi = {10.1016/j.jchf.2024.03.012}, pmid = {38795111}, issn = {2213-1787}, mesh = {Humans ; *Amyloid Neuropathies, Familial/metabolism/physiopathology/complications ; *Cardiomyopathies/etiology/physiopathology/metabolism ; Mitochondria, Heart/metabolism ; Male ; Female ; Immunoglobulin Light-chain Amyloidosis ; Aged ; Middle Aged ; Myocardium/pathology/metabolism ; }, } @article {pmid38791971, year = {2024}, author = {Makhlouf, S and Atallah, NM and Polotto, S and Lee, AHS and Green, AR and Rakha, EA}, title = {Deciphering the Clinical Behaviour of Invasive Lobular Carcinoma of the Breast Defines an Aggressive Subtype.}, journal = {Cancers}, volume = {16}, number = {10}, pages = {}, pmid = {38791971}, issn = {2072-6694}, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC), the most common special type of breast cancer (BC), has unique clinical behaviour and is different from invasive ductal carcinoma of no special type (IDC-NST). However, ILC further comprises a diverse group of tumours with distinct features. This study aims to examine the clinicopathological and prognostic features of different variants of ILC, with a particular focus on characterising aggressive subtypes.

METHODS: A large (n = 7140) well-characterised and histologically reviewed BC cohort with treatment and long-term follow-up data was investigated. The cohort was classified based on the WHO classification of tumours into main histological subtypes, including ILC and IDC-NST. ILCs were further classified into variants. Clinicopathological parameters and patient outcomes in terms of BC-specific survival (BCSS) and disease-free survival (DFS) were evaluated.

RESULTS: ILC constituted 11% of the cohort. The most common non-classic ILC variants were pleomorphic (pILC) and solid (sILC), constituting 19% of ILC. Compared to classic and related variants (alveolar, trabecular, papillary, and tubulolobular; cILC), pILC and sILC variants were associated with aggressive tumour characteristics. The histologic grade of ILC was an important prognostic variable. The survival patterns identified an aggressive ILC subtype encompassing pILC and high-grade sILC. These tumours, which comprised 14% of the cases, were associated with clinicopathological characteristics of poor prognosis and had high BC-specific death and recurrence rates compared not only to cILC (p < 0.001) but also to IDC-NST (p = 0.02) patients. Contrasting this, cILC patients had significantly longer BCSS and DFS than IDC-NST patients in the first 10 to 15 years of follow-up. Adjuvant chemotherapy did not improve the outcome of patients with aggressive ILC subtypes.

CONCLUSIONS: pILC and high-grade sILC variants comprise an aggressive ILC subtype associated with poor prognostic characteristics and a poor response to chemotherapy. These results warrant confirmation in randomised clinical trials.}, } @article {pmid38785380, year = {2024}, author = {Ben-David, BM and Chebat, DR and Icht, M}, title = {"Love looks not with the eyes": supranormal processing of emotional speech in individuals with late-blindness versus preserved processing in individuals with congenital-blindness.}, journal = {Cognition & emotion}, volume = {38}, number = {8}, pages = {1354-1367}, doi = {10.1080/02699931.2024.2357656}, pmid = {38785380}, issn = {1464-0600}, mesh = {Humans ; Male ; Female ; *Blindness/psychology ; *Emotions/physiology ; Adult ; *Speech Perception/physiology ; Middle Aged ; Young Adult ; Executive Function/physiology ; Attention/physiology ; Memory, Short-Term/physiology ; Semantics ; }, abstract = {Processing of emotional speech in the absence of visual information relies on two auditory channels: semantics and prosody. No study to date has investigated how blindness impacts this process. Two theories, Perceptual Deficit, and Sensory Compensation, yiled different expectations about the role of visual experience (or its lack thereof) in processing emotional speech. To test the effect of vision and early visual experience on processing of emotional speech, we compared individuals with congenital blindness (CB, n = 17), individuals with late blindness (LB, n = 15), and sighted controls (SC, n = 21) on identification and selective-attention of semantic and prosodic spoken-emotions. Results showed that individuals with blindness performed at least as well as SC, supporting Sensory Compensation and the role of cortical reorganisation. Individuals with LB outperformed individuals with CB, in accordance with Perceptual Deficit, supporting the role of early visual experience. The LB advantage was moderated by executive functions (working-memory). Namely, the advantage was erased for individuals with CB who showed higher levels of executive functions. Results suggest that vision is not necessary for processing of emotional speech, but early visual experience could improve it. The findings support a combination of the two aforementioned theories and reject a dichotomous view of deficiencies/enhancements of blindness.}, } @article {pmid38784039, year = {2024}, author = {Ahmad, H and Ali, A and Khalil, AT and Ali, R and Khan, I and Khan, MM and Ahmed, I and Basharat, Z and Alorini, M and Mehmood, A}, title = {Clinico-genomic findings, molecular docking, and mutational spectrum in an understudied population with breast cancer patients from KP, Pakistan.}, journal = {Frontiers in genetics}, volume = {15}, number = {}, pages = {1383284}, pmid = {38784039}, issn = {1664-8021}, abstract = {In this study, we report the mutational profiles, pathogenicity, and their association with different clinicopathologic and sociogenetic factors in patients with Pashtun ethnicity for the first time. A total of 19 FFPE blocks of invasive ductal carcinoma (IDC) from the Breast Cancer (BC) tissue and 6 normal FFPE blocks were analyzed by whole-exome sequencing (WES). Various somatic and germline mutations were identified in cancer-related genes, i.e., ATM, CHEK2, PALB2, and XRCC2. Among a total of 18 mutations, 14 mutations were somatic and 4 were germline. The ATM gene exhibited the maximum number of mutations (11/18), followed by CHEK2 (3/18), PALB2 (3/18), and XRCC2 (1/18). Except one frameshift deletion, all other 17 mutations were nonsynonymous single-nucleotide variants (SNVs). SIFT prediction revealed 7/18 (38.8%) mutations as deleterious. PolyPhen-2 and MutationTaster identified 5/18 (27.7%) mutations as probably damaging and 10/18 (55.5%) mutations as disease-causing, respectively. Mutations like PALB2 p.Q559R (6/19; 31.5%), XRCC2 p.R188H (5/19; 26.31%), and ATM p.D1853N (4/19; 21.05%) were recurrent mutations and proposed to have a biomarker potential. The protein network prediction was performed using GeneMANIA and STRING. ISPRED-SEQ indicated three interaction site mutations which were further used for molecular dynamic simulation. An average increase in the radius of gyration was observed in all three mutated proteins revealing their perturbed folding behavior. Obtained SNVs were further correlated with various parameters related to the clinicopathological status of the tumors. Three mutation positions (ATM p. D1853N, CHEK2 p.M314I, and PALB2 p.T1029S) were found to be highly conserved. Finally, the wild- and mutant-type proteins were screened for two drugs: elagolix (DrugBank ID: DB11979) and LTS0102038 (a triterpenoid, isolated from the anticancer medicinal plant Fagonia indica). Comparatively, a higher number of interactions were noted for normal ATM with both compounds, as compared to mutants.}, } @article {pmid38765791, year = {2024}, author = {Wang, S and Zhang, Q and Zhang, T and Mao, X}, title = {Invasive papillary carcinoma of the breast: A case report.}, journal = {Oncology letters}, volume = {28}, number = {1}, pages = {300}, pmid = {38765791}, issn = {1792-1082}, abstract = {Invasive papillary carcinoma (IPC) of the breast is a rare form of cancer. The current report documents a case of IPC characterized by a large tumor size and skin involvement. Surgical exploration revealed no evidence of axillary lymph node metastasis in breast cancer. Due to financial constraints, the patient opted solely for anastrozole endocrine therapy at a dosage of 1 mg/day for a period of 5 years post-surgery, foregoing other treatments such as radiotherapy and chemotherapy. Since discharge, 2.5 years have passed, during which the patient has been followed up via phone every 3 months, showing a good prognosis. A literature review indicated that IPC is prevalent amongst the elderly population and can be misdiagnosed due to its morphological, cytomorphological and immunophenotypic overlap with other types of papillary neoplasms. This tumor exhibits a more favorable prognosis compared with IDC, primarily attributed to its advantageous gene and molecular expression patterns, coupled with its decreased invasiveness. Despite limited evidence-based research on the treatment of IPC, the present case report, albeit with limitations, underscores the importance of avoiding over-treatment and suggests the feasibility of combining surgery with endocrine therapy for IPC.}, } @article {pmid38764186, year = {2025}, author = {Dor, YI and Algom, D and Shakuf, V and Ben-David, BM}, title = {Age-related differences in processing of emotions in speech disappear with babble noise in the background.}, journal = {Cognition & emotion}, volume = {39}, number = {7}, pages = {1532-1541}, doi = {10.1080/02699931.2024.2351960}, pmid = {38764186}, issn = {1464-0600}, mesh = {Humans ; *Emotions ; *Speech Perception ; Female ; Male ; *Noise ; Aged ; Young Adult ; Adult ; *Aging/psychology ; Middle Aged ; Age Factors ; Semantics ; Aged, 80 and over ; }, abstract = {Older adults process emotional speech differently than young adults, relying less on prosody (tone) relative to semantics (words). This study aimed to elucidate the mechanisms underlying these age-related differences via an emotional speech-in-noise test. A sample of 51 young and 47 older adults rated spoken sentences with emotional content on both prosody and semantics, presented on the background of wideband speech-spectrum noise (sensory interference) or on the background of multi-talker babble (sensory/cognitive interference). The presence of wideband noise eliminated age-related differences in semantics but not in prosody when processing emotional speech. Conversely, the presence of babble resulted in the elimination of age-related differences across all measures. The results suggest that both sensory and cognitive-linguistic factors contribute to age-related changes in emotional speech processing. Because real world conditions typically involve noisy background, our results highlight the importance of testing under such conditions.}, } @article {pmid38760482, year = {2024}, author = {Langer, HT and Rohm, M and Goncalves, MD and Sylow, L}, title = {AMPK as a mediator of tissue preservation: time for a shift in dogma?.}, journal = {Nature reviews. Endocrinology}, volume = {20}, number = {9}, pages = {526-540}, pmid = {38760482}, issn = {1759-5037}, mesh = {Humans ; *AMP-Activated Protein Kinases/metabolism ; Animals ; Muscle, Skeletal/metabolism ; Adipose Tissue/metabolism ; Cachexia/metabolism ; Neoplasms/metabolism ; Energy Metabolism/physiology ; }, abstract = {Ground-breaking discoveries have established 5'-AMP-activated protein kinase (AMPK) as a central sensor of metabolic stress in cells and tissues. AMPK is activated through cellular starvation, exercise and drugs by either directly or indirectly affecting the intracellular AMP (or ADP) to ATP ratio. In turn, AMPK regulates multiple processes of cell metabolism, such as the maintenance of cellular ATP levels, via the regulation of fatty acid oxidation, glucose uptake, glycolysis, autophagy, mitochondrial biogenesis and degradation, and insulin sensitivity. Moreover, AMPK inhibits anabolic processes, such as lipogenesis and protein synthesis. These findings support the notion that AMPK is a crucial regulator of cell catabolism. However, studies have revealed that AMPK's role in cell homeostasis might not be as unidirectional as originally thought. This Review explores emerging evidence for AMPK as a promoter of cell survival and an enhancer of anabolic capacity in skeletal muscle and adipose tissue during catabolic crises. We discuss AMPK-activating interventions for tissue preservation during tissue wasting in cancer-associated cachexia and explore the clinical potential of AMPK activation in wasting conditions. Overall, we provide arguments that call for a shift in the current dogma of AMPK as a mere regulator of cell catabolism, concluding that AMPK has an unexpected role in tissue preservation.}, } @article {pmid38756651, year = {2024}, author = {Ma, S and Li, Y and Yin, J and Niu, Q and An, Z and Du, L and Li, F and Gu, J}, title = {Prospective study of AI-assisted prediction of breast malignancies in physical health examinations: role of off-the-shelf AI software and comparison to radiologist performance.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1374278}, pmid = {38756651}, issn = {2234-943X}, abstract = {OBJECTIVE: In physical health examinations, breast sonography is a commonly used imaging method, but it can lead to repeated exams and unnecessary biopsy due to discrepancies among radiologists and health centers. This study explores the role of off-the-shelf artificial intelligence (AI) software in assisting radiologists to classify incidentally found breast masses in two health centers.

METHODS: Female patients undergoing breast ultrasound examinations with incidentally discovered breast masses were categorized according to the 5[th] edition of the Breast Imaging Reporting and Data System (BI-RADS), with categories 3 to 5 included in this study. The examinations were conducted at two municipal health centers from May 2021 to May 2023.The final pathological results from surgical resection or biopsy served as the gold standard for comparison. Ultrasonographic images were obtained in longitudinal and transverse sections, and two junior radiologists and one senior radiologist independently assessed the images without knowing the pathological findings. The BI-RADS classification was adjusted following AI assistance, and diagnostic performance was compared using receiver operating characteristic curves.

RESULTS: A total of 196 patients with 202 breast masses were included in the study, with pathological results confirming 107 benign and 95 malignant masses. The receiver operating characteristic curve showed that experienced breast radiologists had higher diagnostic performance in BI-RADS classification than junior radiologists, similar to AI classification (AUC = 0.936, 0.806, 0.896, and 0.950, p < 0.05). The AI software improved the accuracy, sensitivity, and negative predictive value of the adjusted BI-RADS classification for the junior radiologists' group (p< 0.05), while no difference was observed in the senior radiologist group. Furthermore, AI increased the negative predictive value for BI-RADS 4a masses and the positive predictive value for 4b masses among radiologists (p < 0.05). AI enhances the sensitivity of invasive breast cancer detection more effectively than ductal carcinoma in situ and rare subtypes of breast cancer.

CONCLUSIONS: The AI software enhances diagnostic efficiency for breast masses, reducing the performance gap between junior and senior radiologists, particularly for BI-RADS 4a and 4b masses. This improvement reduces unnecessary repeat examinations and biopsies, optimizing medical resource utilization and enhancing overall diagnostic effectiveness.}, } @article {pmid38753284, year = {2024}, author = {Shaw, AK and Khurana, D and Soni, S}, title = {Assessment of thermal damage for plasmonic photothermal therapy of subsurface tumors.}, journal = {Physical and engineering sciences in medicine}, volume = {47}, number = {3}, pages = {1107-1121}, pmid = {38753284}, issn = {2662-4737}, mesh = {*Photothermal Therapy ; *Gold/chemistry ; Humans ; Nanotubes/chemistry ; Temperature ; Neoplasms/therapy ; Phantoms, Imaging ; Metal Nanoparticles/chemistry ; }, abstract = {Plasmonic photothermal therapy (PPTT) involves the use of nanoparticles and near-infrared radiation to attain a temperature above 50 °C within the tumor for its thermal damage. PPTT is largely explored for superficial tumors, and its potential to treat deeper subsurface tumors is dealt feebly, requiring the assessment of thermal damage for such tumors. In this paper, the extent of thermal damage is numerically analyzed for PPTT of invasive ductal carcinoma (IDC) situated at 3-9 mm depths. The developed numerical model is validated with suitable tissue-tumor mimicking phantoms. Tumor (IDC) embedded with gold nanorods (GNRs) is subjected to broadband near-infrared radiation. The effect of various GNRs concentrations and their spatial distributions [viz. uniform distribution, intravenous delivery (peripheral distribution) and intratumoral delivery (localized distribution)] are investigated for thermal damage for subsurface tumors situated at various depths. Results show that lower GNRs concentrations lead to more uniform internal heat generation, eventually resulting in uniform temperature rise. Also, the peripheral distribution of nanoparticles provides a more uniform spatial temperature rise within the tumor. Overall, it is concluded that PPTT has potential to induce thermal damage for subsurface tumors, at depths of upto 9 mm, by proper choice of nanoparticle distribution, dose/concentration and irradiation parameters based on the tumor location. Moreover, intravenous administration of nanoparticles seems a good choice for shallower tumors, while for deeper tumors, uniform distribution is required to attain the necessary thermal damage. In the future, the algorithm may be extended further, involving 3D patient-specific tumors and through mice model-based experiments.}, } @article {pmid38751676, year = {2024}, author = {Lv, Y and Zhang, H and Zhao, Y and Zhang, H and Wang, T}, title = {A case report of low-dose apatinib in the treatment of advanced triple-negative breast cancer.}, journal = {Translational breast cancer research : a journal focusing on translational research in breast cancer}, volume = {5}, number = {}, pages = {8}, pmid = {38751676}, issn = {2218-6778}, abstract = {BACKGROUND: The current study shows that the incidence rate of triple-negative breast cancer accounts for 10-17% of invasive ductal carcinoma of the breast. There is no specific treatment target, the age of onset is relatively small, and the recurrence rate is relatively fast. The prognosis of breast cancer in different subtypes is the most unsatisfactory, with a 5-year survival rate of less than 15%. We report a typical case of metastatic advanced triple-negative breast cancer who responded well to apatinib mesylate after chemotherapy failure and achieved significant progression-free survival, which is relatively rare in triple-negative breast cancer with limited treatment means.

CASE DESCRIPTION: A 55-year-old female was surgically diagnosed as triple-negative breast cancer on April 17, 2015. After surgery, she had lung metastasis after standard adjuvant chemotherapy and radiotherapy. After receiving the NX regimen (vinorelbine, capecitabine) for 8 cycles, she progressed. Because the patient refused later, she was adjusted to apatinib mesylate, and serious adverse reactions occurred during the treatment process. By adjusting the drug dose, and low-dose apatinib treatment, the lung lesions were close to complete response (CR), reaching a progression-free survival period of 45 months.

CONCLUSIONS: Low-dose apatinib may be a promising anti-tumor drug for triple-negative breast cancer patients, which needs more samples to verify. This case may provide a reference for the treatment selection of triple-negative metastatic breast cancer in the future.}, } @article {pmid38751470, year = {2023}, author = {Luo, T and Zhu, K and Zhong, X and He, P and Yan, X and Tian, T}, title = {CDK4/6 inhibitors for primary endocrine resistant HR-positive/HER2-negative metastatic breast cancer: a case report.}, journal = {Translational breast cancer research : a journal focusing on translational research in breast cancer}, volume = {4}, number = {}, pages = {33}, pmid = {38751470}, issn = {2218-6778}, abstract = {BACKGROUND: We report a case of hormone receptor (HR) positive, human epidermal growth factor receptor-2 (HER2) negative breast cancer with multiple liver metastases who achieved good clinical benefit across cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with endocrine therapy. Prior to this, the patient underwent neoadjuvant therapy and surgery as well as adjuvant endocrine therapy. We present and discuss three important treatment decision nodes associated with it.

CASE DESCRIPTION: A 60-year-old woman was diagnosed with invasive ductal carcinoma of the left breast (cT4bN2M0, stage IIIB, Luminal B HER2-negative type) at the West China Hospital of Sichuan University in 2020, and received neoadjuvant chemotherapy and modified radical mastectomy of the left breast from 2020 to 2021. Postoperative radiotherapy was performed in the left chest wall and left upper and lower clavicular region. Adjuvant therapy is anastrozole endocrine therapy. Multiple liver metastases developed in 2022. The pathological molecular typing of liver metastases was confirmed to be consistent with the primary lesion. In the context of primary endocrine resistance, the first-line treatment of choice was fulvestrant in combination with a targeted CDK4/6 inhibitor (abemaciclib). This combination regimen made the liver metastases visibly shrunk, leading to partial response (PR) and has achieved a progression-free survival of 12 months. And there were no serious drug-related adverse events during first-line treatment.

CONCLUSIONS: CDK4/6 inhibitor is a promising antineoplastic agent for HR positive, HER2 negative breast cancer patients. With the development of research, the application scope of CDK4/6 inhibitors is gradually expanding, and the precision treatment of breast cancer requires more rational drug selection and combination.}, } @article {pmid38751260, year = {2024}, author = {Shirazi, B and Niaz, M and Khan, MA}, title = {The characteristics and risk factors of breast cancer patients trend distinctive regional differences: a cross-sectional study.}, journal = {JPMA. The Journal of the Pakistan Medical Association}, volume = {74}, number = {4}, pages = {672-676}, doi = {10.47391/JPMA.9360}, pmid = {38751260}, issn = {0030-9982}, mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/pathology ; Cross-Sectional Studies ; Pakistan/epidemiology ; Middle Aged ; Risk Factors ; Adult ; Retrospective Studies ; Male ; Neoplasm Staging ; Breast Neoplasms, Male/epidemiology/pathology ; Breast Feeding/statistics & numerical data ; Carcinoma, Ductal, Breast/epidemiology/pathology ; Parity ; Aged ; Neoplasm Grading ; Marital Status ; }, abstract = {OBJECTIVE: To determine the characteristics and risk factors of breast cancer patients in a tertiary care setting.

METHODS: The retrospective, cross-sectional study was conducted at the Sindh Institute of Urology and Transplantation, Karachi, and comprised data of all patients diagnosed with breast cancer from March 2017 to December 2021. Demographic characteristics, clinical presentation, stage of the disease and histopathological characteristics were noted. Data related to all the variables was not available in all cases. Data was analysed using SPSS 23.

RESULTS: Of the 690 patients, 683(99%) were females and 7(1%) were males. The mean age at presentation was 49.3±13.5 years, while the mean duration of symptoms was 10.24±17.64) months. Most of the females were married 642(93%) and multiparous 484(70.9%), while 293(42.5%) had breastfed their children for >1 year, and 412(59.7%) had no history of contraception use. The most common stage at presentation was stage II (48.6%), and most patients had grade II 395(57.2%) invasive ductal carcinoma, with Luminal A molecular subtype noted in 287(41.6%) cases.

CONCLUSIONS: The characteristics of breast cancer in the sample had certain distinctions compared to other populations. It is important to integrate all datasets and develop guidelines appropriate to Pakistani population.}, } @article {pmid38747597, year = {2024}, author = {Stindt, KR and McClean, MN}, title = {Tuning interdomain conjugation to enable in situ population modification in yeasts.}, journal = {mSystems}, volume = {9}, number = {6}, pages = {e0005024}, pmid = {38747597}, issn = {2379-5077}, support = {R01 AI154940/AI/NIAID NIH HHS/United States ; P30CA014520//University of Wisconsin Carbone Cancer Center (UWCCC)/ ; P30 CA014520/CA/NCI NIH HHS/United States ; R35 GM128873/GM/NIGMS NIH HHS/United States ; 135AAI9593//Wisconsin Alumni Research Foundation (WARF)/ ; R35GM128873//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; T32 GM130550/GM/NIGMS NIH HHS/United States ; T32GM130550//Molecular Biophysics Training Grant/ ; R01AI154940//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; }, mesh = {*Saccharomyces cerevisiae/genetics ; *Escherichia coli/genetics/metabolism ; Conjugation, Genetic ; }, abstract = {The ability to modify and control natural and engineered microbiomes is essential for biotechnology and biomedicine. Fungi are critical members of most microbiomes, yet technology for modifying the fungal members of a microbiome has lagged far behind that for bacteria. Interdomain conjugation (IDC) is a promising approach, as DNA transfer from bacterial cells to yeast enables in situ modification. While such genetic transfers have been known to naturally occur in a wide range of eukaryotes and are thought to contribute to their evolution, IDC has been understudied as a technique to control fungal or fungal-bacterial consortia. One major obstacle to the widespread use of IDC is its limited efficiency. In this work, we manipulated metabolic and physical interactions between genetically tractable Escherichia coli and Saccharomyces cerevisiae to control the incidence of IDC. We test the landscape of population interactions between the bacterial donors and yeast recipients to find that bacterial commensalism leads to maximized IDC, both in culture and in mixed colonies. We demonstrate the capacity of cell-to-cell binding via mannoproteins to assist both IDC incidence and bacterial commensalism in culture and model how these tunable controls can predictably yield a range of IDC outcomes. Furthermore, we demonstrate that these controls can be utilized to irreversibly alter a recipient yeast population, by both "rescuing" a poor-growing recipient population and collapsing a stable population via a novel IDC-mediated CRISPR/Cas9 system.IMPORTANCEFungi are important but often unaddressed members of most natural and synthetic microbial communities. This work highlights opportunities for modifying yeast microbiome populations through bacterial conjugation. While conjugation has been recognized for its capacity to deliver engineerable DNA to a range of cells, its dependence on cell contact has limited its efficiency. Here, we find "knobs" to control DNA transfer, by engineering the metabolic dependence between bacterial donors and yeast recipients and by changing their ability to physically adhere to each other. Importantly, we functionally validate these "knobs" by irreversibly altering yeast populations. We use these controls to "rescue" a failing yeast population, demonstrate the capacity of conjugated CRISPR/Cas9 to depress or collapse populations, and show that conjugation can be easily interrupted by disrupting cell-to-cell binding. These results offer building blocks toward in situ mycobiome editing, with significant implications for clinical treatments of fungal pathogens and other fungal system engineering.}, } @article {pmid38746984, year = {2025}, author = {Rampal, R and Jones, S and Hogg, W and Rengabashyam, B and Hogan, B and Achuthan, R and Kim, B}, title = {Evaluation of long-term outcome following therapeutic mammaplasty: the effect of wound complication on initiation of adjuvant therapy and subsequent oncological outcome.}, journal = {Annals of the Royal College of Surgeons of England}, volume = {107}, number = {2}, pages = {112-118}, pmid = {38746984}, issn = {1478-7083}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/surgery/mortality/therapy/pathology ; *Mammaplasty/adverse effects/methods ; Adult ; Aged ; Neoplasm Recurrence, Local/epidemiology ; Chemotherapy, Adjuvant ; Treatment Outcome ; Disease-Free Survival ; Postoperative Complications/epidemiology ; Aged, 80 and over ; Carcinoma, Ductal, Breast/surgery/mortality/pathology/therapy ; Retrospective Studies ; }, abstract = {INTRODUCTION: Therapeutic mammaplasty (TM) facilitates large tumour resection while maintaining optimal aesthetic outcome. It carries higher wound complication risks, which may delay adjuvant therapy initiation. Whether this delay affects oncological outcome requires evaluation.

METHODS: Data were collected for consecutive patients receiving TM at the Leeds breast unit (2009-2017). A prospectively maintained database was used to determine tumour characteristics, wound complication rates, receipt of adjuvant therapy and breast cancer recurrence or death.

RESULTS: In total 112 patients (median age of 54 years) underwent 114 TM procedures. The most common histological subtypes were invasive ductal carcinoma (61.4%), invasive lobular carcinoma (13.2%) and ductal carcinoma in situ (13.2%). Of the patients, 88.2% had oestrogen receptor-positive cancer and 14% had human epidermal growth factor receptor-positive cancer; 26.3% had multifocal cancer. The median tumour size was 30mm. The median Nottingham Prognostic Index was 4.2. The local recurrence rate was 3.5% (median follow-up of 8.6 years). The 5- and 10-year disease-free survival (DFS) was 88.5% and 83.5%, and the equivalent overall survival (OS) rates were 94% and 83.5%. Wound complication rate was 23.6% (n=27), the commonest being wound infection (11.4%; n=13) and T-junction wound breakdown (10.5%; n=12). The median time to adjuvant therapy was 72 days (interquartile range [IQR] 56-90) for patients with wound complications, and 51 days (IQR 42-58) for those without. However, this delay did not affect DFS or OS (log-rank test; p=0.58 and p=0.94, respectively). This was confirmed on Cox regression analysis.

CONCLUSION: Our study finding demonstrates that although wound complications after TM leads to a modest delay to adjuvant therapy, the long-term oncological outcomes were comparable with those in patients without wound complications.}, } @article {pmid38746269, year = {2024}, author = {Thiriveedhi, VK and Krishnaswamy, D and Clunie, D and Pieper, S and Kikinis, R and Fedorov, A}, title = {Cloud-based large-scale curation of medical imaging data using AI segmentation.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38746269}, issn = {2693-5015}, support = {HHSN261201500003C/CA/NCI NIH HHS/United States ; HHSN261201500003I/CA/NCI NIH HHS/United States ; P41 EB028741/EB/NIBIB NIH HHS/United States ; U24 CA258511/CA/NCI NIH HHS/United States ; }, abstract = {Rapid advances in medical imaging Artificial Intelligence (AI) offer unprecedented opportunities for automatic analysis and extraction of data from large imaging collections. Computational demands of such modern AI tools may be difficult to satisfy with the capabilities available on premises. Cloud computing offers the promise of economical access and extreme scalability. Few studies examine the price/performance tradeoffs of using the cloud, in particular for medical image analysis tasks. We investigate the use of cloud-provisioned compute resources for AI-based curation of the National Lung Screening Trial (NLST) Computed Tomography (CT) images available from the National Cancer Institute (NCI) Imaging Data Commons (IDC). We evaluated NCI Cancer Research Data Commons (CRDC) Cloud Resources - Terra (FireCloud) and Seven Bridges-Cancer Genomics Cloud (SB-CGC) platforms - to perform automatic image segmentation with TotalSegmentator and pyradiomics feature extraction for a large cohort containing >126,000 CT volumes from >26,000 patients. Utilizing >21,000 Virtual Machines (VMs) over the course of the computation we completed analysis in under 9 hours, as compared to the estimated 522 days that would be needed on a single workstation. The total cost of utilizing the cloud for this analysis was $1,011.05. Our contributions include: 1) an evaluation of the numerous tradeoffs towards optimizing the use of cloud resources for large-scale image analysis; 2) CloudSegmentator, an open source reproducible implementation of the developed workflows, which can be reused and extended; 3) practical recommendations for utilizing the cloud for large-scale medical image computing tasks. We also share the results of the analysis: the total of 9,565,554 segmentations of the anatomic structures and the accompanying radiomics features in IDC as of release v18.}, } @article {pmid38744306, year = {2024}, author = {Tan, RYC and Ong, WS and Lee, KH and Park, S and Iqbal, J and Park, YH and Lee, JE and Yu, JH and Lin, CH and Lu, YS and Ono, M and Ueno, T and Naito, Y and Onishi, T and Lim, GH and Tan, SM and Lee, HB and Koh, J and Han, W and Im, SA and Tan, VKM and Phyu, N and Wong, FY and Tan, PH and Yap, YS}, title = {Outcomes in Nonmetastatic Hormone Receptor-Positive HER2-Negative Pure Mucinous Breast Cancer: A Multicenter Cohort Study.}, journal = {Journal of the National Comprehensive Cancer Network : JNCCN}, volume = {22}, number = {2 D}, pages = {}, doi = {10.6004/jnccn.2023.7121}, pmid = {38744306}, issn = {1540-1413}, mesh = {Humans ; Female ; *Erb-b2 Receptor Tyrosine Kinases/metabolism ; *Breast Neoplasms/therapy/pathology/mortality/metabolism ; Middle Aged ; Aged ; *Adenocarcinoma, Mucinous/therapy/pathology/metabolism/mortality ; Prognosis ; *Receptors, Estrogen/metabolism ; Adult ; Receptors, Progesterone/metabolism ; Neoplasm Staging ; Carcinoma, Ductal, Breast/therapy/pathology/mortality/metabolism ; Cohort Studies ; Carcinoma, Lobular/therapy/pathology/metabolism/mortality ; Neoplasm Recurrence, Local/pathology/epidemiology ; }, abstract = {BACKGROUND: Although considered a favorable subtype, pure mucinous breast cancer (PMBC) can recur, and evidence for adjuvant therapy is limited. We aimed to compare outcomes of nonmetastatic PMBC with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) to address these uncertainties.

METHODS: Individual patient-level data from 6 centers on stage I-III hormone receptor-positive and HER2-negative PMBC, IDC, and ILC were used to analyze recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), and to identify prognostic factors for PMBC.

RESULTS: Data from 20,684 IDC cases, 1,475 ILC cases, and 943 PMBC cases were used. Median follow-up was 6.6 years. Five-year RFI, RFS, and OS for PMBC were 96.1%, 94.9%, and 98.1%, respectively. On multivariable Cox regression, PMBC demonstrated superior RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) compared with IDC. ILC showed comparable outcomes to IDC. Fewer than half (48.7%) of recurrences in PMBC were distant, which was a lower rate than for IDC (67.3%) and ILC (80.6%). In contrast to RFI, RFS events were driven more by non-breast cancer deaths in older patients. Significant prognostic factors for RFI among PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70). No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age. A separate SEER database analysis also did not find any association of improved survival with adjuvant chemotherapy in these subgroups.

CONCLUSIONS: Compared with IDC, PMBC demonstrated superior RFI, RFS, and OS. Lymph node negativity, adjuvant radiotherapy, and endocrine therapy were associated with superior RFI. Adjuvant chemotherapy was not associated with better outcomes.}, } @article {pmid38741768, year = {2024}, author = {Song, L and Qiu, Y and Huang, W and Sun, X and Yang, Q and Peng, Y and Kang, L}, title = {Untypical bilateral breast cancer with peritoneal fibrosis on [18]F-FDG PET/CT: case report and literature review.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1353822}, pmid = {38741768}, issn = {2296-858X}, abstract = {BACKGROUND: Retroperitoneal fibrosis, a condition of uncertain origin, is rarely linked to 8% of malignant cases, including breast, lung, gastrointestinal, genitourinary, thyroid, and carcinoid. The mechanism leading to peritoneal fibrosis induced by tumors is not well understood, possibly encompassing direct infiltration of neoplastic cells or the initiation of inflammatory responses prompted by cytokines released by tumor cells. We report a case of breast cancer with renal metastasis and retroperitoneal fibrosis detected using [18]F-FDG PET/CT, providing help for clinical diagnosis and treatment.

CASE REPORT: A 49-year-old woman was referred to the hospital with elevated creatinine and oliguria for over a month. Abdominal computer tomography (CT) and magnetic resonance imaging (MRI) showed a retroperitoneal fibrosis-induced acute kidney injury (AKI) was suspected. However, a percutaneous biopsy of the kidney lesion confirmed metastasis from breast cancer. The physical examination revealed inverted nipples and an orange peel appearance on the skin of both breasts. Ultrasonography revealed bilateral hyperplasia (BIRADS 4a) of the mammary glands and bilateral neck and axillary lymphadenopathy. Subsequently, [18]F-deoxyglucose positron emission tomography/computer tomography ([18]F-FDG PET/CT) detected abnormally high uptake (SUVmax) in the bilateral mammary glands and axillary lymph nodes, suggesting bilateral breast cancer. Furthermore, abnormal [18]F-FDG uptake was detected in the kidney, suggesting renal metastasis. In addition, abnormal [18]F-FDG uptake was observed in the vertebrae, accompanied by an elevation in inhomogeneous bone mineral density, raising suspicion of bone metastases. However, the possibility of myelodysplasia cannot be dismissed, and further investigations will be conducted during close follow-ups. There was significant [18]F-FDG uptake in the retroperitoneal position indicating a potential association between retroperitoneal fibrosis and breast cancer. The final pathological diagnosis of the breast tissue confirmed bilateral invasive ductal carcinoma. The patient had been treated with 11 cycles of albumin-bound (nab)-paclitaxel (0.3 mg) and had no significant adverse reaction.

CONCLUSION: In this case, neither the bilateral breast cancer nor the kidney metastatic lesion showed typical nodules or masses, so breast ultrasound, abdominal CT, and MRI did not suggest malignant lesions. PET/CT played an important role in detecting occult metastases and primary lesions, thereby contributing to more accurate staging, monitoring treatment responses, and prediction of prognosis in breast cancer.}, } @article {pmid38741627, year = {2024}, author = {Ahuja, S and G, K and Zaheer, S}, title = {Evaluation of Histomorphological Changes in Breast Cancer Post-Neoadjuvant Chemotherapy.}, journal = {Indian journal of surgical oncology}, volume = {15}, number = {2}, pages = {236-240}, pmid = {38741627}, issn = {0975-7651}, abstract = {Breast cancer, a leading cause of global female mortality, demands comprehensive diagnostic and therapeutic strategies. This study delves into the nuanced realm of post-neoadjuvant chemotherapy breast cancer specimens, emphasizing the imperative need for pathologists to discern stromal and nuclear alterations adeptly. The investigation, encompassing 100 female patients with a mean age of 47.5 years, elucidates the demographic and clinicopathological parameters. Predominantly presenting as palpable lumps (85%), invasive ductal carcinoma emerged as the predominant histological type (98%). The primary focus of the study revolves around the morphological changes post-neoadjuvant chemotherapy, with a meticulous qualitative analysis encompassing stromal elements (fibrosis, elastosis, calcification) and nuclear features (pyknosis, hyperchromasia). Notably, the response to chemotherapy, classified by the International Union against Cancer criteria, delineates a substantial pathological complete response (55%), partial response (35%), and limited non-response (10%). The therapeutic landscape includes a majority of cases undergoing extensive chemotherapy cycles, primarily featuring the cyclophosphamide, doxorubicin, and paclitaxel regimen. Remarkably, this investigation unveils fibrosis (63%) and elastosis/collagenization (51%) as prevalent stromal changes, while pyknosis (58%) and hyperchromasia (48%) dominate nuclear alterations. In conclusion, this retrospective study provides a comprehensive overview of post-neoadjuvant chemotherapy breast cancer specimens, shedding light on the intricate interplay of clinical parameters, treatment responses, and histopathological changes. The findings underscore the pivotal role of pathologists in accurately diagnosing and grading tumors in the evolving landscape of breast cancer management.}, } @article {pmid38737548, year = {2024}, author = {Amado, IR and Romaní-Pérez, M and Fuciños, P and Gil-Lozano, M}, title = {Editorial: Novel and emerging therapies for the treatment of obesity and related disorders.}, journal = {Frontiers in endocrinology}, volume = {15}, number = {}, pages = {1371113}, pmid = {38737548}, issn = {1664-2392}, mesh = {Humans ; *Obesity/therapy ; }, } @article {pmid38734990, year = {2024}, author = {Greenland, NY and Cooperberg, MR and Carroll, PR and Cowan, JE and Simko, JP and Stohr, BA and Chan, E}, title = {Morphologic patterns observed in prostate biopsy cases with discrepant grade group and molecular risk classification.}, journal = {The Prostate}, volume = {84}, number = {11}, pages = {1076-1085}, doi = {10.1002/pros.24725}, pmid = {38734990}, issn = {1097-0045}, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/genetics ; *Neoplasm Grading ; *Prostate/pathology ; Biopsy ; Middle Aged ; Aged ; Biomarkers, Tumor/genetics ; Risk Assessment ; Prostatectomy ; }, abstract = {BACKGROUND: Molecular-based risk classifier tests are increasingly being utilized by urologists and radiation oncologists to guide clinical decision making. The Decipher prostate biopsy test is a 22-gene RNA biomarker assay designed to predict likelihood of high-grade disease at radical prostatectomy and risk of metastasis and mortality. The test provides a risk category of low, intermediate, or high. We investigated histologic features of biopsies in which the Grade Group (GG) and Decipher risk category (molecular risk) were discrepant.

METHODS: Our institutional urologic outcomes database was searched for men who underwent prostate biopsies with subsequent Decipher testing from 2016 to 2020. We defined discrepant GG and molecular risk as either GG1-2 with high Decipher risk category or GG ≥ 3 with low Decipher risk category. The biopsy slide on which Decipher testing was performed was re-reviewed for GG and various histologic features, including % Gleason pattern 4, types of Gleason pattern 4 and 5, other "high risk" features (e.g., complex papillary, ductal carcinoma, intraductal carcinoma [IDC]), and other unusual and often "difficult to grade" patterns (e.g., atrophic carcinoma, mucin rupture, pseudohyperplastic carcinoma, collagenous fibroplasia, foamy gland carcinoma, carcinoma with basal cell marker expression, carcinoma with prominent vacuoles, and stromal reaction). Follow-up data was also obtained from the electronic medical record.

RESULTS: Of 178 men who underwent prostate biopsies and had Decipher testing performed, 41 (23%) had discrepant GG and molecular risk. Slides were available for review for 33/41 (80%). Of these 33 patients, 23 (70%) had GG1-2 (GG1 n = 5, GG2 n = 18) with high Decipher risk, and 10 (30%) had GG ≥ 3 with low Decipher risk. Of the 5 GG1 cases, one case was considered GG2 on re-review; no other high risk features were identified but each case showed at least one of the following "difficult to grade" patterns: 3 atrophic carcinoma, 1 collagenous fibroplasia, 1 carcinoma with mucin rupture, and 1 carcinoma with basal cell marker expression. Of the 18 GG2 high Decipher risk cases, 2 showed GG3 on re-review, 5 showed large cribriform and/or other high risk features, and 10 showed a "difficult to grade" pattern. Of the 10 GG ≥ 3 low Decipher risk cases, 5 had known high risk features including 2 with large cribriform, 1 with IDC, and 1 with Gleason pattern 5.

CONCLUSIONS: In GG1-2 high Decipher risk cases, difficult to grade patterns were frequently seen in the absence of other known high risk morphologic features; whether these constitute true high risk cases requires further study. In the GG ≥ 3 low Decipher risk cases, aggressive histologic patterns such as large cribriform and IDC were observed in half (50%) of cases; therefore, the molecular classifier may not capture all high risk histologic patterns.}, } @article {pmid38734581, year = {2024}, author = {Hua, B and Yang, G and An, Y and Lou, K and Chen, J and Quan, G and Yuan, T}, title = {Clinical and Imaging Characteristics of Contrast-enhanced Mammography and MRI to Distinguish Microinvasive Carcinoma from Ductal Carcinoma In situ.}, journal = {Academic radiology}, volume = {31}, number = {11}, pages = {4299-4308}, doi = {10.1016/j.acra.2024.04.041}, pmid = {38734581}, issn = {1878-4046}, mesh = {Humans ; Female ; *Contrast Media ; *Breast Neoplasms/diagnostic imaging/pathology ; *Magnetic Resonance Imaging/methods ; Middle Aged ; *Mammography/methods ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology ; Diagnosis, Differential ; Aged ; Adult ; Neoplasm Invasiveness/diagnostic imaging ; Retrospective Studies ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; }, abstract = {RATIONALE AND OBJECTIVES: The prognosis of ductal carcinoma in situ with microinvasion (DCISM) is more similar to that of small invasive ductal carcinoma (IDC) than to pure ductal carcinoma in situ (DCIS). It is particularly important to accurately distinguish between DCISM and DCIS. The present study aims to compare the clinical and imaging characteristics of contrast-enhanced mammography (CEM) and magnetic resonance imaging (MRI) between DCISM and pure DCIS, and to identify predictive factors of microinvasive carcinoma, which may contribute to a comprehensive understanding of DCISM in clinical diagnosis and support surveillance strategies, such as surgery, radiation, and other treatment decisions.

MATERIALS AND METHODS: Forty-seven female patients diagnosed with DCIS were included in the study from May 2019 to August 2023. Patients were further divided into two groups based on pathological diagnosis: DCIS and DCISM. Clinical and imaging characteristics of these two groups were analyzed statistically. The independent clinical risk factors were selected using multivariate logistic regression and used to establish the logistic model [Logit(P)]. The diagnostic performance of independent predictors was assessed and compared using receiver operating characteristic (ROC) analysis and DeLong's test.

RESULTS: In CEM, the maximum cross-sectional area (CSAmax), the percentage signal difference between the enhancing lesion and background in the craniocaudal and mediolateral oblique projection (%RSCC, and %RSMLO) were found to be significantly higher for DCISM compared to DCIS (p = 0.001; p < 0.001; p = 0.008). Additionally, there were noticeable statistical differences in the patterns of enhancement morphological distribution (EMD) and internal enhancement pattern (IEP) between DCIS and DCISM (p = 0.047; p = 0.008). In MRI, only CSAmax (p = 0.012) and IEP (p = 0.020) showed significant statistical differences. The multivariate regression analysis suggested that CSAmax (in CEM or MR) and %RSCC were independent predictors of DCISM (all p < 0.05). The area under the curve (AUC) of CSAmax (CEM), %RSCC (CEM), Logit(P) (CEM), and CSAmax (MR) were 0.764, 0.795, 0.842, and 0.739, respectively. There were no significant differences in DeLong's test for these values (all p > 0.10). DCISM was significantly associated with high nuclear grade, comedo type, high axillary lymph node (ALN) metastasis, and high Ki-67 positivity compared to DCIS (all p < 0.05).

CONCLUSION: The tumor size (CSAmax), enhancement index (%RS), and internal enhancement pattern (IEP) were highly indicative of DCISM. DCISM tends to express more aggressive pathological features, such as high nuclear grade, comedo-type necrosis, ALN metastasis, and Ki-67 overexpression. As with MRI, CEM has the capability to help predict when DCISM is accompanying DCIS.}, } @article {pmid38734115, year = {2024}, author = {Clark, AB and Conzen, SD}, title = {Glucocorticoid receptor-mediated oncogenic activity is dependent on breast cancer subtype.}, journal = {The Journal of steroid biochemistry and molecular biology}, volume = {243}, number = {}, pages = {106518}, doi = {10.1016/j.jsbmb.2024.106518}, pmid = {38734115}, issn = {1879-1220}, support = {R01 CA238519/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Receptors, Glucocorticoid/metabolism/genetics ; Female ; *Breast Neoplasms/pathology/metabolism/genetics ; Receptors, Estrogen/metabolism/genetics ; Signal Transduction ; Gene Expression Regulation, Neoplastic ; Triple Negative Breast Neoplasms/genetics/pathology/metabolism/classification ; Animals ; Carcinogenesis/genetics/metabolism ; }, abstract = {Breast cancer incidence has been steadily rising and is the leading cause of cancer death in women due to its high metastatic potential. Individual breast cancer subtypes are classified by both cell type of origin and receptor expression, namely estrogen, progesterone and human epidermal growth factor receptors (ER, PR and HER2). Recently, the importance and context-dependent role of glucocorticoid receptor (GR) expression in the natural history and prognosis of breast cancer subtypes have been uncovered. In ER-positive breast cancer, GR expression is associated with a better prognosis as a result of ER-GR crosstalk. GR appears to modulate ER-mediated gene expression resulting in decreased tumor cell proliferation and a more indolent cancer phenotype. In ER-negative breast cancer, including GR-positive triple-negative breast cancer (TNBC), GR expression enhances migration, chemotherapy resistance and cell survival. In invasive lobular carcinoma, GR function is relatively understudied, and more work is required to determine whether lobular subtypes behave similarly to their invasive ductal carcinoma counterparts. Importantly, understanding GR signaling in individual breast cancer subtypes has potential clinical implications because of the recent development of highly selective GR non-steroidal ligands, which represent a therapeutic approach for modulating GR activity systemically.}, } @article {pmid38730601, year = {2024}, author = {Wasinger, G and Cussenot, O and Compérat, E}, title = {Clinical Management of Intraductal Carcinoma of the Prostate.}, journal = {Cancers}, volume = {16}, number = {9}, pages = {}, pmid = {38730601}, issn = {2072-6694}, abstract = {Intraductal carcinoma of the prostate (IDC-P) has emerged as a distinct entity with significant clinical implications in prostate cancer (PCa) management. Despite historically being considered an extension of invasive PCa, IDC-P shows unique biological characteristics that challenge traditional diagnostic and therapeutic settings. This review explores the clinical management of IDC-P. While the diagnosis of IDC-P relies on specific morphological criteria, its detection remains challenging due to inter-observer variability. Emerging evidence underscores the association of IDC-P with aggressive disease and poor clinical outcomes across various PCa stages. However, standardized management guidelines for IDC-P are lacking. Recent studies suggest considering adjuvant and neoadjuvant therapies in specific patient cohorts to improve outcomes and tailor treatment strategies based on the IDC-P status. However, the current level of evidence regarding this is low. Moving forward, a deeper understanding of the pathogenesis of IDC-P and its interaction with conventional PCa subtypes is crucial for refining risk stratification and therapeutic interventions.}, } @article {pmid38726785, year = {2024}, author = {Li, H and Hou, Y and Xue, LY and Fan, WL and Gao, BL and Yin, XP}, title = {Use of MRI Radiomics Models in Evaluating the Low HER2 Expression in Breast Cancer.}, journal = {Current medical imaging}, volume = {20}, number = {}, pages = {e15734056234429}, doi = {10.2174/0115734056234429240426181002}, pmid = {38726785}, issn = {1573-4056}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging ; *Magnetic Resonance Imaging/methods ; *Erb-b2 Receptor Tyrosine Kinases/metabolism ; Retrospective Studies ; Middle Aged ; *Algorithms ; Adult ; ROC Curve ; Carcinoma, Ductal, Breast/diagnostic imaging ; Aged ; Contrast Media ; Radiomics ; }, abstract = {OBJECTIVE: To investigate the magnetic resonance imaging (MRI) radiomics models in evaluating the human epidermal growth factor receptor 2(HER2) expression in breast cancer.

MATERIALS AND METHODS: The MRI data of 161 patients with invasive ductal carcinoma (non-special type) of breast cancer were retrospectively collected, and the MRI radiomics models were established based on the MRI imaging features of the fat suppression T2 weighted image (T2WI) sequence, dynamic contrast-enhanced (DCE)-T1WIsequence and joint sequences. The T-test and the least absolute shrinkage and selection operator (LASSO) algorithm were used for feature dimensionality reduction and screening, respectively, and the random forest (RF) algorithm was used to construct the classification model.

RESULTS: The model established by the LASSO-RF algorithm was used in the ROC curve analysis. In predicting the low expression state of HER2 in breast cancer, the radiomics models of the fat suppression T2WI sequence, DCE-T1WI sequence, and the combination of the two sequences showed better predictive efficiency. In the receiver operating characteristic (ROC) curve analysis for the verification set of low, negative, and positive HER2 expression, the area under the ROC curve (AUC) value was 0.81, 0.72, and 0.62 for the DCE-T1WI sequence model, 0.79, 0.65 and 0.77 for the T2WI sequence model, and 0.84, 0.73 and 0.66 for the joint sequence model, respectively. The joint sequence model had the highest AUC value.

CONCLUSIONS: The MRI radiomics models can be used to effectively predict the HER2 expression in breast cancer and provide a non-invasive and early assistant method for clinicians to formulate individualized and accurate treatment plans}, } @article {pmid38725791, year = {2024}, author = {Yagyu, T and Miki, H and Kikawa, Y and Kobayashi, T and Sekimoto, M}, title = {Appendiceal Metastasis of Breast Cancer: A Case Report and a Literature Review.}, journal = {Cureus}, volume = {16}, number = {4}, pages = {e57929}, pmid = {38725791}, issn = {2168-8184}, abstract = {Appendiceal metastases of breast cancer (BC) are very rare, and there are few reports of resection. Asymptomatic appendiceal enlargement is often suspected to be a primary appendiceal tumor, making it difficult to suspect metastatic tumors, especially metastases from BC. On the other hand, advances in drug therapy, including hormonal therapy for BC, have prolonged survival, and there is a possibility of encountering metastatic cases that have rarely been seen before. We herein present a case in which an enlarged appendix, identified during hormonal therapy for advanced BC, was laparoscopically removed and diagnosed as BC metastasis. A 53-year-old woman had been diagnosed with invasive ductal carcinoma (IDC) based on a breast biopsy, and the appendiceal specimen was diagnosed as invasive lobular carcinoma (ILC). We herein report this unique case and provide a detailed review of 13 previous reports.}, } @article {pmid38721594, year = {2024}, author = {Owolabi, ATY and Schneider, P and Reece, SE}, title = {Virulence is associated with daily rhythms in the within-host replication of the malaria parasite Plasmodium chabaudi.}, journal = {Evolutionary applications}, volume = {17}, number = {5}, pages = {e13696}, pmid = {38721594}, issn = {1752-4571}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Most malaria (Plasmodium spp.) parasite species undergo asexual replication synchronously within the red blood cells of their vertebrate host. Rhythmicity in this intraerythrocytic developmental cycle (IDC) enables parasites to maximise exploitation of the host and align transmission activities with the time of day that mosquito vectors blood feed. The IDC is also responsible for the major pathologies associated with malaria, and plasticity in the parasite's rhythm can confer tolerance to antimalarial drugs. Both the severity of infection (virulence) and synchrony of the IDC vary across species and between genotypes of Plasmodium; however, this variation is poorly understood. The theory predicts that virulence and IDC synchrony are negatively correlated, and we tested this hypothesis using two closely related genotypes of the rodent malaria model Plasmodium chabaudi that differ markedly in virulence. We also test the predictions that, in response to perturbations to the timing (phase) of the IDC schedule relative to the phase of host rhythms (misalignment), the virulent parasite genotype recovers the correct phase relationship faster, incurs less fitness losses and so hosts benefit less from misalignment when infected with a virulent genotype. Our predictions are partially supported by results suggesting that the virulent parasite genotype is less synchronous in some circumstances and recovers faster from misalignment. While hosts were less anaemic when infected by misaligned parasites, the extent of this benefit did not depend on parasite virulence. Overall, our results suggest that interventions to perturb the alignment between the IDC schedule, and host rhythms and increase synchrony between parasites within each IDC, could alleviate disease symptoms. However, virulent parasites, which are better at withstanding conventional antimalarial treatment, would also be intrinsically better able to tolerate such interventions.}, } @article {pmid38721213, year = {2024}, author = {Samba, S and Bensghier, A and Berhili, S and Moukhlissi, M and Mezouar, L}, title = {Apocrine Breast Cancer: A Case Report.}, journal = {Cureus}, volume = {16}, number = {4}, pages = {e57789}, pmid = {38721213}, issn = {2168-8184}, abstract = {Breast cancer is the most frequent malignancy among women worldwide, including a wide range of histological subtypes, from typical expressions like invasive ductal carcinoma to less common variations like apocrine breast carcinoma. This document discusses the case of a 65-year-old female with apocrine breast cancer, who presented with a chronic mastodynia. This case highlights the importance of being aware of apocrine breast cancer.}, } @article {pmid38715773, year = {2024}, author = {Abu-Rahmah, R and Nechushtan, H and Hidmi, S and Meirovitz, A and Razin, E and Peretz, T}, title = {The functional role of Nudt2 in human triple negative breast cancer.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1364663}, pmid = {38715773}, issn = {2234-943X}, abstract = {The main known function of Nudix hydrolase 2 (Nudt2) is to hydrolyze the secondary messenger diadenosine 5', 5'''-p1, p4-tetraphosphate (Ap4A). In this study we examined the role of Nudt2 in breast carcinoma through its expression in human invasive ductal carcinoma tissues, and its functions in human triple negative breast cancer (TNBC) cell lines. A significantly higher expression of Nudt2 was observed in human invasive ductal carcinoma tissues compared to that in normal breast tissue. Knockdown of Nudt2 in TNBC cell lines resulted in a significant reduction in cellular proliferation via the Ki67 marker, accompanied by G0/G1 phase cell cycle arrest, in the migration and invasion of these cells and in tumorigenicity and anchorage-independent growth. It can therefore be concluded that Nudt2 plays a significant role in promoting TNBC growth.}, } @article {pmid38715717, year = {2024}, author = {Hwang, J and Cheney, P and Kanick, SC and Le, HND and McClatchy, DM and Zhang, H and Liu, N and John Lu, ZQ and Cho, TJ and Briggman, K and Allen, DW and Wells, WA and Pogue, BW}, title = {Hyperspectral dark-field microscopy of human breast lumpectomy samples for tumor margin detection in breast-conserving surgery.}, journal = {Journal of biomedical optics}, volume = {29}, number = {9}, pages = {093503}, pmid = {38715717}, issn = {1560-2281}, support = {F31 CA196308/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Breast Neoplasms/diagnostic imaging/surgery/pathology ; Female ; *Mastectomy, Segmental/methods ; *Algorithms ; *Microscopy/methods ; Breast/diagnostic imaging/pathology/surgery ; Hyperspectral Imaging/methods ; Margins of Excision ; Monte Carlo Method ; Image Processing, Computer-Assisted/methods ; }, abstract = {SIGNIFICANCE: Hyperspectral dark-field microscopy (HSDFM) and data cube analysis algorithms demonstrate successful detection and classification of various tissue types, including carcinoma regions in human post-lumpectomy breast tissues excised during breast-conserving surgeries.

AIM: We expand the application of HSDFM to the classification of tissue types and tumor subtypes in pre-histopathology human breast lumpectomy samples.

APPROACH: Breast tissues excised during breast-conserving surgeries were imaged by the HSDFM and analyzed. The performance of the HSDFM is evaluated by comparing the backscattering intensity spectra of polystyrene microbead solutions with the Monte Carlo simulation of the experimental data. For classification algorithms, two analysis approaches, a supervised technique based on the spectral angle mapper (SAM) algorithm and an unsupervised technique based on the K-means algorithm are applied to classify various tissue types including carcinoma subtypes. In the supervised technique, the SAM algorithm with manually extracted endmembers guided by H&E annotations is used as reference spectra, allowing for segmentation maps with classified tissue types including carcinoma subtypes.

RESULTS: The manually extracted endmembers of known tissue types and their corresponding threshold spectral correlation angles for classification make a good reference library that validates endmembers computed by the unsupervised K-means algorithm. The unsupervised K-means algorithm, with no a priori information, produces abundance maps with dominant endmembers of various tissue types, including carcinoma subtypes of invasive ductal carcinoma and invasive mucinous carcinoma. The two carcinomas' unique endmembers produced by the two methods agree with each other within <2% residual error margin.

CONCLUSIONS: Our report demonstrates a robust procedure for the validation of an unsupervised algorithm with the essential set of parameters based on the ground truth, histopathological information. We have demonstrated that a trained library of the histopathology-guided endmembers and associated threshold spectral correlation angles computed against well-defined reference data cubes serve such parameters. Two classification algorithms, supervised and unsupervised algorithms, are employed to identify regions with carcinoma subtypes of invasive ductal carcinoma and invasive mucinous carcinoma present in the tissues. The two carcinomas' unique endmembers used by the two methods agree to <2% residual error margin. This library of high quality and collected under an environment with no ambient background may be instrumental to develop or validate more advanced unsupervised data cube analysis algorithms, such as effective neural networks for efficient subtype classification.}, } @article {pmid38711196, year = {2024}, author = {Tang, H and Laskin, WB and Luan, Y and McNiff, JM and Zhan, H}, title = {Adenocarcinoma of anogenital mammary gland type arising from encapsulated papillary carcinoma: A rare vulvar tumor mimicking breast carcinoma.}, journal = {Journal of cutaneous pathology}, volume = {51}, number = {8}, pages = {604-608}, doi = {10.1111/cup.14639}, pmid = {38711196}, issn = {1600-0560}, mesh = {Humans ; Female ; *Vulvar Neoplasms/pathology/diagnosis/metabolism ; Aged ; *Breast Neoplasms/pathology/diagnosis ; Diagnosis, Differential ; Carcinoma, Papillary/pathology/diagnosis ; Carcinoma, Intraductal, Noninfiltrating/pathology/diagnosis ; Adenocarcinoma/pathology/diagnosis ; }, abstract = {Anogenital mammary-like glands are normal structures of the anogenital region. Tumors originating from these glands often exhibit a striking resemblance to their mammary gland counterparts. Herein, we present a rare case of adenocarcinoma of mammary gland type in the vulva of a 69-year-old female. Histopathologic examination revealed a complex lesion, which included a large encapsulated papillary carcinoma (EPC) with associated invasive carcinoma of mammary gland type and ductal carcinoma in situ (DCIS). The invasive component consisted mostly of invasive ductal carcinoma of no special type, with a notable focus of invasive mucinous carcinoma. p40 immunostain demonstrated a lack of myoepithelial cells in both the EPC and invasive carcinoma, but such cells expressed p40 around the ducts involved by DCIS. The main component of this lesion, EPC, was characterized by a papillary proliferation within a cystic space surrounded by a fibrous capsule without a myoepithelial layer. The histopathologic features of anogenital EPC closely resemble cutaneous hidradenoma papilliferum. Indeed, there have been a few reports in the literature describing cases where in situ and invasive carcinoma arose from a preexisting hidradenoma papilliferum. As tumors of anogenital mammary-like glands bear a closer resemblance to breast lesions than to skin tumors, we recommend that they be aligned with the classification of well-established breast lesions rather than cutaneous adnexal tumors.}, } @article {pmid38707627, year = {2024}, author = {van den Dobbelsteen, M and Hackett, SL and van Asselen, B and Oolbekkink, S and Raaymakers, BW and de Boer, JCJ}, title = {Treatment planning evaluation and experimental validation of the magnetic resonance-based intrafraction drift correction.}, journal = {Physics and imaging in radiation oncology}, volume = {30}, number = {}, pages = {100580}, pmid = {38707627}, issn = {2405-6316}, abstract = {BACKGROUND AND PURPOSE: MRI-guided online adaptive treatments can account for interfractional variations, however intrafraction motion reduces treatment accuracy. Intrafraction plan adaptation methods, such as the Intrafraction Drift Correction (IDC) or sub-fractionation, are needed. IDC uses real-time automatic monitoring of the tumor position to initiate plan adaptations by repositioning segments. IDC is a fast adaptation method that occurs only when necessary and this method could enable margin reduction. This research provides a treatment planning evaluation and experimental validation of the IDC.

MATERIALS AND METHODS: An in silico treatment planning evaluation was performed for 13 prostate patients mid-treatment without and with intrafraction plan adaptation (IDC and sub-fractionation). The adaptation methods were evaluated using dose volume histogram (DVH) metrics. To experimentally verify IDC a treatment was mimicked whereby a motion phantom containing an EBT3 film moved mid-treatment, followed by repositioning of segments. In addition, the delivered treatment was irradiated on a diode array phantom for plan quality assurance purposes.

RESULTS: The planning study showed benefits for using intrafraction adaptation methods relative to no adaptation, where the IDC and sub-fractionation showed consistently improved target coverage with median target coverages of 100.0%. The experimental results verified the IDC with high minimum gamma passing rates of 99.1% and small mean dose deviations of maximum 0.3%.

CONCLUSION: The straightforward and fast IDC technique showed DVH metrics consistent with the sub-fractionation method using segment weight re-optimization for prostate patients. The dosimetric and geometric accuracy was shown for a full IDC workflow using film and diode array dosimetry.}, } @article {pmid38702279, year = {2024}, author = {Zhang, S and Yang, B and Yang, H and Zhao, J and Zhang, Y and Gao, Y and Monteiro, O and Zhang, K and Liu, B and Wang, S}, title = {Potential rapid intraoperative cancer diagnosis using dynamic full-field optical coherence tomography and deep learning: A prospective cohort study in breast cancer patients.}, journal = {Science bulletin}, volume = {69}, number = {11}, pages = {1748-1756}, doi = {10.1016/j.scib.2024.03.061}, pmid = {38702279}, issn = {2095-9281}, mesh = {Humans ; *Breast Neoplasms/diagnostic imaging/surgery/pathology ; *Tomography, Optical Coherence/methods ; *Deep Learning ; Female ; Prospective Studies ; Middle Aged ; Carcinoma, Ductal, Breast/diagnostic imaging/surgery/pathology ; Aged ; Adult ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/surgery/pathology ; Intraoperative Period ; }, abstract = {An intraoperative diagnosis is critical for precise cancer surgery. However, traditional intraoperative assessments based on hematoxylin and eosin (H&E) histology, such as frozen section, are time-, resource-, and labor-intensive, and involve specimen-consuming concerns. Here, we report a near-real-time automated cancer diagnosis workflow for breast cancer that combines dynamic full-field optical coherence tomography (D-FFOCT), a label-free optical imaging method, and deep learning for bedside tumor diagnosis during surgery. To classify the benign and malignant breast tissues, we conducted a prospective cohort trial. In the modeling group (n = 182), D-FFOCT images were captured from April 26 to June 20, 2018, encompassing 48 benign lesions, 114 invasive ductal carcinoma (IDC), 10 invasive lobular carcinoma, 4 ductal carcinoma in situ (DCIS), and 6 rare tumors. Deep learning model was built up and fine-tuned in 10,357 D-FFOCT patches. Subsequently, from June 22 to August 17, 2018, independent tests (n = 42) were conducted on 10 benign lesions, 29 IDC, 1 DCIS, and 2 rare tumors. The model yielded excellent performance, with an accuracy of 97.62%, sensitivity of 96.88% and specificity of 100%; only one IDC was misclassified. Meanwhile, the acquisition of the D-FFOCT images was non-destructive and did not require any tissue preparation or staining procedures. In the simulated intraoperative margin evaluation procedure, the time required for our novel workflow (approximately 3 min) was significantly shorter than that required for traditional procedures (approximately 30 min). These findings indicate that the combination of D-FFOCT and deep learning algorithms can streamline intraoperative cancer diagnosis independently of traditional pathology laboratory procedures.}, } @article {pmid38699697, year = {2024}, author = {Geng, J and Jinli, S and Guo, W and Li, H and Dan, Y and Gao, Y}, title = {Expression and clinical significance of CA125, CA153 and CEA in nipple discharge of breast cancer patients.}, journal = {Journal of medical biochemistry}, volume = {43}, number = {2}, pages = {234-242}, pmid = {38699697}, issn = {1452-8258}, abstract = {BACKGROUND: It is an important clinical means to identify benign and malignant breast diseases caused by nipple discharge through the detection and analysis of components in nipple discharge. This study was aimed to test the expression and clinical significance of carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153) and carcinoembryonic antigen (CEA) in nipple discharge of breast cancer patients.

METHODS: From January 2017 to December 2018, 86 patients with invasive ductal carcinoma of the breast with nipple discharge (breast cancer group) and 50 patients with ordinary breast duct hyperplasia with nipple discharge (benign control group) were selected, and the levels of CA125, CA153 and CEA in nipple discharge and serum were detected by electrochemiluminescence immunoassay.}, } @article {pmid38695948, year = {2024}, author = {Agreda-Castañeda, F and Freixa-Sala, R and Franco, M and Bultó-Gonzalvo, R and Areal-Calama, J}, title = {Predictive factors of post-HoLEP incontinence: differences between stress and urgency urinary incontinence.}, journal = {World journal of urology}, volume = {42}, number = {1}, pages = {281}, pmid = {38695948}, issn = {1433-8726}, mesh = {Humans ; Male ; *Urinary Incontinence, Stress/surgery/epidemiology ; *Urinary Incontinence, Urge/epidemiology/etiology ; Aged ; Middle Aged ; *Prostatectomy/methods ; Postoperative Complications/epidemiology/etiology ; Retrospective Studies ; Risk Factors ; Prostatic Hyperplasia/surgery/complications ; Urodynamics/physiology ; Age Factors ; }, abstract = {INTRODUCTION: The analysis of post-HoLEP urinary incontinence (UI) has traditionally focused on stress UI. Our aim is to evaluate the factors associated with stress and urgency UI in the first month after the surgery.

METHODS: Data were obtained from patients who underwent HoLEP by the same experienced surgeon. UI was evaluated at one month and at 6 months after the surgery. Three groups were defined: continent patients, patients with pure urgency UI and patients with stress or mixed UI. Preoperative, intraoperative, urodynamic and clinical variables were analyzed and compared between the three groups.

RESULTS: In total, 235 subjects were included. One month after the surgery, 156 (66.5%) were continent (group 1), 49 (20.8%) reported pure urgency UI (group 2), and 30 (12.7%) reported some level of stress UI (group 3). In Group 2, the factors associated with urgency UI in the univariate analysis were age, presurgical urgency UI, having diabetes or hypertension. In Group 3, age, prostatic volume, preoperative PSA, time of enucleation, weight of the resection in grams, having an IDC or being diabetic were significant in the univariate analysis. In the multivariate analysis, age predicts both types of UI, while prostatic volume and having an IDC predict stress or mixed UI.

CONCLUSION: In the first month post-HoLEP, age is a predictive factor of urgency UI and stress UI. In addition, prostatic volume and the presence of an indwelling urinary catheter are predictive factors of stress UI.}, } @article {pmid38695332, year = {2024}, author = {Iradukunda, Y and Kang, JY and Zhao, XB and Fu, XK and Nsanzamahoro, S and Ha, W and Shi, YP}, title = {Triple Sensing Modes for Triggered β-Galactosidase Activity Assays Based on Kaempferol-Deduced Silicon Nanoparticles and Biological Imaging of MCF-7 Breast Cancer Cells.}, journal = {ACS applied bio materials}, volume = {7}, number = {5}, pages = {3154-3163}, doi = {10.1021/acsabm.4c00185}, pmid = {38695332}, issn = {2576-6422}, mesh = {Female ; Humans ; *beta-Galactosidase/metabolism ; Biocompatible Materials/chemistry/pharmacology/chemical synthesis ; *Breast Neoplasms/diagnosis/pathology ; Colorimetry ; *Kaempferols/chemistry/pharmacology ; MCF-7 Cells ; Molecular Structure ; *Nanoparticles/chemistry ; Particle Size ; *Silicon/chemistry ; }, abstract = {β-Galactosidase (β-Gala) is an essential biomarker enzyme for early detection of breast tumors and cellular senescence. Creating an accurate way to monitor β-Gala activity is critical for biological research and early cancer detection. This work used fluorometric, colorimetric, and paper-based color sensing approaches to determine β-Gala activity effectively. Via the sensing performance, the catalytic activity of β-Gala resulted in silicon nanoparticles (SiNPs), fluorescent indicators obtained via a one-pot hydrothermal process. As a standard enzymatic hydrolysis product of the substrate, kaempferol 3-O-β-d-galactopyranoside (KOβDG) caused the fluorometric signal to be attenuated on kaempferol-silicon nanoparticles (K-SiNPs). The sensing methods demonstrated a satisfactory linear response in sensing β-Gala and a low detection limit. The findings showed the low limit of detection (LOD) as 0.00057 and 0.098 U/mL for fluorometric and colorimetric, respectively. The designed probe was then used to evaluate the catalytic activity of β-Gala in yogurt and human serum, with recoveries ranging from 98.33 to 107.9%. The designed sensing approach was also applied to biological sample analysis. In contrast, breast cancer cells (MCF-7) were used as a model to test the in vitro toxicity and molecular fluorescence imaging potential of K-SiNPs. Hence, our fluorescent K-SiNPs can be used in the clinic to diagnose breast cellular carcinoma, since they can accurately measure the presence of invasive ductal carcinoma in serologic tests.}, } @article {pmid38689671, year = {2024}, author = {Pouptsis, A and Cano Gimeno, J and Martinez Rubio, C and Bañuls Marrades, M and Olivan Sasot, P}, title = {Metastatic Occult Primary Lobular Breast Cancer: A Case Report.}, journal = {Cureus}, volume = {16}, number = {4}, pages = {e58586}, pmid = {38689671}, issn = {2168-8184}, abstract = {Breast cancer is the most common malignancy diagnosed in women. Invasive lobular breast cancer (ILC) is the second most common histologic subtype after invasive ductal carcinoma. Metastatic occult primary breast cancer, although rare, is a well-known clinical entity that usually presents with axillary lymphadenopathy without a detectable breast tumour. A perimenopausal woman in her 50s presented with abdominal pain, fatigue, and weight loss. Imaging showed peritoneal carcinomatosis with ascites, ovarian masses, and a lesion in the ascending colon. Gastric and colon biopsies showed infiltration from lobular breast cancer. Diagnostic workup, including mammography, breast ultrasound, and breast MRI, showed no evidence of breast pathology or axillary lymphadenopathy. First-line treatment with goserelin, letrozole, and palbociclib commenced with clinical improvement and radiological response. This case illustrates the challenges faced by clinicians in the diagnosis and treatment of lobular breast cancer without an identifiable primary lesion or axillary lymphadenopathy.}, } @article {pmid38686340, year = {2024}, author = {Sui, X and Feng, P and Sun, X and Liang, P and Liu, Y and Zhang, G}, title = {Correlation Analysis of Digital Mammography, Ultrasonography, and Pathologic Features in Pure Invasive Micropapillary Carcinoma of the Breast (PIMPC).}, journal = {Breast cancer (Dove Medical Press)}, volume = {16}, number = {}, pages = {245-252}, pmid = {38686340}, issn = {1179-1314}, abstract = {PURPOSE: This study determined the digital mammography and ultrasonography imaging features of pure invasive micropapillary carcinoma of the breast (PIMPC) and the correlation with pathologic features.

PATIENTS METHODS: Nineteen patients diagnosed with PIMPC at Yantaishan Hospital from October 2015 to February 2022 were included in the study group. Forty patients with breast masses diagnosed as nonspecific invasive ductal carcinoma of the breast (NIDC) from July to December 2021 were included in the control group. Digital mammography and ultrasonography features were compared between the two groups.

RESULTS: Patients with PIMPC had a younger age profile compared to patients with NIDC (P=0.017). Moreover, PIMPC masses were smaller than NIDC masses (P=0.040). Imaging features analysis revealed significant differences in age groups (<45 years: χ²=5.971, P=0.044) and the presence of spiculations or the crab claw sign (χ²=8.583, P=0.004) between patients with PIMPC and NIDC. However, there were no statistically significant differences in the presence of calcifications, blood flow grading, pathologic molecular subtypes between the study and control groups. The Ki-67 proliferative index (χ²=1.052, P=0.389), vascular invasion (χ²=2.263, P=0.197), and lymph node metastasis (χ²=1.968, P=0.386) showed no significant differences between PIMPC and NIDC patients.

CONCLUSION: PIMPC imaging features show specificity, such as tiny breast masses, spiculated edges, or crab claw-like patterns, and malignant signs appeared when the lesion was <2 cm in diameter. PIMPC mainly occurs in middle-aged women 45-59 y of age. Patients with PIMPC and NIDC of the breast are frequently associated with lymph node metastases and greater than one-half of the cases (74%) were shown to have a Ki-67 index >30%, suggesting a significant risk of recurrence and metastasis. Early therapeutic care for these patients is crucial. These results warrant further validation with additional samples from several centers due to the limited single-center sample size in the current study.}, } @article {pmid38685994, year = {2024}, author = {Koenig, ZA and Koenig, NI and Climov, M and Uygur, HŞ}, title = {Safety and Feasibility of Oncoplastic Reconstruction in the Setting of Prior Breast Reduction.}, journal = {Eplasty}, volume = {24}, number = {}, pages = {e19}, pmid = {38685994}, issn = {1937-5719}, abstract = {BACKGROUND: Breast conservation therapy typically consists of lumpectomy, which often leads to poor cosmetic outcomes. Concurrent oncoplastic reductions are performed to maximize aesthetics and patient outcome. We present an oncoplastic breast reconstruction in a breast re-reduction case in this study.

METHODS: A 62-year-old female was diagnosed with invasive ductal carcinoma of the left upper outer breast by core needle biopsy. The patient had a prior bilateral breast reduction using a superior-central pedicle approach 15 years ago and desired breast conservation therapy.

RESULTS: The oncoplastic reconstruction technique used was a superomedial pedicle Wise-pattern bilateral breast reduction. The lump was excised lateral to the pedicle after initial de-epithelialization and incision of the superomedial pedicle's lateral aspect. The remainder of the pedicle was developed, and the same procedure was performed on the right breast at the same time. Excess tissue was excised bilaterally from the medial, superior, and inferior, and the optimal new nipple position was obtained. Both nipples were viable and well perfused following closure of the incisions.

CONCLUSIONS: Breast cancer is uncommon in patients who have had bilateral breast reductions. Oncoplastic reduction is an uncommon procedure used in patients who want to preserve their breasts while maintaining their aesthetic appearance. There is currently no agreement on the most effective and safest surgical technique for breast re- reduction surgery, and no reports on oncoplastic reconstruction in patients requiring breast re-reductions. In an oncoplastic reconstruction case, we achieved an acceptable outcome with our superomedial pedicled Wise-pattern bilateral breast reduction technique.}, } @article {pmid38684889, year = {2024}, author = {Khani, S and Topel, H and Kardinal, R and Tavanez, AR and Josephrajan, A and Larsen, BDM and Gaudry, MJ and Leyendecker, P and Egedal, NM and Güller, AS and Stanic, N and Ruppert, PMM and Gaziano, I and Hansmeier, NR and Schmidt, E and Klemm, P and Vagliano, LM and Stahl, R and Duthie, F and Krause, JH and Bici, A and Engelhard, CA and Gohlke, S and Frommolt, P and Gnad, T and Rada-Iglesias, A and Pradas-Juni, M and Schulz, TJ and Wunderlich, FT and Pfeifer, A and Bartelt, A and Jastroch, M and Wachten, D and Kornfeld, JW}, title = {Cold-induced expression of a truncated adenylyl cyclase 3 acts as rheostat to brown fat function.}, journal = {Nature metabolism}, volume = {6}, number = {6}, pages = {1053-1075}, pmid = {38684889}, issn = {2522-5812}, support = {675014//EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))/ ; PROTEOFIT//EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))/ ; 33444//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; 28416//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; A/12/97620//Deutscher Akademischer Austauschdienst (German Academic Exchange Service)/ ; TRR333/1 (450149205)//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB 1454 (432325352)//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; TRR83//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SPP1926//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SPP1726//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; FOR2743//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB1123-B10//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 676-2021//European Molecular Biology Organization (EMBO)/ ; }, mesh = {*Adenylyl Cyclases/metabolism/genetics ; *Adipose Tissue, Brown/metabolism ; Animals ; Mice ; *Cold Temperature ; Male ; Humans ; Thermogenesis/genetics ; Energy Metabolism ; Cyclic AMP/metabolism ; Mice, Knockout ; }, abstract = {Promoting brown adipose tissue (BAT) activity innovatively targets obesity and metabolic disease. While thermogenic activation of BAT is well understood, the rheostatic regulation of BAT to avoid excessive energy dissipation remains ill-defined. Here, we demonstrate that adenylyl cyclase 3 (AC3) is key for BAT function. We identified a cold-inducible promoter that generates a 5' truncated AC3 mRNA isoform (Adcy3-at), whose expression is driven by a cold-induced, truncated isoform of PPARGC1A (PPARGC1A-AT). Male mice lacking Adcy3-at display increased energy expenditure and are resistant to obesity and ensuing metabolic imbalances. Mouse and human AC3-AT are retained in the endoplasmic reticulum, unable to translocate to the plasma membrane and lack enzymatic activity. AC3-AT interacts with AC3 and sequesters it in the endoplasmic reticulum, reducing the pool of adenylyl cyclases available for G-protein-mediated cAMP synthesis. Thus, AC3-AT acts as a cold-induced rheostat in BAT, limiting adverse consequences of cAMP activity during chronic BAT activation.}, } @article {pmid38684702, year = {2024}, author = {de Oliveira, RM and Paiva, MUB and Picossi, CRC and Paiva, DVN and Ricart, CAO and Ruperez, FJ and Barbas, C and Atik, FA and Martins, AMA}, title = {Metabolomic insights in advanced cardiomyopathy of chronic chagasic and idiopathic patients that underwent heart transplant.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {9810}, pmid = {38684702}, issn = {2045-2322}, support = {EADS CASA 002/DCTA-COPAC/2014//Airbus Spain/ ; }, mesh = {Humans ; *Heart Transplantation ; Male ; Female ; Middle Aged ; *Chagas Cardiomyopathy/metabolism/blood ; *Metabolomics/methods ; *Cardiomyopathy, Dilated/metabolism/surgery/blood ; Adult ; Metabolome ; Heart Failure/metabolism/etiology ; Aged ; Chronic Disease ; Gas Chromatography-Mass Spectrometry ; }, abstract = {Heart failure (HF) studies typically focus on ischemic and idiopathic heart diseases. Chronic chagasic cardiomyopathy (CCC) is a progressive degenerative inflammatory condition highly prevalent in Latin America that leads to a disturbance of cardiac conduction system. Despite its clinical and epidemiological importance, CCC molecular pathogenesis is poorly understood. Here we characterize and discriminate the plasma metabolomic profile of 15 patients with advanced HF referred for heart transplantation - 8 patients with CCC and 7 with idiopathic dilated cardiomyopathy (IDC) - using gas chromatography/quadrupole time-of-flight mass spectrometry. Compared to the 12 heart donor individuals, also included to represent the control (CTRL) scenario, patients with advanced HF exhibited a metabolic imbalance with 21 discriminating metabolites, mostly indicative of accumulation of fatty acids, amino acids and important components of the tricarboxylic acid (TCA) cycle. CCC vs. IDC analyses revealed a metabolic disparity between conditions, with 12 CCC distinctive metabolites vs. 11 IDC representative metabolites. Disturbances were mainly related to amino acid metabolism profile. Although mitochondrial dysfunction and loss of metabolic flexibility may be a central mechanistic event in advanced HF, metabolic imbalance differs between CCC and IDC populations, possibly explaining the dissimilar clinical course of Chagas' patients.}, } @article {pmid38680708, year = {2024}, author = {Shaghaghi Torkdari, Z and Khalaj-Kondori, M and Hosseinpour Feizi, MA}, title = {Plasma Circulating Terminal Differentiation-Induced Non-Coding RNA Serves as a Biomarker in Breast Cancer.}, journal = {International journal of hematology-oncology and stem cell research}, volume = {18}, number = {1}, pages = {1-6}, pmid = {38680708}, issn = {2008-3009}, abstract = {Background: Breast cancer is identified as the most common malignancy and cause of cancer-related death worldwide. Compared with healthy controls, this study evaluated the expression level and diagnostic power of lncRNA plasma TINCR in breast cancer patients. Materials and Methods: Fifty-eight women diagnosed with invasive ductal carcinoma and fifty healthy age- matched controls were included in the study. TRIzol[®] LS regent was used to isolate the total RNA from the whole plasma. Total RNA was converted to cDNA using Prime Script[TM] RT reagent kit and the expression levels of TINCR were quantified by qRT-PCR. Results: Low levels of TINCR lncRNA were observed in the plasma of breast cancer patients compared with control subjects. Plasma TINCR level was also positively correlated with the diagnostic age of breast cancer patients. Conclusion: A low level of plasma TINCR could discriminate breast cancer patients from healthy control subjects.}, } @article {pmid38678597, year = {2024}, author = {Rostami, B and Kahrizi, S and Ghorbani Yekta, B and Ghadyani, R and Keramatinia, A and Hoseini, SJ and Karima, S and Nikzamir, AR and Mansouri, N and Chen, M and Movafagh, A}, title = {Correlation of IDH1 gene expression error in breast tumor biopsy in patients with invasive ductal carcinoma.}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {70}, number = {4}, pages = {242-247}, doi = {10.14715/cmb/2024.70.4.38}, pmid = {38678597}, issn = {1165-158X}, mesh = {Humans ; *Isocitrate Dehydrogenase/genetics ; Female ; *Breast Neoplasms/genetics/pathology ; Middle Aged ; *Carcinoma, Ductal, Breast/genetics/pathology ; *Gene Expression Regulation, Neoplastic ; Adult ; Biopsy ; RNA, Messenger/genetics/metabolism ; Aged ; }, abstract = {One of the most important cancers in terms of worldwide prevalence is breast tumors, which have been less investigated in correlation with the enzyme Isocitrate Dehydrogenase 1 (IDH1) gene. The aim of this study was that expression of this gene could have significant effects on the progression of metastasis and invasive disease in breast cancer patients. We used the molecular method of RT-PCR with SYBR-Green to analyze breast tumor tissue from patients with metastasis and non-metastasis, the latter confirmed by the pathology department of Shohada-e Tajrish Hospital (serving as a control group). Also, patients population and its relationship with the degree of tumor in the IDH1 gene was investigated. The IDH1 gene has shown high expression in patients with metastatic breast cancer rather than in patients with non-metastatic breast cancer. The metastatic samples were compared with non-metastatic samples for IDH1 mRNA expression. In this research work, 72.5% (29 samples) were up-regulated in comparison to 27.5% of samples (11 samples) that did not exhibit high expression (P=0.000). This study examined the IDH1 gene expression, suggesting that changes in this gene's expression could impact the prognosis of breast cancer. However, further research is needed to draw definitive conclusions.}, } @article {pmid38677859, year = {2024}, author = {de Souza, IC and Langer, FW}, title = {Post-radiation angiosarcoma of the breast in a patient with a history of invasive ductal carcinoma.}, journal = {Lancet (London, England)}, volume = {403}, number = {10437}, pages = {1681-1682}, doi = {10.1016/S0140-6736(24)00688-3}, pmid = {38677859}, issn = {1474-547X}, mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/radiotherapy ; *Carcinoma, Ductal, Breast/radiotherapy ; *Hemangiosarcoma/etiology ; *Neoplasms, Radiation-Induced/etiology ; Neoplasms, Second Primary/etiology ; }, } @article {pmid38672600, year = {2024}, author = {Yousef, YA and Mohammad, M and Khalil, H and Khouri, T and Alsweiti, R and Khzouz, J and Abu Laban, D and Jaradat, I and Ibrahimi, AK and Al-Ibraheem, A and Masri, MA and AlNawiaseh, I and Abdel-Razeq, H}, title = {Ocular and Periocular Metastasis in Breast Cancer: Clinical Characteristics, Prognostic Factors and Treatment Outcome.}, journal = {Cancers}, volume = {16}, number = {8}, pages = {}, pmid = {38672600}, issn = {2072-6694}, abstract = {BACKGROUND: Breast cancer remains a leading cause of cancer-related mortality and morbidity worldwide. Ocular and periocular metastasis present as a rare but clinically significant manifestation. This study aims to explore demographics and clinical aspects of ocular and periocular metastasis in breast cancer patients.

METHODS: A retrospective cohort study comprising 45 breast cancer patients with ocular or periocular metastasis treated between 2013 and 2023. Patient demographics, tumor characteristics, diagnostic methods, treatment modalities, visual outcomes, and survival data were analyzed.

RESULTS: Among 9902 breast cancer patients, 0.5% developed ocular or periocular metastasis, constituting 2.4% of metastatic cases. The median age was 50 years. Ocular metastasis timing varied: 5% before breast cancer, 24% concurrent, 22% within a year, and 49% after. The most common presentations included incidental MRI findings (42%) and vision decline (31%). Metastasis involved the orbit (47%), choroid (40%), optic nerve (11%), and iris (2%), with 44% having bilateral involvement. Predictive factors included invasive lobular carcinoma (ILC) (p < 0.0001) and brain metastasis (p < 0.0001), with ILC exhibiting a sixfold higher likelihood of ocular metastasis than invasive ductal carcinoma (IDC). Primary treatment was radiation therapy (89%), yielding a 55% maintenance of excellent vision (<0.5), with 93% developing dry eye disease. Patients with ocular metastasis faced an increased risk of disease-related mortality (p < 0.0001), with 71% succumbing within 10 months post-diagnosis.

CONCLUSIONS: Ocular metastasis in breast cancer is rare (0.5%) but signifies poor outcome. It is linked to ILC and concurrent brain metastasis. Primary treatment involves radiation therapy, with a favorable visual prognosis.}, } @article {pmid38672591, year = {2024}, author = {Mubarak, F and Kowkabany, G and Popp, R and Bansal, S and Ahmed, SH and Sharan, S and Sukniam, KB and Raikot, SR and Jimenez, PB and Popp, K and Manaise, HK and Gabriel, E}, title = {Early Stage Breast Cancer: Does Histologic Subtype (Ductal vs. Lobular) Impact 5 Year Overall Survival?.}, journal = {Cancers}, volume = {16}, number = {8}, pages = {}, pmid = {38672591}, issn = {2072-6694}, support = {P30 CA016056/CA/NCI NIH HHS/United States ; P30CA016056/CA/NCI NIH HHS/United States ; }, abstract = {Histology is an important predictor of the behavior of breast cancer. We aim to study the impact of histology on the overall survival (OS) of breast cancer patients. We studied 11,085 breast cancer patients diagnosed with T1-T2 tumors, clinically node-negative and non-metastatic, from 2004 to 2019 included in the National Cancer Database. Kaplan-Meier curves, log-rank tests and Cox regression models were used to study the impact of histology and other variables on OS. In our patient population, 8678 (78.28%) had ductal cancer (IDC), while 2407 (21.71%) had lobular cancer (ILC). ILC patients were significantly more likely to be older, Caucasian, have a lower grade at diagnosis and be hormone receptor-positive compared to IDC patients. There was no statistically significant difference in the 5-year OS of early stage ductal (16.8%) and lobular cancer patients (16.7%) (p = 0.200). Patients of Hispanic and African American origin had worse OS rates compared to non-Hispanic and Caucasian patients, respectively. For node-positive disease, HER2+ tumors and triple-negative tumors, chemotherapy had a positive influence on OS (HR 0.85, 95% CI 0.77-0.93, p = 0.0012). Histology did not have a significant impact on the 5-year OS of early stage breast cancer patients.}, } @article {pmid38668337, year = {2024}, author = {Peter, A and Schleicher, E and Kliemank, E and Szendroedi, J and Königsrainer, A and Häring, HU and Nawroth, PP and Fleming, T}, title = {Accumulation of Non-Pathological Liver Fat Is Associated with the Loss of Glyoxalase I Activity in Humans.}, journal = {Metabolites}, volume = {14}, number = {4}, pages = {}, pmid = {38668337}, issn = {2218-1989}, support = {SFB1118//Deutsche Forschungsgemeinschaft/ ; GRK 1874/2 DIAMICOM//Deutsche Forschungsgemeinschaft/ ; }, abstract = {The underlying molecular mechanisms for the development of non-alcoholic fatty liver (NAFL) and its progression to advanced liver diseases remain elusive. Glyoxalase 1 (Glo1) loss, leading to elevated methylglyoxal (MG) and dicarbonyl stress, has been implicated in various diseases, including obesity-related conditions. This study aimed to investigate changes in the glyoxalase system in individuals with non-pathological liver fat. Liver biopsies were obtained from 30 individuals with a narrow range of BMI (24.6-29.8 kg/m[2]). Whole-body insulin sensitivity was assessed using HOMA-IR. Liver biopsies were analyzed for total triglyceride content, Glo1 and Glo2 mRNA, protein expression, and activity. Liquid chromatography-tandem mass spectrometry determined liver dicarbonyl content and oxidation and glycation biomarkers. Liver Glo1 activity showed an inverse correlation with HOMA-IR and liver triglyceride content, but not BMI. Despite reduced Glo1 activity, no associations were found with elevated liver dicarbonyls or glycation markers. A sex dimorphism was observed in Glo1, with females exhibiting significantly lower liver Glo1 protein expression and activity, and higher liver MG-H1 content compared to males. This study demonstrates that increasing liver fat, even within a non-pathological range, is associated with reduced Glo1 activity.}, } @article {pmid38667089, year = {2024}, author = {Galily, Y}, title = {From Sport Psychology to Action Philosophy: Immanuel Kant and the Case of Video Assistant Referees.}, journal = {Behavioral sciences (Basel, Switzerland)}, volume = {14}, number = {4}, pages = {}, pmid = {38667089}, issn = {2076-328X}, abstract = {The implementation of Video Assistant Referees (VARs) in 2018 has had a significant impact on the multi-billion-dollar soccer industry. As the most popular and watched sport globally, soccer's financial stakes are high, with clubs, leagues, broadcasters, sponsors, and fans heavily invested in the game. The ongoing debate surrounding the VAR system brings to light the intricate balance between preserving the authenticity of football (soccer) and harnessing technology to improve accuracy. It is crucial to strike the right equilibrium in order to uphold football's metaphorical power and sustain the timeless joy it has brought to fans throughout generations. In this context, Immanuel Kant's philosophy can offer valuable insights into the utilization of VARs in soccer. According to Kantian ethics, using VARs can be justified if it serves to enhance fairness and accuracy, aligning with the moral duties of referees. Nevertheless, it is important to consider the potential dehumanizing effects and the necessity of preserving the value of human judgment in the game. Therefore, this paper aims to explore in-depth the intricate dynamics that arise when technology is integrated into traditional practices, emphasizing the significance of critical reflection on the implications of such advancements.}, } @article {pmid38659417, year = {2025}, author = {Mocha Campillo, F and Comín Orce, AM and Monreal Cepero, ML and Trincado Cobos, P and Gómez Mugarza, P and Barriendos Sanz, S and Pascual de la Fuente, N and Ruffini Egea, S and Martínez Trufero, J}, title = {Analysis of the Complexity of Palliative Care for Cancer Patients.}, journal = {The American journal of hospice & palliative care}, volume = {42}, number = {2}, pages = {178-185}, doi = {10.1177/10499091241247169}, pmid = {38659417}, issn = {1938-2715}, mesh = {Humans ; *Palliative Care/organization & administration ; Male ; Female ; *Neoplasms/therapy ; Cross-Sectional Studies ; Aged ; Middle Aged ; Aged, 80 and over ; Quality of Life ; Depression/epidemiology ; Adult ; Spain ; Vomiting ; Nausea/therapy ; Functional Status ; }, abstract = {INTRODUCTION: The Spanish National Health System has defined complexity as a set of factors of increased difficulty that require the intervention of a palliative care team. Palliative care aims to improve the quality of life of patients with chronic terminal illnesses. This study aims to describe the degree of complexity of cancer patients in palliative care, to determine which elements of complexity are most prevalent and to determine which other hospital clinical factors are associated with the level of complexity.

METHODS: This study is a descriptive, observational, and cross-sectional analysis that included patients diagnosed with advanced oncological pathology undergoing palliative treatment who were admitted to the Medical Oncology ward of the Miguel Servet University Hospital between March and April 2023.

RESULT: A total of 100 patients were selected for the study. According to the IDC-Pal, 68% of patients were classified as highly complex, 26% of patients were complex and only 6% of patients were classified as non-complex. The presence of pain (P < .001), nausea and vomiting (P = .027), depression (P = .033) and functional status (P = .011) were statistically independent predictors of high complexity.

DISCUSSION: This study has shown that a high proportion of hospitalized palliative care cancer patients have high complexity, suggesting a good matching of healthcare resources to patient complexity. Four factors related to complexity have been identified, namely pain, nausea and vomiting, depression and a bedridden functional state. The presence of any of the 4 factors could help healthcare professionals to identify patients for early specialized palliative care.}, } @article {pmid38656713, year = {2024}, author = {Kikuchi, M and Miyabe, R and Matsushima, H and Kita, H and Kobayashi, J and Ando, T and Atsuta, K and Shintani, T}, title = {Tumor lysis syndrome following letrozole for locally advanced breast cancer: a case report.}, journal = {Surgical case reports}, volume = {10}, number = {1}, pages = {100}, pmid = {38656713}, issn = {2198-7793}, abstract = {BACKGROUND: Letrozole, an aromatase inhibitor, is used to treat breast cancer in postmenopausal women. Tumor lysis syndrome (TLS) is a complication that can trigger multiple organ failure caused by the release of intracellular nucleic acids, phosphate, and potassium into the blood due to rapid tumor cell disintegration induced by drug therapy. TLS is uncommon in solid tumors and occurs primarily in patients receiving chemotherapy. Herein, we report a rare occurrence of TLS that developed in a patient with locally advanced breast cancer following treatment with letrozole.

CASE PRESENTATION: An 80-year-old woman with increased bleeding from a fist-sized left-sided breast mass presented to our hospital. Histological examination led to a diagnosis of invasive ductal carcinoma of the luminal type. The patient refused chemotherapy and was administered hormonal therapy with letrozole. Seven days after letrozole initiation, she complained of anorexia and diarrhea. Blood test results revealed elevated blood urea nitrogen (BUN) and creatinine (Cr) levels, and she was admitted to our hospital for intravenous infusions. On the second day after admission, marked elevations of LDH, BUN, Cr, potassium, calcium, and uric acid levels were observed. Furthermore, metabolic acidosis and prolonged coagulation capacity were observed. We suspected TLS and discontinued letrozole, and the patient was treated with hydration, febuxostat, and maintenance hemodialysis. On the third day after admission, her respiratory status worsened because of acute respiratory distress syndrome associated with hypercytokinemia, and she was intubated. On the fourth day after admission, her general condition did not improve, and she died.

CONCLUSIONS: Although TLS typically occurs after chemotherapy initiation, the findings from the present case confirm that this syndrome can also occur after hormonal therapy initiation and should be treated with caution.}, } @article {pmid38655280, year = {2024}, author = {Butler, SC and Rofeberg, V and Smith-Parrish, M and LaRonde, M and Vittner, DJ and Goldberg, S and Bailey, V and Weeks, MM and McCowan, S and Severtson, K and Glowick, K and Rachwal, CM}, title = {Caring for hearts and minds: a quality improvement approach to individualized developmental care in the cardiac intensive care unit.}, journal = {Frontiers in pediatrics}, volume = {12}, number = {}, pages = {1384615}, pmid = {38655280}, issn = {2296-2360}, abstract = {INTRODUCTION: Infants with congenital heart disease (CHD) are at high risk for developmental differences which can be explained by the cumulative effect of medical complications along with sequelae related to the hospital and environmental challenges. The intervention of individualized developmental care (IDC) minimizes the mismatch between the fragile newborn brain's expectations and the experiences of stress and pain inherent in the intensive care unit (ICU) environment.

METHODS: A multidisciplinary group of experts was assembled to implement quality improvement (QI) to increase the amount of IDC provided, using the Newborn Individualized Developmental Care and Assessment Program (NIDCAP), to newborn infants in the cardiac ICU. A Key Driver Diagram was created, PDSA cycles were implemented, baseline and ongoing measurements of IDC were collected, and interventions were provided.

RESULTS: We collected 357 NIDCAP audits of bedside IDC. Improvement over time was noted in the amount of IDC including use of appropriate lighting, sound management, and developmentally supportive infant bedding and clothing, as well as in promoting self-regulation, therapeutic positioning, and caregiving facilitation. The area of family participation and holding of infants in the CICU was the hardest to support change over time, especially with the most ill infants. Infants with increased medical complexity were less likely to receive IDC.

DISCUSSION: This multidisciplinary, evidence-based QI intervention demonstrated that the implementation of IDC in the NIDCAP model improved over time using bedside auditing of IDC.}, } @article {pmid38649742, year = {2024}, author = {Kaltenecker, D and Al-Maskari, R and Negwer, M and Hoeher, L and Kofler, F and Zhao, S and Todorov, M and Rong, Z and Paetzold, JC and Wiestler, B and Piraud, M and Rueckert, D and Geppert, J and Morigny, P and Rohm, M and Menze, BH and Herzig, S and Berriel Diaz, M and Ertürk, A}, title = {Virtual reality-empowered deep-learning analysis of brain cells.}, journal = {Nature methods}, volume = {21}, number = {7}, pages = {1306-1315}, pmid = {38649742}, issn = {1548-7105}, support = {SFB 824//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 390857198//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB 1052//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; TR 296//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 01KX2121//Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)/ ; 949017//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; 2020 EKSE.23//Else Kröner-Fresenius-Stiftung (Else Kroner-Fresenius Foundation)/ ; }, mesh = {*Deep Learning ; Animals ; *Brain/diagnostic imaging ; Mice ; *Virtual Reality ; Neurons ; Software ; Image Processing, Computer-Assisted/methods ; Proto-Oncogene Proteins c-fos/metabolism ; Humans ; }, abstract = {Automated detection of specific cells in three-dimensional datasets such as whole-brain light-sheet image stacks is challenging. Here, we present DELiVR, a virtual reality-trained deep-learning pipeline for detecting c-Fos[+] cells as markers for neuronal activity in cleared mouse brains. Virtual reality annotation substantially accelerated training data generation, enabling DELiVR to outperform state-of-the-art cell-segmenting approaches. Our pipeline is available in a user-friendly Docker container that runs with a standalone Fiji plugin. DELiVR features a comprehensive toolkit for data visualization and can be customized to other cell types of interest, as we did here for microglia somata, using Fiji for dataset-specific training. We applied DELiVR to investigate cancer-related brain activity, unveiling an activation pattern that distinguishes weight-stable cancer from cancers associated with weight loss. Overall, DELiVR is a robust deep-learning tool that does not require advanced coding skills to analyze whole-brain imaging data in health and disease.}, } @article {pmid38646373, year = {2024}, author = {Kani, V and Chander, V and Sonti, S and Manian, S and Vasudevan, S and Esakki, M and Grace Priyadarshini, S and Rajendran, K}, title = {A Rare and Intriguing Case Report of Metaplastic Breast Carcinoma.}, journal = {Cureus}, volume = {16}, number = {3}, pages = {e56619}, pmid = {38646373}, issn = {2168-8184}, abstract = {Metaplastic breast carcinoma (MBC) is a rare and aggressive subtype of breast cancer characterized by the presence of both epithelial and mesenchymal components within the tumor. Its clinical and radiological appearance is comparable to other types of breast cancer, but it grows rapidly. The diagnosis of metaplastic carcinoma is largely based on the epithelial origin of the cells confirmed by immunohistochemistry (IHC). Compared to invasive ductal carcinoma, metaplastic carcinoma has a worse overall survival rate. Any patient with a rapidly growing breast mass should be assessed with suspicion of sarcomatoid or metaplastic malignant neoplasm. We report this case due to its rarity and the complex nature of the disease.}, } @article {pmid38644311, year = {2024}, author = {Satoh, E and Innami, Y and Uehira, D and Yonekura, K and Murakata, A and Ohinata, R and Toyofuku, Y and Tanami, H and Osanai, T and Sugano, N and Sakoma, T}, title = {[A Long-Surviving Case of Locally Advanced Breast Cancer with Multiple Lung Metastasis].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {4}, pages = {427-429}, pmid = {38644311}, issn = {0385-0684}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/drug therapy ; *Lung Neoplasms/secondary/drug therapy ; Aged ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Time Factors ; Carcinoma, Ductal, Breast/secondary/therapy/drug therapy ; Mastectomy ; }, abstract = {We report a case of right advanced breast cancer with multiple lung metastases in a 66-year-old woman. Her breast cancer(invasive ductal carcinoma, cT4bN1M1, Stage Ⅳ)was resected in October 2007(mastectomy plus axillary lymph node dissection)after local arterial infusion therapy(total dose 5-FU 4,735 mg plus adriamycin 180 mg), which caused bilateral lung arterial embolism due to deep vein thrombosis in right her leg. She had to be treated by anticoagulant therapy, mechanical ventilation and placement of IVC filter before her operation. Subsequent chemo-endocrine therapy(docetaxel 6 courses plus anastrozole)was continued. In October 2008, a CT scan showed disappearance of multiple lung metastases (complete response). In November 2015 (8 years after her operation), a CT scan showed recurrence of multiple lung metastases and endocrine therapy was changed to tamoxifen. A year later, a CT scan showed disappearance of multiple lung metastases(complete response)again and keep a condition of complete response in her breast cancer until May 2023 (15 years after her operation).}, } @article {pmid38644310, year = {2024}, author = {Tanaka, Y and Ohshima, Y and Fukaya, Y and Hosoya, K and Wakahara, M}, title = {[Case Report of Occult Breast Cancer with Triple Negative Subtype].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {4}, pages = {421-423}, pmid = {38644310}, issn = {0385-0684}, mesh = {Humans ; Female ; Middle Aged ; *Triple Negative Breast Neoplasms/pathology ; Lymphatic Metastasis ; Axilla ; }, abstract = {A 61-year-old woman presented at a nearby clinic with a complaint of a mass in the right axilla. Initial imaging examinations, including mammography, ultrasonography, and breast MRI, did not reveal any obvious intramammary lesions, although a swollen lymph node was observed in the right axilla. Fine-needle aspiration cytology confirmed malignancy. Hence, a core needle biopsy was performed. The results indicated a suspected metastasis of invasive ductal carcinoma(ER-, PgR-, HER2-); however, the primary tumor could not be definitively determined. Despite an extensive whole-body examination, the primary tumor remained unidentified. Nonetheless, metastasis of occult breast cancer in the right axillary lymph node was postulated. Subsequent axillary dissection revealed metastases in only one lymph node. Taking the clinical findings into consideration, the patient was diagnosed with right occult breast cancer, and chemotherapy and radiotherapy were planned.}, } @article {pmid38638844, year = {2024}, author = {Zhou, H and Liu, D and Chen, L and Zhang, Y and Zhao, X and Ge, Y and Liu, M and Kong, T}, title = {Metastasis to the bladder from primary breast cancer: A case report and literature review.}, journal = {Oncology letters}, volume = {27}, number = {6}, pages = {249}, pmid = {38638844}, issn = {1792-1082}, abstract = {Breast cancer is the most prevalent malignant tumor affecting women and represents the leading cause of female cancer-related mortality worldwide. Although distant organ metastasis accounts for the majority of breast cancer-related deaths, reports on bladder metastasis are limited in the existing literature. The present study describes the case of a patient with bladder metastasis originating from breast cancer. In addition, the present study also provides a review of 54 cases of similar disease that have been documented in the currently available literature. The literature review aims to elucidate the clinicopathological characteristics and therapeutic approaches for such conditions. The median time from breast cancer diagnosis to bladder metastasis was found to be 5.6 years (range, 0-28 years). The origin of the bladder metastases was predominantly invasive ductal carcinoma (IDC) accounting for 52.3% of cases, followed by invasive lobular carcinoma, accounting for 40.9% of cases. The pathology in the primary tumor was the same as the pathology of the bladder metastases in all cases. There was an 88.9% concordance rate for estrogen receptor status, while the progesterone receptor status was 83.3% and the human epidermal growth factor receptor 2 expression status was 100%. The primary initial symptoms included urinary system manifestations, such as increased frequency, urgency, dysuria, urinary incontinence, nocturia and gross hematuria. For the cystoscopic examination, the predominant findings were bladder wall thickening or masses, along with ureteral orifice masses. Overall, the present study demonstrated that the occurrence of bladder metastasis often follows the metastasis of other organs, with IDC being the most prevalent subtype. The pathological characteristics between the primary tumor and bladder metastasis exhibit a high degree of concordance.}, } @article {pmid38628265, year = {2024}, author = {Chaane, N and Kuehnast, M and Rubin, G}, title = {An audit of breast cancer in patients 40 years and younger in two Johannesburg academic hospitals.}, journal = {SA journal of radiology}, volume = {28}, number = {1}, pages = {2772}, pmid = {38628265}, issn = {1027-202X}, abstract = {BACKGROUND: Breast cancer is the most common cancer in females, usually diagnosed after the age of 50 years. There is a perceived increase in breast cancer cases in young women in two public sector Johannesburg academic hospitals; however, there is a shortage of data to confirm this.

OBJECTIVES: This study aimed to assess data on breast cancer in young patients and determine any increase in the number of cases in patients 40 years and younger.

METHOD: A retrospective analysis of radiology and histopathology reports of patients 40 years and younger, seen at the radiology departments of two Johannesburg academic hospitals, was performed over a 5-year period. The frequency, histology and immunohistochemical results of breast cancer diagnoses were determined in patients with a Breast Imaging - Reporting and Data System (BI-RADS) classification of 4 or above.

RESULTS: Breast cancer was diagnosed in 73% of the total eligible 469 patients. The mean patient age was 34.35 years. Invasive ductal carcinoma was diagnosed in 83% (n = 283) of patients classified as BI-RADS 5 on imaging. Luminal A and B subtypes were the most common. The highest number of patients (n = 142) were seen in 2016 of which 92 had breast cancer.

CONCLUSION: In this very specific sample set, there was a lower number of breast cancer diagnoses in 2015 and then an increase of breast cancer diagnoses in young patients from 2016 to 2018.

CONTRIBUTION: Earlier breast cancer detection benefits the patient, their families and their reproductive ability. Knowledge of breast cancers in young patients can increase awareness, leading to effective, early diagnoses.}, } @article {pmid38627759, year = {2024}, author = {Cipolla, C and Lupo, S and Grassi, N and Tutino, G and Greco, M and Eleonora, D and Gebbia, V and Valerio, MR}, title = {Correlation between sentinel lymph node biopsy and non-sentinel lymph node metastasis in patients with cN0 breast carcinoma: comparison of invasive ductal carcinoma and invasive lobular carcinoma.}, journal = {World journal of surgical oncology}, volume = {22}, number = {1}, pages = {100}, pmid = {38627759}, issn = {1477-7819}, mesh = {Humans ; Female ; Sentinel Lymph Node Biopsy ; Lymphatic Metastasis/pathology ; *Carcinoma, Lobular/pathology ; Retrospective Studies ; *Carcinoma, Ductal, Breast/pathology ; *Breast Neoplasms/surgery/pathology ; *Sentinel Lymph Node/surgery/pathology ; Lymph Node Excision ; Lymph Nodes/pathology ; Axilla/pathology ; }, abstract = {BACKGROUND: Some studies have suggested that axillary lymph node dissection (ALND) can be avoided in women with cN0 breast cancer with 1-2 positive sentinel nodes (SLNs). However, these studies included only a few patients with invasive lobular carcinoma (ILC), so the validity of omitting ALDN in these patients remains controversial. This study compared the frequency of non-sentinel lymph nodes (non-SLNs) metastases in ILC and invasive ductal carcinoma (IDC).

MATERIALS METHODS: Data relating to a total of 2583 patients with infiltrating breast carcinoma operated at our institution between 2012 and 2023 were retrospectively analyzed: 2242 (86.8%) with IDC and 341 (13.2%) with ILC. We compared the incidence of metastasis to SLNs and non-SLNs between the ILC and IDC cohorts and examined factors that influenced non-SLNs metastasis.

RESULTS: SLN biopsies were performed in 315 patients with ILC and 2018 patients with IDC. Metastases to the SLNs were found in 78/315 (24.8%) patients with ILC and in 460 (22.8%) patients with IDC (p = 0.31). The incidence of metastases to non-SLNs was significantly higher (p = 0.02) in ILC (52/78-66.7%) compared to IDC (207/460 - 45%). Multivariate analysis showed that ILC was the most influential predictive factor in predicting the presence of metastasis to non-SLNs.

CONCLUSIONS: ILC cases have more non-SLNs metastases than IDC cases in SLN-positive patients. The ILC is essential for predicting non-SLN positivity in macro-metastases in the SLN. The option of omitting ALND in patients with ILC with 1-2 positive SLNs still requires further investigation.}, } @article {pmid38624259, year = {2024}, author = {Petrakis, IL and Meshberg-Cohen, S and Nich, C and Kelly, MM and Claudio, T and Jane, JS and Pisani, E and Ralevski, E}, title = {Cognitive processing therapy (CPT) versus individual drug counseling (IDC) for PTSD for veterans with opioid use disorder maintained on buprenorphine.}, journal = {The American journal on addictions}, volume = {33}, number = {5}, pages = {525-533}, doi = {10.1111/ajad.13557}, pmid = {38624259}, issn = {1521-0391}, support = {1 I01 CX001517-01//VA MERIT grant, Division of Clinical Science Research and Development/ ; }, mesh = {Humans ; *Stress Disorders, Post-Traumatic/therapy/drug therapy/psychology/complications ; *Buprenorphine/therapeutic use ; *Veterans/psychology ; Male ; *Opioid-Related Disorders/drug therapy/therapy/psychology/complications ; *Cognitive Behavioral Therapy/methods ; *Opiate Substitution Treatment/methods ; Middle Aged ; Female ; Counseling/methods ; Adult ; Narcotic Antagonists/therapeutic use ; }, abstract = {BACKGROUND AND OBJECTIVES: There are high rates of comorbidity between posttraumatic stress disorder (PTSD) and opioid use disorder (OUD). Evidence-based trauma-focused psychotherapies such as Cognitive Processing Therapy (CPT) are a first-line treatment for PTSD. Veterans with OUD are treated primarily in substance use disorder (SUD) clinics where the standard of care is drug counseling; they often do not have access to first-line PTSD treatments. This study tested whether CPT can be conducted safely and effectively in veterans with comorbid OUD treated with buprenorphine.

METHODS: This 12-week, 2-site, randomized clinical trial (RCT) included open-label randomization to two groups: (a) CPT versus (b) Individual Drug Counselling (IDC) in veterans with PTSD and comorbid OUD who were maintained on buprenorphine (N = 38).

RESULTS: Veterans randomized to either IDC (n = 18) or CPT (n = 20) showed a significant reduction in self-reported PTSD symptoms over time as measured by the PTSD checklist (PCL-5) but there were no treatment group differences; there was some indication that reduction in PTSD symptoms in the CPT group were sustained in contrast to the IDC group. Recruitment was significantly impacted by COVID-19 pandemic, so this study serves as a proof-of-concept pilot study.

DISCUSSION AND CONCLUSIONS: Veterans with OUD and PTSD can safely and effectively participate in evidence-based therapy for PTSD; further work should confirm that trauma-focused treatment may be more effective in leading to sustained remission of PTSD symptoms than drug counseling.

SCIENTIFIC SIGNIFICANCE: This is the first study to evaluate CPT for PTSD in the context of buprenorphine treatment for OUD.}, } @article {pmid38623464, year = {2024}, author = {Dye, A and Jhaveri, V and Ozdemir, S and Alkhasawneh, A and Hew, K}, title = {Recurrent invasive ductal carcinoma of the breast with metastasis to the uterine cervix: A case report.}, journal = {Case reports in women's health}, volume = {42}, number = {}, pages = {e00607}, pmid = {38623464}, issn = {2214-9112}, abstract = {This article presents a case of cervical metastasis from recurrence of invasive ductal carcinoma of the breast >20 years after initial diagnosis. The diagnosis was made after the patient presented with three months of intermittent post-menopausal vaginal spotting. She underwent palliative radiotherapy combined with chemotherapy and was disease free at the time of writing. Cervical metastasis of a primary breast cancer is extremely rare and can present with a variety of symptoms. This case report highlights the importance of life-long gynecologic care and surveillance in patients with a history of breast cancer.}, } @article {pmid38623446, year = {2024}, author = {Lue, M and Harrah, P and Shrestha, S and Wang, HT}, title = {Reconstruction after Resection of Undifferentiated Pleomorphic Sarcoma and Invasive Ductal Carcinoma in a Patient with Li-Fraumeni Syndrome.}, journal = {Plastic and reconstructive surgery. Global open}, volume = {12}, number = {4}, pages = {e5737}, pmid = {38623446}, issn = {2169-7574}, abstract = {This case exhibits a presentation of multiple primary malignancies in a patient with Li-Fraumeni syndrome, necessitating surgical excision and multistaged reconstruction. Due to Li-Fraumeni syndrome patients' predisposition to developing malignancies, management includes lifelong surveillance and aggressive treatment of cancers. Plastic surgeons can minimize damage to patient's quality of life by carrying out reconstruction in a thoughtful manner that maximizes function and considers a potential lifetime of future reconstructive needs.}, } @article {pmid38622289, year = {2024}, author = {Roy, S and Shanmugam, G and Rakshit, S and Pradeep, R and George, M and Sarkar, K}, title = {Exploring the immunomodulatory potential of Brahmi (Bacopa monnieri) in the treatment of invasive ductal carcinoma.}, journal = {Medical oncology (Northwood, London, England)}, volume = {41}, number = {5}, pages = {115}, pmid = {38622289}, issn = {1559-131X}, support = {ECR/2016/000965//Science and Engineering Research Board/ ; }, mesh = {Animals ; Plant Extracts/pharmacology/therapeutic use ; *Bacopa ; Histones ; Cytokines ; *Carcinoma, Ductal ; *Neoplasms ; }, abstract = {Bacopa monnieri (L) Wettst, commonly known as Brahmi, stands as a medicinal plant integral to India's traditional medical system, Ayurveda, where it is recognized as a "medhya rasayana"-a botanical entity believed to enhance intellect and mental clarity. Its significant role in numerous Ayurvedic formulations designed to address conditions such as anxiety, memory loss, impaired cognition, and diminished concentration underscores its prominence. Beyond its application in cognitive health, Brahmi has historically been employed in Ayurvedic practices for the treatment of inflammatory diseases, including arthritis. In contemporary biomedical research, Bacopa monnieri can attenuate the release of pro-inflammatory cytokines TNF-α and IL-6 in animal models. However, there remains a paucity of information regarding Bacopa's potential as an anticancer agent, warranting further investigation in this domain. Based on previous findings with Brahmi (Bacopa monnieri), the current study aims to find out the role of Brahmi plant preparation (BPP) in immunomodulatory actions on IDC. Employing a specific BPP concentration, we conducted a comprehensive study using MTT assay, ELISA, DNA methylation analysis, Western blotting, ChIP, and mRNA profiling to assess BPP's immunomodulatory properties. Our research finding showed the role of BPP in augmenting the action of T helper 1 (TH1) cells which secreted interferon-γ (IFN-γ) which in turn activated cytotoxic T-lymphocytes (CTL) to kill the cells of IDC (*p < 0.05). Moreover, we found out that treatment with BPP not only increased the activities of tumor-suppressor genes (p53 and BRCA1) but also decreased the activities of oncogenes (Notch1 and DNAPKcs) in IDC (*p < 0.05). BPP had an immense significance in controlling the epigenetic dysregulation in IDC through the downregulation of Histone demethylation & Histone deacetylation and upregulation of Histone methylation and Histone acetylation (*p < 0.05). Our Chromatin immunoprecipitation (ChIP)-qPCR data showed BPP treatment increased percentage enrichment of STAT1 & BRCA1 (*p < 0.05) and decreased percentage enrichment of STAT3, STAT5 & NF ΚB (*p < 0.05) on both TBX21 and BRCA1 gene loci in IDC. In addition, BPP treatment reduced the hypermethylation of the BRCA1-associated-DNA, which is believed to be a major factor in IDC (*p < 0.05). BPP not only escalates the secretion of type 1 specific cytokines but also escalates tumor suppression and harmonizes various epigenetic regulators and transcription factors associated with Signal Transducer and Activator of Transcription (STAT) to evoke tumor protective immunity in IDC.}, } @article {pmid38621672, year = {2024}, author = {Sánchez-Dávila, JN and Verástegui, EL and Peña-Nieves, A and Allende-Pérez, SR}, title = {Integration of the geriatric palliative care in oncological care of elderly patient with cancer.}, journal = {Palliative & supportive care}, volume = {22}, number = {4}, pages = {792-800}, doi = {10.1017/S1478951524000294}, pmid = {38621672}, issn = {1478-9523}, mesh = {Humans ; Aged ; *Palliative Care/methods/standards ; Aged, 80 and over ; Female ; Male ; *Neoplasms/complications/therapy ; *Geriatrics/methods ; Geriatric Assessment/methods ; }, abstract = {OBJECTIVES: The objective of this article is to describe the profile of the population attended to by the palliative geriatrics clinic and to evaluate the symptomatic control derived from the care provided.

METHODS: During 2017 a model based on a holistic approach was implemented, in this model the team geriatric palliative care plays a fundamental role by being part of the palliative care team and functioning as a liaison with the oncology team and other required services. We outlined the profile of 100 patients aged 70 and older seen between 2017 and 2019 at our geriatric palliative care clinic. Descriptive statistics were used. In addition, the symptoms and the care clinic model effect on the symptomatic control were analyzed, as well as the complexity of patients in palliative care with IDC-Pal.

RESULTS: The patients median age was 83.5 years. Patients were classified by type of management: 47% within the supportive care group and 53% with palliative care only; 58% had metastatic disease and 84% presented at least 1 comorbidity. Frailty was observed in 78% and a Karnofsky scale of 60 or less was observed in 59% of the overall population.

SIGNIFICANCE OF RESULTS: Elderly cancer patients have a complex profile and may have multiple needs. Integrating geriatric palliative care can help to provide better and personalized care along with symptomatic control. Further studies are required to establish the ideal care model for these patients. Importantly, a personalized treatment with a geriatric palliative care specialist is a key element.}, } @article {pmid38618899, year = {2024}, author = {Kosie, JE and Lew-Williams, C}, title = {Infant-directed communication: Examining the many dimensions of everyday caregiver-infant interactions.}, journal = {Developmental science}, volume = {27}, number = {5}, pages = {e13515}, pmid = {38618899}, issn = {1467-7687}, support = {F32HD103439//National Institute of Child Health and Human Development/ ; F32 HD103439/HD/NICHD NIH HHS/United States ; R01HD095912//National Institute of Child Health and Human Development/ ; 2004983//National Science Foundation SBE Postdoctoral Research Fellowship/ ; R01 HD095912/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; Infant ; *Caregivers/psychology ; *Gestures ; Female ; Male ; *Communication ; *Infant Behavior/physiology ; Speech ; Adult ; Nonverbal Communication ; Child Development/physiology ; Child, Preschool ; Cues ; }, abstract = {Everyday caregiver-infant interactions are dynamic and multidimensional. However, existing research underestimates the dimensionality of infants' experiences, often focusing on one or two communicative signals (e.g., speech alone, or speech and gesture together). Here, we introduce "infant-directed communication" (IDC): the suite of communicative signals from caregivers to infants including speech, action, gesture, emotion, and touch. We recorded 10 min of at-home play between 44 caregivers and their 18- to 24-month-old infants from predominantly white, middle-class, English-speaking families in the United States. Interactions were coded for five dimensions of IDC as well as infants' gestures and vocalizations. Most caregivers used all five dimensions of IDC throughout the interaction, and these dimensions frequently overlapped. For example, over 60% of the speech that infants heard was accompanied by one or more non-verbal communicative cues. However, we saw marked variation across caregivers in their use of IDC, likely reflecting tailored communication to the behaviors and abilities of their infant. Moreover, caregivers systematically increased the dimensionality of IDC, using more overlapping cues in response to infant gestures and vocalizations, and more IDC with infants who had smaller vocabularies. Understanding how and when caregivers use all five signals-together and separately-in interactions with infants has the potential to redefine how developmental scientists conceive of infants' communicative environments, and enhance our understanding of the relations between caregiver input and early learning. RESEARCH HIGHLIGHTS: Infants' everyday interactions with caregivers are dynamic and multimodal, but existing research has underestimated the multidimensionality (i.e., the diversity of simultaneously occurring communicative cues) inherent in infant-directed communication. Over 60% of the speech that infants encounter during at-home, free play interactions overlap with one or more of a variety of non-speech communicative cues. The multidimensionality of caregivers' communicative cues increases in response to infants' gestures and vocalizations, providing new information about how infants' own behaviors shape their input. These findings emphasize the importance of understanding how caregivers use a diverse set of communicative behaviors-both separately and together-during everyday interactions with infants.}, } @article {pmid38617864, year = {2024}, author = {Park, SY and Lee, J and Park, JY and Kim, GC and Park, J and Cha, JG and Kim, HJ}, title = {Primary Invasive Ductal Carcinoma Arising in Axillary Accessory Breast: A Case Report.}, journal = {Journal of the Korean Society of Radiology}, volume = {85}, number = {2}, pages = {421-427}, pmid = {38617864}, issn = {2951-0805}, abstract = {Ectopic breast tissue can develop along the mammary ridge from the axilla to the groin, and the most common site is the axillae. Primary carcinoma of ectopic breast tissue is extremely rare. We report a rare case of a 61-year-old woman with a palpable mass in her left axilla who had a history of surgical excision of accessory breast tissue in the same area. Mammography (MMG), including axillary tail view, ultrasound (US), and breast MRI were performed. We evaluated the extent and characteristics of the microcalcifications in the axillary tail view. A US-guided biopsy was done, and histopathology revealed an invasive ductal carcinoma. Enhanced abdominal CT revealed multiple hepatic masses consistent with metastases, and the patient received palliative chemotherapy. Herein, we present a rare case of breast cancer arising from accessory breast tissue in the axilla, best appreciated on the axillary tail view of the patient's MMG.}, } @article {pmid38611640, year = {2024}, author = {Sato, A and Fujioka, T and Onishi, I and Yamaga, E and Katsuta, L and Kubota, K and Kumaki, Y and Ishiba, T and Oda, G and Tateishi, U}, title = {Arterial Calcification Disappearance in Breast Imaging: A Key Indicator for Transition to Invasive Ductal Carcinoma.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {7}, pages = {}, pmid = {38611640}, issn = {2075-4418}, abstract = {A woman in her 70s, initially suspected of having fibroadenoma due to a well-defined mass in her breast, underwent regular mammography and ultrasound screenings. Over several years, no appreciable alterations in the mass were observed, maintaining the fibroadenoma diagnosis. However, in the fourth year, an ultrasound indicated slight enlargement and peripheral irregularities in the mass, even though the mammography images at that time showed no alterations. Interestingly, mammography images over time showed the gradual disappearance of previously observed arterial calcification around the mass. Pathological examination eventually identified the mass as invasive ductal carcinoma. Although the patient had breast tissue arterial calcification typical of atherosclerosis, none was present around the tumor-associated arteries. This case highlights the importance of monitoring arterial calcification changes in mammography, suggesting that they are crucial indicators in breast cancer diagnosis, beyond observing size and shape alterations.}, } @article {pmid38611095, year = {2024}, author = {Bensenane, R and Beddok, A and Lesueur, F and Fourquet, A and Warcoin, M and Le Mentec, M and Cavaciuti, E and Le Gal, D and Eon-Marchais, S and Andrieu, N and Stoppa-Lyonnet, D and Kirova, Y}, title = {Safety of the Breast Cancer Adjuvant Radiotherapy in Ataxia-Telangiectasia Mutated Variant Carriers.}, journal = {Cancers}, volume = {16}, number = {7}, pages = {}, pmid = {38611095}, issn = {2072-6694}, abstract = {The Ataxia-Telangiectasia Mutated (ATM) gene is implicated in DNA double-strand break repair. Controversies in clinical radiosensitivity remain known for monoallelic carriers of the ATM pathogenic variant (PV). An evaluation of the single-nucleotide polymorphism (SNP) rs1801516 (G-A) showed different results regarding late subcutaneous fibrosis after breast radiation therapy (RT). The main objective of this study was to evaluate acute and late toxicities in carriers of a rare ATM PV or predicted PV and in carriers of minor allele A of rs1801516 facing breast RT. Fifty women with localized breast cancer treated with adjuvant RT between 2000 and 2014 at Institut Curie were selected. Acute and late toxicities in carriers of a rare PV or predicted PV (n= 9), in noncarriers (n = 41) and in carriers of SNP rs1801516 (G-A) (n = 8), were examined. The median age at diagnosis was 53 years old and 82% of patients had an invasive ductal carcinoma and 84% were at clinical stage I-IIB. With a median follow-up of 13 years, no significant difference between carriers and noncarriers was found for acute toxicities (p > 0.05). The same results were observed for late toxicities without an effect from the rs1801516 genotype on toxicities. No significant difference in acute or late toxicities was observed between rare ATM variant carriers and noncarriers after breast RT for localized breast cancer.}, } @article {pmid38609794, year = {2024}, author = {Weed, C and Wang, T and Mohan, SC and Wang, X and Tseng, J and Hu, T and Jaswinder, J and Boyle, MK and Amersi, F and Giuliano, A and Chung, A}, title = {Comparison of Clinical Breast Exam to Breast MRI Surveillance in Patients Following Nipple-Sparing Mastectomy.}, journal = {Clinical breast cancer}, volume = {24}, number = {5}, pages = {457-462}, doi = {10.1016/j.clbc.2024.03.011}, pmid = {38609794}, issn = {1938-0666}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery/pathology/diagnostic imaging ; Middle Aged ; *Magnetic Resonance Imaging/methods ; *Neoplasm Recurrence, Local/diagnostic imaging/pathology/epidemiology/prevention & control ; Adult ; *Nipples/surgery/diagnostic imaging/pathology ; Aged ; Carcinoma, Ductal, Breast/surgery/diagnostic imaging/pathology ; Carcinoma, Lobular/surgery/pathology/diagnostic imaging ; Mastectomy, Subcutaneous/methods ; Follow-Up Studies ; Physical Examination ; Prospective Studies ; }, abstract = {BACKGROUND: Nipple sparing mastectomy (NSM) is increasingly being performed for patients with breast cancer. However, optimal postoperative surveillance has not been defined.

METHODS: A prospectively maintained database identified patients with in-situ and invasive cancer who underwent NSM between 2007-2021. Clinical data on postoperative breast surveillance and interventions were collected. Patients who had MRI surveillance versus clinical breast exam (CBE) alone were compared with respect to tumor characteristics, recurrence, and survival.

RESULTS: A total of 483 NSMs were performed on 399 patients. 255 (63.9%) patients had invasive ductal carcinoma, 31 (7.8%) invasive lobular carcinoma, 92 (23.1%) DCIS, 6 (1.5%) mixed ductal and lobular carcinoma, 9 (2.3%) others, and 6 (1.5%) unknown. Postoperatively, 265 (66.4%) patients were followed with CBE alone and 134 (33.6%) had surveillance MRIs. At a median follow-up of 33 months, 20 patients (5.0%) developed in-breast recurrence, 6 patients had (1.5%) an axillary recurrence, and 28 with (7.0%) distant recurrence. 14 (53.8%) LRR were detected in the CBE group and 12 (46.2%) were detected in the MRI group (P = .16). Overall survival (OS) was 99%, with no difference in OS between patients who had CBE alone versus MRI (P = .46). MRI was associated with higher biopsy rates compared to CBE alone (15.8% vs. 7.8%, P = .01).

CONCLUSIONS: Compared to CBE alone, the use of screening MRI following NSM results in higher rate of biopsy and no difference in overall survival.}, } @article {pmid38599926, year = {2024}, author = {Sefidbakht, S and Beizavi, Z and Kanaani Nejad, F and Pishdad, P and Sadighi, N and Ghoddusi Johari, M and Bijan, B and Tahmasebi, S}, title = {Association of imaging and pathological findings of breast cancer in very young women: Report of a twenty-year retrospective study.}, journal = {Clinical imaging}, volume = {110}, number = {}, pages = {110094}, doi = {10.1016/j.clinimag.2024.110094}, pmid = {38599926}, issn = {1873-4499}, mesh = {Humans ; Female ; Retrospective Studies ; Adult ; *Breast Neoplasms/diagnostic imaging/pathology ; *Mammography/methods ; *Ultrasonography, Mammary/methods ; Iran/epidemiology ; Young Adult ; Breast/diagnostic imaging/pathology ; Neoplasm Staging ; }, abstract = {PURPOSE: In this study, we aimed to assess the new trends in characteristics, molecular subtypes, and imaging findings of breast cancer in very young women.

METHODS: We retrospectively reviewed the database of a primary breast cancer referral center in southern Iran in 342 cases of 30-year-old or younger women from 2001 to 2020. Pathologic data, including nuclear subtype and grade, tumor stage, presence of in situ cancer, imaging data including lesion type in mammogram and ultrasound, and treatment data were recorded. Descriptive statistics were applied. Differences between categorical values between groups were compared using Pearson's Chi-square test.

RESULTS: The mean age was 27.89 years. The tumor type was invasive ductal carcinoma in 82 % of cases. Fourteen patients (4.4 %) had only in situ cancer, and 170 patients had in situ components (49.7 %). Molecular subtypes were available in 278 patients, including 117 (42.1 %) Luminal A, 64 (23.0 %) Luminal B, 58 (20.9 %) triple negative, and 39 (14 %) HER2 Enriched. In those with mammograms available, 63 (30.1 %) had no findings, 53 (25.3 %) had mass, 27 (12.9 %) had asymmetry, whether focal or global, 21 (10 %) had microcalcifications solely, and 45 (21.5 %) had more than one finding. Microcalcifications were significantly more common in Luminal cancers than HER2 and triple-negative cancers (p = 0.041).

CONCLUSION: Our study shows the most common subtype to be Luminal A cancer, with 74 % of the tumors being larger than 2 cm at the time of diagnosis. Irregular masses with non-circumscribed margins were the most common imaging findings.}, } @article {pmid38597082, year = {2024}, author = {Wang, S and Zhou, Z and Yuan, Q and Yue, L and Yang, S}, title = {Trueness evaluation of three intraoral scanners for the recording of maximal intercuspal position.}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {42}, number = {2}, pages = {227-233}, pmid = {38597082}, issn = {2618-0456}, mesh = {Humans ; *Molar ; *Incisor ; Mandible ; Maxilla ; Computer-Aided Design ; Imaging, Three-Dimensional ; Dental Impression Technique ; }, abstract = {OBJECTIVES: This clinical study aimed to assess the trueness of three intraoral scanners for the recor-ding of the maximal intercuspal position (MIP) to provide a reference for clinical practice.

METHODS: Ten participants with good occlusal relationship and healthy temporomandibular joint were recruited. For the control group, facebow transferring procedures were performed, and bite registrations at the MIP were used to transfer maxillary and mandibular casts to a mechanical articulator, which were then scanned with a laboratory scanner to obtain digital cast data. For the experimental groups, three intraoral scanners (Trios 3, Carestream 3600, and Aoralscan 3) were used to obtain digital casts of the participants at the MIP following the scanning workflows endorsed by the corresponding manufacturers. Subsequently, measurement points were marked on the control group's digital casts at the central incisors, canines, and first molars, and corresponding distances between these points on the maxillary and mandibular casts were measured to calculate the sum of measured distances (DA). Distances between measurement points in the incisor (DI), canine (DC), and first molar (DM) regions were also calculated. The control group's maxillary and mandibular digital casts with the added measurement points were aligned with the experimental group's casts, and DA, DI, DC, and DM values of the aligned control casts were determined. Statistical analysis was performed on DA, DI, DC, and DM obtained from both the control and experimental groups to evaluate the trueness of the three intraoral scanners for the recording of MIP.

RESULTS: In the control group, DA, DI, DC, and DM values were (39.58±6.40), (13.64±3.58), (14.91±2.85), and (11.03±1.56) mm. The Trios 3 group had values of (38.99±6.60), (13.42±3.66), (14.55±2.87), and (11.03±1.69) mm. The Carestream 3600 group showed values of (38.57±6.36), (13.56±3.68), (14.45±2.85), and (10.55±1.41) mm, while the Aoralscan 3 group had values of (38.16±5.69), (13.03±3.54), (14.23±2.59), and (10.90±1.54) mm. Analysis of variance revealed no statistically significant differences between the experimental and control groups for overall deviation DA (P=0.96), as well as local deviations DI (P=0.98), DC (P=0.96), and DM (P=0.89).

CONCLUSIONS: With standardized scanning protocols, the three intraoral scanners demonstrated comparable trueness to traditional methods in recording MIP, fulfilling clinical requirements.}, } @article {pmid38592540, year = {2024}, author = {Rukhsana, and Supty, AT and Hussain, M and Lee, Y}, title = {STK3 higher expression association with clinical characteristics in intrinsic subtypes of breast cancer invasive ductal carcinoma patients.}, journal = {Breast cancer research and treatment}, volume = {206}, number = {1}, pages = {119-129}, pmid = {38592540}, issn = {1573-7217}, support = {2022R1F1A1069631//National Research Foundation of Korea/ ; }, mesh = {Aged ; Female ; Humans ; Middle Aged ; *Biomarkers, Tumor/genetics ; *Breast Neoplasms/genetics/pathology/mortality/metabolism ; *Carcinoma, Ductal, Breast/genetics/pathology/mortality/metabolism ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Kaplan-Meier Estimate ; Neoplasm Staging ; Prognosis ; Protein Serine-Threonine Kinases/genetics/metabolism ; *Serine-Threonine Kinase 3/analysis/genetics ; Hippo Kinases ; }, abstract = {PURPOSE: STK3 has a central role in maintaining cell homeostasis, proliferation, growth, and apoptosis. Previously, we investigated the functional link between STK3/MST2, and estrogen receptor in MCF-7 breast cancer cells. To expand the investigation, this study evaluated STK3's higher expression and associated genes in breast cancer intrinsic subtypes using publicly available data.

METHODS: The relationship between clinical pathologic features and STK3 high expression was analyzed using descriptive and multivariate analysis.

RESULTS: Increased STK3 expression in breast cancer was significantly associated with higher pathological cancer stages, and a different expression level was observed in the intrinsic subtypes of breast cancer. Kaplan-Meier analysis showed that breast cancer with high STK3 had a lower survival rate in IDC patients than that with low STK3 expression (p < 0.05). The multivariate analysis unveiled a strong correlation between STK3 expression and the survival rate among IDC patients, demonstrating hazard ratios for lower expression. In the TCGA dataset, the hazard ratio was 0.56 (95% CI 0.34-0.94, p = 0.029) for patients deceased with tumor, and 0.62 (95% CI 0.42-0.92, p = 0.017) for all deceased patients. Additionally, in the METABRIC dataset, the hazard ratio was 0.76 (95% CI 0.64-0.91, p = 0.003) for those deceased with tumor. From GSEA outcomes 7 gene sets were selected based on statistical significance (FDR < 0.25 and p < 0.05). Weighted Sum model (WSM) derived top 5% genes also have higher expression in basal and lower in luminal A in association with STK3.

CONCLUSION: By introducing a novel bioinformatics approach that combines GSEA and WSM, the study successfully identified the top 5% of genes associated with higher expression of STK3.}, } @article {pmid38586701, year = {2024}, author = {Nair, N and More, A and Singh, BR and Wadkar, A and Tilak, P}, title = {A Successful Pregnancy Following Intracytoplasmic Sperm Injection in a Breast Cancer Survivor: A Case Report.}, journal = {Cureus}, volume = {16}, number = {3}, pages = {e55756}, pmid = {38586701}, issn = {2168-8184}, abstract = {This report documents the case of a 36-year-old female diagnosed with stage I invasive ductal carcinoma of the left breast who, alongside her 39-year-old husband, sought fertility assistance at our center due to primary infertility. Having survived cancer twice in the span of their seven-year marriage, the couple faced the challenge of overcoming both the repercussions of cancer treatment and difficulties in conceiving. Initial attempts through three intrauterine insemination (IUI) cycles proved unsuccessful, leading the couple to opt for in vitro fertilization (IVF). The fertility assessment of the husband revealed the presence of several pus cells and a high sperm DNA fragmentation index (DFI). To address this, a medication regimen was administered to improve sperm quality. Concurrently, the female underwent controlled ovarian stimulation (COS) with the anti-estrogen agent letrozole to mitigate the risk of estrogen surges that could compromise her health. Subsequently, oocytes were retrieved from the female, and intracytoplasmic sperm injection (ICSI) was used to facilitate fertilization with her husband's sperm. Following successful embryo development, the patient underwent embryo transfer (ET), resulting in a positive beta-human chorionic gonadotropin (beta-hCG) result, signifying a successful conception. This case report highlights the intricate challenges faced by individuals with a history of breast cancer, emphasizing the delicate balance required in managing infertility in such circumstances. The described approach, involving personalized treatments and meticulous care, underscores the possibility of achieving successful conception for females struggling with fertility issues post-cancer survival. The documented journey serves as a testament to the resilience of individuals facing the dual challenges of cancer survival and infertility, offering insights into the complexities of their reproductive healthcare.}, } @article {pmid38578876, year = {2024}, author = {Rodriguez, GF and Shah, A and Maderal, AD}, title = {Telangiectasias induced by combination tucatinib and ado-trastuzumab emtansine in a patient with metastatic breast cancer.}, journal = {Breast disease}, volume = {43}, number = {1}, pages = {61-64}, pmid = {38578876}, issn = {1558-1551}, mesh = {Female ; Humans ; Aged ; Ado-Trastuzumab Emtansine/therapeutic use ; *Breast Neoplasms/pathology ; Trastuzumab/adverse effects ; Quinazolines/therapeutic use ; Erb-b2 Receptor Tyrosine Kinases/genetics/metabolism ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; *Oxazoles ; *Pyridines ; }, abstract = {BACKGROUND: Tucatinib is a tyrosine kinase inhibitor currently used in salvage therapy for human epidermal growth factor receptor 2 (HER2)-positive breast and colorectal cancer. The use of tucatinib alone or in combination with ado-trastuzumab emtansine (T-DM1) in the treatment of advanced HER2-positive cancers is rapidly expanding.

OBJECTIVE/METHODS: We report the case of a 66-year-old female who presented to the dermatology clinic with a one-year history of widespread telangiectasias that began after initiation of combination chemotherapy with tucatinib and T-DM1 for metastatic HER2-positive invasive ductal carcinoma.

RESULTS: The patient's lesions regressed upon cessation of combination therapy and reappeared in the setting of tucatinib re-initiation, with gradual improvement over the following four months following electrocautery to the affected regions.

CONCLUSIONS: We postulate that telangiectasias may be a previously unreported dermatologic side effect of combination treatment with tucatinib and T-DM1. Electrocautery is a safe and effective procedure to reduce the appearance of telangiectasias and improve patient satisfaction during chemotherapy.}, } @article {pmid38578135, year = {2024}, author = {Zheng, MY and Jin, ZB and Ma, ZZ and Gu, ZG and Zhang, J}, title = {Photo-Curable 3D Printing of Circularly Polarized Afterglow Metal-Organic Framework Monoliths.}, journal = {Advanced materials (Deerfield Beach, Fla.)}, volume = {36}, number = {25}, pages = {e2313749}, doi = {10.1002/adma.202313749}, pmid = {38578135}, issn = {1521-4095}, support = {2022YFA1503300//National Key Research and Development Program of China/ ; Y2022081//Youth Innovation Promotion Association of the Chinese Academy of Sciences/ ; 2022J06031//Natural Science Foundation of Fujian Province/ ; 2023T3003//STS Project of Fujian-CAS/ ; 2023T3052//STS Project of Fujian-CAS/ ; }, abstract = {Developing coordination complexes (such as metal-organic frameworks, MOFs) with circularly polarized luminescence (CPL) is currently attracting tremendous attention and remains a significant challenge in achieving MOF with circularly polarized afterglow. Herein, MOFs-based circularly polarized afterglow is first reported by combining the chiral induction approach and tuning the afterglow times by using the auxiliary ligands regulation strategy. The obtained chiral R/S-ZnIDC, R/S-ZnIDC(bpy), and R/S-ZnIDC(bpe)(IDC = 1H-Imidazole-4,5-dicarboxylate, bpy = 4,4'-Bipyridine, bpe = trans-1,2-Bis(4-pyridyl) ethylene) containing a similar structure unit display different afterglow times with 3, 1, and <0.1 s respectively which attribute to that the longer auxiliary ligand hinders the energy transfer through the hydrogen bonding. The obtained chiral complexes reveal a strong chiral signal, obvious photoluminescence afterglow feature, and strong CPL performance (glum up to 3.7 × 10[-2]). Furthermore, the photo-curing 3D printing method is first proposed to prepare various chiral MOFs based monoliths from 2D patterns to 3D scaffolds for anti-counterfeiting and information encryption applications. This work not only develops chiral complexes monoliths by photo-curing 3D printing technique but opens a new strategy to achieve tunable CPL afterglow in optical applications.}, } @article {pmid38577141, year = {2024}, author = {Sukhija, S and Purohit, P and Pareek, P and Garg, PK and Vishnoi, JR and Elhence, PA and Varthya, SB and Sharma, P and Ambwani, S and Charan, J}, title = {Circulating miRNA-21 Levels in Breast Cancer Patients Before and After Chemotherapy and Its Association with Clinical Improvement.}, journal = {Indian journal of clinical biochemistry : IJCB}, volume = {39}, number = {2}, pages = {214-220}, pmid = {38577141}, issn = {0970-1915}, abstract = {Breast cancer is the most frequent type of cancer in women, many patients experience recurrences and metastasis. miR-21 (microRNA-21) as biomarker is under investigation for breast cancer. At present, there is very limited information available regarding effect of chemotherapy on miR-21 expression in breast cancer and its correlation with the clinical improvement. Hence, this study was planned to evaluate the effect of chemotherapy on miR-21 in metastatic breast cancer and its relationship with the clinical outcome. Females, aged-18-90 years diagnosed with Invasive Ductal Carcinoma of breast and candidate of neoadjuvant chemotherapy including Adriamycin (60 mg/m[2]), Cyclophosphamide (600 mg/m[2]) with or without Taxane (75-175 mg/m[2]) were included in the study. Before and after 42 days of staring of chemotherapy sample was collected for circulatory miR-21 and RECIST 1.1 criteria was applied to assess the clinical status. Blood samples for routine clinical biomarkers including liver function test and renal function tests was also collected. miR-21 expression before and after chemotherapy was assessed using standard method based on real time PCR. Expression of miR-21, RECIST criteria and other liver and kidney related biomarkers were compared before and after chemotherapy. After neoadjuvant chemotherapy expression of miR-21 was significantly increased by 5.65-fold. There was significant improvement in clinical scores based on RECIST criteria (0.046). No significant correlation was observed between miR-21 expression and difference in RECIST score (r = - 0.122, p = 0.570). Neoadjuvant chemotherapy causes clinical improvement in breast cancer patients however it is not correlated with the miR-21 expression which significantly increased after chemotherapy.}, } @article {pmid38576929, year = {2024}, author = {Jamal, O and Makhchoune, M and Laidi, A and Misbahi, T and Haouas, MY and Chellaoui, A and Bertal, A and Hilmani, S and Ibahiouine, K and Naja, A and Lakhder, A}, title = {Rupture of a dermoid cyst in the subarachnoid space: a case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {86}, number = {4}, pages = {2366-2369}, pmid = {38576929}, issn = {2049-0801}, abstract = {INTRODUCTION AND IMPORTANCE: Intracranial dermoid cysts (IDC) are defined as rare, slow-growing cystic congenital neoplasms. Rupture of an intracranial dermoid cyst occurs rarely and most often spontaneously and results in potentially serious symptoms.

CASE PRESENTATION: A39-year-old female, with mechanical prosthetic heart valve presented with history of headache for 10 months and generalized tonicoclonic seizures. On the admission, the patient had a normal neurological and cranial nerve exam. The authors performed a computed tomography of the brain, The MRI could not be performed because of the presence of the prosthetic valve, revealed rupture of the dermoid cyst in the bilateral subarachnoid spaces. The patient underwent a large temporal craniotomy and the tumour was well exposed and completely removed without incident, the histopathological examination concludes to dermoid cyst, the patient recovered well from surgery.

CLINICAL DISCUSSION: Rupture is a very rare phenomenon. there are about 60 cases reported in the literature. the contents of the cyst disseminate into the subarachnoid and ventricular spaces in the event of rupture. A variety of clinical symptoms is usually caused. The mechanism of spontaneous rupture of the dermoid cyst is unclear. Among the proposed mechanisms is a rapid expansion of the cyst. Complete surgical resection of dermoid cysts is the only effective treatment for the prevention of recurrences and/or complications.

CONCLUSION: Rupture of an intracranial dermoid cyst is associated with significant morbidity and mortality, although it remains a rare phenomenon. Surgical excision should be considered as soon as the diagnosis is made in order to prevent more severe intracranial complication.}, } @article {pmid38571894, year = {2024}, author = {Maiti, S and Nayak, S and Hebbar, KD and Pendem, S}, title = {Differentiation of invasive ductal and lobular carcinoma of the breast using MRI radiomic features: a pilot study.}, journal = {F1000Research}, volume = {13}, number = {}, pages = {91}, pmid = {38571894}, issn = {2046-1402}, mesh = {Female ; Humans ; *Carcinoma, Lobular/diagnostic imaging/pathology ; Pilot Projects ; Retrospective Studies ; Radiomics ; *Breast Neoplasms/diagnostic imaging/pathology ; Magnetic Resonance Imaging/methods ; }, abstract = {BACKGROUND: Breast cancer (BC) is one of the main causes of cancer-related mortality among women. For clinical management to help patients survive longer and spend less time on treatment, early and precise cancer identification and differentiation of breast lesions are crucial. To investigate the accuracy of radiomic features (RF) extracted from dynamic contrast-enhanced Magnetic Resonance Imaging (DCE MRI) for differentiating invasive ductal carcinoma (IDC) from invasive lobular carcinoma (ILC).

METHODS: This is a retrospective study. The IDC of 30 and ILC of 28 patients from Dukes breast cancer MRI data set of The Cancer Imaging Archive (TCIA), were included. The RF categories such as shape based, Gray level dependence matrix (GLDM), Gray level co-occurrence matrix (GLCM), First order, Gray level run length matrix (GLRLM), Gray level size zone matrix (GLSZM), NGTDM (Neighbouring gray tone difference matrix) were extracted from the DCE-MRI sequence using a 3D slicer. The maximum relevance and minimum redundancy (mRMR) was applied using Google Colab for identifying the top fifteen relevant radiomic features. The Mann-Whitney U test was performed to identify significant RF for differentiating IDC and ILC. Receiver Operating Characteristic (ROC) curve analysis was performed to ascertain the accuracy of RF in distinguishing between IDC and ILC.

RESULTS: Ten DCE MRI-based RFs used in our study showed a significant difference (p <0.001) between IDC and ILC. We noticed that DCE RF, such as Gray level run length matrix (GLRLM) gray level variance (sensitivity (SN) 97.21%, specificity (SP) 96.2%, area under curve (AUC) 0.998), Gray level co-occurrence matrix (GLCM) difference average (SN 95.72%, SP 96.34%, AUC 0.983), GLCM interquartile range (SN 95.24%, SP 97.31%, AUC 0.968), had the strongest ability to differentiate IDC and ILC.

CONCLUSIONS: MRI-based RF derived from DCE sequences can be used in clinical settings to differentiate malignant lesions of the breast, such as IDC and ILC, without requiring intrusive procedures.}, } @article {pmid38570490, year = {2024}, author = {Wang, J and Li, B and Luo, M and Huang, J and Zhang, K and Zheng, S and Zhang, S and Zhou, J}, title = {Progression from ductal carcinoma in situ to invasive breast cancer: molecular features and clinical significance.}, journal = {Signal transduction and targeted therapy}, volume = {9}, number = {1}, pages = {83}, pmid = {38570490}, issn = {2059-3635}, support = {82172344//National Natural Science Foundation of China (National Science Foundation of China)/ ; LY21H160039//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; LGF21H030010//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; }, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; *Breast Neoplasms/pathology ; Clinical Relevance ; Artificial Intelligence ; Gene Expression Profiling ; Tumor Microenvironment/genetics ; }, abstract = {Ductal carcinoma in situ (DCIS) represents pre-invasive breast carcinoma. In untreated cases, 25-60% DCIS progress to invasive ductal carcinoma (IDC). The challenge lies in distinguishing between non-progressive and progressive DCIS, often resulting in over- or under-treatment in many cases. With increasing screen-detected DCIS in these years, the nature of DCIS has aroused worldwide attention. A deeper understanding of the biological nature of DCIS and the molecular journey of the DCIS-IDC transition is crucial for more effective clinical management. Here, we reviewed the key signaling pathways in breast cancer that may contribute to DCIS initiation and progression. We also explored the molecular features of DCIS and IDC, shedding light on the progression of DCIS through both inherent changes within tumor cells and alterations in the tumor microenvironment. In addition, valuable research tools utilized in studying DCIS including preclinical models and newer advanced technologies such as single-cell sequencing, spatial transcriptomics and artificial intelligence, have been systematically summarized. Further, we thoroughly discussed the clinical advancements in DCIS and IDC, including prognostic biomarkers and clinical managements, with the aim of facilitating more personalized treatment strategies in the future. Research on DCIS has already yielded significant insights into breast carcinogenesis and will continue to pave the way for practical clinical applications.}, } @article {pmid38561526, year = {2024}, author = {Foesleitner, O and Sulaj, A and Sturm, V and Kronlage, M and Preisner, F and Kender, Z and Bendszus, M and Szendroedi, J and Heiland, S and Schwarz, D}, title = {Diffusion tensor imaging in anisotropic tissues: application of reduced gradient vector schemes in peripheral nerves.}, journal = {European radiology experimental}, volume = {8}, number = {1}, pages = {37}, pmid = {38561526}, issn = {2509-9280}, support = {SFB 1118//Deutsche Forschungsgemeinschaft/ ; SFB 1118//Deutsche Forschungsgemeinschaft/ ; SFB 1118//Deutsche Forschungsgemeinschaft/ ; SFB 1118//Deutsche Forschungsgemeinschaft/ ; SFB 1158//Deutsche Forschungsgemeinschaft/ ; SFB 1158//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Diffusion Tensor Imaging/methods ; Anisotropy ; *Diabetes Mellitus, Type 2 ; Peripheral Nerves/diagnostic imaging ; Diffusion Magnetic Resonance Imaging ; }, abstract = {BACKGROUND: In contrast to the brain, fibers within peripheral nerves have distinct monodirectional structure questioning the necessity of complex multidirectional gradient vector schemes for DTI. This proof-of-concept study investigated the diagnostic utility of reduced gradient vector schemes in peripheral nerve DTI.

METHODS: Three-Tesla magnetic resonance neurography of the tibial nerve using 20-vector DTI (DTI20) was performed in 10 healthy volunteers, 12 patients with type 2 diabetes, and 12 age-matched healthy controls. From the full DTI20 dataset, three reduced datasets including only two or three vectors along the x- and/or y- and z-axes were built to calculate major parameters. The influence of nerve angulation and intraneural connective tissue was assessed. The area under the receiver operating characteristics curve (ROC-AUC) was used for analysis.

RESULTS: Simplified datasets achieved excellent diagnostic accuracy equal to DTI20 (ROC-AUC 0.847-0.868, p ≤ 0.005), but compared to DTI20, the reduced models yielded mostly lower absolute values of DTI scalars: median fractional anisotropy (FA) ≤ 0.12; apparent diffusion coefficient (ADC) ≤ 0.25; axial diffusivity ≤ 0.96, radial diffusivity ≤ 0.07). The precision of FA and ADC with the three-vector model was closest to DTI20. Intraneural connective tissue was negatively correlated with FA and ADC (r ≥ -0.49, p < 0.001). Small deviations of nerve angulation had little effect on FA accuracy.

CONCLUSIONS: In peripheral nerves, bulk tissue DTI metrics can be approximated with only three predefined gradient vectors along the scanner's main axes, yielding similar diagnostic accuracy as a 20-vector DTI, resulting in substantial scan time reduction.

RELEVANCE STATEMENT: DTI bulk tissue parameters of peripheral nerves can be calculated with only three predefined gradient vectors at similar diagnostic performance as a standard DTI but providing a substantial scan time reduction.

KEY POINTS: • In peripheral nerves, DTI parameters can be approximated using only three gradient vectors. • The simplified model achieves a similar diagnostic performance as a standard DTI. • The simplified model allows for a significant acceleration of image acquisition. • This can help to introduce multi-b-value DTI techniques into clinical practice.}, } @article {pmid38560226, year = {2024}, author = {Lee, CP and Hashimoto, M}, title = {Prediction of textural properties of 3D-printed food using response surface methodology.}, journal = {Heliyon}, volume = {10}, number = {7}, pages = {e27658}, pmid = {38560226}, issn = {2405-8440}, abstract = {3D printing has enabled modifying internal structures of the food affecting textural properties, but predicting desired texture remains challenging. To overcome this challenge, the use of response surface methodology (RSM) was demonstrated to develop empirical models relating 3D printing parameters to textural properties using aqueous inks containing cricket powders as a model system. Regression models were established for our key textural properties (i.e., hardness (H), adhesiveness (A), cohesiveness (C), and springiness (S)) in response to three 3D printing parameters: infill percentage (i), layer height (h), and print speed (s). Our developed model successfully predicted the 3D printing parameters to achieve the intended textural properties using a multi-objective optimization framework. The predicted limits for H, A, C, and S were 0.66-5.39 N, 0.01-12.43 mJ, 0.01-1.05, and 0-19.20 mm, respectively. To validate our models, we simulated the texture of other food using our model ink and achieved high accuracy for H (99%), C (82%), and S (87%). This work highlights a simple way to 3D-print foods with spatially different textures and materials, unlocking the full potential of 3D printing technology for manufacturing a range of customized foods.}, } @article {pmid38558414, year = {2024}, author = {Han, LK and Lee, J and Dodelzon, K and Towne, WS and Zhou, XK and Ginter, PS and Marti, JL}, title = {Outcomes of atypical lobular hyperplasia managed by active surveillance or immediate surgery.}, journal = {World journal of surgery}, volume = {48}, number = {5}, pages = {1149-1156}, doi = {10.1002/wjs.12107}, pmid = {38558414}, issn = {1432-2323}, mesh = {Humans ; Female ; Retrospective Studies ; Middle Aged ; *Breast Neoplasms/surgery/pathology ; Aged ; Adult ; *Watchful Waiting ; Biopsy, Large-Core Needle ; Hyperplasia/surgery/pathology ; Disease Progression ; Treatment Outcome ; }, abstract = {BACKGROUND: Atypical lobular hyperplasia (ALH) is typically diagnosed via needle core biopsy (NCB) and is commonly removed surgically in light of upgrade to malignancy rates of 1%-5%. As studies on radiographic outcomes of ALH managed by active surveillance (AS) are limited, we investigated the upgrade rates of surgically excised ALH as well as radiographic progression during AS.

METHODS: In this retrospective study, 125 patients with 127 ALH lesions diagnosed via NCB at Weill Cornell Medicine from 2015 to 2021 were included. The upgrade rate to cancer was determined for patients who had surgical management ≤6 months after biopsy. Among patients with ALH managed by AS, we investigated radiographic progression on 6-month interval imaging.

RESULTS: Of 127 ALH lesions, 75% (n = 95) were immediately excised and 25% (n = 32) were observed under AS. The upgrade rate of immediately excised ALH was 2.1% (n = 2; invasive ductal carcinoma [IDC], T1N0 and IDC, and T1Nx). In the AS cohort, no ALH lesions progressed radiographically during the follow-up period of 22.5 months (median), with all remaining stable (50%, n = 16), resolving (47%, n = 15), or decreasing in size (3%, n = 1).

CONCLUSIONS: In this study, NCB-diagnosed ALH had a low upgrade to malignancy rate (2.1%), and no ALH lesions managed by AS progressed radiographically during the follow-up period of 22.5 months. These results support AS as the favorable option for patients with pure ALH on biopsy, with surgical excision for lesions that progress on surveillance.}, } @article {pmid38556289, year = {2024}, author = {Nagai, N and Ogata, F and Kadowaki, R and Deguchi, S and Otake, H and Nakazawa, Y and Misra, M and Kawasaki, N}, title = {Design of an Oral Tablet Containing Furosemide Nanoparticles with Elevated Bioavailability.}, journal = {Journal of oleo science}, volume = {73}, number = {4}, pages = {563-571}, doi = {10.5650/jos.ess23229}, pmid = {38556289}, issn = {1347-3352}, mesh = {Rats ; Animals ; Biological Availability ; *Furosemide ; Tablets ; Solubility ; *Nanoparticles ; Water ; Administration, Oral ; }, abstract = {The solubility and permeability of the Biopharmaceutics Classification System (BCS) class IV drugs, such as furosemide (FUR), are low. Thus, the oral bioavailability of these drugs needs to be augmented. Here, we aimed to design orally disintegrating tablets containing FUR nanoparticles to improve bioavailability after oral administration. The FUR nanoparticles were generated by bead-milling in water containing 0.5% methylcellulose and 0.5% 2-hydroxypropyl-β-cyclodextrin (w/w%). Particle size was approximately 47-350 nm (mean particle size, 188 nm). An orally disintegrating tablet (FUR-NP tablet) comprising FUR nanoparticles (1%) was successfully produced by employing suspensions outlined above that incorporated additives (4% D-mannitol, 0.4% polyvinylpyrrolidone, and 16% gum Arabic, w/w%), followed by freeze-drying. The FUR-NP tablet disaggregated after only 5 s in water, liberating nano-sized FUR particles (172 nm). Experiments using rats showed the absorption of the FUR-NP tablet was significantly improved by comparison with a FUR tablet containing microparticles. In summary, the orally disintegrating tablet containing FUR nanoparticles markedly enhanced the bioavailability of FUR. We anticipate this formulation will also improve the bioavailability of other BCS class IV drugs.}, } @article {pmid38554305, year = {2024}, author = {Dogan, I and Khanmammadov, N and Ozkurt, S and Aydiner, A and Saip, P}, title = {Outcomes of the patients with metastatic male breast cancer.}, journal = {Journal of cancer research and therapeutics}, volume = {20}, number = {1}, pages = {98-102}, doi = {10.4103/jcrt.jcrt_1829_22}, pmid = {38554305}, issn = {1998-4138}, mesh = {Humans ; Male ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; *Breast Neoplasms, Male/drug therapy ; Retrospective Studies ; Erb-b2 Receptor Tyrosine Kinases ; Disease-Free Survival ; *Breast Neoplasms/pathology ; Trastuzumab/therapeutic use ; Prognosis ; *Brain Neoplasms/drug therapy/secondary ; Kaplan-Meier Estimate ; }, abstract = {BACKGROUND: The goal of this research is to investigate the clinical characteristics and prognosis of men with metastatic breast cancer (mMBC).

METHODS: A retrospective analysis of the data of 28 patients was conducted. Kaplan-Meier and Cox regression analyses were used to assess overall survival (OS) and prognostic variables.

RESULTS: At the time of diagnosis, the median age was 57 years (range 26-86). The most prevalent pathological subtype was invasive ductal carcinoma (92.6%). HER2 positivity was 21.6% in patients, with estrogen and progesterone receptor positivity at 96.4% and 71.4%, respectively. Bone-75%, lung-39.3%, brain-21.4%, and adrenal gland-10.7% were the most prevalent metastatic sites. Trastuzumab-based chemotherapy was given to six patients. During the study period, 14 patients (or half) died. All patients had a median OS of 42.6 months (range: 21.6-63.7). The OS rates after 1, 3, and 5 years were 95.7%, 54.2%, and 36.6%, respectively. The number of metastatic locations (P = 0.045), brain metastasis (P = 0.033), and a history of regular alcohol intake (P = 0.008) were all shown to be statistically significant factors affecting OS in univariate analysis. However, multivariate analysis did not support the findings. In addition, we discovered that trastuzumab-based therapy and de-novo metastatic disease had no effect on OS for mMBC.

CONCLUSIONS: The data on mMBC is restricted because of its rarity. The prognosis of mMBC was shown to be poor in this investigation. Despite the small number of patients, we discovered that in univariate analysis, having brain metastases, the number of metastatic locations, and a history of alcohol intake may be prognostic factors.}, } @article {pmid38553788, year = {2024}, author = {Dreindl, R and Bolsa-Ferruz, M and Fayos-Sola, R and Padilla Cabal, F and Scheuchenpflug, L and Elia, A and Amico, A and Carlino, A and Stock, M and Grevillot, L}, title = {Commissioning and clinical implementation of an independent dose calculation system for scanned proton beams.}, journal = {Journal of applied clinical medical physics}, volume = {25}, number = {5}, pages = {e14328}, pmid = {38553788}, issn = {1526-9914}, mesh = {Humans ; *Proton Therapy/methods ; *Radiotherapy Dosage ; *Radiotherapy Planning, Computer-Assisted/methods ; *Software ; *Organs at Risk/radiation effects ; Quality Assurance, Health Care/standards ; Phantoms, Imaging ; Radiotherapy, Intensity-Modulated/methods ; Calibration ; Neoplasms/radiotherapy ; Tomography, X-Ray Computed/methods ; Algorithms ; }, abstract = {PURPOSE: Experimental patient-specific QA (PSQA) is a time and resource-intensive process, with a poor sensitivity in detecting errors. Radiation therapy facilities aim to substitute it by means of independent dose calculation (IDC) in combination with a comprehensive beam delivery QA program. This paper reports on the commissioning of the IDC software tool myQA iON (IBA Dosimetry) for proton therapy and its clinical implementation at the MedAustron Ion Therapy Center.

METHODS: The IDC commissioning work included the validation of the beam model, the implementation and validation of clinical CT protocols, and the evaluation of patient treatment data. Dose difference maps, gamma index distributions, and pass rates (GPR) have been reviewed. The performance of the IDC tool has been assessed and clinical workflows, simulation settings, and GPR tolerances have been defined.

RESULTS: Beam model validation showed agreement of ranges within ± 0.2 mm, Bragg-Peak widths within ± 0.1 mm, and spot sizes at various air gaps within ± 5% compared to physical measurements. Simulated dose in 2D reference fields deviated by -0.3% ± 0.5%, while 3D dose distributions differed by 1.8% on average to measurements. Validation of the CT calibration resulted in systematic differences of 2.0% between IDC and experimental data for tissue like samples. GPRs of 99.4 ± 0.6% were found for head, head and neck, and pediatric CT protocols on a 2%/2 mm gamma criterion. GPRs for the adult abdomen protocol were at 98.9% on average with 3%/3 mm. Root causes of GPR outliers, for example, implants were identified and evaluated.

CONCLUSION: IDC has been successfully commissioned and integrated into the MedAustron clinical workflow for protons in 2021. IDC has been stepwise and safely substituting experimental PSQA since February 2021. The initial reduction of proton experimental PSQA was about 25% and reached up to 90% after 1 year.}, } @article {pmid38548533, year = {2024}, author = {Bai, L and You, C and Zhou, J and Xie, L and Zhu, X and Chang, C and Zhi, W}, title = {Quantitative Analysis of Shear Wave Elastography and US-Guided Diffuse Optical Tomography for Evaluating Biological Characteristics of Breast Cancer.}, journal = {Academic radiology}, volume = {31}, number = {9}, pages = {3489-3498}, doi = {10.1016/j.acra.2024.03.006}, pmid = {38548533}, issn = {1878-4046}, mesh = {Humans ; *Elasticity Imaging Techniques/methods ; *Breast Neoplasms/diagnostic imaging ; Female ; Middle Aged ; *Tomography, Optical/methods ; Adult ; Aged ; *Ultrasonography, Mammary/methods ; Feasibility Studies ; Ultrasonography, Interventional/methods ; Aged, 80 and over ; }, abstract = {RATIONALE AND OBJECTIVES: Shear Wave Elastography (SWE) and Ultrasound-guided Diffuse Optical Tomography (US-guided DOT) demonstrate promise in distinguishing between benign and malignant breast lesions. This study aims to assess the feasibility and correlation of SWE and US-guided DOT in evaluating the biological characteristics of breast cancer.

MATERIALS AND METHODS: A cohort of 235 breast cancer patients with 238 lesions, scheduled for surgery within one to three days, underwent B-mode ultrasound (US), US-guided DOT, and SWE. Parameters such as Total Hemoglobin Concentration (THC), Maximal Elasticity (Emax), Mean Elasticity (Emean), Standard Deviation of Elasticity (Esd), and Area Ratio were measured. Correlation with post-surgical pathology reports was examined to explore associations between THC, SWE Parameters, and pathology characteristics.

RESULTS: Lesions in patient groups with ER-, PR-, HER2 + , high Ki67, LVI+ , and ALN+ exhibited higher THC, Emax, and Esd compared to groups with ER+ , PR+ , HER2-, low Ki67, LVI-, and ALN-. The increase was seen in all grades of IDC-I to -III. THC significantly correlated with Smax (r = 0.340, P < 0.001), Emax (r = 0.339, P < 0.001), Emean (r = 0.201, P = 0.003), and Esd (r = 0.313, P < 0.001).

CONCLUSION: US-guided DOT and SWE prove valuable for the quantitative assessment of breast cancer's biological characteristics, with THC positively correlated with Emax, Emean, and Esd.}, } @article {pmid38545425, year = {2024}, author = {Magnoni, F and Corso, G and Maisonneuve, P and Bianchi, B and Accardo, G and Sangalli, C and Massari, G and Rotili, A and Nicosia, L and Pesapane, F and Montagna, E and Mazzarol, G and Galimberti, V and Veronesi, P and Curigliano, G}, title = {Comparison of long-term outcome between clinically high risk lobular versus ductal breast cancer: a propensity score matched study.}, journal = {EClinicalMedicine}, volume = {71}, number = {}, pages = {102552}, pmid = {38545425}, issn = {2589-5370}, abstract = {BACKGROUND: Abemaciclib is currently approved for the adjuvant treatment of high-risk, lymph node (LN)-positive, hormone receptor (HR)-positive breast cancer (BC). In a real-world setting the clinicopathologic features of patients potentially eligible for adjuvant abemaciclib remain to be defined. There are conflicting data regarding the biological behavior and long-term outcomes across invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). In our study we retrospectively assessed the real-world data and long-term outcome of selected high-risk features ILC compared to IDC, according to the MonarchE trial inclusion criteria.

METHODS: We identified 15,071 patients who got surgery at the European Institute of Oncology for a first primary, non-metastatic, HR-positive, HER2-negative BC from 2000 to 2008. 11,981 (79.5%) patients had an IDC and 1524 (10.1%) an ILC. The remaining 1566 patients (10.4%) had either combined ductal and lobular breast cancer or another histological breast cancer subtype. According to the eligibility criteria of the MonarchE study, we identified two high-risk groups, based on high number of positive lymph nodes, large tumor size, or a high cellular proliferation as measured by tumor grade or biomarkers. Patients were matched by propensity score.

FINDINGS: A total of 2872 (21.3%) patients were selected as clinically high-risk, including 361/1524 ILC (23.7%) and 2511/11,981 IDC (21%). 322 high-risk ILC were matched with similar high-risk IDC. The median follow-up was 13.2 years for survival. In the matched set, invasive disease-free survival (IDFS) (log-rank P = 0.09) and overall survival (OS) (log-rank P = 0.48) were not statistically significantly different between the two histological groups. For IDC patients, the 5-year and 10-year IDFS rates (95% CI) were 77.7% (72.9-82.2) and 57.3% (51.7-63.1) respectively, compared to the 5-year and 10-year IDFS rates of ILC patients that were 75.5% (70.6-80.2) and 50.7% (45.0-56.6). The 5-year and 10-year distant relapse free survival (DRFS) rates were 80% (75.3-84.2) and 65.3% (59.8-70.7) in IDC cohort, compared to the 5-year and the 10-year DRFS rates of 78.7% (74.0-83.1) and 61.5% (55.9-67.1) in the ILC cohort. Such data match the recent outcomes efficacy results of the MonarchE control arm. More patients in the ILC (n = 17) than in the IDC group (n = 10) developed axillary recurrence. At multivariable analysis, stratified for specific clinical features, age <35 years, pT2-3, axillary involvement with more than 10 positive axillary nodes were found to be predictors of unfavorable IDFS and OS in the overall matched high-risk population.

INTERPRETATION: Findings from this matched cohort study reported similar IDFS and DRFS rates for high risk HR positive early BC when compared to the control arm overall IDFS and DRFS rates reported from the MonarchE trial. Our study demonstrated rates of concordant long-term outcome status beyond histologic subtype. These data support an escalation strategy for these two different histological entities when diagnosed with high-risk features. In our dataset approximately 21% rate of high-risk HR positive early BC patients are potentially eligible for adjuvant abemaciclib treatment.

FUNDING: Umberto Veronesi Foundation.}, } @article {pmid38539179, year = {2024}, author = {Esmat, E and Haidary, AM and Saadaat, R and Rizvi, SN and Aleena, S and Haidari, M and Hofiani, SMS and Hussaini, N and Hakimi, A and Khairy, A and Abdul-Ghafar, J}, title = {Association of hormone receptors and human epidermal growth factor receptor-2/neu expressions with clinicopathologic factors of breast carcinoma: a cross-sectional study in a tertiary care hospital, Kabul, Afghanistan.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {388}, pmid = {38539179}, issn = {1471-2407}, mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; Afghanistan/epidemiology ; Biomarkers, Tumor/metabolism ; *Breast Neoplasms/epidemiology/genetics/metabolism ; Cross-Sectional Studies ; Hormones ; *Erb-b2 Receptor Tyrosine Kinases/metabolism ; Receptors, Progesterone/metabolism ; Tertiary Care Centers ; }, abstract = {BACKGROUND: Breast cancer (BC) is one of the major causes of death worldwide. It is the most common cause of death before the age of 70 years. The incidence and mortality of BC are rapidly increasing, posing great challenges to the health system and economy of every nation.

METHODOLOGY: A cross-sectional analytical study was conducted at the Department of Pathology and Clinical Laboratory of the French Medical Institute for Mothers and Children (FMIC) to demonstrate the association of human epidermal growth factor receptor 2 (Her2/Neu) and estrogen receptor (ER)/ progesterone receptor (PR) with clinical as well as pathological parameters among women with BC. A consecutive nonprobability sampling method was used for this study over a span of one and a half years.

RESULTS: One hundred twenty participants diagnosed with breast cancer were included in the study. The mean age at diagnosis was 44.58 ± 11.16 years. Out of the total patients, 68 (56.7%) were above 40 years old, 108 (90%) were married, 94 (78.3%) were multiparous, and 88 (73.3%) had a history of breastfeeding. 33.3% of cases were within the age range of menopause (40-50 years). The positive expression rates of ER, PR, and Her2/neu were found to be 48.8%, 44.6%, and 44.6%, respectively, and Her2/neu overexpression was found to be higher among ER/PR-negative cases.

CONCLUSION: In our study, we demonstrated that among Afghan women, grade II invasive ductal carcinoma, not otherwise specified, was the most common type of BC and frequently affected women above the age of 40. We also revealed that the percentage of negative ER (50.4%), negative PR (54.4%), and concordant ER/PR-negative cases were high compared to other possibilities. Additionally, the study revealed that expression of Her2/neu was in contrast with the expression of ER and PR receptors. The findings of our study still support the importance of performing immunohistochemical stains for hormonal receptor classification in terms of better clinical outcomes and prognosis.}, } @article {pmid38534445, year = {2024}, author = {Rapoport, R and Greenberg, A and Yakhini, Z and Simon, I}, title = {A Cyclic Permutation Approach to Removing Spatial Dependency between Clustered Gene Ontology Terms.}, journal = {Biology}, volume = {13}, number = {3}, pages = {}, pmid = {38534445}, issn = {2079-7737}, abstract = {Traditional gene set enrichment analysis falters when applied to large genomic domains, where neighboring genes often share functions. This spatial dependency creates misleading enrichments, mistaking mere physical proximity for genuine biological connections. Here we present Spatial Adjusted Gene Ontology (SAGO), a novel cyclic permutation-based approach, to tackle this challenge. SAGO separates enrichments due to spatial proximity from genuine biological links by incorporating the genes' spatial arrangement into the analysis. We applied SAGO to various datasets in which the identified genomic intervals are large, including replication timing domains, large H3K9me3 and H3K27me3 domains, HiC compartments and lamina-associated domains (LADs). Intriguingly, applying SAGO to prostate cancer samples with large copy number alteration (CNA) domains eliminated most of the enriched GO terms, thus helping to accurately identify biologically relevant gene sets linked to oncogenic processes, free from spatial bias.}, } @article {pmid38530283, year = {2025}, author = {Matta, L and Blaas, L and Gibis, C and Guerra, J}, title = {Functions require junctions: endurance exercise protects from age-induced alterations of the neuromuscular system.}, journal = {The Journal of physiology}, volume = {603}, number = {1}, pages = {37-39}, doi = {10.1113/JP286232}, pmid = {38530283}, issn = {1469-7793}, } @article {pmid38527731, year = {2024}, author = {Aksu, A and Güç, ZG and Küçüker, KA and Alacacıoğlu, A and Turgut, B}, title = {Intra and peritumoral PET radiomics analysis to predict the pathological response in breast cancer patients receiving neoadjuvant chemotherapy.}, journal = {Revista espanola de medicina nuclear e imagen molecular}, volume = {43}, number = {3}, pages = {500002}, doi = {10.1016/j.remnie.2024.500002}, pmid = {38527731}, issn = {2253-8089}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/drug therapy/pathology ; *Neoadjuvant Therapy ; Middle Aged ; Retrospective Studies ; *Fluorodeoxyglucose F18 ; *Radiopharmaceuticals ; *Carcinoma, Ductal, Breast/diagnostic imaging/drug therapy/pathology ; Adult ; Aged ; Positron-Emission Tomography ; Treatment Outcome ; Chemotherapy, Adjuvant ; Radiomics ; }, abstract = {OBJECTIVE: The aim of our study was to evaluate the contribution of 18Fluorine-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) radiomic data obtained from both the tumoral and peritumoral area in predicting pathological complete response (pCR) in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NAC).

METHODS: Female patients with a diagnosis of invasive ductal carcinoma who received NAC were evaluated retrospectively. The volume of interest (VOI) of the primary tumor (VOI-T) was manually segmented, then a voxel-thick VOI was added around VOI-T to define the peritumoral area (VOI-PT). Morphological, intensity-based, histogram and texture parameters were obtained from VOIs. The patients were divided into two groups as pCR and non-complete pathological response (npCR). A "radiomic model" was created with only radiomic features, and a "patho-radiomic model" was created using radiomic features and immunohistochemical data.

RESULTS: Of the 66 patients included in the study, 21 were in the pCR group. The only statistically significant feature from the primary tumor among patients with pCR and npCR was Morphological_Compacity-T (AUC: 0.666). Between response groups, a significant difference was detected in 2 morphological, 1 intensity, 4 texture features from VOI-PT; no correlation was found between Morphological_Compacity-PT and NGTDM_contrast-PT. The obtained radiomic model's sensitivity and accuracy values were calculated as 61.9% and 75.8%, respectively (AUC: 0.786). When HER2 status was added, sensitivity and accuracy values of the patho-radiomic model increased to 85.7% and 81.8%, respectively (AUC: 0.903).

CONCLUSIONS: Evaluation of PET peritumoral radiomic features together with the primary tumor, rather than just the primary tumor, provides a better prediction of the pCR to NAC in patients with breast cancer.}, } @article {pmid38526962, year = {2024}, author = {Hauschildt, KE and Messersmith, J and Iwashyna, TJ}, title = {Inequities in Indirect Cost Rates Between Historically Black Colleges and Universities and Other Institutions.}, journal = {Academic medicine : journal of the Association of American Medical Colleges}, volume = {99}, number = {12}, pages = {1432-1437}, pmid = {38526962}, issn = {1938-808X}, mesh = {Biomedical Research/economics/statistics & numerical data ; Financing, Government/statistics & numerical data ; Research Support as Topic/statistics & numerical data ; United States ; *Universities/statistics & numerical data/economics ; }, abstract = {PURPOSE: Federal research grants provide support for the indirect costs (IDCs) of research infrastructure that are not specific to particular research projects but are nonetheless essential to enable research. Institutions independently negotiate IDC rates. The authors sought to identify whether inequities exist in negotiated IDC rates between historically Black colleges and universities (HBCUs) and other universities (non-HBCUs).

METHOD: In 2023, the authors analyzed mean negotiated IDC rates between the top 20 HBCUs (in fiscal year [FY] 2021 research expenditures) and 3 non-HBCU comparison groups: the top 40 non-HBCUs in FY 2021 research expenditures, metropolitan statistical area (MSA)-matched non-HBCUs (among the top 200 institutions by FY 2021 research expenditures), and FY 2021 research expenditure-matched non-HBCUs.

RESULTS: The authors found that the top 20 HBCUs' mean IDC rates (50.0%) were, after adjustment, 8.5 percentage points (95% confidence interval [CI], 5.7-11.2) lower than those of the top 40 non-HBCUs (58.5%). The mean IDC rates of top HBCUs (n = 14, 48.4%) were, after adjustment, 6.3 percentage points (95% CI, 3.1-9.4) lower than those of MSA-matched non-HBCUs (n = 23, 55.3%). There was no statistically significant difference in the mean IDC rates between the top 20 HBCUs (50.0%) and expenditure-matched non-HBCUs (n = 31; 48.2%).

CONCLUSIONS: Inequities in negotiated IDC rates between top HBCUs and non-HBCUs likely both reflect and may contribute to the persistence of institution-level inequities in federally funded research. Proactive investments in HBCUs' research infrastructures are likely needed to ameliorate these funding inequities and support the role of HBCUs in providing opportunity for underrepresented groups in biomedical sciences.}, } @article {pmid38525191, year = {2024}, author = {Lopez-Vazquez, P and Fernandez-Caggiano, M and Barge-Caballero, E and Barge-Caballero, G and Couto-Mallon, D and Grille-Cancela, Z and Blanco-Canosa, P and Paniagua-Martin, MJ and Enriquez-Vazquez, D and Vazquez-Rodriguez, JM and Domenech, N and Crespo-Leiro, MG}, title = {Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin.}, journal = {Frontiers in cardiovascular medicine}, volume = {11}, number = {}, pages = {1349417}, pmid = {38525191}, issn = {2297-055X}, abstract = {INTRODUCTION AND OBJECTIVES: Mitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies.

METHODS: Protein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA.

RESULTS: Significant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group.

CONCLUSION: Decreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features.}, } @article {pmid38523303, year = {2024}, author = {Yanase, Y and Bando, H and Sato, R and Matsuo, T and Ueda, A and Okazaki, M and Hashimoto, S and Iguchi-Manaka, A and Hara, H}, title = {Recurrent severe hypocalcemia following chemotherapy regimen changes in advanced breast cancer: two case reports.}, journal = {Journal of medical case reports}, volume = {18}, number = {1}, pages = {150}, pmid = {38523303}, issn = {1752-1947}, mesh = {Female ; Humans ; Adult ; Aged ; *Breast Neoplasms/drug therapy/pathology ; *Hypocalcemia/chemically induced ; Lapatinib/adverse effects ; Denosumab/adverse effects ; Calcium/therapeutic use ; *Bone Neoplasms/secondary ; }, abstract = {BACKGROUND: As an oncologic emergency related to abnormalities in calcium metabolism, hypercalcemia associated with paraneoplastic syndrome and bone metastases is well known. Meanwhile, the incidence of hypocalcemia is low, except in cases associated with bone-modifying agents used for bone metastases. Hypocalcemia induced by bone-modifying agents typically occurs early after the initial administration, and its incidence can be significantly reduced by preventive administration of calcium and vitamin D3 supplements.

CASE REPORT: We report two cases of recurrent severe hypocalcemia occurring during chemotherapy for metastatic breast cancer with multiple bone metastases. Case 1: A 35-year-old Japanese woman developed metastases in the bone, liver, and ovaries during postoperative endocrine therapy for invasive lobular carcinoma of the breast. She underwent chemotherapy and treatment with denosumab. She experienced recurrent episodes of severe hypocalcemia subsequent to a change in the chemotherapy regimen. Case 2: A 65-year-old Japanese woman encountered multiple bone metastases after postoperative anti-human epidermal growth factor receptor 2 therapy and during endocrine therapy for invasive ductal carcinoma of the breast. She underwent anti-human epidermal growth factor receptor 2 therapy and treatment with denosumab. She experienced recurrent severe hypocalcemia subsequent to a change in the chemotherapy regimen to letrozole + lapatinib, trastuzumab emtansine, and lapatinib + capecitabine.

CONCLUSIONS: We observed two cases of recurrent severe hypocalcemia in patients with advanced breast cancer and bone metastases after modifications to their therapy regimens. These cases differed from the typical hypocalcemia induced by bone-modifying agents. It is possible that antitumor drugs affect calcium and bone metabolism associated with bone metastases. While these cases are rare, it is crucial for oncologists to be aware of hypocalcemia not only at the initiation of bone-modifying agents but also throughout the entire antitumor therapy, as hypocalcemia can lead to fatal outcomes.}, } @article {pmid38517441, year = {2024}, author = {Garza, KY and King, ME and Nagi, C and DeHoog, RJ and Zhang, J and Sans, M and Krieger, A and Feider, CL and Bensussan, AV and Keating, MF and Lin, JQ and Sun, MW and Tibshirani, R and Pirko, C and Brahmbhatt, KA and Al-Fartosi, AR and Thompson, AM and Bonefas, E and Suliburk, J and Carter, SA and Eberlin, LS}, title = {Intraoperative Evaluation of Breast Tissues During Breast Cancer Operations Using the MasSpec Pen.}, journal = {JAMA network open}, volume = {7}, number = {3}, pages = {e242684}, pmid = {38517441}, issn = {2574-3805}, support = {R33 CA229068/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Female ; Humans ; Middle Aged ; *Breast Neoplasms/diagnosis/surgery/pathology ; Margins of Excision ; Breast/surgery/pathology ; Mastectomy ; Mass Spectrometry ; }, abstract = {IMPORTANCE: Surgery with complete tumor resection remains the main treatment option for patients with breast cancer. Yet, current technologies are limited in providing accurate assessment of breast tissue in vivo, warranting development of new technologies for surgical guidance.

OBJECTIVE: To evaluate the performance of the MasSpec Pen for accurate intraoperative assessment of breast tissues and surgical margins based on metabolic and lipid information.

In this diagnostic study conducted between February 23, 2017, and August 19, 2021, the mass spectrometry-based device was used to analyze healthy breast and invasive ductal carcinoma (IDC) banked tissue samples from adult patients undergoing breast surgery for ductal carcinomas or nonmalignant conditions. Fresh-frozen tissue samples and touch imprints were analyzed in a laboratory. Intraoperative in vivo and ex vivo breast tissue analyses were performed by surgical staff in operating rooms (ORs) within 2 different hospitals at the Texas Medical Center. Molecular data were used to build statistical classifiers.

MAIN OUTCOMES AND MEASURES: Prediction results of tissue analyses from classification models were compared with gross assessment, frozen section analysis, and/or final postoperative pathology to assess accuracy.

RESULTS: All data acquired from the 143 banked tissue samples, including 79 healthy breast and 64 IDC tissues, were included in the statistical analysis. Data presented rich molecular profiles of healthy and IDC banked tissue samples, with significant changes in relative abundances observed for several metabolic species. Statistical classifiers yielded accuracies of 95.6%, 95.5%, and 90.6% for training, validation, and independent test sets, respectively. A total of 25 participants enrolled in the clinical, intraoperative study; all were female, and the median age was 58 years (IQR, 44-66 years). Intraoperative testing of the technology was successfully performed by surgical staff during 25 breast operations. Of 273 intraoperative analyses performed during 25 surgical cases, 147 analyses from 22 cases were subjected to statistical classification. Testing of the classifiers on 147 intraoperative mass spectra yielded 95.9% agreement with postoperative pathology results.

CONCLUSIONS AND RELEVANCE: The findings of this diagnostic study suggest that the mass spectrometry-based system could be clinically valuable to surgeons and patients by enabling fast molecular-based intraoperative assessment of in vivo and ex vivo breast tissue samples and surgical margins.}, } @article {pmid38512628, year = {2024}, author = {Rescinito, G and Brunetti, N and Garlaschi, A and Tosto, S and Gristina, L and Conti, B and Pieroni, D and Calabrese, M and Tagliafico, AS}, title = {Long-term outcome of 9G MRI-guided vacuum-assisted breast biopsy: results of 293 single-center procedures and underestimation rate of high-risk lesions over 12 years.}, journal = {La Radiologia medica}, volume = {129}, number = {5}, pages = {767-775}, pmid = {38512628}, issn = {1826-6983}, mesh = {Humans ; Female ; Retrospective Studies ; *Breast Neoplasms/pathology/diagnostic imaging ; Middle Aged ; *Image-Guided Biopsy/methods ; Adult ; Vacuum ; Aged ; Breast/diagnostic imaging/pathology ; Magnetic Resonance Imaging/methods ; Magnetic Resonance Imaging, Interventional/methods ; Aged, 80 and over ; }, abstract = {PURPOSE: Breast magnetic resonance imaging (MRI) can detect some malignant lesions that are not visible on mammography (MX) or ultrasound (US). If a targeted, second-look fails, MRI-guided breast biopsy is the only available tool to obtain a tissue sample and pathological proof of these "MRI-only lesions". The aim of this study is to report the performance and underestimation rate of 9G MRI-guided vacuum-assisted breast biopsy (VABB) over 12 years at a single center.

MATERIAL AND METHODS: All 9G MRI-VABB procedures performed from January 2010 to December 2021 were retrospectively reviewed. Two MRI scanners (1.5 T and 3 T) were used with the same image resolution and contrast media. All suspicious lesions detected only by breast MRI underwent biopsy. Reference standard was histological diagnosis or at least 1-year negative follow-up. All malignant and atypical lesions underwent surgery, which was used as the reference standard.

RESULTS: A total of 293 biopsies were retrospectively reviewed. Histopathological VABB results revealed 142/293 (48.4%) benign lesions, 77/293 (26.2%) high-risk lesions, and 74/293 (25.2%) malignant lesions. No significant complications were observed. Surgical pathology results allowed for the reclassification of n = 7/48 B3b lesions: n = 4 were ductal carcinoma in situ, while n = 3 presented invasive features at surgical histology (2 IDC; 1 ILC). B3b underestimation occurred overall in 14.6% of B3 cases. Breast follow-up was achieved for all benign VABB results, and only one false-negative case was observed.

CONCLUSION: Our results confirm that 1.5 T and 3 T MRI-guided VABB is an accurate and safe procedure for histopathologic final diagnosis of MRI-only lesions. Critical issues remain the potential high-risk underestimation rate of B3b VABB results and management of follow-up of benign lesions.}, } @article {pmid38509907, year = {2024}, author = {Yaqing, X and Yang, G and Linlin, Y and Youqing, R and Henghui, Y and Ping, Y and Hongying, Y and Shaojia, W}, title = {Identification of different subtypes of ovarian cancer and construction of prognostic models based on glutamine-metabolism associated genes.}, journal = {Heliyon}, volume = {10}, number = {6}, pages = {e27358}, pmid = {38509907}, issn = {2405-8440}, abstract = {Ovarian cancer (OC) is common malignant tumor of female reproductive system. Glutamine metabolism-related genes (GMRGs) play a key role in ovarian cancer. Here, available database-- The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases were applied in our research. OC samples from TCGA were divided into different clusters based on Cox analysis, which filtering GMRGs with survival information. Then, differentially expressed genes (DEGs) between these clusters were intersected with DEGs between normal ovary samples and OC samples, and GMRGs in order to obtain GMRGs-related DEGs. Next, a risk model of OC was constructed and enrichment analysis of risk model was performed based on hallmark gene set. Besides, the immune cells ratio in OC samples were detected via Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT). Finally, we explored a series of potential biomarkers of OC. In this research, 9 GMRGs-related DEGs were obtained. GMRGs-related DEGs were enriched to canonical Wnt signaling pathway.NKD2, C2orf88, and KLHDC8A, which were significantly associated with prognosis, were retained for risk model construction. Based on the risk model, 18 hallmark pathways with significant difference were enriched. Fifteen types of immune cells (such as iDC, NK CD56dim cells, and neutrophils) enjoying significant difference between these 2 risk groups (high risk group vs. low risk group) were detected, which indicates possible disparate TME in different metabolic subtypes of ovarian cancer.}, } @article {pmid38507631, year = {2024}, author = {Feizi, I and Isazadehfar, K and Sadegzadeh, F and Farshadi, P}, title = {Histopathological Feature of Early-Onset Breast Cancer: A Comparative Analysis.}, journal = {The international tinnitus journal}, volume = {27}, number = {2}, pages = {167-173}, doi = {10.5935/0946-5448.20230026}, pmid = {38507631}, issn = {0946-5448}, mesh = {Female ; Humans ; Adult ; *Breast Neoplasms/diagnosis/pathology ; Cross-Sectional Studies ; Lymphatic Metastasis/pathology ; Lymph Nodes/pathology ; Prognosis ; }, abstract = {BACKGROUND: Breast cancer is one of the most common malignancies among women. In some reports, it has been specified that the diagnosis of breast cancer at an earlier ages worsens the prognosis; this can be attributed to a combination of factors such as advanced stage of disease and late demonstration. Considering different results in last studies, this study's aim was investigation of breast cancer histopathology in two age groups of women under and above 40 years old.

MATERIAL AND METHODS: A cross-sectional study was performed on 64 patients with breast cancer referring to hospitals during 2014 and 2015 years. All histopathologic information is collected from patient's cases. Data were compared in two age groups with equal T. Also, the levels of axillary lymph nodes involvement were evaluated in the equal T for both groups.

RESULTS: We evaluated 64 patients, 71.9% of them were over 40 years old and 28.1% were under 40 years of age. The most common type of tumor was invasive ductal carcinoma. Involvement of the axillary lymph nodes in the equal T was significantly higher in patients less than 40 years of age (p 0.005) than patients over 40 years old (T=1 and T=2) (p=0.032 and p=0.05).

CONCLUSION: Our study signified that in equal T rates the level of axillary lymph nodes involvement in patients younger than 40 years old is higher than those older than 40 years of age. Therefore, breast cancer at early ages is associated with a worse prognosis.}, } @article {pmid38499660, year = {2024}, author = {Seifert, L and Létocart, A and Guignard, B and Regaieg, MA}, title = {Effect of breathing conditions on relationships between impairment, breathing laterality and coordination symmetry in elite para swimmers.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {6456}, pmid = {38499660}, issn = {2045-2322}, support = {ANR-19-STHP-0004//Agence Nationale de la Recherche/ ; }, mesh = {Humans ; Biomechanical Phenomena ; *Functional Laterality ; Respiration ; *Musculoskeletal Physiological Phenomena ; Swimming ; Arm ; Vision Disorders ; }, abstract = {The aim was to investigate the effect of breathing conditions and swimming pace on the relationships between the impairment, the breathing laterality and motor coordination symmetry in elite front crawl Para swimmers. Fifteen elite Para swimmers with unilateral physical impairment or with visual impairment and unilateral breathing preference performed eight 25 m using four breathing conditions (every three strokes, every two strokes on preferred and non-preferred breathing side and apnea) at slow and fast paces in a randomized order. Multicamera video system and five sensors have been used to assess arm and leg stroke phases and to compute symmetry of arm coordination (SIIdC) and of leg kick rate (SIKR). Our findings emphasized motor coordination asymmetry whatever the breathing conditions and swimming paces, highlighting the influence of impairment. Multinomial logistic regression exhibited a high probability for motor coordination asymmetry (SIIdC and SIKR) to be present in categories of Para swimmers with impairment and breathing laterality on the same side, suggesting the joined effect of unilateral impairment and unilateral breathing. Moreover, unilateral physical impairment and breathing laterality could also occur on different sides and generate motor coordination asymmetry on different sides and different levels (arms vs. legs). Finally, visual impairment seems amplify the effect of unilateral breathing on motor coordination asymmetry.}, } @article {pmid38497796, year = {2024}, author = {Ward, K and Selvarajah, G and Al-Omishy, H and Sait, M and Khan, HN and McEvoy, K and Robertson, S}, title = {Surgical outcomes of total duct excision in the diagnosis and management of nipple discharge.}, journal = {Annals of the Royal College of Surgeons of England}, volume = {106}, number = {6}, pages = {515-520}, pmid = {38497796}, issn = {1478-7083}, mesh = {Humans ; Female ; Middle Aged ; Adult ; Retrospective Studies ; Aged ; *Nipple Discharge ; Aged, 80 and over ; *Breast Neoplasms/surgery/diagnosis/pathology ; Young Adult ; Nipples/surgery/pathology ; Treatment Outcome ; Carcinoma, Intraductal, Noninfiltrating/surgery/diagnosis/pathology ; Mammary Glands, Human/surgery/pathology ; }, abstract = {INTRODUCTION: Total duct excision (TDE) is performed for the diagnosis and management of nipple discharge. The Association of Breast Surgery's recent guidelines recommend considering diagnostic surgery for single-duct, blood-stained or clear nipple discharge, and for symptomatic management.

METHODS: We retrospectively reviewed the diagnostic and surgical outcomes of all cases of TDE between January 2013 and November 2019.

RESULTS: In total, 259 TDEs were carried out: 219 for nipple discharge, 29 for recurrent mastitis, 3 for screening abnormalities and 8 for breast lumps. Of the nipple discharge group, 121 had blood-stained discharge. Mean patient age was 52 years (range 19-81). Median follow-up time was 45 months (interquartile range 24-63). The following cases were identified on histopathology: 236 benign breast changes, 10 atypical ductal hyperplasia, 4 lobular carcinoma in situ, 2 low-grade ductal carcinoma in situ (DCIS), 3 intermediate-grade DCIS, 2 high-grade DCIS and 2 invasive ductal carcinomas. In total, 3.5% of patients who underwent TDE had a diagnosis of DCIS or invasive carcinoma. Blood-stained discharge was associated with a significant increase in risk of DCIS or carcinoma compared with other nipple discharge colours (p = 0.043). The most common complications of TDE were infection, poor wound healing and haematoma. Nipple discharge recurred in 14.2% of cases.

CONCLUSIONS: TDE can be considered for the diagnostics and management of nipple discharge. Blood-stained nipple discharge increases the risk of DCIS or malignancy, but the majority of the time TDE reveals benign breast pathology.}, } @article {pmid38485913, year = {2024}, author = {Heidari, N and Abbasi-Kenarsari, H and Niknam, B and Asadirad, A and Amani, D and Mirsanei, Z and Hashemi, SM}, title = {Exosomes Derived from Heat-shocked Tumor Cells Promote In vitro Maturation of Bone Marrow-derived Dendritic Cells.}, journal = {Iranian journal of allergy, asthma, and immunology}, volume = {23}, number = {1}, pages = {97-106}, doi = {10.18502/ijaai.v23i1.14957}, pmid = {38485913}, issn = {1735-5249}, mesh = {*Exosomes ; Dendritic Cells ; Bone Marrow ; T-Lymphocytes ; Coculture Techniques ; Cell Differentiation ; }, abstract = {Dendritic cells (DCs), professional antigen-presenting cells that process and deliver antigens using MHC II/I molecules, can be enhanced in numerous ways. Exosomes derived from heat-shocked tumor cells (HS-TEXs) contain high amounts of heat-shock proteins (HSPs). HSPs, as chaperons, can induce DC maturation. This study aimed to investigate whether HS-TEXs can promote DC maturation. To generate DC, bone marrow-derived cells were treated with Interleukin-4 and GM-CSF. Exosomes were isolated from heat-treated CT-26 cells. The expression level of HSP in exosomes was checked by western blot and the increase in the expression of this protein was observed. Then, HS-TEXs were co-cultured with iDCs to determine DC maturity, and then DCs were co-cultured with lymphocytes to determine DC activity. Our results showed that DCs treated with HS-TEXs express high levels of molecules involved in DC maturation and function including MHCII, CD40, CD83, and CD86. HS-TEXs caused phenotypic and functional maturation of DCs. In addition, flow cytometric results reflected a higher proliferative response of lymphocytes in the iDC / Tex + HSP group. HS-TEXs could be used as a strategy to improve DC maturation and activation.}, } @article {pmid38485644, year = {2024}, author = {Shi, Y and Wang, H and Golijanin, B and Amin, A and Lee, J and Sikov, M and Hyams, E and Pareek, G and Carneiro, BA and Mega, AE and Lagos, GG and Wang, L and Wang, Z and Cheng, L}, title = {Ductal, intraductal, and cribriform carcinoma of the prostate: Molecular characteristics and clinical management.}, journal = {Urologic oncology}, volume = {42}, number = {5}, pages = {144-154}, doi = {10.1016/j.urolonc.2024.01.037}, pmid = {38485644}, issn = {1873-2496}, mesh = {Male ; Humans ; Prostate/pathology ; *Adenocarcinoma/pathology ; *Prostatic Neoplasms/genetics/therapy/pathology ; Cell Proliferation ; }, abstract = {Prostatic acinar adenocarcinoma accounts for approximately 95% of prostate cancer (CaP) cases. The remaining 5% of histologic subtypes of CaP are known to be more aggressive and have recently garnered substantial attention. These histologic subtypes - namely, prostatic ductal adenocarcinoma (PDA), intraductal carcinoma of the prostate (IDC-P), and cribriform carcinoma of the prostate (CC-P) - typically exhibit distinct growth characteristics, genomic features, and unique oncologic outcomes. For example, PTEN mutations, which cause uncontrolled cell growth, are frequently present in IDC-P and CC-P. Germline mutations in homologous DNA recombination repair (HRR) genes (e.g., BRCA1, BRCA2, ATM, PALB2, and CHEK2) are discovered in 40% of patients with IDC-P, while only 9% of patients without ductal involvement had a germline mutation. CC-P is associated with deletions in common tumor suppressor genes, including PTEN, TP53, NKX3-1, MAP3K7, RB1, and CHD1. Evidence suggests abiraterone may be superior to docetaxel as a first-line treatment for patients with IDC-P. To address these and other critical pathological attributes, this review examines the molecular pathology, genetics, treatments, and oncologic outcomes associated with CC-P, PDA, and IDC-P with the objective of creating a comprehensive resource with a centralized repository of information on PDA, IDC-P, and CC-P.}, } @article {pmid38483129, year = {2024}, author = {Cheng, M and Jia, Z and Zhang, G and Wang, Y and Li, S and Yang, S and Li, C and Geng, C}, title = {Gastric metastasis from breast cancer: five cases and a single-institutional review.}, journal = {The Journal of international medical research}, volume = {52}, number = {3}, pages = {3000605241233988}, pmid = {38483129}, issn = {1473-2300}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/pathology ; *Stomach Neoplasms/diagnosis/pathology ; *Lymphoma ; }, abstract = {Gastric metastasis from breast cancer has a high rate of misdiagnosis and missed diagnosis. Data of patients who had gastric metastasis from breast cancer were retrieved from our hospital between 2014 and 2020. The gastric metastasis from breast cancer incidence was 0.04% (5/14,169 cases of breast cancer). Four patients had invasive lobular carcinoma, and the other patient had invasive ductal carcinoma. The time from the initial diagnosis of breast cancer to the appearance of gastric metastasis ranged from 0 to 12 years. One patient's endoscopic presentation was similar to mucosal-associated lymphoid tissue lymphoma and presented with gastric mucosal congestion and edema, widened wrinkles, mixed color fading, and redness. The initial pathological diagnosis of this patient was mucosal-associated lymphoid tissue lymphoma, and breast cancer was finally confirmed by immunohistochemistry. Hormonal receptors were highly expressed in four patients with primary and metastasis lesions and were negative in one patient. Human epidermal growth factor receptor 2 was negative in all patients. Mammaglobin and GATA3 were positive in all patients. In conclusion, the gastric metastasis of breast cancer incidence rate is low, and misdiagnosis can lead to insufficient or excessive treatment. Multiple biopsies and immunohistochemistry should be performed to diagnose gastric metastasis of breast cancer.}, } @article {pmid38478781, year = {2023}, author = {VanHoose, L and Eigsti, H}, title = {The Changing Landscape of Intercultural Mindset in 616 Doctor of Physical Therapy Students Over the Past 7 Years and the Implications for Doctor of Physical Therapy Cultural Competence Education.}, journal = {Journal, physical therapy education}, volume = {37}, number = {4}, pages = {271-277}, doi = {10.1097/JTE.0000000000000303}, pmid = {38478781}, issn = {1938-3533}, mesh = {Humans ; Cultural Competency/education ; Longitudinal Studies ; Prospective Studies ; *Mentoring ; *Students, Nursing ; }, abstract = {INTRODUCTION: This prospective longitudinal study will report the results of a quantitative analysis of the change in Intercultural Development Inventory (IDI) scores and the distribution of students in 5 orientations along the Intercultural Developmental Continuum (IDC) in 8 cohorts of Doctor of Physical Therapy (DPT) students during their academic preparation.

REVIEW OF LITERATURE: The expanding interest in developing intercultural sensitivity in an increasingly more complex and diverse health care environment calls for the dissemination of research on the effectiveness of innovative curricular models that include psychometrically strong outcome measures. Research suggests that health care providers can develop intercultural sensitivity when provided with didactic knowledge, experiential learning, self-reflection, mentoring, and a systematic individualized development plan.

SUBJECTS: The participants were from a sample of convenience of 616 DPT students from the graduating classes of 2015-2022.

METHODS: The study is a repeated-measure design. The IDI was selected to guide targeted intervention and assessment of intercultural sensitivity at an individual level and group level and was administered in semesters 3 and 8 as part of the DPT program course requirements.

RESULTS: There was significant improvement in the IDI Perceived and Developmental Orientation (DO; P < .001) scores between semesters 3 and 8. There was a significant change (P = .0001) in the distribution of students along the 5 DOs of the IDC with 10% of students regressing 1 orientation, 51.7% of students remaining the same, 33.3% of students advancing 1 orientation, and 5% of students advancing 2 orientations along the IDC. Nearly 40% of participants had a positive shift along the IDC.

DISCUSSION AND CONCLUSION: The results of this study suggest that intercultural sensitivity or mindset, as measured by the IDI, can be developed in DPT students who participate in a targeted intercultural development curriculum based on the Process Model of Cultural Competence by Deardorff and the Developmental Model of Intercultural Sensitivity by Bennett.}, } @article {pmid38476685, year = {2024}, author = {Kohlhase, DR and O'Rourke, JA and Graham, MA}, title = {GmGLU1 and GmRR4 contribute to iron deficiency tolerance in soybean.}, journal = {Frontiers in plant science}, volume = {15}, number = {}, pages = {1295952}, pmid = {38476685}, issn = {1664-462X}, abstract = {Iron deficiency chlorosis (IDC) is a form of abiotic stress that negatively impacts soybean yield. In a previous study, we demonstrated that the historical IDC quantitative trait locus (QTL) on soybean chromosome Gm03 was composed of four distinct linkage blocks, each containing candidate genes for IDC tolerance. Here, we take advantage of virus-induced gene silencing (VIGS) to validate the function of three high-priority candidate genes, each corresponding to a different linkage block in the Gm03 IDC QTL. We built three single-gene constructs to target GmGLU1 (GLUTAMATE SYNTHASE 1, Glyma.03G128300), GmRR4 (RESPONSE REGULATOR 4, Glyma.03G130000), and GmbHLH38 (beta Helix Loop Helix 38, Glyma.03G130400 and Glyma.03G130600). Given the polygenic nature of the iron stress tolerance trait, we also silenced the genes in combination. We built two constructs targeting GmRR4+GmGLU1 and GmbHLH38+GmGLU1. All constructs were tested on the iron-efficient soybean genotype Clark grown in iron-sufficient conditions. We observed significant decreases in soil plant analysis development (SPAD) measurements using the GmGLU1 construct and both double constructs, with potential additive effects in the GmRR4+GmGLU1 construct. Whole genome expression analyses (RNA-seq) revealed a wide range of affected processes including known iron stress responses, defense and hormone signaling, photosynthesis, and cell wall structure. These findings highlight the importance of GmGLU1 in soybean iron stress responses and provide evidence that IDC is truly a polygenic trait, with multiple genes within the QTL contributing to IDC tolerance. Finally, we conducted BLAST analyses to demonstrate that the Gm03 IDC QTL is syntenic across a broad range of plant species.}, } @article {pmid38471320, year = {2024}, author = {Niu, Q and Li, H and Du, L and Wang, R and Lin, J and Chen, A and Jia, C and Jin, L and Li, F}, title = {Development of a Multi-Parametric ultrasonography nomogram for prediction of invasiveness in ductal carcinoma in situ.}, journal = {European journal of radiology}, volume = {175}, number = {}, pages = {111415}, doi = {10.1016/j.ejrad.2024.111415}, pmid = {38471320}, issn = {1872-7727}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/diagnostic imaging/pathology ; *Nomograms ; *Neoplasm Invasiveness/diagnostic imaging ; *Ultrasonography, Mammary/methods ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology ; Aged ; *Elasticity Imaging Techniques/methods ; Adult ; Prospective Studies ; Contrast Media ; Risk Factors ; Predictive Value of Tests ; Sensitivity and Specificity ; Risk Assessment ; }, abstract = {OBJECTIVE: To investigate the independent risk variables associated with the potential invasiveness of ductal carcinoma in situ (DCIS) on multi-parametric ultrasonography, and further construct a nomogram for risk assessment.

METHODS: Consecutive patients from January 2017 to December 2022 who were suspected of having ductal carcinoma in situ (DCIS) based on magnetic resonance imaging or mammography were prospectively enrolled. Histopathological findings after surgical resection served as the gold standard. Grayscale ultrasound, Doppler ultrasound, shear wave elastography (SWE), and contrast-enhanced ultrasound (CEUS) examinations were preoperative performed. Binary logistic regression was used for multifactorial analysis to identify independent risk factors from multi-parametric ultrasonography. The correlation between independent risk factors and pathological prognostic markers was analyzed. The predictive efficacy of DCIS associated with invasiveness was assessed by logistic analysis, and a nomogram was established.

RESULTS: A total of 250 DCIS lesions were enrolled from 249 patients, comprising 85 pure DCIS and 165 DCIS with invasion (DCIS-IDC), of which 41 exhibited micro-invasion. The multivariate analysis identified independent risk factors for DCIS with invasion on multi-parametric ultrasonography, including image size (>2cm), Doppler ultrasound RI (≥0.72), SWE's Emax (≥66.4 kPa), hyper-enhancement, centripetal enhancement, increased surrounding vessel, and no contrast agent retention on CEUS. These factors correlated with histological grade, Ki-67, and human epidermal growth factor receptor 2 (HER2) (P < 0.1). The multi-parametric ultrasound approach demonstrated good predictive performance (sensitivity 89.7 %, specificity 73.8 %, AUC 0.903), surpassing single US modality or combinations with SWE or CEUS modalities. Utilizing these factors, a predictive nomogram achieved a respectable performance (AUC of 0.889) for predicting DCIS with invasion. Additionally, a separate nomogram for predicting DCIS with micro-invasion, incorporating independent risk factors such as RI (≥0.72), SWE's Emax (≥65.2 kPa), and centripetal enhancement, demonstrated an AUC of 0.867.

CONCLUSION: Multi-parametric ultrasonography demonstrates good discriminatory ability in predicting both DCIS with invasion and micro-invasion through the analysis of lesion morphology, stiffness, neovascular architecture, and perfusion. The use of a nomogram based on ultrasonographic images offers an intuitive and effective method for assessing the risk of invasion in DCIS. Although the nomogram is not currently considered a clinically applicable diagnostic tool due to its AUC being below the threshold of 0.9, further research and development are anticipated to yield positive outcomes and enhance its viability for clinical utilization.}, } @article {pmid38469751, year = {2024}, author = {Abazari, R and Sanati, S and Stelmachowski, P and Wang, Q and Krawczuk, A and Goscianska, J and Liu, M}, title = {Water-Stable Pillared Three-Dimensional Zn-V Bimetal-Organic Framework for Promoted Electrocatalytic Urea Oxidation.}, journal = {Inorganic chemistry}, volume = {63}, number = {12}, pages = {5642-5651}, doi = {10.1021/acs.inorgchem.4c00053}, pmid = {38469751}, issn = {1520-510X}, abstract = {Urea oxidation reaction (UOR) is one of the potential routes in which urea-rich wastewater is used as a source of energy for hydrogen production. Metal-organic frameworks (MOFs) have promising applications in electrocatalytic processes, although there are still challenges in identifying the MOFs' molecular regulation and obtaining practical catalytic systems. The current study sought to synthesize [Zn6(IDC)4(OH)2(Hprz)2]n (Zn-MOF) with three symmetrically independent Zn(II) cations connected via linear N-donor piperazine (Hprz), rigid planar imidazole-4,5-dicarboxylate (IDC[3-]), and -OH ligands, revealing the 3,4T1 topology. The optimized noble-metal-free Zn0.33V0.66-MOF/NF electrocatalysts show higher robustness and performance compared to those of the parent Zn monometallic MOF/NF electrode and other bimetallic MOFs with different Zn-V molar ratios. The low potential of 1.42 V (vs RHE) at 50 mA cm[-2] in 1.0 M KOH with 0.33 M urea required by the developed Zn0.33V0.66-MOF electrode makes its application in the UOR more feasible. The availability of more exposed active sites, ion diffusion path, and higher conductivity result from the distinctive configuration of the synthesized electrocatalyst, which is highly stable and capable of synergistic effects, consequently enhancing the desired reaction. The current research contributes to introducing a practical, cost-effective, and sustainable solution to decompose urea-rich wastewater and produce hydrogen.}, } @article {pmid38468604, year = {2024}, author = {Cappiello, A and Abate, F and Adamo, S and Tepedino, MF and Donisi, L and Ricciardi, C and Avallone, AR and Caterino, M and Cuoco, S and Pellecchia, MT and Amboni, M and Barone, P and Erro, R and Picillo, M}, title = {Direct Current Stimulation of Prefrontal Cortex Is Not Effective in Progressive Supranuclear Palsy: A Randomized Trial.}, journal = {Movement disorders : official journal of the Movement Disorder Society}, volume = {39}, number = {6}, pages = {1043-1048}, doi = {10.1002/mds.29774}, pmid = {38468604}, issn = {1531-8257}, mesh = {Humans ; *Supranuclear Palsy, Progressive/therapy/physiopathology ; Male ; Female ; *Transcranial Direct Current Stimulation/methods ; Aged ; Middle Aged ; Double-Blind Method ; *Prefrontal Cortex/physiopathology ; Treatment Outcome ; Dorsolateral Prefrontal Cortex/physiology ; }, abstract = {BACKGROUND: Progressive supranuclear palsy (PSP) is a rare 4R-tauopathy. Transcranial direct current stimulation (tDCS) may improve specific symptoms.

OBJECTIVES: This randomized, double-blinded, sham-controlled trial aimed at verifying the short-, mid-, and long-term effect of multiple sessions of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) cortex in PSP.

METHODS: Twenty-five patients were randomly assigned to active or sham stimulation (2 mA for 20 minute) for 5 days/week for 2 weeks. Participants underwent assessments at baseline, after the 2-week stimulation protocol, then after 45 days and 3 months from baseline. Primary outcomes were verbal and semantic fluency. The efficacy was verified with analysis of covariance.

RESULTS: We failed to detect a significant effect of active stimulation on primary outcomes. Stimulation was associated to worsening of specific behavioral complaints.

CONCLUSIONS: A 2-week protocol of anodal left DLPFC tDCS is not effective in PSP. Specific challenges in running symptomatic clinical trials with classic design are highlighted. © 2024 International Parkinson and Movement Disorder Society.}, } @article {pmid38466719, year = {2024}, author = {Njee, RM and Imeda, CP and Ali, SM and Mushi, AK and Mbata, DD and Kapala, AW and Makundi, EA and Nyigo, VA and Majura, AM and Akyoo, WO and Mbatia, YJ and Baraka, GT and Msovela, JM and Ngadaya, ES and Senkoro, MF and Malebo, HM}, title = {Menstrual health and hygiene knowledge among post menarche adolescent school girls in urban and rural Tanzania.}, journal = {PloS one}, volume = {19}, number = {3}, pages = {e0284072}, pmid = {38466719}, issn = {1932-6203}, mesh = {Adolescent ; Humans ; Female ; Child ; *Menstruation ; *Menarche ; Hygiene ; Cross-Sectional Studies ; Tanzania ; Health Knowledge, Attitudes, Practice ; }, abstract = {Adolescent girls' capacity to lead healthy lives and perform well in school has been hampered by their lack of awareness about menstruation and the requirements for its hygienic management. Lack of enabling infrastructure, improper menstrual supplies, and limited socioeconomic support for good menstrual health and cleanliness are characteristics of schools in Africa South of the Sahara. We evaluated school-age girls' knowledge of menstrual hygiene and identified bottlenecks that could affect policy and programming for menstrual health and hygiene. A school-based cross-sectional study involved 8,012 adolescent school girls in the age group of 11-18 years (mean age = 14.9 years). The study evaluated students' knowledge of menstrual health and hygiene (MHH) from the viewpoints of schools and communities using a combination of qualitative and quantitative approaches. Data was collected using self-administered surveys, focus group discussions, in-depth interviews, and site observations. Girls' older age (AOR = 1.62, P 0.001), having a female guardian (AOR = 1.39: P = 001), and having a parent in a formal job (AOR = 1.03: P 0.023) were positively associated with Menstrual health and Hygiene Knowledge. MHH knowledge levels varied significantly between girls attending government (53.3) and non-government schools (50.5%, P = 0.0001), although they were comparable for girls attending rural and urban schools. Only 21% of the study's schools had at least one instructor who had received training in MHH instruction for students. We have established that the majority of adolescent girls in schools have inadequate knowledge on menstrual health and hygiene, and that school teachers lack the skills to prepare and support young adolescents as they transition into puberty. Concerted actions aimed at building supportive policy are paramount, for school-aged teenagers to learn about and reap the long-term advantages of good menstrual health practices.}, } @article {pmid38461375, year = {2024}, author = {Turhan, Ş and Sultan, DAO and Altuner, EM and Kurnaz, A and Bakır, TK and Altamemi, RAA}, title = {Determination of radon concentrations and physicochemical parameters of non-alcoholic carbonated beverages consumed in Türkiye and assessment of radiological health risk.}, journal = {International journal of environmental health research}, volume = {34}, number = {11}, pages = {3836-3846}, doi = {10.1080/09603123.2024.2327530}, pmid = {38461375}, issn = {1369-1619}, mesh = {*Radon/analysis ; Humans ; *Carbonated Beverages/analysis ; Risk Assessment ; Turkey ; }, abstract = {The strategy for controlling the existence of radionuclides in drinking water depends upon an individual dose criterion (IDC) of 0.1 mSv/y, which represents a very low level of risk that is not expected to cause any identified adverse health effects. Radon gas, considered a carcinogenic radionuclide, can dissolve and accumulate in drinking water. Non-alcoholic carbonated beverages (NACBs), which mainly contain drinking water, phosphoric acid, citric acid, caffeine, and sugar, represent one of the most consumed groups worldwide and in Türkiye. In this study, the radon activity concentration and some physicochemical characteristics of 45 NACB samples from 24 most preferred commercial brands in Türkiye were determined to assess the radiological health risk associated with the ingestion of these samples. Radon activity concentrations measured in NACB samples using the AlphaGUARD radon analyzer ranged from 22.8 ± 0.7 to 54.9 ± 1.7 mBq/L. The pH, conductivity, total dissolved solids, and brix values in NACB samples ranged from 2.31 to 7.29, 401 to 3281 μSv/cm, 355 to 2453 mg/L, and 0.10 to 12.95%, respectively. Total (ingestion and inhalation) annual effective doses and the corresponding excess lifetime cancer risks estimated for adults to assess the radiological health risk are significantly below the IDC and advised safety limit (10[-3]), respectively.}, } @article {pmid38455655, year = {2024}, author = {Lorza-Gil, E and Ekim, B and Sancar, G}, title = {Editorial: Organ crosstalk in the pathophysiology and treatment of type-2 diabetes.}, journal = {Frontiers in endocrinology}, volume = {15}, number = {}, pages = {1379994}, pmid = {38455655}, issn = {1664-2392}, mesh = {Humans ; *Diabetes Mellitus, Type 2/therapy ; *Extracellular Vesicles ; }, } @article {pmid38451627, year = {2024}, author = {Saeed, U and Uppal, R and Khan, AA and Uppal, MR and Piracha, ZZ and Uppal, SR}, title = {Analytical assessment of clinical sensitivity and specificities of pharmaceutical rapid SARS-CoV-2 detection nasopharyngeal swab testing kits in Pakistan.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {84}, number = {}, pages = {e265550}, doi = {10.1590/1519-6984.265550}, pmid = {38451627}, issn = {1678-4375}, mesh = {Humans ; *COVID-19/diagnosis ; Cross-Sectional Studies ; Nasopharynx/virology ; Pakistan ; Pandemics ; *SARS-CoV-2/genetics ; *Reagent Kits, Diagnostic ; Sensitivity and Specificity ; }, abstract = {Despite of the global unity against COVID-19 pandemic, the threat of SARS-CoV-2 variants on the lives of human being is still not over. SARS-CoV-2 pandemic has urged the need of rapid viral detection at earliest. To cope with gradually expanding scenario of SARS-CoV-2, accurate diagnosis is extremely crucial factor which should be noticed by international health organizations. Limited research followed by sporadic marketing of SARS-CoV-2 rapid pharmaceutical detection kits raises critical questions against quality assurance and quality control measures. Herein we aimed to interrogate effectivity and specificity analysis of SARS-CoV-2 pharmaceutical rapid detection kits (nasopharyngeal swab based) using conventional gold standard triple target real-time polymerase chain reaction (USFDA approved). A cross-sectional study was conducted over 1500 suspected SARS-CoV-2 patients. 100 real time-PCR confirmed patients were evaluated for pharmaceutical RDT kits based upon nasopharyngeal swab based kits. The SARS-CoV-2 nasopharyngeal swab based rapid diagnostic kit (NSP RDTs) analysis showed 78% reactivity. Among real time PCR confirmed negative subjects, 49.3% represented false positivity. The positive predictive analysis revealed 67.82%, while negative predictive values were 64.40%. The NSP RDTs showed limited sensitivities and specificities as compared to gold standard real time PCR. Valid and authentic detection of SARS-CoV-2 is deemed necessary for accurate COVID-19 surveillance across the globe. Current study highlights the potential consequences of inadequate detection of SARS-CoV-2 and emerging novel mutants, compromising vaccine preventable diseases. Current study emphasizes need to wake higher authorities including strategic organizations for designing adequate measures to prevent future SARS-CoV-2 epidemics.}, } @article {pmid38449417, year = {2024}, author = {Yao, S and Goi, T and Takahashi, M and Kono, H and Yokoi, S and Maeda, H}, title = {[A Case Report of Metastatic Breast Cancer with Peritoneal Metastasis and Massive Ascites Responding to CDK4/6 Inhibitor(Palbociclib)].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {2}, pages = {214-216}, pmid = {38449417}, issn = {0385-0684}, mesh = {Female ; Humans ; Middle Aged ; Ascites ; *Breast Neoplasms/drug therapy ; *Peritoneal Neoplasms/drug therapy ; *Ovarian Neoplasms ; Cyclin-Dependent Kinase 4 ; *Piperazines ; *Pyridines ; }, abstract = {A 52-year-old woman was presented with abdominal distension. Chest-abdominal CT showed some tumors in the left breast, enlarged axillary lymph nodes, ovary metastasis peritoneal thickening, a large amount of ascites. The diagnosis of needle biopsy in the breast mass was invasive ductal carcinoma, Luminal A type. The large amount of ascites decreased after the start of administration of fulvestrant and CDK4/6 inhibitor(PAL). Also chest and abdominal CT showed reduction of all lesions. We found the high expression of cyclin D1 protein and the negative of p16 protein in tissues of the needle biopsy. Fifty months later, she continues to do good ADL and PR status. We experienced a case of metastatic breast cancer with massive ascites and peritoneal metastasis that was successfully treated with a CDK4/6 inhibitor(PAL)and achieved long- term survival.}, } @article {pmid38446859, year = {2024}, author = {Gaeta Gazzola, M and Carmichael, ID and Thompson, E and Beitel, M and Madden, LM and Saeed, G and Hoffman, K and Hammouri, M and Hsaio, C and Barry, DT}, title = {A Quantitative Examination of Illness Models Among People With Opioid Use Disorder Receiving Methadone Treatment.}, journal = {Journal of addiction medicine}, volume = {18}, number = {3}, pages = {262-268}, pmid = {38446859}, issn = {1935-3227}, mesh = {Humans ; *Methadone/therapeutic use ; Female ; *Opioid-Related Disorders/drug therapy/rehabilitation ; Male ; Adult ; *Opiate Substitution Treatment ; Middle Aged ; Analgesics, Opioid/therapeutic use ; Models, Psychological ; }, abstract = {BACKGROUND: Few studies have examined illness models among people with addiction. We investigated illness models and their associations with demographics and treatment beliefs among patients receiving methadone treatment for opioid use disorder.

METHODS: From January 2019 to February 2020, patients receiving methadone treatment at outpatient opioid treatment programs provided demographics and rated using 1 to 7 Likert-type scales agreement with addiction illness models (brain disease model, chronic medical condition model [CMCM], and no explanation [NEM]) and treatment beliefs. Pairwise comparisons and multivariate regressions were used to examine associations between illness models, demographics, and treatment beliefs. Statistical significance was set at P < 0.05.

RESULTS: A total of 450 patients participated in the study. Forty percent self-identified as female, 13% as Hispanic, and 78% as White; mean age was 38.5 years. Brain disease model was the most frequently endorsed illness model (46.2%), followed by CMCM (41.7%) and NEM (21.9%). In multivariate analyses, agreement with brain disease model was significantly positively associated with beliefs that methadone treatment would be effective, counseling is important, and methadone is lifesaving, whereas agreement with CMCM was significantly positively associated with beliefs that methadone treatment would be effective, counseling is important, 12-step is the best treatment, taking methadone daily is important, and methadone is lifesaving. In multivariate analyses, agreement with NEM was negatively significantly associated with beliefs that methadone would be effective, counseling is important, taking methadone daily is important, and methadone is lifesaving.

DISCUSSION: Many patients in methadone treatment endorsed medicalized addiction models. Agreement with addiction illness models appear to be related to treatment beliefs.}, } @article {pmid38439896, year = {2024}, author = {Hu, J and Shen, Y and Zhang, K and Chen, Y}, title = {Germline RECQL gene mutations in Chinese patients with breast cancer.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1366769}, pmid = {38439896}, issn = {2296-858X}, abstract = {INTRODUCTION: Breast cancer is the most common malignant tumor in women, seriously threatening health and survival. TP-dependent DNA helicase Q1 (RECQL) is a breast cancer susceptibility gene with possible familial links. However, RECQL gene mutations among Chinese women with breast cancer have not been evaluated. Therefore, this study assessed RECQL mutations and their relationships with clinicopathological and epidemiological characteristics in Chinese women with breast cancer.

METHOD: Clinical information was also obtained via the hospital information system and a follow-up questionnaire. Peripheral venous blood (2 mL) was extracted from all patients and stored at -80°C for future use; the early venous blood samples were from our hospital's sample bank. RECQL gene sequencing were performed by the Shanghai Aishe Gene Company (China).

RESULTS: We found that a RECQL mutation is a susceptibility factor for breast cancer. Moreover, patients with RECQL mutations were more likely to have a family history of breast cancer than those without. Also, patients with RECQL variants of uncertain significance (VUS) were less likely to develop invasive ductal carcinoma than those without. In addition, unexplained RECQL mutations occurred more often in patients with human epidermal growth factor receptor 2+ breast cancer than in those with other subtypes.

DISCUSSION: These results provide a basis for creating screening criteria specific to Chinese women. However, the frequency of RECQL mutations was low, and the number of pathogenic mutations was too small and could not be analyzed. Thus, more extensive, long-term studies that include other functional experiments are needed to verify these results.}, } @article {pmid38438841, year = {2024}, author = {Molière, S and Lodi, M and Leblanc, S and Gressel, A and Mathelin, C and Alpy, F and Chenard, MP and Tomasetto, C}, title = {MMP-11 expression in early luminal breast cancer: associations with clinical, MRI, pathological characteristics, and disease-free survival.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {295}, pmid = {38438841}, issn = {1471-2407}, support = {ANR-10-IDEX-0002//IdEx Unistra/ ; ANR-10-IDEX-0002//IdEx Unistra/ ; ANR-10-IDEX-0002//IdEx Unistra/ ; ANR-17-EURE-0023//EUR IMCBio/ ; ANR-17-EURE-0023//EUR IMCBio/ ; ANR-17-EURE-0023//EUR IMCBio/ ; Ligue Contre le Cancer//Ligue Contre le Cancer/ ; Ligue Contre le Cancer//Ligue Contre le Cancer/ ; Ligue Contre le Cancer//Ligue Contre le Cancer/ ; SEVE (Sein et Vie)//SEVE (Sein et Vie)/ ; SEVE (Sein et Vie)//SEVE (Sein et Vie)/ ; SEVE (Sein et Vie)//SEVE (Sein et Vie)/ ; Alsace Contre le Cancer//Alsace Contre le Cancer/ ; Alsace Contre le Cancer//Alsace Contre le Cancer/ ; Alsace Contre le Cancer//Alsace Contre le Cancer/ ; }, mesh = {Humans ; Female ; Disease-Free Survival ; *Breast Neoplasms/diagnostic imaging ; Ki-67 Antigen ; Matrix Metalloproteinase 11 ; Retrospective Studies ; Magnetic Resonance Imaging ; Hormones ; }, abstract = {BACKGROUND: Early hormone-positive breast cancers typically have favorable outcomes, yet long-term surveillance is crucial due to the risk of late recurrences. While many studies associate MMP-11 expression with poor prognosis in breast cancer, few focus on early-stage cases. This study explores MMP-11 as an early prognostic marker in hormone-positive breast cancers.

METHODS: In this retrospective study, 228 women with early hormone-positive invasive ductal carcinoma, treated surgically between 2011 and 2016, were included. MMP-11 expression was measured by immunohistochemistry, and its association with clinical and MRI data was analyzed.

RESULTS: Among the patients (aged 31-89, median 60, with average tumor size of 15.7 mm), MMP-11 staining was observed in half of the cases. This positivity correlated with higher uPA levels and tumor grade but not with nodal status or size. Furthermore, MMP-11 positivity showed specific associations with MRI features. Over a follow-up period of 6.5 years, only 12 oncological events occurred. Disease-free survival was linked to Ki67 and MMP-11.

CONCLUSION: MMP-11, primarily present in tumor-surrounding stromal cells, correlates with tumor grade and uPA levels. MMP-11 immunohistochemical score demonstrates a suggestive trend in association with disease-free survival, independent of Ki67 and other traditional prognostic factors. This highlights the potential of MMP-11 as a valuable marker in managing early hormone-positive breast cancer.}, } @article {pmid38438204, year = {2024}, author = {Omer, AA and Bin Dayel, SA and Hummedi, AS and Almuhaimed, NI}, title = {The epidemiological and clinicopathological features of breast cancer in Riyadh, Saudi Arabia.}, journal = {Saudi medical journal}, volume = {45}, number = {3}, pages = {288-294}, pmid = {38438204}, issn = {1658-3175}, mesh = {Humans ; Middle Aged ; Female ; *Breast Neoplasms/epidemiology/therapy ; Saudi Arabia/epidemiology ; Mastectomy ; Biopsy ; Family ; }, abstract = {OBJECTIVES: To investigate the epidemiological and clinicopathological features of breast cancer (BC) in Saudi Arabia to improve decisions regarding resource allocation, disease control, and management.

METHODS: We retrieved the records of all patients who presented with histologically proven BC at King Fahad Medical City between 2019 and 2020. The data were analyzed quantitatively, and the results were expressed as percentages and frequencies.

RESULTS: This study comprised 419 patients. The mean age was 50.13 (± 10.96) years. The majority of the patients were obese (56.6%), and approximately a quarter had a history of oral contraceptive pill use, breast biopsy, or an affected family member. Most cases were from the central region (80.1%), followed by the southern provinces (12.7%). Breast lumps were the most common complaint (89%), whereas hypertension and diabetes mellitus were the most common comorbidities. Invasive ductal carcinoma was the most common pathologic type (89.7%). Most patients presented with TNM stages II and III (55.2%), and 27.7% had metastasis. The main therapeutic modalities included radical mastectomy (63.8%), neoadjuvant chemotherapy (60.4%), and adjuvant radiotherapy (82.9%).

CONCLUSION: In Saudi Arabia, a trend of BC incidence migration towards older patients may be ensuing. However, prediction of an advanced and aggressive presentation requires the enhancement of screening programs and standardized protocols for disease management.}, } @article {pmid38437141, year = {2024}, author = {Hall, G and Liang, W and Bhujwalla, ZM and Li, X}, title = {SHG Fiberscopy Assessment of Collagen Morphology and Its Potential for Breast Cancer Optical Histology.}, journal = {IEEE transactions on bio-medical engineering}, volume = {71}, number = {8}, pages = {2414-2420}, pmid = {38437141}, issn = {1558-2531}, support = {R01 CA082337/CA/NCI NIH HHS/United States ; R01 CA153023/CA/NCI NIH HHS/United States ; R35 CA209960/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Breast Neoplasms/diagnostic imaging/pathology ; Female ; *Collagen/chemistry ; Second Harmonic Generation Microscopy/methods ; Retrospective Studies ; Pilot Projects ; Equipment Design ; }, abstract = {OBJECTIVE: This study is to investigate the feasibility of our recently developed nonlinear fiberscope for label-free in situ breast tumor detection and lymph node status assessment based on second harmonic generation (SHG) imaging of fibrillar collagen matrix with histological details. The long-term goal is to improve the current biopsy-based cancer paradigm with reduced sampling errors.

METHODS: In this pilot study we undertook retrospective SHG imaging study of ex vivo invasive ductal carcinoma human biopsy tissue samples, and carried out quantitative image analysis to search for collagen structural signatures that are associated with the malignance of breast cancer.

RESULTS: SHG fiberscopy image-based quantitative assessment of collagen fiber morphology reveals that: 1) cancerous tissues contain generally less extracellular collagen fibers compared with tumor-adjacent normal tissues, and 2) collagen fibers in lymph node positive biopsies are more aligned than lymph node negative counterparts.

CONCLUSION/SIGNIFICANCE: The results demonstrate the promising potential of our SHG fiberscope for in situ breast tumor detection and lymph node involvement assessment and for offering real-time guidance during ongoing tissue biopsy.}, } @article {pmid38433052, year = {2024}, author = {Sun, Q and Sun, JJ and Wang, M and Zhang, L and Zhang, XW and Wei, JG and Kong, LF and Li, J}, title = {[Intraductal carcinomas of the salivary glands: a clinicopathological and molecular genetic analysis of twenty-seven cases].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {53}, number = {3}, pages = {250-256}, doi = {10.3760/cma.j.cn112151-20230808-00056}, pmid = {38433052}, issn = {0529-5807}, support = {YBKB202106//Establishment of a Biobank for Head and Neck Cancer Based on Heterogeneity of Invasion and Metastasis of Shanghai Ninth People's Hospital/ ; }, mesh = {Female ; Male ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; *Carcinoma, Intraductal, Noninfiltrating ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen ; Retrospective Studies ; China ; Salivary Glands ; Molecular Biology ; }, abstract = {Objective: To investigate the clinicopathological features, molecular genetic features, and differential diagnosis of intraductal carcinomas (IDC) of the salivary glands. Methods: Twenty-five cases of salivary gland IDC diagnosed at the Department of Oral Pathology, Shanghai Ninth People's Hospital and two cases from Department of Pathology, Henan Provincial People's Hospital, Zhengzhou, China from January 2008 to July 2023 were collected. Their clinical and pathological features were analyzed retrospectively. Fluorescence in situ hybridization and Sanger sequencing were performed. The patients were followed up and related literatures were reviewed. Results: There were 27 patients with IDC, including 15 males and 12 females, ranging in age from 20.0 to 80.0 years (mean 55.9 years). Clinically, the tumor often presented as a painless mass with a tumor diameter of 1.0-3.0 cm (mean 2.0 cm). All patients received surgical treatment. Twenty patients were followed up. One of them (1/20) died of lung cancer, while the rest survived without tumor recurrence. Histologically, IDC were classified as: intercalated (63.0%, 17/27), apocrine (25.9%, 7/27), oncocytic (7.4%, 2/27) and mixed (3.7%, 1/27) types. Intercalated tumors showed positive S-100 and negative androgen receptor (AR) immunoreactivity. Ki-67 proliferation index was low (about 1%-5%). Nine cases had the RET gene disruption, and 2 cases showed the BRAF V600E mutation. Apocrine tumors showed strong AR immunoreactivity but no S-100 immunoreactivity. Ki-67 proliferation index was high (about 10%-60%), and the RET gene rupture was detected in 1 case. Oncocytic tumors were similar to that of intercalated type in 2 cases, and RET gene disruption was detected in the both cases. Mixed tumors showed histologic features of oncocytic and apocrine patterns and harbored the RET gene disruption. Conclusions: IDC is a rare low-grade malignant tumor of the salivary gland and easily confused with other salivary gland tumors with similar morphology. Molecular testing is helpful for its differential diagnosis.}, } @article {pmid38432595, year = {2024}, author = {Chuang, ML}, title = {Analyzing key elements of breathing patterns, deriving remaining variables, and identifying cutoff values in individuals with chronic respiratory disease and healthy subjects.}, journal = {Respiratory physiology & neurobiology}, volume = {324}, number = {}, pages = {104242}, doi = {10.1016/j.resp.2024.104242}, pmid = {38432595}, issn = {1878-1519}, mesh = {Humans ; Healthy Volunteers ; Respiration ; Exhalation ; *Respiration Disorders ; *Pulmonary Disease, Chronic Obstructive ; *Lung Diseases, Interstitial ; }, abstract = {BACKGROUND: Pulmonary physiology encompasses intricate breathing patterns (BPs), characterized by breathing frequency (Bf), volumes, and flows. The complexities intensify in the presence of interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD), especially during exercise. This study seeks to identify pivotal factors driving changes among these variables and establish cutoff values, comparing their efficacy in differentiating BPs to traditional methods, specifically a breathing reserve (BR) of 30% and a Bf of 50 bpm.

METHODS: Screening 267 subjects revealed 23 with ILD, 126 with COPD, 33 healthy individuals, and the exclusion of 85 subjects. Lung function tests and ramp-pattern cardiopulmonary exercise testing (CPET) were conducted, identifying crucial BP elements. Changes were compared between groups at peak exercise. The area under the receiver operating characteristic curve (AUC) analysis determined cutoff values.

RESULTS: Inspiratory time (TI) remained constant at peak exercise for all subjects (two-group comparisons, all p=NS). Given known differences in expiratory time (TE) and tidal volume (VT) among ILD, COPD, and healthy states, constant TI could infer patterns for Bf, total breathing cycle time (TTOT=60/Bf), I:E ratio, inspiratory duty cycle (IDC, TI/TTOT), rapid shallow breathing index (Bf/VT), tidal inspiratory and expiratory flows (VT/TI and VT/TE), and minute ventilation (V̇E=Bf×VT) across conditions. These inferences aligned with measurements, with potential type II errors causing inconsistencies. RSBI of 23 bpm/L and VT/TI of 104 L/min may differentiate ILD from control, while V̇E of 54 L/min, BR of 30%, and VT/TE of 108 may differentiate COPD from control. BR of 21%, TE of 0.99 s, and IDC of .45 may differentiate ILD from COPD. The algorithm outperformed traditional methods (AUC 0.84-0.91 versus 0.59-0.90).

CONCLUSION: The quasi-fixed TI, in conjunction with TE and VT, proves effective in inferring time-related variables of BPs. The findings have the potential to significantly enhance medical education in interpreting cardiopulmonary exercise testing. Moreover, the study introduces a novel algorithm for distinguishing BPs among individuals with ILD, COPD, and those who are healthy.}, } @article {pmid38432310, year = {2024}, author = {Gimeno-Morales, M and Martínez-Monge, R and Martinez-Lage, A and Jablonska, PA and Blanco, J and Martínez-Regueira, F and Rodriguez-Spiteri, N and Olartecoechea, B and Ramos, L and Insausti, LP and Elizalde, A and Abengozar, M and Cambeiro, M}, title = {Long-term results of intraoperative multicatheter breast implant (IOMBI) for accelerated partial breast irradiation (APBI) on early breast cancer patients.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {194}, number = {}, pages = {110193}, doi = {10.1016/j.radonc.2024.110193}, pmid = {38432310}, issn = {1879-0887}, mesh = {Humans ; Female ; *Breast Neoplasms/radiotherapy/surgery/pathology ; Middle Aged ; *Brachytherapy/methods/instrumentation/adverse effects ; Aged ; Adult ; Breast Implants ; Mastectomy, Segmental ; Radiotherapy Dosage ; Treatment Outcome ; }, abstract = {BACKGROUND AND PURPOSE: Multicatheter breast brachytherapy is a standard technique for accelerated partial breast irradiation (APBI) in early breast cancer patients. Intraoperative multicatheter breast implant (IOMBI) followed by perioperative high-dose-rate brachytherapy (PHDRBT) offers a novel and advantageous approach. We present long-term oncological, toxicity, and cosmesis outcomes for a well-experienced single institution.

MATERIALS AND METHODS: Eligible women aged ≥ 40 years with clinically and radiologically confirmed unifocal invasive or in situ ≤ 3 cm breast tumors underwent IOMBI during breast-conserving surgery. Patients meeting APBI criteria by definitive pathologic results received 3.4 Gy × 10fx with PHDRBT. Patients not suitable for APBI received PHDRBT-boost followed by WBRT.

RESULTS: A total of 171 patients underwent IOMBI during BCS, 120 patients (70.1 %) were suitable for APBI and 51 (29.8 %) for anticipated PHDRBT-boost. The median age was 61 years (range: 40-78), the median tumor size was 1.1 cm (range: 0.2-3.5), with a histological diagnosis of invasive ductal carcinoma in 78.9 % and ductal in situ in 21.1 %. A median of 9 catheters (range: 4-14) were used. For APBI, the median CTV and V100 were 40.8 cc (range: 8.6-99) and 35.4 cc (range: 7.2-94). The median of healthy breast tissue irradiated represents 7.2 % (range: 2.3-28 %) and the median local treatment duration was 10 days (range: 7-16). With a median follow-up of 8.8 years (range: 0.3-16.25), the 8-year local, locoregional, and distant control rates were 99 %, 98.1 %, and 100 %. G1-G2 late-toxicity rate was 53.4 %. Long-term cosmetic evaluation was excellent-good in 90.8 %.

CONCLUSION: IOMBI&PHDRBT program reports excellent long-term oncological outcomes, with a reduction from unnecessary irradiation exposure which translates into low long-term toxicity and good cosmesis outcomes, especially on well-selected APBI patients.}, } @article {pmid38419665, year = {2024}, author = {Liao, YC and Yang, CJ and Yu, HY and Huang, CJ and Hong, TY and Li, WC and Chen, LF and Hsieh, JC}, title = {Inner sense of rhythm: percussionist brain activity during rhythmic encoding and synchronization.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1342326}, pmid = {38419665}, issn = {1662-4548}, abstract = {INTRODUCTION: The main objective of this research is to explore the core cognitive mechanisms utilized by exceptionally skilled percussionists as they navigate complex rhythms. Our specific focus is on understanding the dynamic interactions among brain regions, respectively, related to externally directed cognition (EDC), internally directed cognition (IDC), and rhythm processing, defined as the neural correlates of rhythm processing (NCRP).

METHODS: The research involved 26 participants each in the percussionist group (PG) and control group (CG), who underwent task-functional magnetic resonance imaging (fMRI) sessions focusing on rhythm encoding and synchronization. Comparative analyses were performed between the two groups under each of these conditions.

RESULTS: Rhythmic encoding showed decreased activity in EDC areas, specifically in the right calcarine cortex, left middle occipital gyrus, right fusiform gyrus, and left inferior parietal lobule, along with reduced NCRP activity in the left dorsal premotor, right sensorimotor cortex, and left superior parietal lobule. During rhythmic synchronization, there was increased activity in IDC areas, particularly in the default mode network, and in NCRP areas including the left inferior frontal gyrus and bilateral putamen. Conversely, EDC areas like the right dorsolateral prefrontal gyrus, right superior temporal gyrus, right middle occipital gyrus, and bilateral inferior parietal lobule showed decreased activity, as did NCRP areas including the bilateral dorsal premotor cortex, bilateral ventral insula, bilateral inferior frontal gyrus, and left superior parietal lobule.

DISCUSSION: PG's rhythm encoding is characterized by reduced cognitive effort compared to CG, as evidenced by decreased activity in brain regions associated with EDC and the NCRP. Rhythmic synchronization reveals up-regulated IDC, down-regulated EDC involvement, and dynamic interplay among regions with the NCRP, suggesting that PG engages in both automatic and spontaneous processing simultaneously. These findings provide valuable insights into expert performance and present opportunities for improving music education.}, } @article {pmid38419320, year = {2024}, author = {Toshima, K and Shien, T and Nishimura, MF and Suzuki, Y and Nakamoto, S and Uno, M and Yoshioka, R and Tsukioki, T and Takahashi, Y and Iwamoto, T and Iwatani, T and Yanai, H}, title = {Ectopic Breast Cancer Arising within an Axillary Lymph Node.}, journal = {Acta medica Okayama}, volume = {78}, number = {1}, pages = {89-93}, doi = {10.18926/AMO/66676}, pmid = {38419320}, issn = {0386-300X}, mesh = {Female ; Humans ; Aged ; *Breast Neoplasms/pathology ; Mastectomy ; Lymph Nodes/pathology ; Breast ; Lymph Node Excision ; *Choristoma/surgery/pathology ; }, abstract = {We report our experience with the diagnosis and treatment of an ectopic breast cancer arising within an axillary lymph node. The patient was a 65-year-old woman diagnosed breast cancer and axillary lymph node metastasis. We performed a partial mastectomy and axillary lymph node dissection. Postoperative pathology revealed no malignant lesions in the breast; however, a nodule in one of axillary lymph nodes had mixed benign and malignant components, leading to a diagnosis of invasive ductal carcinoma derived from ectopic mammary tissue. This case represents a very rare form of breast cancer, and the malignancy was difficult to distinguish from metastasis.}, } @article {pmid38417222, year = {2024}, author = {Hu, J and Chen, X and Sun, F and Liu, L and Liu, L and Yang, Z and Zhang, H and Yu, Z and Zhao, R and Wang, Y and Liu, H and Yang, X and Sun, F and Han, B}, title = {Identification of recurrent BRAF non-V600 mutations in intraductal carcinoma of the prostate in Chinese populations.}, journal = {Neoplasia (New York, N.Y.)}, volume = {50}, number = {}, pages = {100983}, pmid = {38417222}, issn = {1476-5586}, mesh = {Humans ; Male ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; China ; Mutation ; Prostate/pathology ; *Prostatic Neoplasms/genetics/pathology ; *Proto-Oncogene Proteins B-raf/genetics ; }, abstract = {While BRAF alterations have been established as a driver in various solid malignancies, the characterization of BRAF alterations in prostate cancer (PCa) has not been thoroughly interrogated. By bioinformatics analysis, we first found that BRAF alterations were associated with advanced PCa and exhibited mutually exclusive pattern with ERG alteration across multiple cohorts. Of the most interest, recurrent non-V600 BRAF mutations were found in 3 of 21 (14.3 %) PCa patients demonstrating IDC-P morphology. Furthermore, experimental overexpression of BRAF[K601E] and BRAF[L597R] exhibited emergence of oncogenic phenotypes with intensified MAPK signaling in vitro, which could be targeted by MEK inhibitors. Comparison of the incidence of BRAF alterations in IDC-P between western and Chinese ancestry revealed an increased prevalence in the Chinese population. The BRAF mutation may represent important genetic alteration in a subset of IDC-P, highlighting the role of MAPK signaling pathway in this subtype of PCa. To the best of knowledge, this is the first description of non-V600 BRAF mutation in setting of IDC-P, which may in part explain the aggressive phenotype seen in IDC-P and could also bring more treatment options for PCa patients with IDC-P harboring such mutations.}, } @article {pmid38416903, year = {2023}, author = {Miceli, R and Mercado, CL and Hernandez, O and Chhor, C}, title = {Active Surveillance for Atypical Ductal Hyperplasia and Ductal Carcinoma In Situ.}, journal = {Journal of breast imaging}, volume = {5}, number = {4}, pages = {396-415}, doi = {10.1093/jbi/wbad026}, pmid = {38416903}, issn = {2631-6129}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/diagnosis ; Watchful Waiting ; Artificial Intelligence ; *Breast Neoplasms/diagnosis ; Mammography ; Early Detection of Cancer ; }, abstract = {Atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) are relatively common breast lesions on the same spectrum of disease. Atypical ductal hyperblasia is a nonmalignant, high-risk lesion, and DCIS is a noninvasive malignancy. While a benefit of screening mammography is early cancer detection, it also leads to increased biopsy diagnosis of noninvasive lesions. Previously, treatment guidelines for both entities included surgical excision because of the risk of upgrade to invasive cancer after surgery and risk of progression to invasive cancer for DCIS. However, this universal management approach is not optimal for all patients because most lesions are not upgraded after surgery. Furthermore, some DCIS lesions do not progress to clinically significant invasive cancer. Overtreatment of high-risk lesions and DCIS is considered a burden on patients and clinicians and is a strain on the health care system. Extensive research has identified many potential histologic, clinical, and imaging factors that may predict ADH and DCIS upgrade and thereby help clinicians select which patients should undergo surgery and which may be appropriate for active surveillance (AS) with imaging. Additionally, multiple clinical trials are currently underway to evaluate whether AS for DCIS is feasible for a select group of patients. Recent advances in MRI, artificial intelligence, and molecular markers may also have an important role to play in stratifying patients and delineating best management guidelines. This review article discusses the available evidence regarding the feasibility and limitations of AS for ADH and DCIS, as well as recent advances in patient risk stratification.}, } @article {pmid38416170, year = {2024}, author = {Maggi, G and Loayza, F and Vitale, C and Santangelo, G and Obeso, I}, title = {Anatomical correlates of apathy and impulsivity co-occurrence in early Parkinson's disease.}, journal = {Journal of neurology}, volume = {271}, number = {5}, pages = {2798-2809}, pmid = {38416170}, issn = {1432-1459}, mesh = {Humans ; *Parkinson Disease/complications/pathology/diagnostic imaging/physiopathology ; *Apathy/physiology ; Male ; Female ; Middle Aged ; Aged ; *Magnetic Resonance Imaging ; *Gray Matter/diagnostic imaging/pathology ; *Disruptive, Impulse Control, and Conduct Disorders/etiology/physiopathology/diagnostic imaging/pathology ; Longitudinal Studies ; Impulsive Behavior/physiology ; }, abstract = {BACKGROUND: Although apathy and impulse control disorders (ICDs) are considered to represent opposite extremes of a continuum of motivated behavior (i.e., hypo- and hyperdopaminergic behaviors), they may also co-occur in Parkinson's disease (PD).

OBJECTIVES: We aimed to explore the co-occurrence of ICDs and apathy and its neural correlates analyzing gray matter (GM) changes in early untreated PD patients. Moreover, we aimed to investigate the possible longitudinal relationship between ICDs and apathy and their putative impact on cognition during the first five years of PD.

METHODS: We used the Parkinson's Progression Markers Initiative (PPMI) database to identify the co-occurrence of apathy and ICDs in 423 early drug-naïve PD patients at baseline and at 5-year follow-up. Baseline MRI volumes and gray matter changes were analyzed between groups using voxel-based morphometry. Multi-level models assessed the longitudinal relationship (across five years) between apathy and ICDs and cognitive functioning.

RESULTS: At baseline, co-occurrence of apathy and ICDs was observed in 23 patients (5.4%). This finding was related to anatomical GM reduction along the cortical regions involved in the limbic circuit and cognitive control systems. Longitudinal analyses indicated that apathy and ICDs were related to each other as well as to the combined use of levodopa and dopamine agonists. Worse apathetic and ICDs states were associated with poorer executive functions.

CONCLUSIONS: Apathy and ICDs are joint non-exclusive neuropsychiatric disorders also in the early stages of PD and their co-occurrence was associated with GM decrease in several cortical regions of the limbic circuit and cognitive control systems.}, } @article {pmid38414161, year = {2024}, author = {Geppert, J and Rohm, M}, title = {Cancer cachexia: biomarkers and the influence of age.}, journal = {Molecular oncology}, volume = {18}, number = {9}, pages = {2070-2086}, pmid = {38414161}, issn = {1878-0261}, support = {//Helmholtz-Gemeinschaft/ ; 949017//European Commission/ ; }, mesh = {*Cachexia/metabolism/diagnosis ; Humans ; *Neoplasms/complications/metabolism ; *Aging/metabolism ; Animals ; Biomarkers/metabolism ; Biomarkers, Tumor/metabolism ; Inflammation/metabolism ; }, abstract = {Cancer cachexia (Ccx) is a complex metabolic condition characterized by pronounced muscle and fat wasting, systemic inflammation, weakness and fatigue. Up to 30% of cancer patients succumb directly to Ccx, yet therapies that effectively address this perturbed metabolic state are rare. In recent decades, several characteristics of Ccx have been established in mice and humans, of which we here highlight adipose tissue dysfunction, muscle wasting and systemic inflammation, as they are directly linked to biomarker discovery. To counteract cachexia pathogenesis as early as possible and mitigate its detrimental impact on anti-cancer treatments, identification and validation of clinically endorsed biomarkers assume paramount importance. Ageing was recently shown to affect both the validity of Ccx biomarkers and Ccx development, but the underlying mechanisms are still unknown. Thus, unravelling the intricate interplay between ageing and Ccx can help to counteract Ccx pathogenesis and tailor diagnostic and treatment strategies to individual needs.}, } @article {pmid38410339, year = {2024}, author = {Al Husban, H and Al Rabadi, A and Odeh, AH and Abu Rumman, K and Alkhawaldeh, F and Noures, H and Abo Ashoor, M and Abu Rumman, A and Atmeh, M and Bawaneh, M}, title = {Clinical Characteristics and Management of Triple-Negative Breast Cancer (TNBC) in Jordan: A Retrospective Analysis.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e53053}, pmid = {38410339}, issn = {2168-8184}, abstract = {Introduction Triple-negative breast cancer (TNBC) is known for its aggressive nature and poor prognosis. Despite its responsiveness to chemotherapy, TNBC presents challenges in terms of survival, recurrence, and mortality rates, particularly in diverse populations. Limited research in the Middle East hampers comprehensive understanding and tailored management. Methods A retrospective study at the King Hussein Medical Center in Jordan between the period 2009 to 2023 explored TNBC patients (n=110) who underwent adjuvant chemotherapy after local excision or modified radical mastectomy (MRM). Data encompassed demographics, clinical variables, and operative details. Statistical analysis employed Wilcoxon and chi-squared tests, examining mortality risks and associations between variables. Results Among 110 TNBC patients (mean age 52), 84% underwent MRM, 16% wide local excision and axillary clearance (WLE&AC). Lymphovascular invasion (LVI) was observed in 41%, linked to higher lymph node positivity. Neoadjuvant therapy preceded MRM in 25% of cases. While 75% had grade III tumors, the prevalence of invasive ductal carcinoma was 85%. Conclusions This study contributes crucial insights into TNBC characteristics and management in Jordan. Despite limitations such as retrospective design and sample size, the findings underscore the need for tailored interventions in TNBC patients, emphasizing the importance of neoadjuvant therapy and vigilant consideration of LVI status in treatment planning. Future longitudinal research should delve into disease progression and treatment outcomes in diverse populations, facilitating optimized TNBC management strategies.}, } @article {pmid38410238, year = {2024}, author = {Chen, Y and Xu, Z and Chen, Y and Dai, Y and Ding, J}, title = {Comparison of the prognosis of medullary breast carcinoma and invasive ductal carcinoma: a SEER-based study.}, journal = {Translational cancer research}, volume = {13}, number = {1}, pages = {231-248}, pmid = {38410238}, issn = {2219-6803}, abstract = {BACKGROUND: Medullary breast carcinoma (MBC) is a rare type of breast cancer. Our study aimed to compare the differences in clinical characteristics and prognosis between MBC and invasive ductal carcinoma (IDC), and to further develop and validate nomograms to predict overall survival (OS) and cancer-specific survival (CSS) in MBC patients.

METHODS: A total of 179,613 patients from the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2015, including 596 MBC patients, were analyzed using the Kaplan-Meier method and propensity score matching (PSM) to compare patients' OS and CSS. Cox proportional hazard regression model was used to determine independent prognostic factors for OS and CSS in MBC patients. Nomograms were constructed based on Cox regression analysis whereas receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the predictive accuracy.

RESULTS: There were significant differences in the clinical characteristics between MBC and IDC. According to the logrank test, MBC had better OS and CSS than IDC before and after PSM. Cox multivariate analysis showed that age, race, tumor size, lymph node (LN), and radiation therapy were independent prognostic factors for OS, whereas age, tumor size, American Joint Committee on Cancer (AJCC) stage, laterality, type of surgery, and chemotherapy were independent prognostic factors for CSS. Nomograms of OS and CSS were constructed based on independent prognostic factors.

CONCLUSIONS: MBC had better OS and CSS than IDC. Nomograms based on clinicopathological features were sufficiently accurate in predicting the OS and CSS for MBC patients, which can effectively predict the survival risk of MBC patients and guide clinicians to provide more effective treatment measures.}, } @article {pmid38409747, year = {2024}, author = {Ruan, GJ and Zanwar, S and Ravindran, A and Schram, S and Abeykoon, JP and Hazim, A and Young, JR and Shah, MV and Bennani, NN and Jiang, L and Morlote, D and Rech, KL and Goyal, G and Go, RS and , }, title = {Clinical characteristics, molecular aberrations, treatments, and outcomes of malignant histiocytosis.}, journal = {American journal of hematology}, volume = {99}, number = {5}, pages = {871-879}, pmid = {38409747}, issn = {1096-8652}, support = {K12 CA090628/CA/NCI NIH HHS/United States ; P50 CA097274/CA/NCI NIH HHS/United States ; R01 CA262613/CA/NCI NIH HHS/United States ; R21 CA097422/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; *Histiocytic Sarcoma/genetics/therapy/pathology ; Macrophages/pathology ; Bone Marrow/pathology ; Prognosis ; Liver/pathology ; }, abstract = {Malignant histiocytosis (MH) is an extremely rare neoplasm of the macrophage-dendritic cell lineage. We report the clinical characteristics, molecular aberrations, treatments, and outcomes of patients with MH seen at two referral centers from January 2000 to May 2023. We identified 43 patients with MH, of which 26 had histiocytic sarcoma (MH-H), 9 interdigitating dendritic cell sarcoma (MH-IDC), and 8 Langerhans cell sarcoma (MH-LC). The median age at diagnosis was 61 years (range, 3-83). Thirty-three patients (77%) had multifocal disease, while 10 had unifocal involvement. Tumor specimens from 22 patients (51%) underwent targeted next generation sequencing, and 19 of 22 (86%) had at least one pathogenic mutation, including mutations in MAPK pathway genes (73%). The median overall survival (OS) among the entire cohort was 16 months (95% CI: 8-50). The outcomes of those with multifocal disease were significantly shorter than their unifocal counterpart: median OS of 10 months versus 50 months (p = .07). Patients with risk organ involvement (bone marrow, spleen, or liver) had significantly inferior outcomes. Chemotherapy and surgery were the most common first-line treatments for multifocal and unifocal disease, respectively. While the outcome for patients with multifocal disease was poor, there was a subset of patients who had durable responses to treatment. Our study highlights that MH has heterogeneous clinical presentation, frequent oncogenic mutations, and prognosis, which is strongly tied to disease extent and type of organ involvement.}, } @article {pmid38409268, year = {2024}, author = {Alkhafaji, S and Wolf, DM and Magbanua, MJM and J van 't Veer, L and Park, JW and Esserman, L and Mukhtar, RA}, title = {Circulating tumor cells in early lobular versus ductal breast cancer and their associations with prognosis.}, journal = {NPJ breast cancer}, volume = {10}, number = {1}, pages = {17}, pmid = {38409268}, issn = {2374-4677}, support = {K08 CA256047/CA/NCI NIH HHS/United States ; }, abstract = {This is a secondary data analysis of the TIPPING study, which included 1,121 patients with stage I-III breast cancer who had enumeration of CTCs (by either CellSearch or immunomagnetic enrichment and flow cytometry [IE/FC]) and disseminated tumor cells (DTCs) at the time of surgical resection between 1999 and 2012. The primary endpoint was mean number of CTCs by histology, taking into account method of detection and treatment type, and evaluation of histology specific prognostic cutpoints. Overall, patients with ILC had significantly higher CTC counts than those with IDC, a finding which persisted in the 382 patients with CTC enumeration by IE/FC method. Additionally, among those with primary surgery, patients with ILC had significantly higher mean CTC counts than those with IDC (mean 2.11 CTCs/mL versus 0.71 CTCs/mL respectively, p < 0.001), which persisted on multivariate analysis. Patients with ILC and CTC-high/DTC-high status trended towards reduced DRFS HR = 9.27, 95% CI 0.95-90.5, p = 0.055) and had significantly decreased BCSS (HR = 10.4, 95% CI 1.07-99.7, P = 0.043) compared with those who were CTC-low/DTC-low. In the IDC group, CTC-high/DTC-high status was not associated with either DRFS or BCSS. In neoadjvuantly treated patients, there was no significant difference in CTC counts in the ILC group versus the IDC group (mean 0.89 CTCs/mL versus 1.06 CTCs/mL respectively, p = 0.82). Our findings contribute to the limited literature on CTCs and DTCs in ILC, and suggest that clinical utility and optimal thresholds for CTC and DTC assays may differ by histologic subtype in early-stage breast cancer.}, } @article {pmid38406950, year = {2023}, author = {Asad, S and Khan, SA and Khan, FA and Jalal-Ud-Din, M and Bhatti, G and Kamran, H}, title = {Pattern Of Breast Cancer: Experience At Ayub Teaching Hospital, Abbottabad.}, journal = {Journal of Ayub Medical College, Abbottabad : JAMC}, volume = {35}, number = {4}, pages = {629-632}, doi = {10.55519/JAMC-04-12089}, pmid = {38406950}, issn = {1819-2718}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Lymph Nodes/pathology ; Hospitals, Teaching ; Biopsy ; Axilla/pathology ; }, abstract = {BACKGROUND: Breast cancer is the most common malignancy found in females all over the world and the second leading cause of cancer death in European countries. The purpose of this study was to find out the pattern of disease presentation in our region where a proper tumour registry system is lacking.

METHODS: This descriptive study was carried out in the Department of Surgery, Ayub Teaching Hospital Abbottabad, from July 2021 to June 2022. All female patients with biopsy-proven breast cancer were included in the study: benign lumps, refused to enrol, and those who were lost to follow-up were excluded.

RESULTS: A total of 87 patients with carcinoma breast were included: 92 % (n=80) had invasive ductal carcinoma. Axillary lymph nodes were involved in 88.5% (n=77), 75.8% of the tumours, (n=66), were Grade 2, 34.5% (n=30) were in the 40-49 years age group, and 30 % (n=27) of the disease was categorized as Stage III or IV. In 55 % (n=48), the tumour was on the right side and in 39% (n=34), the upper outer quadrant was involved. Most of the patients, 90.8% (n=79), were married and had used contraceptive measures. Only 19.5% of patients (n=17), had a history of nipple discharge and 56% (n=49) had a positive family history: 71% (n=62) had nipple retraction, and 54% (n=47), proved to be ER PR positive.

CONCLUSIONS: Our patients presented late: axilla was commonly involved and a third had advanced disease. Screening and community awareness programs may help in early detection. Hormone use for contraception needs to be weighed carefully. Better data collection may help in designing screening and care programs.}, } @article {pmid38406898, year = {2023}, author = {, and Haider, G and Shaikh, Z and Memon, P and Shahid, A and Rahul, R and Kumar, P and Beg, S and Parkash, J}, title = {Significance of ca15-3 in carcinoma of the breast with Visceral metastases.}, journal = {Journal of Ayub Medical College, Abbottabad : JAMC}, volume = {35(Suppl 1)}, number = {4}, pages = {S710-S714}, doi = {10.55519/JAMC-S4-7329}, pmid = {38406898}, issn = {1819-2718}, mesh = {Female ; Humans ; Middle Aged ; Cross-Sectional Studies ; Mucin-1 ; Biomarkers, Tumor ; *Breast Neoplasms/diagnosis ; *Carcinoma ; Prognosis ; }, abstract = {BACKGROUND: The most common malignancy and second most common cause of death is breast cancer among women. About 2.09 million fatalities from breast cancer happened in 2018. The objective was to evaluate the elevated CA15-3 in breast cancer patients with visceral metastases presenting at the tertiary care hospital of Karachi.

METHODS: It was a cross-sectional study conducted at the Department of Oncology of Jinnah Postgraduate Medical Center from 15th December 2018 to 15th November 2019. Female patients aged 26-80 years diagnosed with visceral metastatic (defined as metastasis to lung, liver, brain and adrenal glands) breast cancer were included in the study. The diagnosis of breast cancer was confirmed on histopathology whereas the metastatic sites were evaluated using physical examination and imaging. The serum CA15-3 concentration was assessed using assay kits. The serum CA15-3 level of 0-32 U/ml was taken as normal range for all the patients whereas CA15-3 level greater than 32 U/L was considered as elevated CA15-3. SPSS version 23 was used to enter and analyze data.

RESULTS: A total of 139 females were included in the study. The mean age & BMI of the patients were reported as 46.5 years & 26.69 kg/m2. In the majority of the patients' metastases were detected in the liver (n=54), 92 in the lungs+ parenchymal disease, 20 in adrenal glands, 12 in pleural effusion and 10 in the brain. Out of 139 patients with visceral metastases, 52(37.4%) had normal CA15-3 level whereas 87 (62.6%) had elevated serum CA15-3 levels (>32 U/L).

CONCLUSION: The serum CA15-3 tumour marker is elevated significantly in visceral metastases and can be used as a prognostic marker in metastatic breast cancer patients.}, } @article {pmid38406616, year = {2023}, author = {Netea, PDMG}, title = {I. IDC Key-note Lecture: Trained immunity: a memory for innate host defense.}, journal = {Journal of stem cells & regenerative medicine}, volume = {19}, number = {2}, pages = {37-39}, pmid = {38406616}, issn = {0973-7154}, } @article {pmid38406064, year = {2024}, author = {Udquim, KT and Lam, NB and Altshuler, E and Lin, RY}, title = {Primary Invasive Ductal Carcinoma of the Breast Occurring in a Patient With a History of Hepatocellular Carcinoma Developing From Focal Nodular Hyperplasia: A Case Report and Literature Review.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e52818}, pmid = {38406064}, issn = {2168-8184}, abstract = {The risk of developing another primary malignancy after an initial liver cancer diagnosis is rare, and the management of multiple primary cancers is not typically discussed. Focal nodular hyperplasia (FNH) is considered a benign tumor, but there have been cases reported that describe hepatocellular carcinoma (HCC) arising from or within FNH. Here, we report a woman in her 70s who had a longstanding history of FNH, later found to be HCC upon resection, who also developed invasive ductal carcinoma. She had no family history of cancer and no genetic testing results were available. Each of her cancers was managed independently, hepatectomy for HCC and neoadjuvant therapy followed by mastectomy for her breast carcinoma. This case demonstrates that the diagnosis of FNH based on radiographic imaging may necessitate a biopsy to confirm diagnosis for a symptomatic patient or those with lesions suspicious for malignancy. It also showcases the importance of close follow-up after a primary cancer diagnosis for the possibility of another primary malignancy emerging. Fresh tissue biopsy for new lesions could help determine primary malignancy or metastasis. Genetic sequencing may help identify driver mutations or genetic alterations that can be targeted.}, } @article {pmid38405107, year = {2024}, author = {Bhimani, F and Lin, S and McEvoy, M and Cavalli, A and Obaid, L and Chen, Y and Gupta, A and Pastoriza, J and Shihabi, A and Feldman, S}, title = {Does Nipple-Ward Positive Margin Contribute to a Higher Rate of Re-Excision Procedures After a Lumpectomy with Pathology-Confirmed Positive Margins? A Retrospective Study.}, journal = {Breast cancer (Dove Medical Press)}, volume = {16}, number = {}, pages = {41-50}, pmid = {38405107}, issn = {1179-1314}, abstract = {BACKGROUND: Positive margins on lumpectomy specimens are associated with a twofold increased risk of local breast tumor recurrence. Prior literature has demonstrated various techniques and modalities for assessing margin status to reduce re-excision rates. However, there is paucity of literature analyzing which margin contributes to the highest re-excision rates. Therefore, the primary aim of the study was to investigate whether the nipple-ward margins resulted in a higher rate of re-excision in our patient population.

METHODS:  A retrospective chart review was performed on patients who had re-excision surgery. Nipple-ward margin was identified by correlating radiological and pathological reports. A cut-off of more than 25% was used to demonstrate correlation between nipple-ward margin and re-excision rate.

RESULTS: A total of 98 patients' data were analyzed, with 41 (41.8%), 14 (14.3%), 5 (5.1%), and 38 (38.8%) diagnosed with DCIS, IDC, ILC, and mixed pathology on their margins, respectively. Overall, 48% (n=47) of the positive margins were nipple-ward, with 44.7% (n=21) reporting DCIS. Upon stratification, 45 (45.9%) cases were single-margin positive, with 26 (57.8%) being nipple-ward. Furthermore, the remaining 53 (54.1%) patients had multiple positive margins, with 21 (39.6.7%) nipple-ward cases.

CONCLUSION: Positive nipple-ward margins significantly contribute to a higher re-excision rate p < 0.001; 48% of re-excision surgeries had positive nipple-ward margins, and 57.8% of positive single-margin cases were nipple-ward. Taking an additional shave during initial lumpectomy decreases re-excision rates. However, planning a lumpectomy procedure with a more elliptical rather than a spherical resection with additional cavity shave (ie, larger volume) in the nipple-ward direction and minimizing the remaining cavity shaves so the total volume resected remains unchanged. Nevertheless, future studies with larger sample sizes are required to bolster our findings.}, } @article {pmid38404556, year = {2024}, author = {Munien, K and Ravichandran, K and Flynn, H and Shugg, N and Flynn, D and Chambers, J and Desai, D}, title = {Catheter-associated meatal pressure injuries (CAMPI) in patients with long-term urethral catheters-a cross-sectional study of 200 patients.}, journal = {Translational andrology and urology}, volume = {13}, number = {1}, pages = {42-52}, pmid = {38404556}, issn = {2223-4691}, abstract = {BACKGROUND: Indwelling urethral catheters (IDC) are ubiquitous to healthcare settings, and are associated with many familiar risks like haematuria, infections, bladder spasms and stones. However, a less known complication is catheter-associated meatal pressure injury (CAMPI), especially in those with long-term IDCs. The objective of this study was to explore the prevalence, associated features and management of CAMPI in adults with a long-term IDC.

METHODS: A cross-sectional multi-centre study was undertaken of 200 adults with a long-term IDC across regional south-west Queensland, Australia between June 2019 to June 2021. The prevalence of CAMPI was determined by clinical examination, voluntary surveys completed by participants and documentation in medical records. Key IDC statistics included total duration of IDC, location of IDC changes, IDC size, type and fixation.

RESULTS: Out of 200 adults with a long-term IDC, 9% (18/200) had a CAMPI. There was a higher prevalence of male CAMPI (17/169, 10%) compared to female CAMPI (1/31, 3%). The median time to identification of a CAMPI after initial IDC insertion was 12 weeks (2-136 weeks), but occurred as soon as 2 weeks. CAMPI formation was associated with IDC changes in the community, impaired mobility and congestive cardiac failure (CCF). CAMPI were mostly treated by conservative means given the frailty of the population.

CONCLUSIONS: Poor mobility, community-managed IDCs, and CCF were all found to have statistically significant associations with the development of CAMPI. CAMPI represents an important and underserved iatrogenic complication within urology practice, and greater awareness is needed to prevent it in vulnerable patients with long-term IDCs.}, } @article {pmid38404027, year = {2024}, author = {Greenblatt-Kimron, L and Palgi, Y and Regev, T and Ben-David, BM}, title = {Associations among loneliness, internal locus of control and subjective accelerated ageing in older adults who received the booster vaccination.}, journal = {BJPsych open}, volume = {10}, number = {2}, pages = {e54}, pmid = {38404027}, issn = {2056-4724}, abstract = {BACKGROUND: A rise in loneliness among older adults since the COVID-19 outbreak, even after vaccination, has been highlighted. Loneliness has deleterious consequences, with specific effects on perceptions of the ageing process during the COVID-19 pandemic. Coping with stressful life events and the challenges of ageing may result in a perception of acceleration of this process.

AIM: Studies have shown a buffering effect of an internal locus of control in the relationship between COVID-19 stress and mental distress. The current study examined whether loneliness predicts subjective accelerated ageing and whether internal locus of control moderates this relationship.

METHOD: Two waves of community-dwelling older adults (M = 70.44, s.d. = 5.95; age range 61-88 years), vaccinated three times, were sampled by a web-survey company. Participants completed the questionnaire after the beginning of the third vaccination campaign and reported again 4 months later on loneliness, internal locus of control and subjective accelerated ageing level in the second wave.

RESULTS: Participants with higher levels of loneliness presented 4 months later with higher subjective accelerated ageing. Participants with a low level of internal locus of control presented 4 months later with high subjective accelerated ageing, regardless of their loneliness level. Participants with a high level of internal locus of control and a low level of loneliness presented with the lowest subjective accelerated ageing 4 months later.

CONCLUSIONS: The findings emphasise the deleterious effects of loneliness and low internal locus of control on older adults' perception of their ageing process. Practitioners should focus their interventions not only on loneliness but also on improving the sense of internal locus of control to improve subjective accelerated ageing.}, } @article {pmid38402816, year = {2024}, author = {Laroiya, I and Tan, M and Kaehne, A and Shetty, G}, title = {A prospective study evaluating patient reported outcome measures in patients who have undergone chest wall perforator flaps.}, journal = {Journal of plastic, reconstructive & aesthetic surgery : JPRAS}, volume = {91}, number = {}, pages = {79-82}, doi = {10.1016/j.bjps.2024.02.044}, pmid = {38402816}, issn = {1878-0539}, mesh = {Humans ; Middle Aged ; *Mammaplasty ; *Perforator Flap/blood supply ; Prospective Studies ; Cohort Studies ; *Thoracic Wall/surgery ; Postoperative Complications/epidemiology/surgery ; Patient Reported Outcome Measures ; }, abstract = {AIMS: To evaluate Patient Reported Outcome Measures (PROMs) and surgical outcomes in patients undergoing Chest Wall Perforator Flaps (CWPFs).

METHODS: This was an observational single cohort study using an audit approach and a survey instrument. 84 patients who had undergone CWPFs in the last 5 years at the Department of Breast Surgery, City Hospital Birmingham, were identified from a pre-existing database. Surgical outcomes were recorded. Patients were contacted telephonically or in person at the time of follow-up and were asked to fill up a PROMs questionnaire.

RESULTS: Out of 84 patients, 58 patients chose to respond. The average age of the patients was 51.3 years (±8.2 years). The average follow-up was 15.4 months (±9.9 months). The most common histological subtype was Infiltrating ductal carcinoma (IDC)-Not otherwise specified 34/58 (58.6%). Majority of the patients had T2 cancers-28/58 (48.3%). 26/58 (44.8%) were node negative. Eight patients (13.7%) had post-operative complications. No patient had total/partial flap loss. Nine patients (15.5%) had margin re-excision. One patient developed distant metastasis while 1 patient developed a second primary. Fifty-one patients (88%) were either satisfied or very satisfied with the post-operative appearance of the breasts. Thirty-six patients (62%) had no/little persistent pain or tenderness post-surgery. Eighty-six per cent (38/44) of the patients undergoing Lateral Intercostal Artery Perforator (LICAP) Flap and 16/18 (89%) of patients undergoing Anterior Intercostal Artery Perforator (AICAP) flap had no/little difficulty in carrying out normal activities at follow up.

CONCLUSION: CWPFs are associated with a low complication rate and a high patient satisfaction rate.}, } @article {pmid38399000, year = {2024}, author = {Khan, MRR}, title = {Development of a Battery-Free, Chipless, and Highly Sensitive Radio Frequency Glucose Biosensor.}, journal = {Micromachines}, volume = {15}, number = {2}, pages = {}, pmid = {38399000}, issn = {2072-666X}, abstract = {In our study, we designed and developed a glucose biosensor that operates without a battery or chip. This biosensor utilizes the principles of radio frequency (RF) to operate. For the construction of a glucose-sensitive interdigitated capacitor (IDC), a famous glucose-sensitive substance called phenylboronic acid (PBA) is combined with a polyvinyl chloride (PVC) and n,n-dimethylacetamide (DMAC) solution. According to the theory of radio frequency sensing, the resonance frequency shifts whenever there is a change in the capacitance of the glucose-sensitive IDC. This change is caused by the fluctuations in glucose concentrations. As far as we are aware, this is the first glucose sensor that employs the RF principle to detect changes in glucose solution concentrations using PBA as the principal glucose-sensitive material. The sensor can detect glucose levels with remarkable sensitivity, around 40.89 kHz/decade, and a broad dynamic range covering 10 μM to 1 M. Additionally, the designed biosensor has excellent linearity performance, with a value of around 0.988. The proposed glucose biosensor has several benefits: lightweight, inexpensive, easy to build, and an acceptable selectivity response. Our study concludes by comparing the proposed RF sensor's effectiveness to that of existing glucose sensors, which it outperforms.}, } @article {pmid38396137, year = {2024}, author = {Matsumoto, T and Tanaka, G and Mori, S and Niki, M and Sato, S and Shiraki, T and Iso, Y and Nagashima, K and Irisawa, A and Nozawa, Y and Takada-Owada, A and Ishida, K and Aoki, T}, title = {A resected case of pancreatic head cancer developing 40 years after lateral pancreaticojejunostomy for chronic pancreatitis.}, journal = {Clinical journal of gastroenterology}, volume = {17}, number = {3}, pages = {537-542}, pmid = {38396137}, issn = {1865-7265}, mesh = {Humans ; Male ; *Pancreaticojejunostomy ; Aged ; *Pancreatic Neoplasms/surgery ; *Pancreatitis, Chronic/surgery/complications/etiology ; Pancreaticoduodenectomy/adverse effects ; Carcinoma, Pancreatic Ductal/surgery ; Postoperative Complications/etiology ; Tomography, X-Ray Computed ; }, abstract = {A 72-year-old male patient presented to our department complaining of with upper abdominal pain and jaundice. He had a history of a side-to-side pancreaticojejunostomy performed 40 years previously for chronic pancreatitis. A diagnostic workup revealed a tumor 3 cm in size in the pancreatic head as the etiology of the jaundice. Subsequently, the patient was diagnosed with resectable pancreatic cancer. Following two cycles of neoadjuvant chemotherapy, an extended pancreatoduodenectomy was performed because of tumor invasion at the previous pancreaticojejunostomy site. Concurrent portal vein resection and reconstruction were performed. Pathological examination confirmed invasive ductal carcinoma (T2N1M0, Stage IIB). This case highlights the clinical challenges in pancreatic head carcinoma following a side-to-side pancreaticojejunostomy. Although pancreaticojejunostomy is believed to reduce the risk of pancreatic cancer in patients with chronic pancreatitis, clinicians should be aware that, even after this surgery, there is still a chance of developing pancreatic cancer during long-term follow-up.}, } @article {pmid38393931, year = {2024}, author = {Yang, XL and Ni, DH and Yu, Y and Zhao, JC and Lin, R and Xiu, C and Chang, ZX}, title = {Value of magnetic resonance imaging radiomics features in predicting histologic grade of invasive ductal carcinoma of the breast.}, journal = {Technology and health care : official journal of the European Society for Engineering and Medicine}, volume = {32}, number = {3}, pages = {1609-1618}, pmid = {38393931}, issn = {1878-7401}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/diagnostic imaging ; Middle Aged ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; *Magnetic Resonance Imaging/methods ; Adult ; Aged ; Neoplasm Grading ; Retrospective Studies ; Contrast Media ; Radiomics ; }, abstract = {BACKGROUND: Breast cancer has the second highest mortality rate of all cancers and occurs mainly in women.

OBJECTIVE: To investigate the relationship between magnetic resonance imaging (MRI) radiomics features and histological grade of invasive ductal carcinoma (IDC) of the breast and to evaluate its diagnostic efficacy.

METHODS: The two conventional MRI quantitative indicators, i.e. the apparent diffusion coefficient (ADC) and the initial enhancement rate, were collected from 112 patients with breast cancer. The breast cancer lesions were manually segmented in dynamic contrast-enhanced MRI (DCE-MRI) and ADC images, the differences in radiomics features between Grades I, II and III IDCs were compared and the diagnostic efficacy was evaluated.

RESULTS: The ADC values (0.77 ± 0.22 vs 0.91 ± 0.22 vs 0.92 ± 0.20, F= 4.204, p< 0.01), as well as the B_sum_variance (188.51 ± 67.803 vs 265.37 ± 77.86 vs 263.74 ± 82.58, F= 6.040, p< 0.01), L_energy (0.03 ± 0.02 vs 0.13 ± 0.11 vs 0.12 ± 0.14, F= 7.118, p< 0.01) and L_sum_average (0.78 ± 0.32 vs 16.34 ± 4.23 vs 015.45 ± 3.74, F= 21.860, p< 0.001) values of patients with Grade III IDC were significantly lower than those of patients with Grades I and II IDC. The B_uniform (0.15 ± 0.12 vs 0.11 ± 0.04 vs 0.12 ± 0.03, F= 3.797, p< 0.01) and L_SRE (0.85 ± 0.07 vs 0.78 ± 0.03 vs 0.79 ± 0.32, F= 3.024, p< 0.01) values of patients with Grade III IDC were significantly higher than those of patients with Grades I and II IDC. All differences were statistically significant (p< 0.05). The ADC radiomics signature model had a higher area-under-the-curve value in identifying different grades of IDC than the ADC value model and the DCE radiomics signature model (0.869 vs 0.711 vs 0.682). The accuracy (0.812 vs 0.647 vs 0.710), specificity (0.731 vs 0.435 vs 0.342), positive predictive value (0.815 vs 0.663 vs 0.669) and negative predictive value (0.753 vs 0.570 vs 0.718) of the ADC radiomics signature model were all significantly better than the ADC value model and the DCE radiomics signature model.

CONCLUSION: ADC values and breast MRI radiomics signatures are significant in identifying the histological grades of IDC, with the ADC radiomics signatures having greater value.}, } @article {pmid38388422, year = {2024}, author = {Gan, J and Liu, M and Liu, F and Wen, J and Fu, W and Jia, J}, title = {Synchronous double primary small cell lung cancer and invasive ductal breast carcinoma: a case report.}, journal = {BMC pulmonary medicine}, volume = {24}, number = {1}, pages = {93}, pmid = {38388422}, issn = {1471-2466}, mesh = {Aged ; Female ; Humans ; *Breast Neoplasms/therapy/pathology ; Chemotherapy, Adjuvant ; Ki-67 Antigen ; *Lung Neoplasms ; *Small Cell Lung Carcinoma/diagnostic imaging ; *Neoplasms, Multiple Primary/diagnosis ; *Carcinoma, Ductal, Breast ; }, abstract = {BACKGROUND: Although lung and breast cancers are common malignancies, the occurrence of primary synchronous neoplasms involving these organs has been rarely reported in literature.

CASE PRESENTATION: A 75-year-old female patient presented at a local hospital with a ten-day history of dizziness and slurred speech. A CT contrast-enhanced scan revealed a 4.2 cm mass in the lower lobe of the right lung and a 3.8 cm space-occupying lesion in the right breast. Subsequent breast ultrasound identified a hypoechoic lesion measuring5.41 × 4.75 × 3.06 cm in the right breast, and an ultrasound-guided biopsy confirmed the presence of infiltrating ductal carcinoma of the right breast. The immunohistochemistry analysis of the breast mass revealed positive staining for ER, PR, HER-2, AR and Ki67 in the tumor cells, while negative staining was observed for P63, Calponin, CK5/6 and CK14. MR imaging of the head detected abnormal signals in the right frontal lobe (3.6 cm×2.9 cm in size), left cerebellar hemisphere, and punctate enhancement in the left temporal lobe, indicating potential metastasis. Pathological examination of a lung biopsy specimen confirmed the presence of small cell lung cancer (SCLC). Furthermore, immunohistochemistry analysis of the lung lesions demonstrated positive staining for TTF-1, CK-Pan, Syn, CgA, CD56, P53 (90%) and Ki67 (70%), and negative staining for NapsinA and P40 in the tumor cells. The patient's diagnosis of SCLC with stage cT2bN0M1c IVB and brain metastases (BM), as well as invasive ductal breast carcinoma (IDC), was confirmed based on the aforementioned results. Whereupon we proposed a treatment plan consisting of whole-brain radiation (40 Gy/20fractions), focal radiotherapy (60 Gy/20fractions), and adjuvant concurrent chemotherapy with oral etoposide (50 mg on days 1 to 20).

CONCLUSIONS: To the best of our knowledge, the present case is the first of its kind to describe the synchronous double cancer, consisting of primary SCLC and IDC.}, } @article {pmid38380465, year = {2024}, author = {Anichkina, KA and Pasternak, AV and Arslanov, KS and Kvetenadze, GE and Shivilov, EV and Klimashevich, AV}, title = {[Domestic system for fluorescent diagnostics in breast cancer: pros and cons].}, journal = {Khirurgiia}, volume = {}, number = {2. Vyp. 2}, pages = {55-60}, doi = {10.17116/hirurgia202402255}, pmid = {38380465}, issn = {0023-1207}, mesh = {Humans ; Middle Aged ; Female ; *Breast Neoplasms/surgery ; Sentinel Lymph Node Biopsy ; Lymph Nodes/pathology ; Indocyanine Green ; Coloring Agents ; }, abstract = {OBJECTIVE: To analyze the effectiveness of identifying the sentinel lymph node in breast cancer using the «MARS» system for fluorescent diagnostics in near infrared light.

MATERIAL AND METHODS: There were 51 patients with breast cancer cT0-2N0M0 between July 2023 and October 2023. Mean age of patients was 52.3 years. Invasive ductal carcinoma was diagnosed in 39 (76.5%) patients, invasive lobular carcinoma - in 8 (15.7%) patients, other forms of breast cancer - in 4 (7.8%) patients.

RESULTS: Sentinel lymph node was successfully identified in all cases (n=51). A total of 122 sentinel lymph nodes were detected and mapped (2.4 nodes per a patient).

CONCLUSION: The MARS system for intraoperative fluorescence diagnostics in near-infrared light is effective for identifying the sentinel lymph node in breast cancer.}, } @article {pmid38379333, year = {2024}, author = {Zhu, S and Xu, N and Zeng, H}, title = {Molecular complexity of intraductal carcinoma of the prostate.}, journal = {Cancer medicine}, volume = {13}, number = {2}, pages = {e6939}, pmid = {38379333}, issn = {2045-7634}, support = {NSFC 82203110//National Natural Science Foundation of China/ ; 82172785//National Natural Science Foundation of China/ ; 81974398//National Natural Science Foundation of China/ ; 2022-I2M-C&T-B-098//Clinical and Translational Medicine Research Project, Chinese Academy of Medical Sciences/ ; 2021YFS0119//Science and Technology Support Program of Sichuan Province/ ; X-J-2020-016//Bethune Foundation, Oncology Basic Research Program/ ; ZYJC21020//West China Hospital, Sichuan University/ ; ZYGD22004//West China Hospital, Sichuan University/ ; mnzl202002//Bethune Foundation, Urological Oncology Special Research Fund/ ; mnzl202007//Bethune Foundation, Urological Oncology Special Research Fund/ ; }, mesh = {Male ; Humans ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Prostate/pathology ; *Prostatic Neoplasms/diagnosis/genetics/therapy ; Prognosis ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is an aggressive subtype of prostate cancer characterized by the growth of tumor cells within the prostate ducts. It is often found alongside invasive carcinoma and is associated with poor prognosis. Understanding the molecular mechanisms driving IDC-P is crucial for improved diagnosis, prognosis, and treatment strategies. This review summarizes the molecular characteristics of IDC-P and their prognostic indications, comparing them to conventional prostate acinar adenocarcinoma, to gain insights into its unique behavior and identify potential therapeutic targets.}, } @article {pmid38379091, year = {2024}, author = {Bufman, H and Faermann, R and Halshtok-Neiman, O and Shalmon, A and Gotlieb, M and Samoocha, D and Yagil, Y and Feldman, DM and Friedman, E and Sklair-Levy, M}, title = {Breast cancer diagnosed after age 70 years in Israeli BRCA1/BRCA2 pathogenic sequence variant carriers: a single institution experience.}, journal = {Breast cancer research and treatment}, volume = {205}, number = {2}, pages = {281-285}, pmid = {38379091}, issn = {1573-7217}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/diagnosis/epidemiology ; Aged ; Israel/epidemiology ; Aged, 80 and over ; *BRCA1 Protein/genetics ; *BRCA2 Protein/genetics ; Heterozygote ; Genetic Predisposition to Disease ; Early Detection of Cancer/methods ; Mutation ; }, abstract = {PURPOSE: A semi-annual surveillance scheme from age 25 to 30 years is offered to BRCA1/BRCA2 pathogenic sequence variants (PSVs) carriers for early detection of breast cancer (BC). There is a paucity of data on the yield of adhering to this scheme beyond 70 years of age.

METHODS: Female BRCA1/BRCA2 PSV carriers followed at the Meirav high-risk clinic, Sheba Medical center, Israel were eligible. Type and frequencies if use of Imaging modalities, breast biopsies and histological outcomes for participants after age 70 years were retrieved and analyzed.

RESULTS: Overall, the study encompassed 88 consenting participants (46 BRCA1 carriers) mean age ± SD 73.7 ± 3.3 years (range 70-90 years), followed for an average of 3.8 years (range 1-11 years). Ten carriers (11.3%) were diagnosed with BC after age 70 years (mean age at diagnosis 72 ± 2 years) and an additional case was diagnosed with breast lymphoma. The imaging modality that has led to most diagnoses was MRI (8/11 cases). Eight of these ten cases were previously diagnosed with BC prior to age 70 and in six, BC past 70 years was in the contralateral breast. The lesions size averaged 1.29 ± 0.75 cm, with IDC and DCIS diagnosed in five cases each, and none had lymph node involvement.

CONCLUSION: In ~10% of BRCA1/BRCA2 PSV carriers BC is diagnosed by breast imaging after age 70 years. If these results are validated in a larger study, the guidelines for the maximum age for BC surveillance in high risk women should be revisited and set at 75 years.}, } @article {pmid38378247, year = {2025}, author = {Nguyen, NJ and Liu, K and Lajkosz, K and Iczkowski, KA and van der Kwast, TH and Downes, MR}, title = {Addition of cribriform pattern 4 and intraductal prostatic carcinoma into the CAPRA-S tool improves post-radical prostatectomy patient stratification in a multi-institutional cohort.}, journal = {Journal of clinical pathology}, volume = {78}, number = {12}, pages = {805-813}, doi = {10.1136/jcp-2023-209222}, pmid = {38378247}, issn = {1472-4146}, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/surgery/mortality ; *Prostatectomy ; Retrospective Studies ; Aged ; Middle Aged ; Risk Assessment/methods ; Prognosis ; Neoplasm Grading ; Disease-Free Survival ; Risk Factors ; }, abstract = {AIMS: Pre-surgical risk classification tools for prostate cancer have shown better patient stratification with the addition of cribriform pattern 4 (CC) and intraductal prostatic carcinoma (IDC) identified in biopsies. Here, we analyse the additional prognostic impact of CC/IDC observed in prostatectomies using Cancer of Prostate Risk Assessment post-surgical (CAPRA-S) stratification.

METHODS: A retrospective cohort of treatment-naïve radical prostatectomy specimens from three North American academic institutions (2010-2018) was assessed for the presence of CC/IDC. Patients were classified, after calculating the CAPRA-S scores, into low-risk (0-2), intermediate-risk (3-5) and high-risk (6-12) groups. Kaplan-Meier curves were created to estimate biochemical recurrence (BCR)-free survival. Prognostic performance was examined using Harrell's concordance index, and the effects of CC/IDC within each risk group were evaluated using the Cox proportional hazards models.

RESULTS: Our cohort included 825 prostatectomies (grade group (GG)1, n=94; GG2, n=475; GG3, n=185; GG4, n=13; GG5, n=58). CC/IDC was present in 341 (41%) prostatectomies. With a median follow-up of 4.2 years (range 2.9-6.4), 166 (20%) patients experienced BCR. The CAPRA-S low-risk, intermediate-risk and high-risk groups comprised 357 (43%), 328 (40%) and 140 (17%) patients, and discriminated for BCR-free survival (p<0.0001). For CAPRA-S scores 3-5, the addition of CC/IDC status improved stratification for BCR (HR 2.27, 95% CI 1.41 to 3.66, p<0.001) and improved the overall c-index (0.689 vs 0.667, analysis of variance p<0.001).

CONCLUSION: The addition of CC/IDC into the CAPRA-S classification significantly improved post-radical prostatectomy patient stratification for BCR among the intermediate-risk group (CAPRA-S scores 3-5). The reporting of CC and IDC should be included in future prostate cancer stratification tools for improved outcome prediction.}, } @article {pmid38376291, year = {2023}, author = {Piracha, ZZ and Saeed, U}, title = {Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is downregulated in Invasive ductal carcinoma and potential prognostic marker of breast cancer.}, journal = {Journal of cancer research and therapeutics}, volume = {19}, number = {7}, pages = {1870-1879}, pmid = {38376291}, issn = {1998-4138}, mesh = {Female ; Humans ; beta Catenin ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal ; *Fibroadenoma/genetics ; Glycogen Synthase Kinase 3 ; Immunoglobulin Domains ; Leucine ; *Membrane Glycoproteins/genetics ; Prognosis ; Proto-Oncogene Proteins c-akt ; }, abstract = {BACKGROUND: LRIG1 belongs to the family of transmembrane proteins containing leucine-rich repeats. LRIGs are considered as tumor suppressors as they negatively regulate receptor tyrosine kinases. The role of LRIG1 as an EGFR regulator makes it an important marker to be studied in various epithelial-derived cancers.

METHODS: LRIG1 expression was determined in Erbb2 + cell lines by western blotting, and cell motility was examined by cell migration assay. The AKT/GSK3-β/β-catenin pathway was determined in the presence of LRIG1 and Erbb2 by using western blotting.

RESULTS: So far, no study has reported the expression of LRIG1 in benign forms of tumor such as fibroadenoma. The current study aims to analyze LRIG1 expression in fibroadenoma and invasive ductal carcinoma (IDC) tissues. In this study, we compared the LRIG1 expression with different clinicopathological parameters of patients having IDC or fibroadenoma. LRIG1 expression was low in Erbb2+ cell lines, and more cell motility was observed. The AKT/GSK3-β/β-catenin pathway was activated when LRIG1 was downregulated; consequently, Erbb2 was upregulated. Our results indicated that LRIG1 expression can be significantly correlated with age, Nottingham index, and Her2/neu status of cancer. The expression of LRIG1 in IDC and fibroadenoma were found to be significantly different.

CONCLUSION: The fibroadenoma tissue sections were found to express LRIG1 more intensely as compared to the IDC sections, which are in line with the studies reporting reduced copy number of the gene either due to gene deletion or transcriptional inhibition. This further supports that the downregulation of LRIG1 may lead to malignant tumor acting as a tumor suppressor.}, } @article {pmid38376280, year = {2023}, author = {Bhatia, M and Ahmed, R and Nagarajakumar, A and Alani, A and Doddi, S and Metafa, A}, title = {Measurement of malignant spiculated mass lesions on mammogram: Do we include the length of the spicules?.}, journal = {Journal of cancer research and therapeutics}, volume = {19}, number = {7}, pages = {1794-1796}, doi = {10.4103/jcrt.jcrt_2052_21}, pmid = {38376280}, issn = {1998-4138}, mesh = {Humans ; Retrospective Studies ; *Mammography ; Biopsy ; }, abstract = {AIM: The aim of this study is to determine if the core size or size with spicules has a better correlation with the final histologic size of spiculated mass lesions.

METHODS: A retrospective study of 48-month duration from January 2014 to December 2017 of biopsy-proven invasive ductal carcinoma presenting as spiculated mass lesions on mammogram was conducted.

RESULTS: There were 195 patients in the study. The mean of the core size was 16.6 mm; when spicules were included the mean size was 27.4mm and final histologic size 21.1 mm. Using unpaired Student 't' test difference in the means was statistically significant (p<0.0001). Pearson number (R) core size versus final histologic size was 0.535 (P < 0.001) and for size with spicules versus final histologic size was 0.495 (P < 0.001).

CONCLUSION: Our study demonstrated that the core size has a stronger positive correlation to final histologic size and should be used preoperatively in decision-making about surgery.}, } @article {pmid38370290, year = {2024}, author = {Khalid, IB and Sarwar, A and Khalid, HB and Sajjad, B and Rehman, B and Parvaiz, MA}, title = {Clinicopathological Features and Treatment Outcomes of Male Breast Cancer in Pakistani Population: A 10-Year Retrospective Cross-Sectional Study.}, journal = {Breast cancer : basic and clinical research}, volume = {18}, number = {}, pages = {11782234241233120}, pmid = {38370290}, issn = {1178-2234}, abstract = {BACKGROUND: Male breast cancer (MBC) accounts for 1% of global breast cancer cases. On account of its rarity, very few prospective clinical trials have been carried out on MBC. Pakistan has the highest incidence of breast cancer in Asia, but very limited data are available on MBC.

OBJECTIVES: The objective is to determine the clinicopathological characteristics and treatment patterns of MBC in Pakistani population.

DESIGN: This is a retrospective cross-sectional study.

METHODS: A retrospective cross-sectional study carried out using the cancer database of Shaukat Khanum Memorial Cancer Hospital & Research Center. Men with a histologically proven breast cancer, stage 0 to III disease and requiring surgical intervention were included. The Kaplan-Meier curve and log-rank test were used for survival analysis.

RESULTS: Sixty-eight patients with MBC were included with a median age at diagnosis of 55 years. Most patients were stage II (47.1%). Invasive ductal carcinoma (IDC) was the commonest type (89.7%). Estrogen receptor (ER), progesterone receptor (PR), and Her-2 receptor positivity were 92.6%, 86.8%, and 32.4%, respectively. Mastectomy was performed in 95.6% of the cases. Neoadjuvant and adjuvant chemotherapy was administered in 25 (36.8%) and 26 (38.2%) patients, respectively. Fifty-five (80.9%) patients received adjuvant radiotherapy. Most of the patients (89.7%) received tamoxifen. The 5-year overall and disease-free survival was 88.2% and 80.9%, respectively. Patients receiving neoadjuvant chemotherapy had a better overall and disease-free survival (P = .025).

CONCLUSIONS: Male breast cancer occurs at a relatively earlier age in Pakistani population as compared with Western men. Mastectomy is the preferred surgical option for MBC on account of the advanced disease and delayed presentation. Neoadjuvant chemotherapy has a statistically significant effect on overall and disease-free survival, but in spite of these benefits, it remains underutilized.}, } @article {pmid38369589, year = {2024}, author = {Liu, XS and Chen, YX and Wan, HB and Wang, YL and Wang, YY and Gao, Y and Wu, LB and Pei, ZJ}, title = {TRIP6 a potential diagnostic marker for colorectal cancer with glycolysis and immune infiltration association.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {4042}, pmid = {38369589}, issn = {2045-2322}, mesh = {Humans ; *Adaptor Proteins, Signal Transducing/genetics/metabolism ; *Colorectal Neoplasms/diagnosis/genetics/pathology ; Glycolysis ; *LIM Domain Proteins/genetics/metabolism ; Proteasome Endopeptidase Complex/metabolism ; *Transcription Factors/genetics/metabolism ; }, abstract = {Thyroid hormone receptor interactor 6 (TRIP6) it is an adaptor protein belonging to the zyxin family of LIM proteins, participating in signaling events through interactions with various molecules. Despite this, TRIP6's role in colorectal cancer (CRC), particularly its correlation with glucose metabolism and immune cell infiltration, remains unclear. Through the TCGA and GEO databases, we obtained RNA sequencing data to facilitate our in-depth study and analysis of TRIP6 expression. To investigate the prognostic value of TRIP6 in CRC, we also used univariate Cox regression analysis. In addition, this study also covered a series of analyses, including clinicopathological analysis, functional enrichment analysis, glycolysis correlation analysis, immunoinfiltration analysis, immune checkpoint analysis, and angiogenesis correlation analysis, to gain a comprehensive and in-depth understanding of this biological phenomenon. It has been found that TRIP6 expression is significantly upregulated in CRC and correlates with the stage of the disease. Its overexpression portends a worse survival time. Functional enrichment analysis reveals that TRIP6 is associated with focal adhesion and glycolysis. Mechanistically, TRIP6 appears to exert its tumorigenic effect by regulating the glycolysis-related gene GPI. A higher level of expression of TRIP6 is associated with an increase in the number of iDC immune cells and a decrease in the number of Th1 immune cells. Also, TRIP6 may promote angiogenesis in tumor cells by promoting the expression of JAG2. Our study uncovers the upregulation of TRIP6 in CRC, illuminating its prognostic and diagnostic value within this context. Furthermore, we examine the relationship between TRIP6 expression levels, glycolysis, angiogenesis and immune cell infiltration. This underscores its potential as a biomarker for CRC treatment and as a therapeutic target.}, } @article {pmid38368743, year = {2024}, author = {Shoshani, A}, title = {The roots of compassion in early childhood: Relationships between theory of mind and attachment representations with empathic concern and prosocial behavior.}, journal = {Journal of experimental child psychology}, volume = {242}, number = {}, pages = {105880}, doi = {10.1016/j.jecp.2024.105880}, pmid = {38368743}, issn = {1096-0457}, mesh = {Child ; Adult ; Humans ; Child, Preschool ; *Empathy ; Altruism ; Social Behavior ; *Theory of Mind ; Emotions ; }, abstract = {This study focused on attachment representations and theory of mind as potential developmental origins of individual differences in preschoolers' peer- and adult-directed empathic concern and prosocial behavior. In two experiments, 3- to 6-year-olds were exposed to either a high-distressed or low-distressed adult or child using a laboratory setting (Experiment 1; N = 263) or hypothetical vignettes (Experiment 2; N = 202). Self-reported and coded expressions of empathic concern and prosocial behaviors were used as early indicators of compassion. The findings indicated that children expressed more empathic concern and engaged in more prosocial behavior in the high-distress condition than in the low-distress condition. Children's empathic concern and prosocial behavior increased with age. Secure attachment and theory of mind abilities played significant moderating roles in the association between distress conditions and empathic concern. Children with more advanced theory of mind abilities and secure attachment were better at recognizing the concerns of distressed peers or adults and showed significantly more empathic concern. Resistant and disorganized children exhibited more self-distress in response to others' distress. The implications for early interventions directed at increasing empathic concern and prosocial behavior are discussed.}, } @article {pmid38368669, year = {2024}, author = {Gomez, D and Seneviratne, S}, title = {Invasive breast carcinoma with ipsilateral axillary squamous carcinoma of unknown primary: A case report.}, journal = {International journal of surgery case reports}, volume = {116}, number = {}, pages = {109397}, pmid = {38368669}, issn = {2210-2612}, abstract = {INTRODUCTION & IMPORTANCE: Invasive ductal carcinoma is the commonest primary breast carcinoma to metastasize to the axillary nodes. Squamous carcinoma (SCC) of the breast is seen rarely as a primary breast malignancy. Breast SCC with coexistent invasive ductal/lobular carcinoma as a 'collision tumour' is rare.

CASE PRESENTATION: A 52-year-old Sri Lankan female presented with a right sided breast lump and ipsilateral cystic axillary mass. She was diagnosed with locally advanced invasive breast carcinoma and underwent neoadjuvant chemotherapy followed by mastectomy and axillary clearance where tumour infiltration of the brachial plexus was observed. Histology revealed two separate carcinomas; an invasive carcinoma of the breast and squamous carcinoma in the axilla. A squamous primary was not found despite evaluation. The patient developed recurrent axillary ulceration due to residual tumour and was transferred for oncological care.

CLINICAL DISCUSSION: This patient had a biopsy-proven invasive breast carcinoma with a cystic axillary mass with lymphadenopathy. This was concluded as locally advanced breast cancer. Pathological examination of the specimen indicated the presence of two separate malignancies of the breast and axilla. No evidence of squamous metaplasia or carcinoma of the breast was seen on histology, neither was a squamous primary identified on imaging or endoscopy. Neoadjuvant therapy may have caused resolution of the squamous component.

CONCLUSION: The presence of two separate cancers of varied histology in the breast and ipsilateral axilla in close proximity to each other is a rare phenomenon. Clinicians must be cautious not to misinterpret it as evidence of lymphatic spread.}, } @article {pmid38363600, year = {2024}, author = {Sahin, SI and Balci, S and Guler, G and Altundag, K}, title = {Clinicopathological analysis of 38 male patients diagnosed with breast cancer.}, journal = {Breast disease}, volume = {43}, number = {1}, pages = {1-8}, pmid = {38363600}, issn = {1558-1551}, mesh = {Humans ; Male ; Aged ; *Breast Neoplasms/pathology ; *Breast Neoplasms, Male/pathology ; Prognosis ; Lymph Nodes/pathology ; *Bone Neoplasms ; *Carcinoma, Ductal, Breast/pathology ; Receptors, Progesterone ; }, abstract = {BACKGROUND: Male breast cancer (MBC) accounts for one percent of all breast cancers. Due to the lack of awareness and routine screening programs, most patients present with systemic disease at the time of diagnosis with low overall survival.

OBJECTIVES: This study aims to investigate the prognostic factors of male breast cancer and its correlation with established prognostic parameters and patient outcomes.

METHODS: Thirty-eight male breast cancer patients are identified from the MKA Breast Cancer Clinic database, and their corresponding clinical and pathological characteristics are obtained. Cut-off values of 1% and 10% are applied to further classify ER and PR results.

RESULTS: Older men are more likely to develop MBC than younger men and are more likely to have spread to axillary lymph nodes. Invasive ductal carcinoma is a more common histologic type in MBC. All the tested patients have ER and PR positivity. Distant metastasis developed in 17/38 (44.7%) patients. Bone metastasis is seen commonly in metastatic MBC.

CONCLUSIONS: According to our cohort, MBC is seen in older males, presents in later stages, and shows hormone receptor positivity and a tendency to bone involvement. MBC is a heterogenous but distinct biological entity requiring a specific clinical and pathological approach.}, } @article {pmid38361878, year = {2023}, author = {Abusanad, A}, title = {Utilizing peripheral blood inflammatory biomarker (PBIB) to predict response to systemic therapy in patients with breast cancer.}, journal = {Journal of family medicine and primary care}, volume = {12}, number = {12}, pages = {3368-3373}, pmid = {38361878}, issn = {2249-4863}, abstract = {BACKGROUND: Inflammation is a recognized factor in cancer progression and resistance to treatments. Several studies correlated inflammation-related peripheral blood inflammatory biomarkers (PBIB) to disease progression and poor survival in various cancer types and different populations. Nonetheless, inflammation is affected by the distinctive characteristics and environmental exposure of each population. There is no prior study addressing the association of pre-treatment inflammatory markers with outcomes in patients with breast cancer (BC) from Saudi Arabia. In this study, we evaluated the prognosis of locally advanced breast cancer (LABC) in relation to several PBIB.

MATERIALS AND METHODS: We retrospectively analyzed the data of female patients with LABC undergoing neoadjuvant chemotherapy (NACT). Demographics, body mass index (BMI), clinicopathologic characteristics and stage of the tumor, follow-up status, and response to treatment were collected. Outcomes were evaluated in relation to pre-treatment peripheral blood indices that were grouped based on the local laboratory cutoff values. Objective response rate (ORR) was predefined and assessed according to the post-NACT magnetic resonance imaging (MRI) breast and subcategorized into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).

RESULTS: A total of 172 female patients with BC met the eligibility criteria from January 2014 to December 2019. The mean age at diagnosis was 53.4 ± 11, and BMI was 31.2 ± 6. Left BC accounted for 54.7%, and the majority was invasive ductal carcinoma (85.5%), moderately differentiated (51%), stage III (AJCC 8[th] edition) (73%), and estrogen receptor (ER)-positive tumor (79.1%). Human epidermal growth factor receptor 2 (HER2)-positive BC was reported in 32% and triple-negative breast cancer (TNBC) in 10%. Radiologic CR accounted for the majority of ORR (71.5%). Higher percentage of patients with normal red cell distribution width (RDW) of red blood cell (RBC) and low neutrophil-lymphocyte ratio (NLR) had CR with a significant P value of 0.003 and 0.014, respectively.

CONCLUSION: Among several peripheral blood indices, RDW and NLR significantly influenced ORR. They can be explored further to potentially predict response after systemic therapy in patients with LABC. The great advantage of these biomarkers stems from their availability and affordability in routine clinical practice.}, } @article {pmid38361780, year = {2024}, author = {Wilson, KL and Grewelle, RE and Gupta, T and Kim, SH and Katsumoto, TR}, title = {Aromatase inhibitor-induced arthralgia ameliorated by Mediterranean diet and active lifestyle guided by continuous glucose monitoring: a case report and review of the literature.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1189287}, pmid = {38361780}, issn = {2234-943X}, abstract = {Aromatase inhibitors (AIs) are a cornerstone adjuvant treatment of many hormone receptor-positive breast cancers, and nearly half of women taking aromatase inhibitors suffer from AI-induced arthralgia (AIA), also known as AI-associated musculoskeletal syndrome (AIMSS), for which there are limited evidence-based treatments. Pharmacologic management and complementary methods including supplements, exercise, physical therapy, yoga, acupuncture, and massage have all shown mixed results. Comprehensive diet and lifestyle strategies are understudied in AIA/AIMSS despite their disease-modifying effects across many chronic conditions. Here we report a case of a woman with stage 2 estrogen and progesterone receptor-positive invasive ductal carcinoma on adjuvant anastrozole whose AI-induced arthralgia was durably controlled through a Mediterranean plant-forward diet and daily physical activity guided by continuous glucose monitoring. We posit that diet and a lifestyle inclusive of daily physical activity constitute a low-cost, low-risk, and potentially high-reward strategy for controlling common AI-induced musculoskeletal symptoms and that more investigation in this arena, including well-designed randomized trials, is warranted.}, } @article {pmid38360632, year = {2024}, author = {Yuan, H and Zhang, R and Li, N and Yao, H}, title = {Primary fallopian tube cancer followed by primary breast cancer in RAD51C mutation carrier treated with niraparib as first line maintenance therapy: a case report.}, journal = {Hereditary cancer in clinical practice}, volume = {22}, number = {1}, pages = {2}, pmid = {38360632}, issn = {1731-2302}, support = {No. CFA202202018//Chinese Academy of Medical Sciences Cancer Hospital - Shenzhen Hospital Cooperation Fund/ ; No. 2021-RW310-002//Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Medical Sciences/ ; }, abstract = {Given the rarity of RAD51C mutations, the risk and treatment of metachronous breast cancer after the diagnosis of ovarian cancer in RAD51C mutation carriers is not clear, especially for those who have received PARPi treatment. We report the case of a 65-year-old woman diagnosed with stage IIIC high-grade serous primary fallopian tube cancer. The patient had no family history of breast or ovarian cancer. The patient received three cycles of neoadjuvant chemotherapy with paclitaxel and carboplatin and achieved a complete response. After interval debulking surgery, the patient received three cycles of adjuvant chemotherapy. Collection and extraction of saliva DNA for next-generation sequencing identified a RAD51C mutation c.838-2 A > G. The patient received niraparib as front-line maintenance treatment. After 36 months of niraparib treatment, the patient had grade II invasive ductal carcinoma of the left breast that was positive for estrogen receptor (90%) and Ki-67 (30%) and negative for progesterone receptor and human epidermal growth factor receptor 2. Computed tomography revealed the absence of distant metastases. Modified radical mastectomy and axillary lymph node dissection were then performed. The final pathological report of the breast showed a 1.8 cm Bloom-Richardson grade II invasive ductal carcinoma in the left breast with axillary lymph node metastasis (1/21). Finally, the breast cancer was stage IIA, pT1cN1M0. The metachronous breast cancer in this case may be the first report of second primary cancer in fallopian tube cancer patient harboring a RAD51C mutation during niraparib treatment. Further studies are required to determine optimal treatment.}, } @article {pmid38351793, year = {2023}, author = {Aleksiev, T and Ivanova, Z and Dobrev, H}, title = {Asynchronous bilateral male breast cancer. A rare case report.}, journal = {Folia medica}, volume = {65}, number = {6}, pages = {1011-1014}, doi = {10.3897/folmed.65.e96190}, pmid = {38351793}, issn = {1314-2143}, mesh = {Male ; Humans ; Aged ; *Breast Neoplasms, Male/diagnostic imaging/therapy ; Mastectomy ; Mammography ; *Carcinoma/surgery ; *Carcinoma, Ductal/surgery ; }, abstract = {We describe a rare case of asynchronous bilateral carcinoma of the mammary glands in a 66-year-old man. The patient was admitted to the Department of Dermatology and Venereology due to exacerbation of chronic eczema. During the examination, a 3×2-cm tumor with retraction of the mammilla was found in the right mammary gland. Mastectomy and regional lymphatic dissection were performed. Histological examination showed invasive ductal carcinoma, ER (+) 70%, PR (-), HER2 (-). Treatment included chemotherapy, radiotherapy, and hormone therapy. Three years later, the patient reported a lump in the left breast. The presence of a tumor formation was confirmed by mammography and ultrasound examination. A radical mastectomy with regional lymphatic dissection was performed. Histological examination showed invasive ductal carcinoma of the mammary gland, ER (3+) 80%, PP (2+) 60%, HER2 (+++), and Ki67 (+) 80%. Treatment with chemotherapy and radiation therapy was carried out. Five years after diagnosis of the second carcinoma, the patient is in a good general condition. Regardless of its rarity, the described case should draw doctors' attention to this pathology. Assessment of risk factors and periodic breast examination in men would allow early diagnosis, timely treatment, and better prognosis of the disease.}, } @article {pmid38348593, year = {2024}, author = {Schweiger, M and Arredondo-Lasso, MN and Friano, ME and Gil-Lozano, M and Herzig, S and Uhlenhaut, NH}, title = {Lipid sensing nuclear receptors involved in the pathogenesis of fatty liver disease.}, journal = {FEBS letters}, volume = {598}, number = {23}, pages = {2854-2855}, pmid = {38348593}, issn = {1873-3468}, support = {UH 275/6-1-ID 457050056//German Research Foundation DFG/ ; TRR333 BATEnergy ID 450149205//German Research Foundation DFG/ ; TRR205 Adrenal Gland ID 314061271//German Research Foundation DFG/ ; CRC1064 Chromatin Dynamics ID 213249687//German Research Foundation DFG/ ; 457050056//German Research Foundation/ ; 450149205//TRR333 BAT-Energy/ ; }, mesh = {Humans ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; Animals ; *Lipid Metabolism ; *Non-alcoholic Fatty Liver Disease/metabolism/pathology/genetics ; Fatty Liver/metabolism/pathology/genetics ; Receptor, Farnesoid X-Activated ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation and progresses toward inflammation and fibrosis. Nuclear receptors (NRs), like the Peroxisome Proliferator-Activated Receptors alpha and gamma (PPARα and PPARy), the Farnesoid X Receptor (FXR), and the Liver X receptor (LXR), regulate genes by heterodimerizing with Retinoid X receptor (RXR). These receptors are emerging targets for pharmaceutical intervention for metabolic diseases.}, } @article {pmid38344422, year = {2024}, author = {Akhgarjand, C and Anoushirvani, A and Tavakoli, A and Ghorbi, MD}, title = {Breast Cancer and Chronic Lymphocytic Leukemia and Renal Cell Carcinoma: A Case Report of a Rare Cancer Combination.}, journal = {Case reports in oncology}, volume = {17}, number = {1}, pages = {232-238}, pmid = {38344422}, issn = {1662-6575}, abstract = {INTRODUCTION: The incidence of second malignancies in breast cancer survivors has increased because of early detection and improved cancer treatment modalities. The synchronous occurrence of chronic lymphocytic lymphoma (CLL) and renal cell carcinoma (RCC) in the same patient is higher than in the general population. Several factors, including the history of chemotherapy with alkylating agents, genetic alteration, and long-term survival of breast cancer patients may explain this condition, but further research is needed.

CASE PRESENTATION: In the present report, we discussed the case of a 48-year-old female who had clear cell RCC; 5 months after the diagnosis of CLL and 15 years after invasive ductal carcinoma.

CONCLUSION: Considering the continued elevated risk of second cancers in patients with breast cancer and CLL in a clinical setting, clinicians should be made aware of ongoing medical surveillance.}, } @article {pmid38343885, year = {2023}, author = {Santos, MM and Baerga, CG and Lamsal, S and Engel, C and Ozdemir, S}, title = {Breast cancer in a Hispanic patient with Werner syndrome.}, journal = {Journal of radiology case reports}, volume = {17}, number = {10}, pages = {21-31}, pmid = {38343885}, issn = {1943-0922}, mesh = {Adult ; Female ; Humans ; *Breast Neoplasms/diagnostic imaging/genetics ; Hispanic or Latino ; Mastectomy ; Mutation ; *Werner Syndrome/complications/diagnostic imaging/genetics ; Werner Syndrome Helicase/genetics ; Tumor Suppressor Protein p53 ; }, abstract = {Werner Syndrome is a rare autosomal recessive condition characterized by premature aging and increased risk of malignancies due to gene mutations associated with DNA stability. We present the first case report of a 29-year-old Hispanic female with WS diagnosed with breast cancer. Diagnostic mammography and ultrasound, breast MRI and PET examinations revealed two lesions biopsy proven as invasive ductal carcinoma. The patient underwent neoadjuvant chemotherapy and radical mastectomy. Recurrence occurred 10 months postoperatively with molecular analysis demonstrating TP53 mutations. The multifactorial assessment of breast cancer in this case study is crucial towards optimizing screening, diagnosis and management of this disease in patients with WS.}, } @article {pmid38336663, year = {2024}, author = {Ye, C and Shi, M and Xie, D and Wu, H and Chen, Q and Yang, L}, title = {A rare case of intervertebral disc calcification combined with ossification of the posterior longitudinal ligament in a child: a case report and literature review.}, journal = {BMC musculoskeletal disorders}, volume = {25}, number = {1}, pages = {118}, pmid = {38336663}, issn = {1471-2474}, support = {82372431//National Natural Science Foundation of China/ ; 2022LJ007//Shanghai Municipal Health Commission Health Leading Talents Program/ ; 22ZR1476700//the Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality/ ; 201409003200//the Science and Technology Innovation Action Plan of the Science and Technology Commission of Shanghai Municipality/ ; 0906//the Fifth Round Innovation Team of Shanghai Changning District, the Pyramid Talent Project of Shanghai Changzheng Hospital in 2020/ ; 2021X002//the Discipline Team Support Project of No. 905 Hospital of PLA Navy/ ; }, mesh = {Humans ; Child ; Longitudinal Ligaments/diagnostic imaging ; Osteogenesis ; *Intervertebral Disc Degeneration/complications/diagnostic imaging ; *Ossification of Posterior Longitudinal Ligament/complications/diagnostic imaging/therapy ; *Calcinosis/complications/diagnostic imaging/therapy ; *Chondrocalcinosis/complications ; Cervical Vertebrae/diagnostic imaging ; *Intervertebral Disc/diagnostic imaging ; }, abstract = {BACKGROUND: Intervertebral disc calcification (IDC) combined with calcification in children has been sporadically reported, while ossification of the posterior longitudinal ligament (OPLL) in the cervical spine in pediatric patients is exceedingly rare. The aim of this study is to investigate the potential prognosis and outcomes associated with this condition.

CASE PRESENTATION: We present an unusual case involving a 10-year-old Chinese child diagnosed with calcified cervical disc herniation and ossification of the posterior longitudinal ligament. Conservative treatment measures were implemented, and at the 1-month and 6-month follow-up, the patient's pain exhibited significant improvement. Subsequent cervical MRI and CT scans revealed the complete disappearance of OPLL and substantial absorption of the calcified disc. During the three-month follow-up, CT demonstrated slight residual disc calcification, however, the patient remained asymptomatic with no discernible limitation in cervical motion.

CONCLUSIONS: We conducted a comprehensive review of several cases presenting with the same diagnosis. It is noteworthy that IDC combined with OPLL in children constitutes a rare clinical entity. Despite imaging indications of potential spinal canal occupation, the majority of such cases demonstrate complete absorption following conservative treatment, with OPLL exhibiting a faster absorption rate than calcified discs.}, } @article {pmid38336012, year = {2024}, author = {Tank, P and Vora, S and Tripathi, S and D'Souza, F}, title = {Qualification of a LC-HRMS platform method for biosimilar development using NISTmab as a model.}, journal = {Analytical biochemistry}, volume = {688}, number = {}, pages = {115475}, doi = {10.1016/j.ab.2024.115475}, pmid = {38336012}, issn = {1096-0309}, mesh = {*Biosimilar Pharmaceuticals/analysis/chemistry ; Antibodies, Monoclonal/chemistry ; Liquid Chromatography-Mass Spectrometry ; Peptide Mapping/methods ; Peptides ; }, abstract = {Biosimilars are a cost-effective alternative to biopharmaceuticals, necessitating rigorous analytical methods for consistency and compliance. Liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) is a versatile tool for assessing key attributes, encompassing molecular mass, primary structure, and post-translational modifications (PTMs). Adhering to ICH Q2R1, we validated an LC-HRMS based peptide mapping method using NISTmab as a reference. The method validation parameters, covering system suitability, specificity, accuracy, precision, robustness, and carryover, were comprehensively assessed. The method effectively differentiated the NISTmab from similar counterparts as well as from artificially introduced spiked conditions. Notably, the accuracy of mass error for NISTmab specific complementarity determining region peptides was within a maximum of 2.42 parts per million (ppm) from theoretical and the highest percent relative standard deviation (%RSD) observed for precision was 0.000219 %. It demonstrates precision in sequence coverage and PTM detection, with a visual inspection of total ion chromatogram approach for variability assessment. The method maintains robustness when subjected to diverse storage conditions, encompassing variations in column temperature and mobile phase composition. Negligible carryover was noted during the carryover analysis. In summary, this method serves as a versatile platform for multiple biosimilar development by effectively characterizing and identifying monoclonal antibodies, ultimately ensuring product quality.}, } @article {pmid38329829, year = {2024}, author = {Fang, L and Simman, R and Workman, L and Ayoub, S and Bratton, C}, title = {Malignant wound aetiology, diagnosis and management: a case series and literature review.}, journal = {Journal of wound care}, volume = {33}, number = {2}, pages = {102-117}, doi = {10.12968/jowc.2024.33.2.102}, pmid = {38329829}, issn = {0969-0700}, mesh = {Aged ; Humans ; *Carcinoma, Squamous Cell/diagnosis/therapy/complications ; *Melanoma/diagnosis/therapy ; Neoplasm Recurrence, Local ; Skin/pathology ; *Skin Neoplasms/diagnosis/therapy ; }, abstract = {OBJECTIVE: Malignant wounds develop when neoplastic cells invade the skin either locally or by lymphatic and haematogenous spread. They can present as hard-to-heal wounds and underlying causes include: primary skin cancer; metastasis of extracutaneous primary malignancy; malignant transformation of a hard-to-heal wound; iatrogenic injury; and cutaneous forms of cancers of non-skin origin. High clinical suspicion for a malignant wound should be confirmed with skin biopsy. The aim of this case series is to highlight a combination of both clinically clear cutaneous malignancies and not-so-obvious wounds caused by malignancy.

METHOD: This case series examines patients with malignant wounds of varying aetiology and appearance. For each case, we explain the pathophysiology, atypical features, diagnostic approach and treatment. We also discuss types of wound biopsy and general wound management principles.

RESULTS: Among the 11 cases analysed using descriptive statistics, median wound duration before presentation at our clinic was one year, while median age at presentation was 65 years. Our case series included the following diagnoses: cutaneous metastasis of invasive ductal carcinoma of the breast (n=2); cutaneous metastasis of colorectal adenocarcinoma (n=1); Marjolin's ulcer (n=1), basal cell carcinoma (BCC) (n=2), primary cutaneous squamous cell carcinoma (SCC) (n=1), metastatic malignant melanoma (n=1), cutaneous T-cell lymphoma (n=1), cutaneous angiosarcoma (n=1), Kaposi sarcoma (n=1) and recurrent tonsillar SCC with osteoradionecrosis (n=1); one case had both BCC and SCC.

CONCLUSION: Punch and excisional biopsies were the most frequently used diagnostic techniques. Local wound therapy addressed bleeding, malodour, exudate, pain and infection. However, wound healing is usually achieved once the underlying malignancy is treated. In advanced or metastatic disease, palliative wound care aims to prevent exacerbation of existing wounds and focuses on patient comfort.}, } @article {pmid38329532, year = {2024}, author = {Guerra, J and Matta, L and Bartelt, A}, title = {Cardiac proteostasis in obesity and cardiovascular disease.}, journal = {Herz}, volume = {49}, number = {2}, pages = {118-123}, pmid = {38329532}, issn = {1615-6692}, mesh = {Humans ; Proteostasis ; *Cardiovascular Diseases ; Myocytes, Cardiac ; *Heart Diseases ; Proteasome Endopeptidase Complex/metabolism ; Obesity/metabolism ; }, abstract = {Cardiovascular diseases (CVD) are closely linked to protein homeostasis (proteostasis) and its failure. Beside genetic mutations that impair cardiac protein quality control, obesity is a strong risk factor for heart disease. In obesity, adipose tissue becomes dysfunctional and impacts heart function and CVD progression by releasing cytokines that contribute to systemic insulin resistance and cardiovascular dysfunction. In addition, chronic inflammation and lipotoxicity compromise endoplasmic reticulum (ER) function, eliciting stress responses that overwhelm protein quality control beyond its capacity. Impairment of proteostasis-including dysfunction of the ubiquitin-proteasome system (UPS), autophagy, and the depletion of chaperones-is intricately linked to cardiomyocyte dysfunction. Interventions targeting UPS and autophagy pathways are new potential strategies for re-establishing protein homeostasis and improving heart function. Additionally, lifestyle modifications such as dietary interventions and exercise have been shown to promote cardiac proteostasis and overall metabolic health. The pursuit of future research dedicated to proteostasis and protein quality control represents a pioneering approach for enhancing cardiac health and addressing the complexities of obesity-related cardiac dysfunction.}, } @article {pmid38327751, year = {2024}, author = {Zhang, M and Sun, Y and Wu, H and Xiao, J and Chen, W and Wang, H and Yang, B and Luo, H}, title = {Prognostic analysis of cT1-3N1M0 breast cancer patients who have responded to neoadjuvant therapy undergoing various axillary surgery and breast surgery based on propensity score matching and competitive risk model.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1319981}, pmid = {38327751}, issn = {2234-943X}, abstract = {BACKGROUND: Sentinel lymph node biopsy (SLNB) in breast cancer patients with positive clinical axillary lymph nodes (cN1+) remains a topic of controversy. The aim of this study is to assess the influence of various axillary and breast surgery approaches on the survival of cN1+ breast cancer patients who have responded positively to neoadjuvant therapy (NAT).

METHODS: Patients diagnosed with pathologically confirmed invasive ductal carcinoma of breast between 2010 and 2020 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. To mitigate confounding bias, propensity score matching (PSM) analysis was employed. Prognostic factors for both overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated through COX regression risk analysis. Survival curves were generated using the Kaplan-Meier method. Furthermore, cumulative incidence and independent prognostic factors were assessed using a competing risk model.

RESULTS: The PSM analysis matched 4,890 patients. Overall survival (OS) and BCSS were slightly worse in the axillary lymph node dissection (ALND) group (HR = 1.10, 95% CI 0.91-1.31, p = 0.322 vs. HR = 1.06, 95% CI 0.87-1.29, p = 0.545). The mastectomy (MAST) group exhibited significantly worse OS and BCSS outcomes (HR = 1.25, 95% CI 1.04-1.50, p = 0.018 vs. HR = 1.37, 95% CI 1.12-1.68, p = 0.002). The combination of different axillary and breast surgery did not significantly affect OS (p = 0.083) but did have a significant impact on BCSS (p = 0.019). Competing risk model analysis revealed no significant difference in the cumulative incidence of breast cancer-specific death (BCSD) in the axillary surgery group (Grey's test, p = 0.232), but it showed a higher cumulative incidence of BCSD in the MAST group (Grey's test, p = 0.001). Multivariate analysis demonstrated that age ≥ 70 years, black race, T3 stage, ER-negative expression, HER2-negative expression, and MAST were independent prognostic risk factors for both OS and BCSS (all p < 0.05).

CONCLUSION: For cN1+ breast cancer patients who respond positive to NAT, the optimal surgical approach is combining breast-conserving surgery (BCS) with SLNB. This procedure improves quality of life and long-term survival outcomes.}, } @article {pmid38326829, year = {2024}, author = {Verma, VK and Beevi, SS and Nair, RA and Kumar, A and Kiran, R and Alexander, LE and Dinesh Kumar, L}, title = {MicroRNA signatures differentiate types, grades, and stages of breast invasive ductal carcinoma (IDC): miRNA-target interacting signaling pathways.}, journal = {Cell communication and signaling : CCS}, volume = {22}, number = {1}, pages = {100}, pmid = {38326829}, issn = {1478-811X}, mesh = {Animals ; Female ; Mice ; Biomarkers ; Biomarkers, Tumor/genetics ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *MicroRNAs/genetics/metabolism ; Signal Transduction ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is the most common form of breast cancer which accounts for 85% of all breast cancer diagnoses. Non-invasive and early stages have a better prognosis than late-stage invasive cancer that has spread to lymph nodes. The involvement of microRNAs (miRNAs) in the initiation and progression of breast cancer holds great promise for the development of molecular tools for early diagnosis and prognosis. Therefore, developing a cost effective, quick and robust early detection protocol using miRNAs for breast cancer diagnosis is an imminent need that could strengthen the health care system to tackle this disease around the world.

METHODS: We have analyzed putative miRNAs signatures in 100 breast cancer samples using two independent high fidelity array systems. Unique and common miRNA signatures from both array systems were validated using stringent double-blind individual TaqMan assays and their expression pattern was confirmed with tissue microarrays and northern analysis. In silico analysis were carried out to find miRNA targets and were validated with q-PCR and immunoblotting. In addition, functional validation using antibody arrays was also carried out to confirm the oncotargets and their networking in different pathways. Similar profiling was carried out in Brca2/p53 double knock out mice models using rodent miRNA microarrays that revealed common signatures with human arrays which could be used for future in vivo functional validation.

RESULTS: Expression profile revealed 85% downregulated and 15% upregulated microRNAs in the patient samples of IDC. Among them, 439 miRNAs were associated with breast cancer, out of which 107 miRNAs qualified to be potential biomarkers for the stratification of different types, grades and stages of IDC after stringent validation. Functional validation of their putative targets revealed extensive miRNA network in different oncogenic pathways thus contributing to epithelial-mesenchymal transition (EMT) and cellular plasticity.

CONCLUSION: This study revealed potential biomarkers for the robust classification as well as rapid, cost effective and early detection of IDC of breast cancer. It not only confirmed the role of these miRNAs in cancer development but also revealed the oncogenic pathways involved in different progressive grades and stages thus suggesting a role in EMT and cellular plasticity during breast tumorigenesis per se and IDC in particular. Thus, our findings have provided newer insights into the miRNA signatures for the classification and early detection of IDC.}, } @article {pmid38318566, year = {2024}, author = {Youh, J and Yamaguchi, Y and Hiraguchi, E}, title = {Centrifugally Spreading Annular Erythema as a Dermatological Indicator of Metastatic Breast Carcinoma.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e51641}, pmid = {38318566}, issn = {2168-8184}, abstract = {Breast cancer is the leading cause of skin metastasis in women with internal malignancies. This report highlights an atypical case of cutaneous metastasis of breast cancer (CMBC) in a 66-year-old woman. Starting four months before her dermatology consultation, the patient underwent a chemotherapy regimen comprising pertuzumab, trastuzumab, and vinorelbine for right breast cancer, right axillary lymph node enlargement, and bone metastases. After commencing chemotherapy, erythematous macules appeared around her right nipple. Subsequently, the cutaneous lesions developed into annular erythematous patches around her right nipple and began to coalesce and expand to the contralateral breast. A skin biopsy revealed dysplastic cells indicative of metastasis from invasive ductal carcinoma. In addition, lymphovascular tumor cell invasion was noted in the reticular dermis. Based on these clinical progressions and histopathologic findings, a diagnosis of CMBC was made, specifically considering the possibility of inflammatory breast cancer (IBC). The patient continued the same chemotherapy regimen for 17 cycles, which improved the skin lesions, but she succumbed to breast cancer two years later. This case emphasizes the importance of considering CMBC in breast cancer patients with expanding, treatment-resistant thoracic cutaneous lesions, especially in aggressive subtypes like IBC. The diverse presentations of CMBC require thorough histopathological evaluation.}, } @article {pmid38313690, year = {2024}, author = {Lind, M and Folmo, EJ and Kaufman, EA}, title = {Editorial: Self-understanding and other-understanding in personality pathology.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1328860}, pmid = {38313690}, issn = {1664-0640}, } @article {pmid38311000, year = {2024}, author = {Cavaller, L and Goupille, C and Arbion, F and Vilde, A and Body, G and Ouldamer, L}, title = {Metastatic profiles and survival differences between infiltrating ductal carcinoma and infiltrating lobular carcinoma in invasive breast cancer.}, journal = {Journal of gynecology obstetrics and human reproduction}, volume = {53}, number = {4}, pages = {102740}, doi = {10.1016/j.jogoh.2024.102740}, pmid = {38311000}, issn = {2468-7847}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/pathology ; *Carcinoma, Ductal, Breast/pathology ; Treatment Outcome ; Prognosis ; }, abstract = {BACKGROUND: In this study, we conducted a comprehensive evaluation of metastatic profiles and survival outcomes in patients with infiltrating ductal carcinoma (IDC) and infiltrating lobular carcinoma (ILC) treated at our university hospital center.

METHODS: We collected and analyzed data from all patients diagnosed with invasive breast cancer at our center between January 1, 2007, and 31 December 2014. We specifically compared three subgroups: patients with IDC, patients with ILC and patients with mixed carcinoma, which is a combination of IDC and ILC.

RESULTS: Among the 1963 patients treated for invasive breast cancer in our center during the study period, 1435 had IDC, 466 had ILC, and 59 had mixed carcinoma. The incidence of patients with at least one positive axillary lymph node differed significantly: 40 % for IDC, 36 % for ILC, and 45 % for mixed carcinoma (p = 0.001). However, there was no significant difference in the mean number of positive nodes (p = 0.1633). The occurrence of distant metastases was lower in patients with ILC (p = 0.04), particularly in the case of brain metastases (p = 0.01), although there was no difference in bone or visceral metastatic sites. Patients with ILC exhibited a longer mean time to metastasis from the initial diagnosis of invasive breast carcinoma. Overall survival (p = 0.0525) and survival without locoregional recurrence (p = 0.026) were significantly different. Specifically, the 5-year overall survival rates for IDC, ILC, and mixed carcinoma were approximately 95 %. Distance metastatic-free survival at 5 years was 85 % for IDC, 91 % for ILC, and 87 % for mixed carcinoma (p = 0.00506).

CONCLUSION: Our findings indicate variations in the distribution of distant metastatic sites among patients with IDC, ILC, and mixed carcinoma, as well as differences in survival outcomes. This study sheds light on the unique characteristics and clinical implications associated with these two distinct subtypes of invasive breast cancer.}, } @article {pmid38308423, year = {2024}, author = {Agaoglu, NB and Unal, B and Hayes, CP and Walker, M and Ng, OH and Doganay, L and Can, ND and Rana, HQ and Ghazani, AA}, title = {Genomic disparity impacts variant classification of cancer susceptibility genes in Turkish breast cancer patients.}, journal = {Cancer medicine}, volume = {13}, number = {3}, pages = {e6852}, pmid = {38308423}, issn = {2045-7634}, support = {Number YNY2016/144//The Istanbul Development Agency (ISTKA)/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/genetics ; *Carcinoma, Lobular ; Genomics ; *Carcinoma, Ductal, Breast ; Oncogenes ; }, abstract = {OBJECTIVE: Turkish genome is underrepresented in large genomic databases. This study aims to evaluate the effect of allele frequency in the Turkish population in determining the clinical utility of germline findings in breast cancer, including invasive lobular carcinoma (ILC), mixed invasive ductal and lobular carcinoma (IDC-L), and ductal carcinoma (DC).

METHODS: Two clinic-based cohorts from the Umraniye Research and Training Hospital (URTH) were used in this study: a cohort consisting of 132 women with breast cancer and a non-cancer cohort consisting of 492 participants. The evaluation of the germline landscape was performed by analysis of 27 cancer genes. The frequency and type of variants in the breast cancer cohort were compared to those in the non-cancer cohort to investigate the effect of population genetics. The variant allele frequencies in Turkish Variome and gnomAD were statistically evaluated.

RESULTS: The genetic analysis identified 121 variants in the breast cancer cohort (actionable = 32, VUS = 89) and 223 variants in the non-cancer cohort (actionable = 25, VUS = 188). The occurrence of 21 variants in both suggested a possible genetic population effect. Evaluation of allele frequency of 121 variants from the breast cancer cohort showed 22% had a significantly higher value in Turkish Variome compared to gnomAD (p < 0.0001, 95% CI) with a mean difference of 60 times (ranging from 1.37-354.4). After adjusting for variant allele frequency using the ancestry-appropriate database, 6.7% (5/75) of VUS was reclassified to likely benign.

CONCLUSION: To our knowledge, this is the first study of population genetic effects in breast cancer subtypes in Turkish women. Our findings underscore the need for a large genomic database representing Turkish population-specific variants. It further highlights the significance of the ancestry-appropriate population database for accurate variant assessment in clinical settings.}, } @article {pmid38307851, year = {2024}, author = {Coria, LM and Rodriguez, JM and Demaria, A and Bruno, LA and Medrano, MR and Castro, CP and Castro, EF and Del Priore, SA and Hernando Insua, AC and Kaufmann, IG and Saposnik, LM and Stone, WB and Prado, L and Notaro, US and Amweg, AN and Diaz, PU and Avaro, M and Ortega, H and Ceballos, A and Krum, V and Zurvarra, FM and Sidabra, JE and Drehe, I and Baqué, JA and Li Causi, M and De Nichilo, AV and Payes, CJ and Southard, T and Vega, JC and Auguste, AJ and Álvarez, DE and Flo, JM and Pasquevich, KA and Cassataro, J}, title = {A Gamma-adapted subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants and protects mice from infection.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {997}, pmid = {38307851}, issn = {2041-1723}, support = {R01 AI153433/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Mice ; Humans ; *SARS-CoV-2 ; Broadly Neutralizing Antibodies ; COVID-19 Vaccines ; *COVID-19/prevention & control ; Vaccines, Subunit ; Adjuvants, Immunologic ; Epitopes, B-Lymphocyte ; Antibodies, Viral ; Antibodies, Neutralizing ; Spike Glycoprotein, Coronavirus/genetics ; }, abstract = {In the context of continuous emergence of SARS-CoV-2 variants of concern (VOCs), one strategy to prevent the severe outcomes of COVID-19 is developing safe and effective broad-spectrum vaccines. Here, we present preclinical studies of a RBD vaccine derived from the Gamma SARS-CoV-2 variant adjuvanted with Alum. The Gamma-adapted RBD vaccine is more immunogenic than the Ancestral RBD vaccine in terms of inducing broader neutralizing antibodies. The Gamma RBD presents more immunogenic B-cell restricted epitopes and induces a higher proportion of specific-B cells and plasmablasts than the Ancestral RBD version. The Gamma-adapted vaccine induces antigen specific T cell immune responses and confers protection against Ancestral and Omicron BA.5 SARS-CoV-2 challenge in mice. Moreover, the Gamma RBD vaccine induces higher and broader neutralizing antibody activity than homologous booster vaccination in mice previously primed with different SARS-CoV-2 vaccine platforms. Our study indicates that the adjuvanted Gamma RBD vaccine is highly immunogenic and a broad-spectrum vaccine candidate.}, } @article {pmid38306823, year = {2024}, author = {Nimbalkar, R and Baheti, AM and Pawar, AT and Tagalpallewar, AA and Nimbalkar, MR}, title = {Eleven years of disease free survival in a case of Invasive Ductal Carcinoma (IDC) Rt Breast grade 3, stage 3, treated with add on Ayurveda treatment: A case report.}, journal = {Journal of Ayurveda and integrative medicine}, volume = {15}, number = {1}, pages = {100881}, pmid = {38306823}, issn = {0975-9476}, abstract = {Breast cancer shows high mortality, especially in women worldwide. This report discusses a case of female patient with a history of Invasive Ductal Carcinoma (IDC) Rt Breast, ER, PR negative, Grade 3 (Gr3) Stage 3 (St3) seen in our OPD treated with supporting herbo-mineral-metallic combination of Ayurveda medicines. Generally, breast cancers of such subtype and that too in Lower Outer Quadrant (LOQ) are always of a concern and can be more troublesome to the patient. When the patient came for the first time, her chief complaint was palpable lump in her right breast for previous three months. We advised her to undergo relevant investigations and, it was found to be malignant. She underwent surgery, Modified Radical Mastectomy,(MRM), followed by chemotherapy. During chemotherapy, which was Adriamycin + Cyclophosphamide (AC) protocol 4 cycles, followed by Docetaxel 4 cycles, every 21 days. After 2 cycles, she started complaints of pain in both calf regions, numbness in fingers of hand and foot, severe generalized skin rash with itching, hyperacidity and constipation. She visited our clinic again for the same, and Ayurveda treatment was started to her at this point. So, at the time of commencement of treatment, the diagnosis was "IDC Rt Breast, LOQ, Gr3 St3, ER, PR negative HER2Neu positive, post op, on chemo". After appropriate analysis based on Ayurvedic and modern parameters, she was diagnosed to have vitiation of Rakta and Pitta (Dushti avastha), due to cyto-toxic nature of (Visha exposure) chemotherapy and medication was planned accordingly, along with chemotherapy protocol. The Ayurveda treatment showed significant relief in the chemotoxicity symptoms, within one month and she could tolerate further chemotherapy cycles very conveniently. On completion of chemotherapy, she was diagnosed to have need of good immunity (Vyadhi-Kshamatva). Based on this diagnosis, Ayurveda treatment protocol was changed and this new regimen continued for almost 6 years afterwards. Laboratory and imaging investigations performed periodically showed marked improvement, and even currently not showing any abnormality. Till date, there is no recurrence and patient is living completely normally for last 11 years. As all the symptoms and investigations showed near complete improvement; it may be concluded that probably add on Ayurveda treatment (Integrative approach) proved effective in this patient of IDC. We have observed 11 years of disease-free survival and excellent quality of life in this patient and still ongoing.}, } @article {pmid38306382, year = {2024}, author = {Moreau, A and Mognetti, T and Kryza, D}, title = {Misleading FDG Uptake in Oncology Assessment: Beyond COVID-19 Vaccination-The Role of Pneumococcal Vaccination.}, journal = {Clinical nuclear medicine}, volume = {49}, number = {3}, pages = {283-284}, doi = {10.1097/RLU.0000000000005049}, pmid = {38306382}, issn = {1536-0229}, mesh = {Female ; Humans ; Adult ; Fluorodeoxyglucose F18 ; Positron Emission Tomography Computed Tomography ; COVID-19 Vaccines ; Radiopharmaceuticals ; Lymphatic Metastasis/pathology ; *COVID-19 ; Lymph Nodes/diagnostic imaging/pathology ; *Breast Neoplasms/pathology ; Vaccination ; }, abstract = {Here, we report the case of a 35-year-old woman who performed PET/CT 18F-FDG as an initial workup for HER2+ right breast invasive ductal carcinoma. Examination revealed multifocal breast involvement with homolateral lymph node involvement. Contralateral axillary adenopathy and diffuse splenic and osteomedullary hypermetabolism were also observed, suggesting associated lymphoma in the absence of a recent COVID-19 vaccination. Cytopuncture was discussed and finally postponed after the patient was found to have recently received a pneumococcal vaccination.}, } @article {pmid38305220, year = {2024}, author = {Tsilingiris, D and Schimpfle, L and Κender, Z and Sulaj, A and von Rauchhaupt, E and Herzig, S and Szendroedi, J and Kopf, S}, title = {Utility of bioelectrical phase angle for cardiovascular risk assessment among individuals with and without diabetes mellitus.}, journal = {Diabetes & vascular disease research}, volume = {21}, number = {1}, pages = {14791641231223701}, pmid = {38305220}, issn = {1752-8984}, mesh = {Adult ; Humans ; Male ; Female ; *Cardiovascular Diseases/diagnosis/etiology ; Carotid Intima-Media Thickness ; Pulse Wave Analysis ; *Diabetes Mellitus, Type 1 ; Risk Factors ; Heart Disease Risk Factors ; *Diabetes Mellitus, Type 2 ; Natriuretic Peptide, Brain ; Peptide Fragments ; Biomarkers ; }, abstract = {PURPOSE: Low values of bioimpedance-derived phase angle (PA) have been associated with various adverse outcomes. We investigated the association of PA with cardiovascular markers in individuals with and without diabetes mellitus (DM).

METHODS: PA was measured in 452 adults (without DM n = 153, T1DM n = 67, T2DM n = 232). Carotid intima-media thickness (IMT), renal resistive index (RRI), ankle-brachial index (ABI) and carotid-femoral Pulse Wave Velocity (cfPWV) were estimated. Furthermore, the levels of high-sensitive Troponin-T [hsTnT], N-terminal brain natriuretic peptide [NT-pro-BNP]) were measured.

RESULTS: PA values were lower in DM independently of age, gender, and BMI (estimated marginal means 6.21, 5.83, 5.95 for controls, T1DM, T2DM p < .05), a finding which persisted after propensity score matching. PA correlated negatively with IMT (r = -0.181), RRI (r = -0.374), cfPWV (r = -0.358), hsTnT (r = -0.238) and NT-pro-BNP (r = -0.318) (all p < .001). In multivariable analysis, the associations with RRI, cfPWV, hsTnT and NT-pro-BNP remained unchanged. PA values 6.0-6.5° for males and 5.2-5.8° for females were predictive of commonly used cutoffs. The combination of ΑCC/AHA ASCVD Score with PA outperformed either factor in predicting cfPWV, RRI for males and hsTnT, BNP for both genders.

CONCLUSIONS: PA exhibits independent correlations with various parameters pertinent to cardiovascular risk and may be useful for cardiovascular assessment.}, } @article {pmid38304352, year = {2024}, author = {Mogere, E and Mutebi, M and Njau, A and Mansour, MH and Abuodha, J and Okiro, P}, title = {A rare case of breast carcinoma metastasis into a meningioma in a 64-year-old female patient.}, journal = {Radiology case reports}, volume = {19}, number = {4}, pages = {1519-1523}, pmid = {38304352}, issn = {1930-0433}, abstract = {This report discusses the occurrence of tumor-to-tumor metastasis-an atypical phenomenon in oncology where a secondary malignancy develops within an existing primary tumor. The case of a 64-year-old woman is presented, who, with a history of stage II invasive ductal carcinoma of the breast treated with mastectomy and chemoradiotherapy, developed neurological symptoms indicative of a secondary brain tumor. MRI and subsequent histopathological analysis post-craniotomy confirmed a meningioma with a metastatic breast carcinoma, demonstrating the clinical importance of considering tumor-to-tumor metastasis in similar patient histories.}, } @article {pmid38304030, year = {2023}, author = {Cao, T and Duan, Z and Zhu, J and Wu, J and Chen, J and Jiang, M and Lu, X and Li, Y}, title = {Case report: Urothelial injury in a female with breast cancer: a rare adverse event after the combination of paclitaxel and trastuzumab.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1258474}, pmid = {38304030}, issn = {2234-943X}, abstract = {Several breast cancer (BC) patients showed urinary tract infection after adjuvant trastuzumab plus paclitaxel, but no case of urothelial injury has been reported. In this case, we report a 47-year-old female patient with stage I invasive ductal carcinoma in the left breast presenting with urothelial injury after the combination of trastuzumab and paclitaxel. Initially, the patient was highly suspected of having urinary tract infection as she showed abdominal and low back pain, as well as urinary irritation symptoms and hematuria. Unfortunately, the conditions were not attenuated after anti-infection therapy. Contrast-enhanced CT showed extensive exudation and edema in the bilateral renal pelvis, ureter, and bladder, together with dilatation and effusion in the renal pelvis and ureter. Cystoscopy showed extensive congestion, edema, and erosion in the bladder epithelium. Pathological analysis demonstrated slight thinning or even loss in the uroepithelial cell layer and interstitial congestion. In addition, there was growth arrest in the epithelial cells. Immunohistochemistry indicated HER2 expression in the urothelial cells. Finally, the patient was diagnosed with urothelial injury after combination of paclitaxel and trastuzumab. The symptoms were spontaneously cured with no administration of any antibiotics in the 3-month follow-up.}, } @article {pmid38303360, year = {2023}, author = {Maeda, N and Yu, X and Nabeya, M and Suyama, R and Suzuki, N and Takeda, S and Tamesa, M and Nagashima, Y and Kubo, H and Yamamoto, S and Nagano, H}, title = {[Invasive Ductal Carcinoma within a Borderline Malignancy Phyllodes Tumor-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {13}, pages = {1618-1620}, pmid = {38303360}, issn = {0385-0684}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/pathology ; *Phyllodes Tumor/surgery/diagnosis ; Mastectomy ; *Fibroadenoma/diagnosis ; *Carcinoma, Ductal/surgery ; }, abstract = {Phyllodes tumors are uncommon breast neoplasms that constitute 1-2% of breast malignancies. Invasive ductal carcinoma in the epithelial component of phyllodes tumor is very rare. When carcinoma is detected within the specimen, the management of treatment changes completely. We report a rare case of invasive ductal carcinoma arising in a giant borderline malignancy phyllodes tumor in a 51-year-old female patient. A painful 20 cm mass was found in her right breast, and a needle biopsy revealed fibroadenoma or benign phyllodes tumor, and a total mastectomy was performed. Pathological results showed that a borderline malignant phyllodes tumor coexisted with invasive ductal carcinoma. We explained that axillary surgery was necessary because invasive cancer was diagnosed after surgery, but the patient requested follow-up using images. Endocrine therapy was performed as postoperative adjuvant therapy, and the follow-up is underway without recurrence.}, } @article {pmid38303330, year = {2023}, author = {Awazu, M and Yamamoto, Y and Agawa, K and Omura, N and Nakayama, S and Idei, Y and Maeda, H}, title = {[Long-Term Survival with Distal Pancreatectomy and Postoperative Chemotherapy in a Patient of Pancreatic Invasive Ductal Adenocarcinoma of the Tail with Peritoneal Dissemination].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {13}, pages = {1528-1530}, pmid = {38303330}, issn = {0385-0684}, mesh = {Male ; Humans ; Aged ; Pancreatectomy ; *Pancreatic Neoplasms/drug therapy/surgery/pathology ; *Carcinoma, Pancreatic Ductal/drug therapy/surgery/pathology ; Lymph Node Excision ; *Liver Neoplasms/surgery ; }, abstract = {A 68-year-old man was referred to our hospital for detailed examination of the pancreatic tail tumor. The tumor was diagnosed as the pancreatic invasive ductal adenocarcinoma and the distal pancreatectomy was scheduled. During surgery, a 2 mm white nodule was observed on the posterior wall of the stomach. Intraoperative frozen section showed no obvious malignant findings, suggesting leiomyoma or gastrointestinal stromal tumor. Distal pancreatectomy with D2 lymphadenectomy was completed as planned. However, this nodule was later confirmed by permanent pathological specimen to be peritoneal dissemination of pancreatic cancer and final diagnosis was invasive ductal carcinoma of pancreatic tail, pT3, pN1a, M1 (PER), pStage Ⅳ. He received chemotherapy for 17 months. Although liver metastasis was appeared 26 months after surgery, the disease is still being controlled with chemotherapy at 33 months.}, } @article {pmid38303308, year = {2023}, author = {Aoyagi, T and Namura, M and Sakata, H and Tamanuki, T and Iwai, M and Iwata, K and Takahashi, H and Matsuzaki, H}, title = {[A Case of Recurrent Breast Cancer That Was BRCA1 Pathogenic Variant-Positive Successfully Treated with PARP Inhibitor].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {13}, pages = {1462-1464}, pmid = {38303308}, issn = {0385-0684}, mesh = {Female ; Humans ; Aged ; Middle Aged ; *Breast Neoplasms/drug therapy/genetics/surgery ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Mastectomy ; Neoplasm Recurrence, Local/drug therapy/surgery ; *Antineoplastic Agents/therapeutic use ; BRCA1 Protein/genetics ; }, abstract = {The patient was a 51-year-old woman at the time of diagnosis of left breast cancer. She underwent a mastectomy and axillary dissection. Pathological findings were invasive ductal carcinoma of the breast, tumor diameter 25 mm, and metastasis in 2 of 16 removed axillary lymph nodes. The subtype was triple negative. Postoperative chemotherapy was administered, and the patient was followed by follow-up imaging. At the age of 63 years, ultrasonography showed local recurrence, and local mass excision was performed. Genetic abnormalities were suspected since she had a family history of breast cancer, and it was a recurrent case. After genetic counseling, she underwent genetic testing, which revealed a BRCA1 pathogenic variant, so we initiated imaging surveillance. At age 65, a chest CT scan was performed due to respiratory symptoms, and she was diagnosed with multiple lung metastases. Respiratory symptoms improved at the examination 1 month after administration of Poly ADP ribose polymerase(PARP)inhibitor, and the metastatic masses shrank at the CT scan 3 months later. She continues to maintain CR and has no respiratory symptoms at present.}, } @article {pmid38303307, year = {2023}, author = {Hayakawa, T and Hasegawa, K and Maejima, K and Takatsuno, Y and Kaneko, J and Higashi, Y and Isogai, J and Tagawa, K and Yoshida, H}, title = {[A Case of Complete Remission in a Patient with Synchronous Double Cancers of the Breast and Lung].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {13}, pages = {1459-1461}, pmid = {38303307}, issn = {0385-0684}, mesh = {Female ; Humans ; Aged ; *Breast Neoplasms/surgery/diagnosis ; Mastectomy ; Sentinel Lymph Node Biopsy ; Lung/pathology ; *Lung Neoplasms/surgery ; }, abstract = {The patient is a 74-year-old woman. She had breast cancer(invasive ductal carcinoma, ER[+], PgR[+], HER2[-], Ki-67: 30-40%)and primary right lung cancer with lumbar metastasis, which led to the diagnosis synchronous double cancers of the breast and the lung. We decided to precede surgery for lung cancer because breast cancer was indicated hormonal receptor positive. Breast cancer is treated with anastrozole, thoracoscopic right upper lobectomy was performed for the lung cancer. Radiation therapy was performed for metastatic bone tumors. 13 months later, partial mastectomy sentinel lymph node biopsy performed. The histopathological diagnosis of breast cancer was pT2, pN0, cM0, pStage ⅡA, and histological response was Grade 2a. The remaining breast was treated radiation therapy. The breast cancer has not recurred and is doing well 6 months after surgery. As for primary lung cancer, 19 months have passed since surgery, and the patient is in complete remission without recurrence.}, } @article {pmid38303227, year = {2023}, author = {Adachi, K and Nagae, J and Kubota, H and Suzuki, S and Hirano, T and Sakurai, K}, title = {[Recurrent Breast Cancer with Bone Metastasis Effectively Treated with Abemaciclib plus Endocrine Therapy-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {13}, pages = {1845-1847}, pmid = {38303227}, issn = {0385-0684}, mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/surgery ; Antineoplastic Agents, Hormonal/therapeutic use ; Positron Emission Tomography Computed Tomography ; Mastectomy ; Neoplasm Recurrence, Local/surgery ; Tamoxifen/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Aminopyridines ; *Benzimidazoles ; }, abstract = {We report a case of recurrent breast cancer with bone metastasis in a premenopausal woman. A 46-year-old woman underwent mastectomy for right breast cancer 6 years ago. Histopathological diagnosis was invasive ductal carcinoma, T2N3aM0, stage ⅢC. She received adjuvant chemotherapy and irradiation followed by tamoxifen. Four and a half years after surgery, serum tumor marker levels elevated, and bone metastasis in the sacral region was revealed by PET-CT scan. After suppressing ovarian function with LH-RH agonist, we switched the endocrine therapy from tamoxifen to letrozole with a CDK4/6 inhibitor. Five months after starting administration of abemaciclib, the bone metastasis disappeared on PET-CT. The elevated tumor markers normalized and have continued to decrease. Abemaciclib combined with endocrine therapy was significantly effective as first-line treatment for premenopausal women with metastatic breast cancer.}, } @article {pmid38303226, year = {2023}, author = {Kikukawa, Y and Kawajiri, H and Tanda, H and Sakimura, C and Tendo, M and Hori, T and Nakata, B and Ishikawa, T and Hirakawa, K}, title = {[A Case of Multicentric HER2-Positive Breast Cancer with Alterations of the Intrinsic Subtype].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {13}, pages = {1842-1844}, pmid = {38303226}, issn = {0385-0684}, mesh = {Humans ; Female ; Adult ; *Breast Neoplasms/drug therapy/surgery/pathology ; *Carcinoma, Ductal, Breast/drug therapy ; Erb-b2 Receptor Tyrosine Kinases/analysis ; Biopsy, Large-Core Needle ; Pain ; Receptors, Progesterone ; Neoadjuvant Therapy ; Biomarkers, Tumor/analysis ; }, abstract = {In cases where there are 2 or more tumors, it is crucial to conduct core needle biopsies on each of them. A 39-year-old woman presented at our hospital with pain in her left breast. Ultrasonography(US)revealed the presence of 2 contiguous tumors: a 35 mm tumor(tumor 1)and a 20 mm tumor(tumor 2)in the AC area of the left breast. US-guided core needle biopsies(CNB)were performed. The histological findings confirmed an invasive ductal carcinoma, characterized by ER(-)/ PR(-)/HER2(3+). Neoadjuvant chemotherapy indicated tumor 1 as PD and tumor 2 as PR, and surgery was subsequently performed(Bt plus SLN). Upon histopathological examination, the findings demonstrated a non-pCR invasive ductal carcinoma, featuring an ER(+)/PR(-)/HER2(-)profile. Depending on the specific subtype identified, post-operative treatment included HER2-targeted therapy or ER/PR-targeting hormone therapy in conjunction with chemotherapy.}, } @article {pmid38303198, year = {2023}, author = {Yabe, N and Watanuki, R and Harada, Y and Kondo, A and Yanagisawa, T and Maeda, H and Kishi, M and Yoshikawa, T and Osumi, K and Kamiya, N and Sotome, K and Ishii, Y and Jinno, H and Ikeda, T and Watanabe, M}, title = {[A Case of Triple Negative Breast Cancer with Successful Control of Recurrent Disease Activity for More than Ten Years].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {13}, pages = {1759-1761}, pmid = {38303198}, issn = {0385-0684}, mesh = {Female ; Humans ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/drug therapy/surgery/pathology ; Capecitabine/therapeutic use ; *Liver Neoplasms/drug therapy ; Mastectomy ; Neoplasm Recurrence, Local/drug therapy/surgery ; *Triple Negative Breast Neoplasms/drug therapy ; Aged ; }, abstract = {A woman in her 70s underwent mastectomy plus axillary lymph node excision(Bt plus Ax)in December 2011 for left breast cancer classified as pT2N1M0, pStage ⅡB. The tumor was identified as an invasive ductal carcinoma(IDC), neural/ glial antigen 2(NG2), pT2(35 mm), INF γ, ly2, v0, g+, f+, s+, extensive intraductal component(EIC)-negative, ICT- positive, NCAT-positive, n(4/18), estrogen receptor(ER)-negative, progesterone receptor(PgR)-negative, human epidermal growth factor receptor 2(HER2)-negative, Ki-67 30-40%. Postoperative adjuvant fluorouracil plus epirubicin HCl plus cyclophosphamide(FEC)plus paclitaxel(PTX)therapy was administered. The patient refused to undergo postoperative radiation therapy. Two years after the surgery, she was diagnosed as having a lung metastasis and local disease recurrence. Biopsy of the local recurrent lesion revealed the same histopathological diagnosis as before. Capecitabine was selected for treatment of the recurrent lesion. After 2 years of capecitabine treatment, the response was rated as progressive disease (PD). At this time, eribulin mesylate was selected, along with intensity-modulated radiation therapy(IMRT). This resulted in disappearance of the tumor on imaging. However, considering that the histological findings did not suggest complete response(CR)and that the tumor was triple-negative(TN), we adopted a strategy of continuing the drug therapy at reduced dose level. With this strategy, the disease activity could be successfully controlled for 6.5 years. Subsequently, liver metastasis was detected, and the drug was switched to vinorelbine ditartrate(a drug with less non-hematological toxicity). Meanwhile, a breast cancer susceptibility gene(BRCA)analysis was performed in January 2021, which was negative. Subsequently, in September 2021, we obtained a positive result for PDL1-SP142 and negative result for 22C3. About half a year later, ie, in October 2021(11 years after the surgery), we detected an increase in the size of the liver metastasis and selected atezolizumab and nab-PTX for treatment. Applicable regimens of drug therapy are still available at present and drug therapy has been continued based on a discussion and mutual understanding of the adverse reactions, etc. with the patient. Few reports have been published concerning long-term survivors among TN breast cancer cases.}, } @article {pmid38303174, year = {2023}, author = {Takeda, Y and Ohmura, Y and Katsura, Y and Shinke, G and Kinoshita, M and Aoyama, S and Kihara, Y and Yanagisawa, K and Katsuyama, S and Ikeshima, R and Hiraki, M and Sugimura, K and Masuzawa, T and Hata, T and Murata, K}, title = {[Robotic and Laparoscopic Pancreaticoduodenectomy for the Elderly Patients-A Single Institutional Experience].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {13}, pages = {1688-1690}, pmid = {38303174}, issn = {0385-0684}, mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; Pancreaticoduodenectomy/adverse effects ; *Pancreatic Neoplasms/surgery/complications ; Pancreatic Fistula/etiology ; *Robotic Surgical Procedures/adverse effects ; Retrospective Studies ; *Laparoscopy/adverse effects ; Postoperative Complications/epidemiology/etiology ; Length of Stay ; *Carcinoma, Ductal/complications ; }, abstract = {INTRODUCTION: Laparoscopic pancreaticoduodenectomy(LPD)has been covered by insurance since 2016 in Japan. Advance LPD and robotic pancreaticoduodenectomy(RPD)has been also covered by insurance since 2020 in Japan. The aim of this study was to analyze the perioperative results and outcomes of RPD and LPD for the elderly patients and to compare to the non-elderly patients.

PATIENTS AND METHOD: Between July 2020 and April 2023, 67 patients underwent RPD and between May 2012 and February 2021, 63 patients underwent LPD at Kansai Rosai Hospital. Sixty-seven RPD and 62 LPD patients without extended resection were divided into 2 groups those who were over 75 years old(R/LPD E)(n=55)and under 74 years old(R/LPD non-E)(n=74). Control patients who received open pancreaticoduodenectomy(OPD)without extended resection between April 2010 and April 2023 were also divided into 2 groups those who were over 75 years old(OPD E)(n =60)and under 74 years old(OPD non-E)(n=78). The patient age was 79.0 and 60.5 years, the male to female ratio was 35/20 and 45/29, disease ratio(invasive ductal carcinoma or not)was 7/48 and 9/65 in R/LPD E and R/LPD non-E groups, respectively. The patient age was 79.0 and 79.5 years, the male to female ratio was 35/20 and 31/29, disease ratio (invasive ductal carcinoma or not)was 7/48 and 30/30(p<0.0001)in R/LPD E and OPD E groups, respectively. This study was approved by the Human Ethics Review Committee of Kansai Rosai Hospital(Certificate Number: 2001019).

RESULTS: The average operation time was 644.6 and 675.2 minutes, an estimated blood loss was 220.8 and 134.4 g, postoperative pancreatic fistula(ISGPS 2016, [-]/BL/Grade B/C)was 24/18/13/0 and 28/25/21/0, delayed gastric emptying(ISGPS 2007, [-]/Grade A/B/C)was 48/0/4/3 and 61/2/6/5 and postoperative hospital stay was 27.9 and 25.9 and in R/LPD E and R/LPD non-E groups, respectively. No significant differences were noted between the groups, However, postoperative complication over Ⅲa Clavien-Dindo classification was 8(15.7%)and 3(4.4%)cases(p=0.0319)in R/LPD E and R/ LPD non-E groups. The average operation time was 644.6 and 492.1 minutes(p<0.0001), an estimated blood loss was 220.8 and 534.8 g(p=0.0004), postoperative pancreatic fistula(ISGPS 2016, [-]/BL/Grade B/C)was 24/18/13/0 and 27/8/24/1(p=0.0442), postoperative hospital stay was 27.9 and 42.0(p=0.0490)in R/LPD E and OPD E groups, respectively.

CONCLUSION: The R/LPD was undergone in safety, even for the over 75 years old patients.}, } @article {pmid38299501, year = {2024}, author = {Bernardino, R and Sayyid, RK and Lajkosz, K and Al-Daqqaq, Z and Tiwari, R and Cockburn, J and Leão, R and Metser, U and Berlin, A and van der Kwast, T and Fleshner, NE}, title = {Intraductal Prostate Cancer Affinity for Lymphatic-Predominant Metastases Through [18]F-DCFPyL‒Prostate-Specific Membrane Antigen‒Positron Emission Tomography/CT Scans in Pretreatment Prostate Cancer Patients.}, journal = {The Journal of urology}, volume = {211}, number = {4}, pages = {586-593}, doi = {10.1097/JU.0000000000003850}, pmid = {38299501}, issn = {1527-3792}, mesh = {Male ; Humans ; Lymphatic Metastasis/pathology ; *Positron Emission Tomography Computed Tomography/methods ; Prostate/pathology ; Cross-Sectional Studies ; *Prostatic Neoplasms/pathology ; Positron-Emission Tomography ; Tumor Microenvironment ; }, abstract = {PURPOSE: Intraductal prostate cancer (IDC) is linked to unfavorable oncologic outcomes, marked by distinctive cellular intrinsic pathway changes and intricate immunosuppressive microenvironments that could impact the way cancer spreads. The aim of this study was to determine whether the presence of IDC in prostate biopsy specimens obtained from patients before primary prostate cancer (PCa) treatment is associated with a lymph node metastatic propensity in prostate-specific membrane antigen (PSMA)‒positron emission tomography (PET)/CT.

MATERIALS AND METHODS: This was a cross-sectional analysis of all PCa patients undergoing a pretreatment [18]F-DCFPyL-PSMA-PET/CT between January 1, 2016, and August 2021 at The Princess Margaret Cancer Centre. Outcomes were presence of any metastasis in the overall cohort, presence of lymphatic vs no metastases, and presence of lymphatic vs bone metastasis among patients who underwent PSMA-PET/CT as PCa primary staging. The associations between IDC presence on the prostate biopsy and the study outcomes were evaluated using univariable and multivariable logistic regression analyses.

RESULTS: The cohort consisted of 120 patients. IDC and cribriform pattern were observed in 55 (46%) and 48 (40%) prostate biopsies, respectively. Overall, 52 patients (43%) had evidence of metastasis. Presence of IDC on biopsy was associated with increased odds of overall metastasis (odds ratio: 2.47, 95% CI: 1.09-5.61, P = .03). Of the 52 patients with evidence of metastasis, 41 (79%) had evidence of lymphatic metastasis. Presence of IDC on biopsy was associated with significantly increased odds of lymphatic metastasis vs nonmetastases (odds ratio: 3.03, 95% CI: 1.24-7.40, P = .01).

CONCLUSIONS: The identification of IDC morphology in prostate biopsy specimens has been observed to be significantly linked with lymph node metastasis on [18]F-DCFPyL-PET/CT imaging in a PCa pretreatment staging setting. We found that presence of IDC in prostate biopsy appears to be a marker for lymph node metastasis on [18]F-DCFPyL-PET/CT.}, } @article {pmid38298032, year = {2024}, author = {Gan, L and Xie, J and Li, K and Xu, Z and Wang, X and Pei, X and Xue, B}, title = {Triple-Negative or Close-to-Triple-Negative Breast Cancer Presenting as a Thick-Walled Cystic Lesion.}, journal = {The American surgeon}, volume = {90}, number = {6}, pages = {1756-1759}, doi = {10.1177/00031348241230089}, pmid = {38298032}, issn = {1555-9823}, mesh = {Adult ; Female ; Humans ; Middle Aged ; Breast Cyst/diagnosis/pathology/diagnostic imaging/surgery ; Breast Neoplasms/pathology/diagnosis/surgery/diagnostic imaging ; *Carcinoma, Ductal, Breast/pathology/diagnosis/surgery ; Magnetic Resonance Imaging ; Mammography ; *Triple Negative Breast Neoplasms/pathology/surgery/diagnosis ; Ultrasonography, Mammary ; }, abstract = {Clinical and pathologic characteristics of the invasive ductal carcinoma (IDC) presenting as a thick-walled breast cyst are little known. Three female patients were included in this report. A palpable, nontender breast lump was found in all cases. While mammography showed a hyperdense mass, ultrasonography demonstrated a thick-walled cystic mass. Magnetic resonance imaging clearly showed the cystic breast lesions with ring-like or irregular rim enhancement. A grade III IDC was confirmed in all cases. All IDCs but one were estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 negative, with merely weak progesterone receptor positivity (5%) in one case. All cases underwent surgical management first and postoperative chemotherapy. Breast malignancy presenting as a thick-walled cystic mass could be a highly aggressive IDC, even triple-negative breast cancer. It is imperative for breast cancer-related practitioners to identify the potentially malignant cystic lesions timely and adopt appropriate management.}, } @article {pmid38297914, year = {2024}, author = {Alex, J and Ferguson, C and Ramjan, LM and Maneze, D and Montayre, J and Salamonson, Y}, title = {Development and psychometric evaluation of an expanded urinary catheter self-management scale: A cross-sectional study.}, journal = {Journal of advanced nursing}, volume = {80}, number = {8}, pages = {3199-3210}, doi = {10.1111/jan.16081}, pmid = {38297914}, issn = {1365-2648}, support = {2020 Nursing & Midwifery Career Development Grant Scheme//Westmead Charitable Trust/ ; CF is supported by an NHMRC Investigator Grant 202//National Health and Medical Research Council/ ; 2018 Western Sydney Local Health District Research//Western Sydney Local Health District/ ; 2019 Integrated and Community Health Research Laun//Western Sydney Local Health District/ ; }, mesh = {Humans ; *Psychometrics ; Cross-Sectional Studies ; Male ; Female ; *Self-Management/psychology ; Aged ; Middle Aged ; *Urinary Catheterization/psychology ; Aged, 80 and over ; Adult ; Reproducibility of Results ; Urinary Catheters ; Surveys and Questionnaires/standards ; Self Care/psychology ; Catheters, Indwelling ; }, abstract = {AIM: To develop and test the psychometric properties of an expanded catheter self-management scale for patients with in-dwelling urinary catheters.

DESIGN: A cross-sectional validation study. Despite the utility of the original 13-item catheter self-management scale, this instrument did not include bowel management, general hygiene and drainage bag care, which are fundamental skills in urinary catheter self-management to prevent common problems resulting in unnecessary hospital presentations. The expanded catheter self-management scale was developed with 10 additional items to comprehensively assess all five essential aspects of urinary catheter self-management.

METHODS: A total of 101 adult community-dwelling patients living with indwelling urinary catheters were recruited from Western Sydney, Australia. Using exploratory factor analysis with Varimax rotation, the number of factors to be extracted from the expanded 23-item expanded catheter self-management scale was determined using a scree plot. The reliability of the overall scale and subscales was measured using Cronbach's alpha. Convergent validity was assessed using Spearman's correlations between clinical characteristics, overall scale and subscales.

RESULTS: The 23-item expanded catheter self-management scale yielded a 5-factor solution, labelled as: (i) self-monitoring of catheter function, (ii) proactive, help-seeking behaviour function, (iii) bowel self-care function, (iv) hygiene-related catheter site function and (v) drainage bag care function. Cronbach's alpha of the expanded catheter self-management scale indicating all 23 items contributed to the overall alpha value. Convergent validity results showed a negative correlation between the overall expanded catheter self-management scale and catheter-related problems.

CONCLUSION: The 5-factor structure provided a comprehensive assessment of key aspects of urinary catheter self-management essential to reduce the likelihood of catheter-related hospital presentations.

IMPLICATIONS: The expanded catheter self-management scale can be used to assess and monitor effective patient-centred interventions for optimal self-management to prevent catheter-related problems and improve the quality of life of patients.

IMPACT: Many patients start their journey of living with a urinary catheter unexpectedly and are not supported with quality information to care for their catheter. The findings of this study show the correlation between catheter self-management skills and catheter-related problems. The expanded catheter self-management scale (E-CSM) assists with analysing the self-management skills of patients living with a catheter and developing tailored interventions to prevent problems and improve their quality of life. In addition, this screening tool can be included in policies, guidelines, and care plans as a standard for improving catheter management and developing educational resources for patients.

REPORTING METHOD: STROBE checklist was used to report all aspects of this study comprehensively and accurately.

Patients living with indwelling urinary catheter and their carers have participated in surveys, interviews and co-designing interventions. This paper reports the psychometric analysis of the expanded catheter self-management scale (E-CSM) used in the patient survey as part of the main study 'Improving Quality of Life of Patients Living with Indwelling Urinary Catheters: IQ-IDC Study' (Alex et al. in Collegian, 29:405-413, 2021). We greatly value our consumers' contributions and continue to communicate the progress of the study to them. Their contributions will be acknowledged in all publications and presentations. In addition, all participants will be provided the option of receiving the interventions and publications generated from this study.}, } @article {pmid38288100, year = {2023}, author = {Chan, B and Lee, JS and Yuan, Y}, title = {Case report: An exceptional responder of low-dose continuous 5-FU in a patient with de-novo stage IV triple-negative breast cancer with liver and bone marrow failure.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1305584}, pmid = {38288100}, issn = {2234-943X}, abstract = {Continuous low-dose 5-FU was popularized as a therapy for pretreated metastatic breast cancer for the past few decades, spurred by the advent of the electronic infusion pump. Capecitabine, otherwise known by its trade name Xeloda, is a prodrug of 5-fluorouracil (5-FU), which is administered orally in many chemotherapy regimens, and plays a role in metastatic breast cancer treatment refractory to traditional anthracyclines and taxane therapy. In this case presentation, we describe a unique case of refractory de-novo stage IV triple-negative breast cancer presented with right breast primary invasive ductal carcinoma, extensive lymphadenopathy, with biopsy proven bone marrow infiltration, diffuse hepatomegaly, splenomegaly, significant hyperbilirubinemia, and bone marrow failure treated with continuous 5-FU infusion and subsequently oral capecitabine after initial treatment failure with nab-paclitaxel and sacituzimab govitecan. With this case presentation, the authors aim to showcase the versatility of 5-FU and its prodrug in treatment of metastatic triple-negative breast cancer with severe bone marrow and liver involvement while highlighting key physiologic and pharmacologic mechanisms.}, } @article {pmid38285778, year = {2024}, author = {El-Deek, HEM and El-Naggar, MS and Sayed, SG}, title = {Immunohistochemical Expression of Autophagy-Related Marker (LC3B) and Stem Cell Marker (CD44) in Molecular Subtypes of Breast Cancer.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {25}, number = {1}, pages = {145-152}, pmid = {38285778}, issn = {2476-762X}, mesh = {Female ; Humans ; Autophagy ; Biomarkers, Tumor/metabolism ; Breast/pathology ; *Breast Neoplasms/pathology ; *Hyaluronan Receptors/metabolism ; Neoplastic Stem Cells/metabolism ; Prognosis ; *Microtubule-Associated Proteins/metabolism ; Immunohistochemistry ; }, abstract = {BACKGROUND: Breast cancer (BC) is among the most prevalent aggressive type of malignancy affecting females worldwide. Despite the advance in early detection and management of BC; recurrence, metastasis and mortality remains high. This may be attributed to heterogeneity of BC which explained by the presence of breast cancer stem cells (BCSCs). BCSCs is characterized by their ability of self-renewal, unlimited proliferation and their differentiation potential. BCSCs maintain their activity through process of autophagy. Autophagy is a catabolic pathway important for maintenance of cellular hemostasis in response to different stressful conditions. Autophagy allows BCSCs to adapt to different stressful conditions. So, it protects BCSCs from cytotoxic effects of anti-cancer therapy and anticancer resistance.

METHODS: Formalin-fixed paraffin embedded fifty specimens of Invasive duct carcinoma of no special type(IDC/NST) of breast was selected and immunostained with stem cell marker CD44 and autophagy related marker LC3B antibodies. Correlation with different clinicopathological, histopathological characteristics and molecular subtypes of studied specimens were evaluated.

RESULTS: Both CD44 and LC3B expression were significantly associated with lymph nodal metastasis (p =0.001 and 0.010 respectively), advanced pathological stage (p= 0.045 and 0.004 respectively) and with triple negative molecular subtype of BC (p=0.044 and 0.048 respectively). Statistically positive correlation was also found between both tumor markers expression.

CONCLUSION: Results of this study suggests that CD44 and LC3B expression play a role in the clinical behavior and progression of different molecular subtypes of BC.}, } @article {pmid38285770, year = {2024}, author = {Younas, H and Shahid, M and Khan, Z and Fatima, K and Tasadduq, R}, title = {Investigating the association of Angiotensin II Type I Receptor A1166C Polymorphism with Breast Cancer Risk in the Pakistani Population.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {25}, number = {1}, pages = {79-85}, pmid = {38285770}, issn = {2476-762X}, mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/genetics ; Angiotensin II/genetics ; Pakistan/epidemiology ; Polymorphism, Genetic ; Renin-Angiotensin System/genetics ; Genotype ; Genetic Predisposition to Disease ; }, abstract = {The polymorphisms of the Renin-Angiotensin System are related to many disorders like diabetes, cardiovascular disease, and different types of cancer. Among all the polymorphisms related to AGTR1, A1166C has been associated with several disorders, including cardiovascular diseases and breast cancer. This study was conducted to discover the association of AGTR1 polymorphism (A1166C) Renin-Angiotensin and its effect on the development and progression of breast cancer in the Pakistani population. One hundred forty participants, including seventy diagnosed breast cancer patients and seventy healthy individuals, were included in this study and genotyped with an allele-specific polymerase chain reaction. The most frequent genotype in healthy participants and breast cancer patients was CC. An insignificant (p value>0.05) risk of breast cancer was found with A1166C polymorphism in codominant (CC vs. AA OR=1.200 [0.256-5.631] and AC vs. AA 0.941 [OR=0.223-3.976]), dominant (OR=1.00 [0.240-4.167]), recessive (OR=1.230 [0.593-2.552]) and additive models (OR=1.028 [0.533-1.983]) of general population genotypes. Nonetheless, when the AA genotype was considered a reference group, a significant association was found between AC and CC genotypes and invasive ductal and ductal carcinoma development in breast cancer patients. In conclusion, this study demonstrated no significant association between AGTR1 (A1166C) polymorphism and breast cancer risk.}, } @article {pmid38284471, year = {2024}, author = {Shoshani, A and Kor, A and Farbstein-Yavin, S and Gvion, Y}, title = {Risk and protective factors for substance use and media addictive behaviors in adolescents during the COVID-19 pandemic.}, journal = {Journal of adolescence}, volume = {96}, number = {4}, pages = {746-759}, doi = {10.1002/jad.12295}, pmid = {38284471}, issn = {1095-9254}, mesh = {Humans ; Adolescent ; *COVID-19/epidemiology/psychology/prevention & control ; Male ; Female ; Israel/epidemiology ; *Substance-Related Disorders/epidemiology/psychology ; *Behavior, Addictive/psychology/epidemiology ; Risk Factors ; *Protective Factors ; *Social Media/statistics & numerical data ; Longitudinal Studies ; Child ; Adolescent Behavior/psychology ; Internet Addiction Disorder/epidemiology/psychology ; SARS-CoV-2 ; Surveys and Questionnaires ; Screen Time ; }, abstract = {OBJECTIVE: This study examined the long-term effects of the COVID-19 pandemic on adolescents' substance use, digital media use, and symptoms of internet, gaming, and social media addiction.

METHOD: A nationally representative longitudinal cohort of 1665 Israeli teens and preteens, aged 9-16, completed questionnaires assessing substance use prevalence, daily screen time, symptoms of media addiction, and potential risk and protective factors. Data were collected before the pandemic (October 2019), after the second wave lockdown (November 2020), and after the fifth wave (April 2022) in Israel.

RESULTS: The analysis documented significant increases in substance use, daily screen time, and social media addiction indices over time. Gratitude, life satisfaction, positive emotions, future orientation, grit, and secure attachment emerged as significant protective factors. Sensation-seeking, negative emotions, and mental health symptoms were identified as risk factors.

CONCLUSIONS: These findings highlight the importance of educational and public mental health services in addressing the pandemic's long-term impact on the mental health and addictive behaviors of adolescents. They also emphasize the significance of enhancing protective factors and reducing risk factors to effectively mitigate substance and digital media abuse among adolescents.}, } @article {pmid38283858, year = {2024}, author = {Qin, R and Wang, X and Fan, T and Wu, T and Lu, C and Shao, X and Yin, L}, title = {Bilateral inflammatory recurrence of HER-2 positive breast cancer: a unique case report and literature review.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1276637}, pmid = {38283858}, issn = {2234-943X}, abstract = {Inflammatory breast cancer (IBC) is an aggressive and rare form of breast cancer with a poor prognosis. The occurrence of bilateral IBC in a short period of time is extremely rare. In this case report, a 54-year-old woman diagnosed with invasive ductal carcinoma of the left breast underwent lumpectomy, lymph node dissection, chemotherapy, and radiotherapy but opted against trastuzumab treatment. Four years later, she experienced bilateral breast inflammation, skin changes, edema, and heat (calor). Biopsies confirmed breast cancer metastasis to both breasts. Whole-Exome Sequencing revealed genetic mutations, including PIK3CA and C4orf54, in both primary and recurrent tumors, with significant downregulation in the recurrent tumors. KEGG analysis suggested potential enrichment of axon guidance signal pathways in both tumors. The patient showed a partial response after treatment with liposome paclitaxel, along with targeted therapy using trastuzumab and pertuzumab. This case report sheds light on the rare occurrence of bilateral inflammatory breast cancer post-HER-2 treatment and highlights the importance of genetic profiling in understanding the disease. Further research on clinical targets for breast cancer management is warranted.}, } @article {pmid38282218, year = {2024}, author = {Kool, M and Hafkamp, E and Gol, J and Aukema, EJ and Malfitano, C and Reyners, A and Hales, S and van de Poll, L and Rodin, G and de Vries, F}, title = {Managing cancer and living meaningfully (CALM): Implementation in Dutch cancer care.}, journal = {Psycho-oncology}, volume = {33}, number = {1}, pages = {e6281}, doi = {10.1002/pon.6281}, pmid = {38282218}, issn = {1099-1611}, support = {//Roparun/ ; }, mesh = {Humans ; Emotions ; Anxiety/therapy ; *Psychotherapy, Brief ; Surveys and Questionnaires ; Netherlands ; *Neoplasms/therapy ; }, abstract = {OBJECTIVE: Managing Cancer and Living Meaningfully (CALM) is a brief, evidence-based psychotherapy tailored for patients with advanced cancer that has not yet been implemented routinely in Dutch cancer care. The aim of this study was to assess the feasibility, acceptability, sustainability and effectiveness of CALM in different clinical settings in the Netherlands.

METHODS: In 2019 and 2020 a multi-center, intervention-only study was performed in three Dutch cancer care settings. Professionals were trained to provide CALM under supervision. Patients diagnosed with advanced cancer were included and filled out questionnaires to measure depression (Patient Health Questionnaire-9), death anxiety (Death and Dying Distress Scale), and anxiety (hospital anxiety and depression scale-anxiety) at baseline, 3 and 6 months. The Clinical Evaluation Questionnaire was used to assess acceptability of CALM at 3 and 6 months.

RESULTS: Sixty-four patients (55% of the eligible patients) were included in the study and 85% of the included patients received 3 or more CALM sessions. Of the 24 trained therapists, 15 (63%) started providing CALM. Two years post-study, CALM was provided in each center by a total of 19 therapists. On average, patients perceived CALM to be at least somewhat helpful. A significant decrease in severity of depression (p = 0.006), death anxiety (p = 0.008), and anxiety (p = 0.024) was observed over time.

CONCLUSIONS: This study shows that CALM therapy is feasible, acceptable, and sustainable in three Dutch cancer care settings, although not all predefined feasibility criteria for therapists were met. CALM can be effective in decreasing feelings of depression, anxiety, and death anxiety in patients with advanced cancer.}, } @article {pmid38281565, year = {2024}, author = {Dimitrov, G and Shousha, S and Troianova, P}, title = {CD10 expression as a potential predictor of pathological complete response in ER-negative and triple-negative breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy.}, journal = {Experimental and molecular pathology}, volume = {135}, number = {}, pages = {104885}, doi = {10.1016/j.yexmp.2024.104885}, pmid = {38281565}, issn = {1096-0945}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/metabolism ; *Triple Negative Breast Neoplasms/drug therapy/genetics ; Anthracyclines/therapeutic use ; Retrospective Studies ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Neoadjuvant Therapy ; Antibiotics, Antineoplastic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Treatment Outcome ; Biomarkers, Tumor/metabolism ; }, abstract = {BACKGROUND: Neoadjuvant chemotherapy (NCT) can induce a pathological complete response (pCR) in breast cancer patients, leading to improved outcomes. However, predicting which patients will achieve pCR remains a challenge. CD10, a myoepithelial marker, has shown diagnostic and prognostic value in metastatic tumors. Its potential as a predictor of chemosensitivity to anthracycline-based NCT in breast cancer is unknown.

AIM: This retrospective study aimed to investigate the potential of CD10 cancer cell expression as a predictive marker of chemosensitivity in breast cancers treated with anthracycline-based neoadjuvant chemotherapy.

METHODS: We analyzed 130 patients with invasive ductal carcinoma who received anthracycline-based NCT. CD10 expression was assessed by immunohistochemistry on pre-treatment biopsies. Statistical analysis evaluated the association between CD10 expression and pCR rates.

RESULTS: Univariate analysis revealed that ER-positive and CD10-negative tumors had lower pCR rates [OR 7.4830 (95% CI 2.7762-20.1699); p = 0.0001]. Multivariate analysis confirmed ER status as a strong predictor of poor response [OR 0.085 (95% CI 0.024-0.30); p < 0.001] and CD10 expression as a predictor of a favourable response [OR 0.11 (0.8-0.19); p = 0.049]. CD10 expression significantly predicted pCR in ER-negative cases [OR 0.1098 (0.0268-0.4503); p = 0.0022] and triple-negative breast cancer [OR 0.0966 (95% CI 0.0270-0.3462); p = 0.0003]. Concordance was observed between core biopsies and excised samples.

CONCLUSION: Positive CD10 cancer cell expression may predict increased response to anthracycline-based neoadjuvant chemotherapy in ER-negative and triple-negative breast cancer cases. Further research is needed to validate these findings in larger cohorts and determine the clinical utility of CD10 as a predictive marker.}, } @article {pmid38281261, year = {2024}, author = {Cui, Y and Lin, J and Sun, D and Zhang, H and Diao, T and Fu, Q}, title = {Nomogram for predicting the overall survival and cancer-specific survival of patients with intraductal carcinoma of the prostate.}, journal = {Journal of cancer research and clinical oncology}, volume = {150}, number = {2}, pages = {45}, pmid = {38281261}, issn = {1432-1335}, support = {ZR2021QH366//project ZR2021QH366 supported by Shandong Provincial Natural Science Foundation/ ; ZR2021QH366//project ZR2021QH366 supported by Shandong Provincial Natural Science Foundation/ ; }, mesh = {Male ; Humans ; Prostate ; Nomograms ; *Carcinoma, Intraductal, Noninfiltrating ; *Prostatic Neoplasms ; *Lung Neoplasms ; Prognosis ; SEER Program ; }, abstract = {PURPOSE: Intraductal carcinoma of the prostate (IDC-P) is a histological subtype that differs from conventional acinar adenocarcinoma in terms of its origin, appearance, and pathological features. For IDC-P, there is currently no recognized best course of action, and its prognosis is unclear. The goal of this study is to analyze independent prognostic factors in IDC-P patients and to develop and validate a nomogram to predict overall survival (OS) and cancer-specific survival (CSS).

METHODS: Clinical data for IDC-P patients were collected from the Surveillance, Epidemiology, and End Results database. To identify the independent variables influencing prognosis, multivariate Cox regression analysis was performed. A nomogram model was created utilizing these variables after comparing the variations in OS and CSS among various subgroups using Kaplan‒Meier curves. Internal validation of the nomograms was verified using the bootstrap resampling method.

RESULTS: The study included 280 IDC-P patients in total. Marital status, summary stage, grade, and the presence of lung metastases were significant factors impacting OS, and CSS was significantly influenced by marital status, summary stage, AJCC stage, the presence of lung metastases, the presence of bone metastases, and PSA according to univariate and multivariate Cox regression models (P < 0.05). Nomogram models were created to estimate OS and CSS using these parameters. The OS prediction model's C-index was 0.744, whereas the CSS prediction model's C-index was 0.831.

CONCLUSION: We developed and verified nomogram models for the prediction of 1-, 3-, and 5-year OS and CSS in patients with IDC-P. These nomograms serve as a resource for evaluating patient prognosis, therapy, and diagnosis, ultimately improving clinical decision-making accuracy.}, } @article {pmid38278448, year = {2024}, author = {Mahlow, J and Barry, M and Albertson, DJ and Jo, YJ and Balatico, M and Seasor, T and Gebrael, G and Kumar, SA and Sayegh, N and Tripathi, N and Agarwal, N and Swami, U and Sirohi, D}, title = {Histologic patterns in prostatic adenocarcinoma are not predictive of mutations in the homologous recombination repair pathway.}, journal = {Human pathology}, volume = {144}, number = {}, pages = {28-33}, doi = {10.1016/j.humpath.2024.01.005}, pmid = {38278448}, issn = {1532-8392}, mesh = {Male ; Humans ; Recombinational DNA Repair ; BRCA1 Protein/genetics ; *Carcinoma, Lobular ; BRCA2 Protein/genetics ; Mutation ; *Prostatic Neoplasms/genetics ; }, abstract = {Somatic or germline homologous recombination repair (HRR) pathway gene mutations are commonly detected in prostate cancer, especially in advanced disease, and are associated with response to poly (ADP-ribose) polymerase (PARP) inhibitors. In this study, we evaluated whether histological patterns are predictive of HRR pathway gene mutations. The study population comprised 130 patients with advanced prostate carcinoma who underwent comprehensive genomic profiling (CGP) of tumor tissue at a CLIA-certified laboratory. HRR genes in the study included BRCA1, BRCA2, ATM, BARD1, BRIP, CHEK2, MRE11A, NBN, PALB2, RAD51C, RAD51D, EMSY, ATR, CHEK1, and FAM175A. Overall, 38 patients had mutations in BRCA1/2, 36 in other HRR genes, and 56 were negative for HRR mutations. All cases were re-reviewed and quantified by two genitourinary pathologists blinded to mutational status for the following histological patterns of prostate carcinoma: cribriform, ductal, intraductal carcinoma (IDC), small cell carcinoma, signet ring-like pattern, and lobular carcinoma-like pattern. Discordances were resolved by consensus review. Histologic patterns were analyzed for any correlation with mutations in HRR pathway genes (grouped as BRCA1/2 mutated or non-BRCA1/2 mutated) compared to tumors without mutations in HRR genes by Chi-square testing. Patterns with >20 % and >30 % of tumor volume were additionally evaluated for correlation with mutational status. We found no significant association between HRR pathway mutations and cribriform pattern, IDC, ductal carcinoma, small cell carcinoma, signet ring-like pattern, or lobular carcinoma-like patterns. Tumors with >20 % or >30 % histologic patterns by volume also demonstrated no significant association with mutational status. This study suggests that histopathologic examination alone is insufficient to distinguish prostate cancer with germline or somatic mutations in HRR pathway genes, highlighting the continuing importance of ancillary molecular diagnostics in guiding therapy selection for prostate cancer patients who may benefit from PARP inhibitors.}, } @article {pmid38276982, year = {2024}, author = {Deng, Y and Lu, Y and Li, X and Zhu, Y and Zhao, Y and Ruan, Z and Mei, N and Yin, B and Liu, L}, title = {Prediction of human epidermal growth factor receptor 2 (HER2) status in breast cancer by mammographic radiomics features and clinical characteristics: a multicenter study.}, journal = {European radiology}, volume = {34}, number = {8}, pages = {5464-5476}, pmid = {38276982}, issn = {1432-1084}, support = {No. SHDC2020CR4069//Clinical Research Plan of SHDC/ ; No. yg2021-029//Medical Engineering Fund of Fudan University/ ; No. 21YF1404800//Shanghai Sailing Program/ ; No. 3030256001//Youth Medical Talents -Medical Imaging Practitioner Program/ ; No. 2018SHZDZX01//Shanghai Municipal Science and Technology Major Project/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging ; *Erb-b2 Receptor Tyrosine Kinases/metabolism ; Middle Aged ; *Mammography/methods ; Adult ; Aged ; Carcinoma, Ductal, Breast/diagnostic imaging ; Radiomics ; }, abstract = {OBJECTIVES: To preoperatively evaluate the human epidermal growth factor 2 (HER2) status in breast cancer using mammographic radiomics features and clinical characteristics on a multi-vendor and multi-center basis.

METHODS: This multi-center study included a cohort of 1512 Chinese female with invasive ductal carcinoma of no special type (IDC-NST) from two different hospitals and five devices (1332 from Institution A, used for training and testing the models, and 180 women from Institution B, as the external validation cohort). The Gradient Boosting Machine (GBM) was employed to establish radiomics and multiomics models. Model efficacy was evaluated by the area under the curve (AUC).

RESULTS: The number of HER2-positive patients in the training, testing, and external validation cohort were 245(26.3%), 105 (26.3.8%), and 51(28.3%), respectively, with no statistical differences among the three cohorts (p = 0.842, chi-square test). The radiomics model, based solely on the radiomics features, achieved an AUC of 0.814 (95% CI, 0.784-0.844) in the training cohort, 0.776 (95% CI, 0.727-0.825) in the testing cohort, and 0.702 (95% CI, 0.614-0.790) in the external validation cohort. The multiomics model, incorporated radiomics features with clinical characteristics, consistently outperformed the radiomics model with AUC values of 0.838 (95% CI, 0.810-0.866) in the training cohort, 0.788 (95% CI, 0.741-0.835) in the testing cohort, and 0.722 (95% CI, 0.637-0.811) in the external validation cohort.

CONCLUSIONS: Our study demonstrates that a model based on radiomics features and clinical characteristics has the potential to accurately predict HER2 status of breast cancer patients across multiple devices and centers.

CLINICAL RELEVANCE STATEMENT: By predicting the HER2 status of breast cancer reliably, the presented model built upon radiomics features and clinical characteristics on a multi-vendor and multi-center basis can help in bolstering the model's applicability and generalizability in real-world clinical scenarios.

KEY POINTS: • The mammographic presentation of breast cancer is closely associated with the status of human epidermal growth factor receptor 2 (HER2). • The radiomics model, based solely on radiomics features, exhibits sub-optimal performance in the external validation cohort. • By combining radiomics features and clinical characteristics, the multiomics model can improve the prediction ability in external data.}, } @article {pmid38273267, year = {2024}, author = {Yang, ZJ and Xin, F and Chen, ZJ and Yu, Y and Wang, X and Cao, XC}, title = {Real-world data on neoadjuvant chemotherapy with dual-anti HER2 therapy in HER2 positive breast cancer.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {134}, pmid = {38273267}, issn = {1471-2407}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/metabolism ; Neoadjuvant Therapy ; Treatment Outcome ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Ki-67 Antigen ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; }, abstract = {BACKGROUND: Neoadjuvant chemotherapy with dual-targeted therapy is the standard treatment for human epidermal growth factor 2 (HER2)-positive breast cancer. Although the dual-targeted therapy has significantly improved the pathological complete response (pCR) rate, further investigation is needed to identify biomarkers that predict the response to neoadjuvant therapy.

METHODS: This retrospective study analyzed 353 patients with HER2-positive breast invasive ductal carcinoma. The correlation between clinicopathological factors and pCR rate was evaluated. A nomogram was constructed based on the results of the multivariate logistic regression analysis to predict the probability of pCR.

RESULTS: The breast pCR (b-pCR) rate was 56.1% (198/353) and the total pCR (t-pCR) rate was 52.7% (186/353). Multivariate analysis identified ER status, PR status, HER2 status, Ki-67 index, and neoadjuvant chemotherapy regimens as independent indicators for both b-pCR and t-pCR. The nomogram had an area under the receiver operating characteristic curve (AUC) of 0.73 (95% CI: 0.68-0.78). According to the nomogram, the t- pCR rate was highest in the ER-PR- HER2-positive patients (131/208) and lowest in the ER + PR + HER2-positive patients (19/73). The subgroup analyses showed that there was no significant difference in pCR rate among the neoadjuvant chemotherapy regimens in ER positive, PR positive, HER2 IHC 2 + , Ki67 index < 30% population. However, for ER-PR-HER2-positive patients, the neoadjuvant chemotherapy regimen has a great influence on the pCR rates.

CONCLUSIONS: Patients with ER-negative, PR-negative, HER2 3 + and high KI-67 index were more likely to achieve pCR. THP may be used as an alternative to AC-THP or TCbHP in selected HER2-positive patients.}, } @article {pmid38273260, year = {2024}, author = {Saad, HA and Baz, A and Riad, M and Eraky, ME and El-Taher, A and Farid, MI and Sharaf, K and Said, HEM and Ibrahim, LA}, title = {Tumor microenvironment and immune system preservation in early-stage breast cancer: routes for early recurrence after mastectomy and treatment for lobular and ductal forms of disease.}, journal = {BMC immunology}, volume = {25}, number = {1}, pages = {9}, pmid = {38273260}, issn = {1471-2172}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery ; Mastectomy ; Vimentin/therapeutic use ; *Carcinoma, Ductal, Breast/pathology/secondary/surgery ; Tumor Microenvironment ; Matrix Metalloproteinase 1/therapeutic use ; *Carcinoma, Lobular/pathology/secondary/surgery ; }, abstract = {BACKGROUND: Intra-ductal cancer (IDC) is the most common type of breast cancer, with intra-lobular cancer (ILC) coming in second. Surgery is the primary treatment for early stage breast cancer. There are now irrefutable data demonstrating that the immune context of breast tumors can influence growth and metastasis. Adjuvant chemotherapy may be administered in patients who are at a high risk of recurrence. Our goal was to identify the processes underlying both types of early local recurrences.

METHODS: This was a case-control observational study. Within 2 years of receiving adjuvant taxan and anthracycline-based chemotherapy, as well as modified radical mastectomy (MRM), early stage IDC and ILC recurred. Vimentin, α-smooth muscle actin (SMA), platelet-derived growth factor (PDGF), matrix metalloproteinase (MMP1), and clustered differentiation (CD95) were investigated.

RESULTS: Of the samples in the ductal type group, 25 showed local recurrence, and 25 did not. Six individuals in the lobular-type group did not experience recurrence, whereas seven did. Vimentin (p = 0.000 and 0.021), PDGF (p = 0.000 and 0.002), and CD95 (p = 0.000 and 0.045) expressions were significantly different in ductal and lobular carcinoma types, respectively. Measurement of ductal type was the sole significant difference found in MMP1 (p = 0.000) and α-SMA (p = 0.000). α-SMA and CD95 were two variables that helped the recurrence mechanism in the ductal type according to the pathway analysis. In contrast, the CD95 route is a recurrent mechanism for the lobular form.

CONCLUSIONS: While the immune system plays a larger role in ILC, the tumor microenvironment and immune system both influence the recurrence of IDC. According to this study, improving the immune system may be a viable cancer treatment option.}, } @article {pmid38272241, year = {2024}, author = {Failayev, H and Ganoth, A and Tsfadia, Y}, title = {Molecular insights on the coronavirus MERS-CoV interaction with the CD26 receptor.}, journal = {Virus research}, volume = {342}, number = {}, pages = {199330}, pmid = {38272241}, issn = {1872-7492}, mesh = {Humans ; Animals ; Dogs ; Dipeptidyl Peptidase 4/genetics ; *Middle East Respiratory Syndrome Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/genetics ; *Coronavirus Infections ; Amino Acids ; }, abstract = {The Middle East respiratory syndrome (MERS) is a severe respiratory disease with high fatality rates, caused by the Middle East respiratory syndrome coronavirus (MERS-CoV). The virus initiates infection by binding to the CD26 receptor (also known as dipeptidyl peptidase 4 or DPP4) via its spike protein. Although the receptor-binding domain (RBD) of the viral spike protein and the complex between RBD and the extracellular domain of CD26 have been studied using X-ray crystallography, conflicting studies exist regarding the importance of certain amino acids outside the resolved RBD-CD26 complex interaction interface. To gain atomic-level knowledge of the RBD-CD26 complex, we employed computational simulations to study the complex's dynamic behavior as it evolves from its crystal structure to a conformation stable in solution. Our study revealed previously unidentified interaction regions and interacting amino acids within the complex, determined a novel comprehensive RBD-binding domain of CD26, and by that expanded the current understanding of its structure. Additionally, we examined the impact of a single amino acid substitution, E513A, on the complex's stability. We discovered that this substitution disrupts the complex through an allosteric domino-like mechanism that affects other residues. Since MERS-CoV is a zoonotic virus, we evaluated its potential risk of human infection via animals, and suggest a low likelihood for possible infection by cats or dogs. The molecular structural information gleaned from our insights into the RBD-CD26 complex pre-dissociative states may be proved useful not only from a mechanistic view but also in assessing inter-species transmission and in developing anti-MERS-CoV antiviral therapeutics.}, } @article {pmid38271174, year = {2024}, author = {Wang, C and Xu, R and Xu, S and Meng, W and Wang, R and Zhang, X}, title = {Exploring Intrinsic Discrimination and Consistency for Weakly Supervised Object Localization.}, journal = {IEEE transactions on image processing : a publication of the IEEE Signal Processing Society}, volume = {33}, number = {}, pages = {1045-1058}, doi = {10.1109/TIP.2024.3356174}, pmid = {38271174}, issn = {1941-0042}, abstract = {Weakly supervised object localization (WSOL) is a challenging and promising task that aims to localize objects solely based on the supervision of image category labels. In the absence of annotated bounding boxes, WSOL methods must employ the intrinsic properties of the image classification task pipeline to generate object localizations. In this work, we propose a WSOL method for exploring the Intrinsic Discrimination and Consistency in the image classification task pipeline, and call it as IDC. First, we develop a Triplet Metrics Based Foreground Modeling (TMFM) framework to directly predict object foreground regions using intrinsic discrimination. Unlike Class Activation Map (CAM) based methods that also rely on intrinsic discrimination, our TMFM framework alleviates the problem of only focusing on the most discriminative parts by optimizing foreground and background regions synergistically. Second, we design a Dual Geometric Transformation Consistency Constraints (DGTC2) training strategy to introduce additional supervision and regularization constraints for WSOL by leveraging intrinsic geometric transformation consistency. The proposed pixel-wise and object-wise consistency constraint losses cost-effectively provide spontaneous supervision for WSOL. Extensive experiments show that our IDC method achieves significant and consistent performance gains compared to existing state-of-the-art WSOL approaches. Code is available at: https://github.com/vignywang/IDC.}, } @article {pmid38265547, year = {2024}, author = {Dai, Q and Feng, K and Liu, G and Cheng, H and Tong, X and Wang, X and Feng, L and Wang, Y}, title = {Prognostic Impact of HER2-Low and HER2-Zero in Resectable Breast Cancer with Different Hormone Receptor Status: A Landmark Analysis of Real-World Data from the National Cancer Center of China.}, journal = {Targeted oncology}, volume = {19}, number = {1}, pages = {81-93}, pmid = {38265547}, issn = {1776-260X}, support = {CIFMS//Cancer Institute and Hospital, Chinese Academy of Medical Sciences/ ; ID Number: 2021-I2M-1-014//Cancer Institute and Hospital, Chinese Academy of Medical Sciences/ ; ID Number: LC2022A02//Beijing Hope Run Special Fund of Cancer Foundation of China/ ; }, mesh = {Humans ; Female ; Prognosis ; *Breast Neoplasms/drug therapy/pathology ; Erb-b2 Receptor Tyrosine Kinases ; Retrospective Studies ; Hormones ; }, abstract = {BACKGROUND: The prognostic impact of HER2-low on overall survival (OS) and disease-free survival (DFS) in patients with resectable breast cancer (BC) remains controversial, partly resulting from the hormone receptor (HR) status.

OBJECTIVE: To investigate the prognostic impact of HER2-low in different HR subgroups.

PATIENTS AND METHODS: We retrospectively retrieved medical records of treatment-naive primary HER2-low and HER2-zero BC patients who were diagnosed with invasive ductal carcinoma and underwent surgery in the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2009 to September 2017 (n = 7371). We compared the clinicopathologic features and performed Cox regression and landmark survival analyses to explore the prognostic impact of HER2-low on survival outcomes during distinct post-surgery intervals-36 months, 60 months, and 120 months.

RESULTS: HER2-low BC, compared to HER2-zero BC, exhibited less aggressive clinicopathologic features, such as smaller invasion size, lower grade, increased nerve invasion, higher HR positivity, and a higher proportion of low-Ki67 cases. In the HR-positive subgroup, HER2-low demonstrated improved OS (p = 0.046) and DFS (p = 0.026) within 60 months. Conversely, HER2-low displayed worse DFS (p = 0.046) in the HR-negative subgroup after 36 months from surgery. The findings remained robust in uni- and multi-variable Cox models.

CONCLUSIONS: HER2-low BCs manifested less aggressive clinicopathologic features than the HER2-zero cases. The prognostic impact of HER2-low in resectable BCs exhibits variability contingent upon the patients' HR status.}, } @article {pmid38263821, year = {2024}, author = {Wang, Y and Li, Y and Jiang, H and Zuo, C and Xu, W}, title = {Elevated splenic 18F-fluorodeoxyglucose positron emission tomography/computed tomography activity is associated with 5-year risk of recurrence in non-metastatic invasive ductal carcinoma of the breast.}, journal = {The British journal of radiology}, volume = {97}, number = {1153}, pages = {237-248}, pmid = {38263821}, issn = {1748-880X}, support = {//The First Affiliated Hospital of Naval Medical University/ ; //Shanghai Changhai Hospital/ ; GH145-22//Guhai Plan in the 14th Five-Year Plan/ ; }, mesh = {Humans ; Female ; Spleen ; Fluorodeoxyglucose F18 ; Positron Emission Tomography Computed Tomography ; Breast ; *Breast Neoplasms ; *Carcinoma, Ductal ; }, abstract = {OBJECTIVE: To construct prediction models including baseline 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) metabolic parameters of tumoural lesions and non-tumour lymphoid tissue for recurrence-free survival within 5 years (5y-RFS) after imaging examination in patients with invasive ductal carcinomas (IDCs) of the breast.

METHODS: The study included 101 consecutive female patients. Univariable and multivariable Cox regression were used to identify clinicopathological and metabolic parameters associated with risk of recurrence. Four prediction models based on the results of multivariable analysis were constructed and visualized as nomograms. Performance of each nomogram was evaluated using the concordance index (C-index), integrated discrimination improvement, decision curve analysis (DCA), and calibration curve.

RESULTS: N3 status, total metabolic tumour volume, the maximum standardized uptake value of spleen, and spleen-to-liver ratio were significant predictors of 5y-RFS. The nomogram including all significant predictors demonstrated superior predictive performance for 5y-RFS, with a C-index of 0.907 (95% CI, 0.833-0.981), greatest net benefit on DCA, good accuracy on calibration curves, and excellent risk stratification on Kaplan-Meier curves.

CONCLUSIONS: The model that included metabolic parameters of the spleen had the best performance for predicting 5y-RFS in patients with IDCs of the breast. This model may guide personalized treatment decisions and inform patients and clinicians about prognosis.

ADVANCES IN KNOWLEDGE: This research identifies 18F-FDG PET/CT metabolic parameters of non-tumour lymphoid tissue as predictors of recurrence in breast cancer.}, } @article {pmid38262156, year = {2024}, author = {Zeng, F and Yang, Z and Tang, X and Lin, L and Lin, H and Wu, Y and Wang, Z and Chen, M and Chen, L and Chen, L and Wu, PY and Wang, C and Xue, Y}, title = {Whole-tumor histogram models based on quantitative maps from synthetic MRI for predicting axillary lymph node status in invasive ductal breast cancer.}, journal = {European journal of radiology}, volume = {172}, number = {}, pages = {111325}, doi = {10.1016/j.ejrad.2024.111325}, pmid = {38262156}, issn = {1872-7727}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology ; Retrospective Studies ; Breast/pathology ; Magnetic Resonance Imaging/methods ; Lymph Nodes/diagnostic imaging ; }, abstract = {PURPOSE: To investigate the potential of using histogram analysis of synthetic MRI (SyMRI) images before and after contrast enhancement to predict axillary lymph node (ALN) status in patients with invasive ductal carcinoma (IDC).

METHODS: From January 2022 to October 2022, a total of 212 patients with IDC underwent breast MRI examination including SyMRI. Standard T2 weight images, DCE-MRI and quantitative maps of SyMRI were obtained. 13 features of the entire tumor were extracted from these quantitative maps, standard T2 weight images and DCE-MRI. Statistical analyses, including Student's t-test, Mann-Whiney U test, logistic regression, and receiver operating characteristic (ROC) curves, were used to evaluate the data. The mean values of SyMRI quantitative parameters derived from the conventional 2D region of interest (ROI) were also evaluated.

RESULTS: The combined model based on T1-Gd quantitative map (energy, minimum, and variance) and clinical features (age and multifocality) achieved the best diagnostic performance in the prediction of ALN between N0 (with non-metastatic ALN) and N+ group (metastatic ALN ≥ 1) with the AUC of 0.879. Among individual quantitative maps and standard sequence-derived models, the synthetic T1-Gd model showed the best performance for the prediction of ALN between N0 and N+ groups (AUC = 0.823). Synthetic T2_entropy and PD-Gd_energy were useful for distinguishing N1 group (metastatic ALN ≥ 1 and ≤ 3) from the N2-3 group (metastatic ALN > 3) with an AUC of 0.722.

CONCLUSIONS: Whole-tumor histogram features derived from quantitative parameters of SyMRI can serve as a complementary noninvasive method for preoperatively predicting ALN metastases.}, } @article {pmid38256464, year = {2024}, author = {Al-Madani, SO and Jaber, M and Prasad, P and Maslamani, MJMA}, title = {The Patterns of Impacted Third Molars and Their Associated Pathologies: A Retrospective Observational Study of 704 Patients.}, journal = {Journal of clinical medicine}, volume = {13}, number = {2}, pages = {}, pmid = {38256464}, issn = {2077-0383}, abstract = {Background: The study aims to investigate parameters in patients attending Fujairah Dental Center, including assessing the prevalence of impacted teeth, determining the frequency of associated pathological conditions, and evaluating the patterns and angulations of impacted third molars. Methods: It is a retrospective descriptive study of the panoramic radiographs of patients who attended Fujairah Dental Center for dental care between January 2011 and December 2017. The minimum age for inclusion was 17 years. Clinical records were used to obtain the demographic details of patients, such as age, gender, nationality, medical history, and smoking history. Seven hundred and four panoramic radiographs and clinical records of patients were analyzed. The age range was between 17 and 112 years old, with a mean age of 34 years (S.D 13.5). Results: Of the 704 panoramic radiographs evaluated, 236 (33.6%) X-rays showed teeth impaction with a total of 562 impacted teeth in the upper and lower jaws. Five hundred and twenty-five (93.4%) were impacted third molars, and 37 (6.5%) teeth were other kinds of impacted teeth. Females showed a higher frequency of impacted teeth (62.6%) compared to males (37.4%). The highest prevalence of impacted teeth was found in the 17-25 year age group (61%), and the prevalence declined with advancing age. Impacted third molars were more likely to occur in the mandible (57.3%) than in the maxilla (42.7%). Most of the impacted third molars were in the mesioangular position, followed by the vertical position. The evaluation of the depth of impacted third molars demonstrated that level C impaction was the most frequently seen, followed by level B impaction. Impacted third-molar teeth often presented with two roots (60.7%), followed by a single root (31.3%). An evaluation of the relationship between lower third molars and the inferior dental canal (IDC) revealed that the most frequently observed relation was interrupted (61.5%), followed by a distant relation to the ID canal, and 13% were superimposed. The most common morphological pattern of roots of the impacted third molars was either straight-type or curved and dilacerated roots (5.7%). Additionally, the most noticed pathological conditions associated with impacted teeth were carious second molars adjacent to impacted third molars (42%), which was more likely to be seen in the 17-25-year age group, with females having a higher prevalence than males.}, } @article {pmid38252633, year = {2024}, author = {Zarif, S and Abdulkader, H and Elaraby, I and Alharbi, A and Elkilani, WS and Pławiak, P}, title = {Using hybrid pre-trained models for breast cancer detection.}, journal = {PloS one}, volume = {19}, number = {1}, pages = {e0296912}, pmid = {38252633}, issn = {1932-6203}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging ; Area Under Curve ; Breast ; *Carcinoma in Situ ; Image Processing, Computer-Assisted ; }, abstract = {Breast cancer is a prevalent and life-threatening disease that affects women globally. Early detection and access to top-notch treatment are crucial in preventing fatalities from this condition. However, manual breast histopathology image analysis is time-consuming and prone to errors. This study proposed a hybrid deep learning model (CNN+EfficientNetV2B3). The proposed approach utilizes convolutional neural networks (CNNs) for the identification of positive invasive ductal carcinoma (IDC) and negative (non-IDC) tissue using whole slide images (WSIs), which use pre-trained models to classify breast cancer in images, supporting pathologists in making more accurate diagnoses. The proposed model demonstrates outstanding performance with an accuracy of 96.3%, precision of 93.4%, recall of 86.4%, F1-score of 89.7%, Matthew's correlation coefficient (MCC) of 87.6%, the Area Under the Curve (AUC) of a Receiver Operating Characteristic (ROC) curve of 97.5%, and the Area Under the Curve of the Precision-Recall Curve (AUPRC) of 96.8%, which outperforms the accuracy achieved by other models. The proposed model was also tested against MobileNet+DenseNet121, MobileNetV2+EfficientNetV2B0, and other deep learning models, proving more powerful than contemporary machine learning and deep learning approaches.}, } @article {pmid38250443, year = {2023}, author = {Wang, Y and Zhang, X and Yan, Y and Niu, T and Zhang, M and Fan, C and Liang, W and Shu, Y and Guo, C and Guo, D and Bi, Y}, title = {GmABCG5, an ATP-binding cassette G transporter gene, is involved in the iron deficiency response in soybean.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1289801}, pmid = {38250443}, issn = {1664-462X}, abstract = {Iron deficiency is a major nutritional problem causing iron deficiency chlorosis (IDC) and yield reduction in soybean, one of the most important crops. The ATP-binding cassette G subfamily plays a crucial role in substance transportation in plants. In this study, we cloned the GmABCG5 gene from soybean and verified its role in Fe homeostasis. Analysis showed that GmABCG5 belongs to the ABCG subfamily and is subcellularly localized at the cell membrane. From high to low, GmABCG5 expression was found in the stem, root, and leaf of young soybean seedlings, and the order of expression was flower, pod, seed stem, root, and leaf in mature soybean plants. The GUS assay and qRT-PCR results showed that the GmABCG5 expression was significantly induced by iron deficiency in the leaf. We obtained the GmABCG5 overexpressed and inhibitory expressed soybean hairy root complexes. Overexpression of GmABCG5 promoted, and inhibition of GmABCG5 retarded the growth of soybean hairy roots, independent of nutrient iron conditions, confirming the growth-promotion function of GmABCG5. Iron deficiency has a negative effect on the growth of soybean complexes, which was more obvious in the GmABCG5 inhibition complexes. The chlorophyll content was increased in the GmABCG5 overexpression complexes and decreased in the GmABCG5 inhibition complexes. Iron deficiency treatment widened the gap in the chlorophyll contents. FCR activity was induced by iron deficiency and showed an extraordinary increase in the GmABCG5 overexpression complexes, accompanied by the greatest Fe accumulation. Antioxidant capacity was enhanced when GmABCG5 was overexpressed and reduced when GmABCG5 was inhibited under iron deficiency. These results showed that the response mechanism to iron deficiency is more actively mobilized in GmABCG5 overexpression seedlings. Our results indicated that GmABCG5 could improve the plant's tolerance to iron deficiency, suggesting that GmABCG5 might have the function of Fe mobilization, redistribution, and/or secretion of Fe substances in plants. The findings provide new insights into the ABCG subfamily genes in the regulation of iron homeostasis in plants.}, } @article {pmid38247077, year = {2023}, author = {Terasawa, T and Sakurai, Y and Yanai, A and Fukuda, K and Shibuya, R}, title = {[A Case of Pathological Complete Response Following Neoadjuvant S-1 Monotherapy in an Elderly Patient with Locally Advanced Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {12}, pages = {1339-1341}, pmid = {38247077}, issn = {0385-0684}, mesh = {Aged ; Female ; Humans ; Aged, 80 and over ; *Breast Neoplasms/drug therapy/surgery ; Mastectomy ; Neoadjuvant Therapy ; *Lymphadenopathy ; Axilla ; Pathologic Complete Response ; }, abstract = {An 86-year-old woman was referred to our hospital after an incidental CT scan of the trunk revealed a mass in the left breast and enlarged axillary lymph nodes. A core needle biopsy(CNB)from a 2 cm mass in the left breast revealed invasive ductal carcinoma, weakly positive result for ER, negative result for PgR, and negative result for HER2. She also had multiple enlarged left supraclavicular lymph nodes and was T2N3cM0, Stage ⅢC on pretreatment evaluation. She was given the S-1 oral drug of choice, starting with 80 mg/day/4-week dosing with a 2-week rest. Eight months after the start of S-1, a partial mastectomy and sentinel lymph node biopsy were performed. Pathological findings showed a pathological complete response(ypTis/ypN0)with only a 2 mm non-invasive carcinoma remnant in the left mammary gland. S-1 is weakly recommended as primary chemotherapy for HER2-negative metastatic recurrent breast cancer, but there are no reports to date of complete response in resection cases. S-1 may be administered to patients with locally advanced breast cancer who cannot tolerate standard drug therapy and may be converted to resection after a successful response.}, } @article {pmid38233262, year = {2024}, author = {Wang, B and Fu, Y and Chen, M and Peng, S and Marra, G and Zhuang, J and Zhang, S and Guo, H and Qiu, X}, title = {The presence of intraductal carcinoma of prostate is a risk factor for poor pathologic response in men with high-risk prostate cancer receiving neoadjuvant therapy.}, journal = {Urologic oncology}, volume = {42}, number = {3}, pages = {67.e9-67.e15}, doi = {10.1016/j.urolonc.2023.11.018}, pmid = {38233262}, issn = {1873-2496}, mesh = {Male ; Humans ; Prostate/surgery/pathology ; *Prostatic Neoplasms/drug therapy/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Neoadjuvant Therapy ; Androgen Antagonists/therapeutic use ; Prospective Studies ; Prostatectomy ; Risk Factors ; }, abstract = {OBJECTIVE: To explore the potential association between the presence of intraductal carcinoma of the prostate (IDC-P) on biopsy and pathologic response of primary tumor to neoadjuvant therapy in patients with high-risk prostate cancer.

METHODS: Eighty-five patients with high-risk localized/locally advanced prostate cancer (CaP) who were given 6-month neoadjuvant therapies of androgen deprivation therapy plus docetaxel or abiraterone prior to radical prostatectomy in 2 prospective trials were included in this study. The presence of IDC-P in biopsy pathology was rereviewed by 2 experienced pathologists. Favorable pathologic response was defined as pathologic complete response or minimal residual disease <5 mm on whole-mount histopathology. Characteristics of clinical and biopsy pathology variables were included in univariate and multivariate logistic regression analyses to identify risk factors for the prediction of favorable pathologic response on final pathology.

RESULTS: IDC-P was identified to be present on biopsy pathology of 35 patients (41.2%) while favorable pathologic responses were confirmed in 25 patients (29.4%). Initial prostate-specific antigen (PSA) (OR 3.592, 95% CI 1.176-10.971, P = 0.025) and the presence of IDC-P on biopsy pathology (OR 3.837, 95% CI 1.234-11.930, P = 0.020) were found to be significantly associated with favorable pathologic response in multivariate logistic regression analysis.

CONCLUSION: IDC-P on biopsy pathology was found to be an independent risk factor to predict a poor pathology response of primary CaP to neoadjuvant therapies.}, } @article {pmid38231892, year = {2024}, author = {Konwinski, L and Steenland, C and Miller, K and Boville, B and Fitzgerald, R and Connors, R and Sterling, E and Stowe, A and Rajasekaran, S}, title = {Evaluating Independent Double Checks in the Pediatric Intensive Care Unit: A Human Factors Engineering Approach.}, journal = {Journal of patient safety}, volume = {20}, number = {3}, pages = {209-215}, pmid = {38231892}, issn = {1549-8425}, mesh = {Child ; Humans ; *Medication Errors/prevention & control ; Pharmaceutical Preparations ; *Intensive Care Units, Pediatric ; Patient Safety ; Safety Management/methods ; }, abstract = {OBJECTIVES: The goal of this human factors engineering-led improvement initiative was to examine whether the independent double check (IDC) during administration of high alert medications afforded improved patient safety when compared with a single check process.

METHODS: The initiative was completed at a 24-bed pediatric intensive care unit and included all patients who were on the unit and received a medication historically requiring an IDC. The total review examined 37,968 high-risk medications administrations to 4417 pediatric intensive care unit patients over a 40-month period. The following 5 measures were reviewed: (1) rates of reported medication administration events involving IDC medications; (2) hospital length of stay; (3) patient mortality; (4) nurses' favorability toward single checking; and (5) nursing time spent on administration of IDC medications.

RESULTS: The rate of reported medication administration events involving IDC medications was not significantly different across the groups (95% confidence interval, 0.02%-0.08%; P = 0.4939). The intervention also did not significantly alter mortality (P = 0.8784) or length of stay (P = 0.4763) even after controlling for the patient demographic variables. Nursing favorability for single checking increased from 59% of nurses in favor during the double check phase, to 94% by the end of the single check phase. Each double check took an average of 9.7 minutes, and a single check took an average of 1.94 minutes.

CONCLUSIONS: Our results suggest that performing independent double checks on high-risk medications administered in a pediatric ICU setting afforded no impact on reported medication events compared with single checking.}, } @article {pmid38231374, year = {2024}, author = {Maggi, G and Vitale, C and Giacobbe, C and Barone, A and Mastromarino, C and Iannotta, F and Amboni, M and Weintraub, D and Santangelo, G}, title = {Validation of the Italian version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) in an Italian Parkinson's disease cohort.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {7}, pages = {3153-3161}, pmid = {38231374}, issn = {1590-3478}, mesh = {Humans ; *Parkinson Disease/complications/psychology/diagnosis ; Female ; Male ; Italy ; *Disruptive, Impulse Control, and Conduct Disorders/diagnosis/etiology ; Aged ; Middle Aged ; *Psychiatric Status Rating Scales/standards ; Reproducibility of Results ; Cohort Studies ; Severity of Illness Index ; Surveys and Questionnaires/standards ; Psychometrics/standards ; }, abstract = {INTRODUCTION: Impulse control disorders (ICDs) frequently occur in Parkinson's disease (PD), and an early identification is essential to prevent severe psychosocial consequences. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) has been developed to evaluate the severity of ICDs along with a range of impulsive-compulsive behaviors (ICBs) in PD; however, its Italian version has not yet been validated.

METHODS: One hundred consecutive outpatients with PD were administered an Italian version of the QUIP-RS and a brief neuropsychological assessment to evaluate global cognitive status and scales to measure depression, apathy and impulsive disorders. We evaluated the internal consistency, convergent and divergent validity, and factorial structure of QUIP-RS. We also explored the possible association between QUIP-RS scores and clinical factors and dopaminergic medication.

RESULTS: Subsyndromal ICDs manifestations were observed in 54% of the patients, and one in four (22%) reported two or more ICDs or related behaviors. The QUIP-RS demonstrated good internal consistency (Cronbach's alpha = 0.806) and construct validity, and its factorial structure reflected different ICDs and ICBs domains. No association emerged between QUIP-RS scores and the clinical aspects of PD and dopaminergic medication.

CONCLUSION: We provided, for the first time, an Italian translation of the QUIP-RS and demonstrated its feasibility in clinical and research settings. Severity of ICDs was independent of clinical factors and dopaminergic medication, underlining the need to adopt a broader perspective on their etiopathology in PD.}, } @article {pmid38229789, year = {2023}, author = {Singhal, VK}, title = {Receptor Positive Breast Lesions and Status of Axillary Lymph Node.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e50645}, pmid = {38229789}, issn = {2168-8184}, abstract = {Objective This study aimed to examine the axillary pathological condition through the development of an assessment framework for hormone receptor-positive breast cancer subsequent to neoadjuvant chemotherapy (NAC). Furthermore, the primary objective of this study was to examine the association between axillary status and breast tumors that are positive for hormone receptors following neoadjuvant chemotherapy. Methodology The present retrospective investigation encompassed a cohort including 300 individuals who were administered neoadjuvant chemotherapy before receiving surgical intervention. The data collection period for this study was from September 2021 to December 2022. All patients received neoadjuvant chemotherapy, per the guidelines established by the National Comprehensive Cancer Network (NCCN). We divided patients into two distinct groups: a test set of 250 patients and a validity set of 50 patients. Patients with no evidence of lymphoid involvement underwent a biopsy of sentinel lymph nodes (SLNB) and would have undergone axillary dissection if the biopsy results had indicated positive findings. A logistic regression analysis was employed to investigate the variables linked to the presence of residual positive axillary lymph nodes in the test set. Subsequently, a multivariate analysis was conducted on the variables that exhibited a p-value below 0.2 in the univariate study. In addition, a value of 1 was assigned to all risk factors to construct a comprehensive correlation prediction model. Results The participants included in this study had a mean age and body mass index (BMI) of 46.24 ± 9.1 years and 25.8 ± 2.5 kg, respectively. The present investigation examined the presence of pathological axillary metastases in a cohort of 188 patients, which accounted for 62.55% of the total sample, by utilizing core-needle biopsy. Furthermore, the incidence rates of individuals presenting with clinical T1 were reported as 14.6%, while 55.2% cases of T2, 17.8% cases of T3, and 13% cases of T4 tumors were reported, respectively. Of the overall occurrences, the prevailing histological subtype was invasive ductal carcinoma, accounting for 91.4% (222 out of 243) of the cases. Multiple criteria were identified as independent predictors of the presence of residual positive axillary lymph nodes. The factors under consideration encompass lymphovascular invasion (odds ratio= 7.108; 95% breast cancer stage (odd ratio = 5.025; 95%, HER2 negativity (odd ratio= 2.997), low Ki-67 expression (odd ratio = 4.231), and suspected positive axillary lymph nodes before surgical intervention. Conclusion The present study presents a novel prediction model that integrates imaging and pathology data, aiming to assist patients and healthcare practitioners in evaluating the efficacy of NAC for hormone-receptor-positive breast tumors. The model holds particular significance for individuals who exhibit clinical positivity in their lymph nodes (LNs). Consequently, the model has the potential to provide guidance for the management of axillary lymph nodes and prevent unnecessary dissection.}, } @article {pmid38229073, year = {2024}, author = {Ido, M and Fujii, K and Mishima, H and Kubo, A and Saito, M and Banno, H and Ito, Y and Goto, M and Ando, T and Mouri, Y and Kousaka, J and Imai, T and Nakano, S}, title = {Comprehensive genomic evaluation of advanced and recurrent breast cancer patients for tailored precision treatments.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {85}, pmid = {38229073}, issn = {1471-2407}, mesh = {Humans ; Middle Aged ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; Phosphatidylinositol 3-Kinases/genetics ; Neoplasm Recurrence, Local/drug therapy/genetics ; Genomics ; Mutation ; *Carcinoma ; High-Throughput Nucleotide Sequencing ; }, abstract = {AIM: The aim of this study was to investigate genetic alterations within breast cancer in the setting of recurrent or de novo stage IV disease.

PATIENTS AND METHODS: This study included 22 patients with recurrent breast cancer (n = 19) and inoperable de novo stage IV breast cancer (n = 3). For next generation sequencing, FoundationOneCDx (F1CDx) (Foundation Medicine Inc., Cambridge, MA, USA) was performed in 21 patients and FoundationOneLiquid CDx was performed in 1 patient.

RESULTS: Median age was 62.9 years (range, 33.4-82.1). Pathological diagnoses of specimens included invasive ductal carcinoma (n = 19), invasive lobular carcinoma (n = 2), and invasive micropapillary carcinoma (n = 1). F1CDx detected a median of 4.5 variants (range, 1-11). The most commonly altered gene were PIK3CA (n = 9), followed by TP53 (n = 7), MYC (n = 4), PTEN (n = 3), and CDH1 (n = 3). For hormone receptor-positive patients with PIK3CA mutations, hormonal treatment plus a phosphoinositide 3-kinase inhibitor was recommended as the treatment of choice. Patients in the hormone receptor-negative and no human epidermal growth factor receptor 2 expression group had significantly higher tumor mutational burden than patients in the hormone receptor-positive group. A BRCA2 reversion mutation was revealed by F1CDx in a patient with a deleterious germline BRCA2 mutation during poly ADP ribose polymerase inhibitor treatment.

CONCLUSION: Guidance on tailored precision therapy with consideration of genomic mutations was possible for some patients with information provided by F1CDx. Clinicians should consider using F1CDx at turning points in the course of the disease.}, } @article {pmid38225996, year = {2023}, author = {Wemimo, RM and Eziagu, UB and Sulaiman, OA and Abiodun, AE and Idowu, NA and Ayinde, AA and Taiwo, AA}, title = {Immunohistochemical and Clinicopathological Characteristics of Invasive Breast Carcinoma in Nigeria.}, journal = {Oman medical journal}, volume = {38}, number = {5}, pages = {e548}, pmid = {38225996}, issn = {1999-768X}, abstract = {OBJECTIVES: We aimed to study the immunohistochemical and clinicopathological characteristics of invasive breast carcinoma among Nigerian women.

METHODS: We conducted a retrospective assessment of female patients diagnosed with breast carcinoma at a tertiary hospital in Nigeria between 2012 and 2019. Archived pathology request forms and processed specimens (tissue blocks and slides) were used as source data in addition to the patients' demographic and other relevant data.

RESULTS: Reports pertaining to 113 patients were assessed. Their age range was 30 to 80 years (mean = 52.1±12.1 years). Breast carcinoma was most common in patients aged 40 to 49 years (32.7%), closely followed by those aged 50 to 59 years (30.1%). Invasive ductal carcinoma was the most common histopathological subtype (94.7%). Nottingham grade III and grade II breast carcinoma accounted for 41.6% and 40.7% of the cases, respectively. Mastectomy specimens formed 68.1% of the samples. The most common tumor size (75.9%) was > 5cm (mean = 6.8±3.2cm), consistent with the most common staging of T3 (46.0%). The most common lymph node involvement was N1 (56.6%). Immunohistochemical assessment of these tumors with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 (HER-2) biomarkers expressed positivity of 36.3%, 28.3%, and 41.6%, respectively. These tumors were immunohistochemically classified into luminal A (16.8%), luminal B (20.4%), HER-2 enriched (20.4%), and triple-negative (42.5%) subtypes.

CONCLUSIONS: The most common immunohistochemical subtype of invasive breast carcinoma among this sample of Nigerian women was the triple-negative subtype, similar to the finding among African Americans.}, } @article {pmid38225559, year = {2024}, author = {Nisar, MI and das, S and Khanam, R and Khalid, J and Chetia, S and Hasan, T and Shahid, S and Marijani, ML and Ahmed, S and Khalid, F and Ali, SM and Chowdhury, NH and Mehmood, U and Dutta, A and Rahman, S and Qazi, MF and Deb, S and Mitra, DK and Usmani, AA and Dhingra, U and Raqib, R and Manu, A and Yoshida, S and Minckas, N and Bahl, R and Baqui, AH and Sazawal, S and Jehan, F}, title = {Early to mid-pregnancy HbA1c levels and its association with adverse pregnancy outcomes in three low middle-income countries in Asia and Sub-Saharan Africa.}, journal = {BMC pregnancy and childbirth}, volume = {24}, number = {1}, pages = {66}, pmid = {38225559}, issn = {1471-2393}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Pregnancy ; Female ; Infant, Newborn ; Humans ; *Pregnancy Outcome/epidemiology ; Stillbirth/epidemiology ; *Premature Birth/epidemiology ; Glycated Hemoglobin ; Cesarean Section ; Developing Countries ; Bangladesh ; Pakistan ; Tanzania ; }, abstract = {BACKGROUND: Hyperglycemia during pregnancy leads to adverse maternal and fetal outcomes. Thus, strict monitoring of blood glucose levels is warranted. This study aims to determine the association of early to mid-pregnancy HbA1c levels with the development of pregnancy complications in women from three countries in South Asia and Sub-Saharan Africa.

METHODS: We performed a secondary analysis of the AMANHI (Alliance for Maternal and Newborn Health Improvement) cohort, which enrolled 10,001 pregnant women between May 2014 and June 2018 across Sylhet-Bangladesh, Karachi-Pakistan, and Pemba Island-Tanzania. HbA1c assays were performed at enrollment (8 to < 20 gestational weeks), and epidemiological data were collected during 2-3 monthly household visits. The women were followed-up till the postpartum period to determine the pregnancy outcomes. Multivariable logistic regression models assessed the association between elevated HbA1c levels and adverse events while controlling for potential confounders.

RESULTS: A total of 9,510 pregnant women were included in the analysis. The mean HbA1c level at enrollment was found to be the highest in Bangladesh (5.31 ± 0.37), followed by Tanzania (5.22 ± 0.49) and then Pakistan (5.07 ± 0.58). We report 339 stillbirths and 9,039 live births. Among the live births were 892 preterm births, 892 deliveries via cesarean section, and 532 LGA babies. In the multivariate pooled analysis, maternal HbA1c levels of ≥ 6.5 were associated with increased risks of stillbirths (aRR = 6.3, 95% CI = 3.4,11.6); preterm births (aRR = 3.5, 95% CI = 1.8-6.7); and Large for Gestational Age (aRR = 5.5, 95% CI = 2.9-10.6).

CONCLUSION: Maternal HbA1c level is an independent risk factor for predicting adverse pregnancy outcomes such as stillbirth, preterm birth, and LGA among women in South Asia and Sub-Saharan Africa. These groups may benefit from early interventional strategies.}, } @article {pmid38223107, year = {2024}, author = {Yao, M and Luo, S and Li, L and Wang, Y and Zhu, W and Liu, Y and Liang, C}, title = {Sonographic and clinicopathologic features of metaplastic breast carcinoma and infiltrating ductal carcinoma: a comparative single-center cohort study.}, journal = {Quantitative imaging in medicine and surgery}, volume = {14}, number = {1}, pages = {909-919}, pmid = {38223107}, issn = {2223-4292}, abstract = {BACKGROUND: The rarity of metaplastic breast carcinoma (MBC) has resulted in limited sonographic data. Given the inferior prognosis of MBC compared to invasive ductal carcinoma (IDC), accurate preoperative differentiation between the two is imperative for effective treatment planning and prognostic prediction. The objective of this study was to assess the diagnostic accuracy of MBC and differentiate it from IDC by analyzing sonographic and clinicopathologic features.

METHODS: In this retrospective cohort study, 197 women comprising 200 IDC lesions were enrolled between January 2012 and December 2021 and 20 women comprising 20 pure MBC lesions were enrolled between January 2019 and December 2019. A comparison was made between the sonographic and clinicopathologic characteristics of MBC and IDC.

RESULTS: The results indicated that patients with MBC had a higher proportion of tumor grade 3 (95.0% vs. 32.5%; P<0.001), high Ki-67 expression (100.0% vs. 75.0%; P<0.001), and the triple-negative subtype (90.0% vs. 13.0%; P<0.001) as compared to those with IDC. On ultrasound (US) findings, MBC lesions tended to have a larger size (≥5 cm: 45.0% vs. 1.5%; P<0.001), regular shape (45.0% vs. 1.5%, P<0.001), circumscribed margin (40.0% vs. 0.5%, P<0.001), a complex cystic and solid echo pattern (50.0% vs. 3.5%; P<0.001), and posterior acoustic enhancement (95.0% vs. 14.5%; P<0.001). Additionally, MBC was more likely to be misinterpreted as a benign lesion by sonographers than was IDC (30.0% vs. 4.5%; P<0.001). Multilayer perceptron analysis revealed posterior acoustic enhancement, circumscribed margins, and size as distinguishing factors between these two tumor types. The estimated rates of local recurrence, distant metastasis, and 5-year overall survival in 19 cases with MBC were found to be 10.5%, 31.6%, and 65.0%, respectively.

CONCLUSIONS: MBC typically presents as a large breast mass with more benign US features in older women, findings which may facilitate its accurate diagnosis and differentiation from other breast masses.}, } @article {pmid38223094, year = {2024}, author = {Li, W and Zheng, Y and Liu, H and Tai, Z and Zhu, H and Li, Z and Gu, Q and Li, Y}, title = {Multimodal ultrasound imaging for diagnostic differentiation of sclerosing adenosis from invasive ductal carcinoma.}, journal = {Quantitative imaging in medicine and surgery}, volume = {14}, number = {1}, pages = {877-887}, pmid = {38223094}, issn = {2223-4292}, abstract = {BACKGROUND: Sclerosing adenosis (SA) is a common proliferative benign lesion without atypia in the breast that may mimic invasive ductal carcinoma (IDC) on medical imaging, leading to it often being misdiagnosed and mistreated. Consequently, the purpose of this study was to assess the diagnostic value of multimodal ultrasound imaging in distinguishing SA from IDC.

METHODS: Multimodal ultrasound imaging, including automated breast volume scan (ABVS), elasticity imaging (EI), and color Doppler flow imaging (CDFI), were performed on 120 consecutive patients comprising 122 breast lesions (54 SA, 68 IDC). All lesions were pathologically confirmed. Multimodal ultrasound imaging features were compared between the two groups. Binary logistic regression analysis based on ABVS, EI, and CDFI was conducted to formulate a logistic regression equation for differentiating SA from IDC. The diagnostic performances of ABVS, EI, CDFI, and their combination were compared by the receiver operating characteristic (ROC) curve analysis.

RESULTS: The sensitivity, specificity, and accuracy of ABVS, EI, CDFI, and their combination in differentiating SA from IDC were, respectively, 75.00%, 72.22%, and 73.77%; 86.76%, 72.22%, and 80.33%; 73.53%, 64.81%, and 69.67%; and 88.24%, 74.07%, and 81.97%. Combining multimodal ultrasound imaging yielded an area under the curve (AUC) of 0.895 (95% confidence interval: 0.827-0.943), which was higher than that of ABVS, EI, and CDFI, with AUC values of 0.736, 0.795, and 0.692, respectively, and the difference was statistically significant (ABVS vs. combined model, P<0.001; CDFI vs. combined model, P<0.001; EI vs. combined model, P<0.001). There was no significant difference in the diagnostic efficacy among the three imaging modalities (ABVS vs. EI, P=0.266; ABVS vs. CDFI, P=0.4671; EI vs. CDFI, P=0.051). Compared with those in IDC, the calcification (16.67% vs. 57.35%; P<0.001) and retraction phenomena in the coronal planes (18.52% vs. 57.35%; P<0.001) were less common in patients with SA, while circumscribed margin (38.89% vs. 5.88%; P<0.001), vascularity grade 0-I (64.81% vs. 26.47%; P<0.001), and elasticity scores 1-3 (72.22% vs. 13.24%; P<0.001) were more frequently found in patients with SA. Patients with SA were significantly younger than were patients with IDC (43±11 vs. 54±11 years; P<0.001), and the lesion size was smaller in patients with SA than in those with IDC (median size 1.0 cm; interquartile range (IQR), 0.9 cm vs. median size 1.3 cm; IQR, 1.3 cm; P<0.001).

CONCLUSIONS: The preliminary results suggested that multimodal ultrasound imaging can improve the diagnostic accuracy of SA and provide additional information for differential diagnosis of SA and IDC.}, } @article {pmid38222730, year = {2024}, author = {Gul, MH and Arooj, H and Siddiqui, A and Abdullah, L and Waseem, Z and Hashmi, MU}, title = {Breast cancer's hidden partner: meningoencephalitis as a paraneoplastic revelation: a rare presentation of invasive ductal carcinoma of breast: a case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {86}, number = {1}, pages = {512-516}, pmid = {38222730}, issn = {2049-0801}, abstract = {INTRODUCTION AND IMPORTANCE: Paraneoplastic neurologic syndromes encompass a group of neurologic disorders arising from pathological processes unrelated to metastasis, metabolic disturbances, infections, coagulopathy, or treatment-related side effects. These syndromes can affect various regions of the nervous system, resulting in diverse clinical manifestations.

CASE PRESENTATION: The authors present a rare case of anti-amphiphysin-associated meningoencephalitis in a South Asian Pakistani woman. Initially, the patient was managed for suspected infectious meningitis, but empirical treatment failed to yield improvement. Subsequent investigations unveiled a paraneoplastic syndrome secondary to breast cancer.

DISCUSSION: Diagnosing these clinical entities is challenging due to their multifaceted presentations, often leading to delayed identification, increased patient suffering, economic burdens, and preventable complications.

CONCLUSION: Anti-amphiphysin-associated meningoencephalitis is a rare manifestation of paraneoplastic syndromes. It is crucial to raise awareness among healthcare professionals about the diverse presentations of paraneoplastic syndromes.}, } @article {pmid38216630, year = {2024}, author = {Zhang, M and Yuan, J and Wang, M and Zhang, M and Chen, H}, title = {Chemotherapy is of prognostic significance to metaplastic breast cancer.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {1210}, pmid = {38216630}, issn = {2045-2322}, support = {21Y11912100//Science and Technology Innovation Plan of Shanghai Science and Technology Commission/ ; 075_ZC//a project to foster clinical research from Obstetrics and Gynecology Hospital of Fudan University/ ; }, mesh = {Female ; Humans ; Prognosis ; *Breast Neoplasms/drug therapy/pathology ; *Triple Negative Breast Neoplasms/pathology ; Treatment Outcome ; Kaplan-Meier Estimate ; Retrospective Studies ; Chemotherapy, Adjuvant/methods ; }, abstract = {This study aimed to evaluate the significance of chemotherapy (CT) among metaplastic breast cancer (MpBC), and to compare the survival outcomes between triple negative MpBC (MpBC-TNBC) and triple negative invasive ductal carcinoma (IDC-TNBC). SEER database was indexed to identify female unilateral primary MpBC diagnosed from 2010 to 2017. Patients were classified into neoadjuvant chemotherapy (NAC) with response (NAC-response), NAC-no response, adjuvant chemotherapy, and no CT. Breast cancer-specific survival (BCSS) and overall survival (OS) was estimated using the Kaplan-Meier method and compared by log-rank test. Cox regression was used to evaluate the independent prognostic factors. A 1:4 propensity score matching method was adopted to balance baseline differences. Altogether 1186 MpBC patients were enrolled, among them 181 received NAC, 647 received adjuvant CT and 358 did not receive any CT. Chemotherapy was an independent favorable prognostic factor. NAC-response and adjuvant CT had a significant or an obvious trend of survival improvement compared with NAC-no response or no CT. MpBC-TNBC was an independent unfavorable prognostic factor compared with IDC-TNBC. Among them, there was significant or trend of survival improvement among all TNBCs receiving NAC or adjuvant CT compared with no CT. Chemotherapy was of important significance to MpBC prognosis and should be integrated in comprehensive treatment for MpBC.}, } @article {pmid38215056, year = {2024}, author = {Schimpfle, L and Tsilingiris, D and Mooshage, CM and Kender, Z and Sulaj, A and von Rauchhaupt, E and Szendroedi, J and Herzig, S and Goepfert, J and Groener, J and Nawroth, PP and Bendszus, M and Heiland, S and Kurz, FT and Jende, JME and Kopf, S}, title = {Phase Angle of Bioelectrical Impedance Analysis as an Indicator for Diabetic Polyneuropathy in Type 2 Diabetes Mellitus.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {109}, number = {11}, pages = {e2110-e2119}, pmid = {38215056}, issn = {1945-7197}, support = {B05//Collaborative Research Council 1118/ ; A03//Collaborative Research Council 1158/ ; //Deutsches Zentrum für Diabetesforschung (DZD e.V.)/ ; }, mesh = {Humans ; *Diabetes Mellitus, Type 2/complications/physiopathology ; *Diabetic Neuropathies/diagnosis/physiopathology ; Female ; Male ; *Electric Impedance ; Middle Aged ; Cross-Sectional Studies ; Aged ; Neural Conduction/physiology ; Adult ; }, abstract = {CONTEXT: Due to the heterogenous clinical symptoms and deficits, the diagnosis of diabetic polyneuropathy (DPN) is still difficult in clinical routines, leading to increased morbidity and mortality.

OBJECTIVE: We studied the correlation of phase angle (PhA) of bioelectrical impedance analysis (BIA) with clinical, laboratory, and physical markers of DPN to evaluate PhA as a possible diagnostic method for DPN.

MATERIALS AND METHODS: In this cross-sectional observational study as part of the Heidelberg Study on Diabetes and Complications, we examined 104 healthy individuals and 205 patients with type 2 diabetes mellitus (T2D), among which 63 had DPN. The PhA was calculated from multifrequency BIA. Nerve conduction studies, quantitative sensory testing (QST) and diffusion-weighted magnetic resonance neurography to determine fractional anisotropy (FA) reflecting peripheral nerve integrity were performed.

RESULTS: T2D patients with DPN had lower PhA values (5.71 ± 0.10) compared to T2D patients without DPN (6.07 ± 0.08, P = .007, + 6.1%) and healthy controls (6.18 ± 0.08, P < .001, + 7.9%). Confounder-adjusted analyses showed correlations of the PhA with conduction velocities and amplitudes of the peroneal (β=.28; β=.31, P < .001) and tibial nerves (β=.28; β=.32, P < .001), Z-scores of QST (thermal detection β=.30, P < .05) and the FA (β=.60, P < .001). Receiver-operating characteristic analysis showed similar performance of PhA in comparison to the mentioned diagnostic methods.

CONCLUSION: The study shows that PhA is, in comparison to other test systems used, at least an equally good and much easier to handle investigator-independent marker for detection of DPN.}, } @article {pmid38213367, year = {2023}, author = {Mada, SR and Zay, HH and Bies, JJ and Massebo, E and Didia, C}, title = {A Rare Case of Remittent Male Invasive Ductal Carcinoma With New Metastasis After Incomplete Adjuvant Therapy.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e50400}, pmid = {38213367}, issn = {2168-8184}, abstract = {Breast cancer is a rare disease in men with many barriers to effective management such as limited research and treatment modalities. While the current standard of care utilizes mastectomy and axillary dissection with chemotherapy, clinicians must follow the female-staged breast cancer protocol, as there is no established regimen for men. In this case presentation, we report a 43-year-old male with a prior history of ER-positive invasive ductal carcinoma (IDC) who presented with a recurrent breast lesion. The patient had previously undergone left breast mastectomy with sentinel node biopsy with negative margins. The patient declined adjuvant chemotherapy and tamoxifen therapy after the initial dissection. Three years after the primary dissection, the patient presents with a breast lesion and metastasis to bilateral axillary lymph nodes, lungs, and spine. The diagnosis was supported by a right axillary biopsy which revealed an ER-positive and PR-positive lesion. We want to shed light on the importance of complete and thorough treatment of primary IDC in men while highlighting the implications of incomplete treatment. We hope that this clinical case will serve as a guide for physicians in promoting adjuvant treatments after primary tumor removal in male IDC.}, } @article {pmid38205326, year = {2024}, author = {Ibuki, E and Kadota, K and Kimura, N and Ishikawa, R and Oshima, M and Okano, K and Haba, R}, title = {Prognostic significance of tumor budding in patients with pancreatic invasive ductal carcinoma who received neoadjuvant therapy.}, journal = {Heliyon}, volume = {10}, number = {1}, pages = {e23928}, pmid = {38205326}, issn = {2405-8440}, abstract = {Neoadjuvant therapy is commonly used for invasive pancreatic ductal carcinoma (PDAC). Tumor budding and high podoplanin expression in cancer-associated fibroblasts (CAFs) are prognostic factors in patients with various carcinomas including PDAC who have not received neoadjuvant therapy. In this study, we investigated whether tumor budding and podoplanin-positive CAFs are associated with outcomes in Japanese PDAC patients with neoadjuvant therapy. Histopathological findings of surgically resected PDACs with neoadjuvant therapy from 2005 to 2018 were reviewed (n = 97). With reference to International Tumor Budding Consensus Conference recommendations, tumors were evaluated for budding at 20 × magnification (/0.785 mm[2]) and at 40 × magnification (/0.237 mm[2]; mean number of fields: 3) for podoplanin expression in CAFs (%). Overall survival, disease-free survival, and disease-specific survival (DSS) were analyzed using the log-rank test and Cox proportional hazards model. After adjusting for T category, N category, resection margin, and adjuvant therapy, multivariate analyses demonstrated that tumor budding at 40 × magnification was an independent prognostic factor for worse DSS (hazard ratio: 2.41, p = 0.022). Tumor budding at 20 × magnification and podoplanin-positive CAFs tended to be associated with worse DSS; however, these findings were not statistically significant. Our findings indicate that tumor budding is an independent prognostic factor in PDAC patients with neoadjuvant therapy.}, } @article {pmid38201445, year = {2023}, author = {Lim, GH and Hoo, JX and Shin, YC and Choo, RZT and Wong, FY and Allen, JC}, title = {Is Metastatic Staging Needed for All Patients with Synchronous Bilateral Breast Cancers?.}, journal = {Cancers}, volume = {16}, number = {1}, pages = {}, pmid = {38201445}, issn = {2072-6694}, abstract = {BACKGROUND: Patients with bilateral breast cancers are uncommon and are associated with a poorer prognosis. While metastatic staging guidelines in patients with unilateral cancer were established, the indication of metastatic staging in patients with bilateral breast cancers is unclear. We aimed to determine which patients with synchronous bilateral breast cancers require metastatic staging at diagnosis. This is the first such reported study, to the best of our knowledge.

METHODS: A retrospective review of newly diagnosed synchronous bilateral invasive breast cancer patients at our institution was performed. We excluded patients with malignant phyllodes or no metastatic staging. Patients' demographics and pathological and staging results were analysed to determine the group of bilateral breast cancer patients who required metastatic staging.

RESULTS: A total of 92 patients with synchronous bilateral invasive cancers were included. The mean age was 58 years old, and 64.1% had bilateral invasive ductal carcinoma. 23.9% had systemic metastasis. Nodal status was statistically significant for systemic metastasis on staging (p = 0.0081), with only three patients (3.3%) having negative nodal status and positive metastatic staging. These three patients, however, showed symptoms of distant metastasis. 92.3% of patients with negative nodes also had negative metastatic staging. Using negative nodal status as a guide avoided metastatic staging in 40.4% of all patients.

CONCLUSIONS: Negative nodal status was the most predictive factor for no systemic metastasis on staging in patients with synchronous bilateral invasive breast cancers. Hence, metastatic staging could be reserved for patients with symptoms of systemic metastasis and/or metastatic nodes. This finding could be validated in larger studies.}, } @article {pmid38201413, year = {2024}, author = {Nicosia, L and Mariano, L and Bozzini, AC and Pesapane, F and Bagnardi, V and Frassoni, S and Oriecuia, C and Dominelli, V and Latronico, A and Palma, S and Venturini, M and Fontana, F and Priolo, F and Abiuso, I and Sangalli, C and Cassano, E}, title = {Radiological Features of Male Breast Neoplasms: How to Improve the Management of a Rare Disease.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, pmid = {38201413}, issn = {2075-4418}, abstract = {The primary aim of our study was to assess the main mammographic and ultrasonographic features of invasive male breast malignancies. The secondary aim was to evaluate whether a specific radiological presentation would be associated with a worse receptor profile. Radiological images (mammography and/or ultrasound) of all patients who underwent surgery for male invasive breast cancer in our institution between 2008 and 2023 were retrospectively analyzed by two breast radiologists in consensus. All significant features of radiological presentation known in the literature were re-evaluated. Fifty-six patients were selected. The mean age at surgery of patients was 69 years (range: 35-81); in 82% of cases (46 patients), the histologic outcome was invasive ductal carcinoma. A total of 28 out of 56 (50%) patients had preoperative mammography; in 9/28 cases (32%), we found a mass with microcalcifications on mammography. The mass presented high density in 25 out of 28 patients (89%); the mass showed irregular margins in 15/28 (54%) cases. A total of 46 out of 56 patients had preoperative ultrasounds. The lesion showed a solid mass in 41/46 (89%) cases. In 5/46 patients (11%), the lesion was a mass with a mixed (partly liquid-partly solid) structure. We did not find any statistically significant correlation between major types of radiological presentation and tumor receptor arrangement. Knowledge of the main radiologic presentation patterns of malignant male breast neoplasm can help better manage this type of disease, which is rare but whose incidence is increasing.}, } @article {pmid38200268, year = {2024}, author = {Cuoco, S and Blundo, C and Ricci, M and Cappiello, A and Bisogno, R and Carotenuto, I and Avallone, AR and Erro, R and Pellecchia, MT and Amboni, M and Barone, P and Picillo, M}, title = {Psychometric properties of the Caregiver's inventory neuropsychological diagnosis dementia (CINDD) in mild cognitive impairment and dementia.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {131}, number = {2}, pages = {173-180}, pmid = {38200268}, issn = {1435-1463}, mesh = {Humans ; Caregivers/psychology ; *Dementia ; Psychometrics ; Reproducibility of Results ; *Cognitive Dysfunction/diagnosis/psychology ; Neuropsychological Tests ; }, abstract = {OBJECTIVES: The Caregiver's Inventory Neuropsychological Diagnosis Dementia (CINDD) is an easy tool designed to quantify cognitive, behavioural and functional deficits of patients with cognitive impairment. Aim of the present study was to analyse the psychometric properties of the CINDD in Mild Cognitive Impairment (MCI) and Dementia (D).

The CINDD, composed by 9 sub-domains, was administered to fifty-six caregivers of patients with different types of dementia (D) and 44 caregivers of patients with MCI. All patients underwent an extensive neuropsychological assessment, the Neuropsychiatric Inventory (NPI) and functional autonomy scales. The reliability, convergent construct validity and possible cut-off of CINND were measured by Cronbach's alpha (α), Pearson's correlation and ROC analysis, respectively.

RESULTS: The D and MCI patients differed only for age (p=0.006). The internal consistency of CINDD was high (α= 0.969). The α-value for each CINDD domain was considered acceptable, except the mood domain (α=0.209). The CINDD total score correlated with cognitive screening tests; each domain of the CINDD correlated with the corresponding score from either tests or NPI (p<0.05), except for visuo-spatial perception skills and apathy. A screening cut-off equal to 59, can be used discriminate D from MCI (Sensitivity=0.70, Specificity=0.57).

CONCLUSION: The CINDD is a feasible, accurate and reliable tool for the assessment of cognitive and behavioural difficulties in patients with different degree of cognitive impairment. It may be used to quantify and monitor caregiver-reported ecological data in both clinical and research settings.}, } @article {pmid38196268, year = {2024}, author = {Rizzo, V and Cicciarelli, F and Galati, F and Moffa, G and Maroncelli, R and Pasculli, M and Pediconi, F}, title = {Could breast multiparametric MRI discriminate between pure ductal carcinoma in situ and microinvasive carcinoma?.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {65}, number = {6}, pages = {565-574}, doi = {10.1177/02841851231225807}, pmid = {38196268}, issn = {1600-0455}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology ; Middle Aged ; Retrospective Studies ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology ; Aged ; Adult ; Diagnosis, Differential ; *Multiparametric Magnetic Resonance Imaging/methods ; Neoplasm Invasiveness ; Breast/diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Aged, 80 and over ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) is often reclassified as invasive cancer in the final pathology report of the surgical specimen. It is of significant clinical relevance to acknowledge the possibility of underestimating invasive disease when utilizing preoperative biopsies for a DCIS diagnosis. In cases where such histologic upgrades occur, it is imperative to consider them in the preoperative planning process, including the potential inclusion of sentinel lymph node biopsy due to the risk of axillary lymph node metastasis.

PURPOSE: To assess the capability of breast multiparametric magnetic resonance imaging (MP-MRI) in differentiating between pure DCIS and microinvasive carcinoma (MIC).

MATERIAL AND METHODS: Between January 2018 and November 2022, this retrospective study enrolled patients with biopsy-proven DCIS who had undergone preoperative breast MP-MRI. We assessed various MP-MRI features, including size, morphology, margins, internal enhancement pattern, extent of disease, presence of peritumoral edema, time-intensity curve value, diffusion restriction, and ADC value. Subsequently, a logistic regression analysis was conducted to explore the association of these features with the pathological outcome.

RESULTS: Of 129 patients with biopsy-proven DCIS, 36 had foci of micro-infiltration on surgical specimens and eight were diagnosed with invasive ductal carcinoma (IDC). The presence of micro-infiltration foci was significantly associated with several MP-MRI features, including tumor size (P <0.001), clustered ring enhancement (P <0.001), segmental distribution (P <0.001), diffusion restriction (P = 0.005), and ADC values <1.3 × 10[-3] mm[2]/s (P = 0.004).

CONCLUSION: Breast MP-MRI has the potential to predict the presence of micro-infiltration foci in biopsy-proven DCIS and may serve as a valuable tool for guiding therapeutic planning.}, } @article {pmid38195987, year = {2024}, author = {Knödlseder, N and Fábrega, MJ and Santos-Moreno, J and Manils, J and Toloza, L and Marín Vilar, M and Fernández, C and Broadbent, K and Maruotti, J and Lemenager, H and Carolis, C and Zouboulis, CC and Soler, C and Lood, R and Brüggemann, H and Güell, M}, title = {Delivery of a sebum modulator by an engineered skin microbe in mice.}, journal = {Nature biotechnology}, volume = {42}, number = {11}, pages = {1661-1666}, pmid = {38195987}, issn = {1546-1696}, support = {Marie Skłodowska-Curie Grant Agreement 882387//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; Award N62909-18-1-2155//United States Department of Defense | United States Navy | Office of Naval Research (ONR)/ ; - IdC 2019 PROD 00057//Government of Catalonia | Agència de Gestió d'Ajuts Universitaris i de Recerca (Agency for Management of University and Research Grants)/ ; Fellowship number 8240//European Molecular Biology Organization (EMBO)/ ; Award Juan de la Cierva FJC 2018-037096-I//Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)/ ; Grant Agreement 882387//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Skłodowska-Curie Actions (H2020 Excellent Science - Marie Skłodowska-Curie Actions)/ ; }, mesh = {*Sebum/metabolism ; Animals ; Mice ; *Skin/microbiology/metabolism ; Humans ; Propionibacteriaceae/genetics ; }, abstract = {Microorganisms can be equipped with synthetic genetic programs for the production of targeted therapeutic molecules. Cutibacterium acnes is the most abundant commensal of the human skin, making it an attractive chassis to create skin-delivered therapeutics. Here, we report the engineering of this bacterium to produce and secrete the therapeutic molecule neutrophil gelatinase-associated lipocalin, in vivo, for the modulation of cutaneous sebum production.}, } @article {pmid38195458, year = {2024}, author = {Hemida, AS and Shabaan, MI and Taha, MA and Abdou, AG}, title = {Impact of immunohistochemical expression of kinesin family member 18A (Kif18A) and β-catenin in infiltrating breast carcinoma of no special type.}, journal = {World journal of surgical oncology}, volume = {22}, number = {1}, pages = {15}, pmid = {38195458}, issn = {1477-7819}, mesh = {Humans ; Female ; *beta Catenin ; Kinesins ; *Breast Neoplasms ; Carcinogenesis ; Family ; }, abstract = {BACKGROUND: KIF18A is a regulator of the cell cycle that stimulates the proliferation of cancer cells. The Wnt/β-catenin pathway is involved in different issues' carcinogenesis and is being examined as a therapeutic target. The relationship between KIF18A and β-catenin in breast cancer was not previously investigated. Therefore, this work aims to study the immunohistochemical expression and correlation of KIF18A and β-catenin in breast-infiltrating duct carcinoma (IDC) and their relation to prognosis.

MATERIAL AND METHODS: Slides cut from paraffin blocks of 135 IDC and 40 normal breast tissues were stained by KIF18A and β-catenin antibodies. KIF18A cytoplasmic or nucleocytoplasmic staining and β-catenin aberrant expression either nucleo-cytoplasmic or cytoplasmic staining were considered.

RESULTS: Normal breast tissue and IDC showed a significant difference regarding KIF18A and aberrant β-catenin expression. High KIF18A and β-catenin H score values were associated with poor prognostic factors such as high grade, advanced stage, distant metastasis, high Ki67 status, and Her2neu-enriched subtype. There was a significant direct correlation between KIF18A and β-catenin as regards percent and H score values. Prolonged overall survival (OS) was significantly associated with mild intensity and low H score of KIF18A, and low β-catenin H score.

CONCLUSIONS: KIF18A could be involved in breast carcinogenesis by activating β-catenin. Overexpression of KIF18A and aberrant expression of β-catenin are considered proto-oncogenes of breast cancer development. KIF18A and β-catenin could be poor prognostic markers and predictors of aggressive behavior of breast cancer.}, } @article {pmid38193247, year = {2024}, author = {Okano, K and Miyai, K and Mikoshi, A and Edo, H and Ito, K and Tsuda, H and Shinmoto, H}, title = {Histological parameters and stromal desmoplastic status affecting accurate diagnosis of extraprostatic extension of prostate cancer using multi-parametric magnetic resonance imaging.}, journal = {International journal of urology : official journal of the Japanese Urological Association}, volume = {31}, number = {5}, pages = {475-482}, doi = {10.1111/iju.15385}, pmid = {38193247}, issn = {1442-2042}, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/diagnostic imaging/surgery ; Aged ; Middle Aged ; *Prostatectomy ; *Multiparametric Magnetic Resonance Imaging ; Prostate/pathology/diagnostic imaging ; Cell Adhesion Molecules/analysis/metabolism ; Neoplasm Grading ; Retrospective Studies ; Magnetic Resonance Imaging ; }, abstract = {OBJECTIVE: To investigate the clinicopathological factors affecting discrepancies between multi-parametric magnetic resonance imaging (mpMRI) and histopathological evaluation for diagnosis of extraprostatic extension (EPE) of prostate cancer.

METHODS: One hundred-and-three lesions from 96 cases with suspected EPE on preoperative mpMRI, of which 60 and 43 showed bulging and frank capsular breach, respectively, were grouped according to pathological (p)EPE in radical prostatectomy specimens. Additionally, clinicopathological/immunohistochemical findings for periostin reflecting a desmoplastic stromal reaction were compared between these groups.

RESULTS: pEPE was detected in 49 (48%) of the 103 lesions. Of these, 25 (42%) showed bulging and 24 (56%) showed frank capsular breach on MRI. In the total cohort, the absence of pEPE was significantly associated with a lower Gleason Grade Group (GG) (p < 0.0001), anterior location (p = 0.003), absence of intraductal carcinoma of the prostate (IDC-P) (p = 0.026), and high stromal periostin expression (p < 0.0001). These trends were preserved in subgroups defined by MRI findings, except for anterior location/IDC-P in the bulging subgroup.

CONCLUSIONS: GG, anterior location, and periostin expression may cause mpMRI-pathological discrepancies regarding EPE. Periostin expression was a significant pEPE-negative factor in all subgroup analyses. Our results indicate that patients with suspected EPE on MRI, regardless of their pEPE results, should be followed as carefully as those with definite pEPE.}, } @article {pmid38191821, year = {2024}, author = {Mooshage, CM and Schimpfle, L and Tsilingiris, D and Kender, Z and Aziz-Safaie, T and Hohmann, A and Szendroedi, J and Nawroth, P and Sturm, V and Heiland, S and Bendszus, M and Kopf, S and Jende, JME and Kurz, FT}, title = {Magnetization transfer ratio of the sciatic nerve differs between patients in type 1 and type 2 diabetes.}, journal = {European radiology experimental}, volume = {8}, number = {1}, pages = {6}, pmid = {38191821}, issn = {2509-9280}, support = {SFB 1158//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Diabetes Mellitus, Type 2/diagnostic imaging ; *Diabetes Mellitus, Type 1/diagnostic imaging ; *Diabetic Neuropathies/diagnostic imaging ; Sciatic Nerve/diagnostic imaging ; Thigh ; }, abstract = {BACKGROUND: Previous studies on magnetic resonance neurography (MRN) found different patterns of structural nerve damage in type 1 diabetes (T1D) and type 2 diabetes (T2D). Magnetization transfer ratio (MTR) is a quantitative technique to analyze the macromolecular tissue composition. We compared MTR values of the sciatic nerve in patients with T1D, T2D, and healthy controls (HC).

METHODS: 3-T MRN of the right sciatic nerve at thigh level was performed in 14 HC, 10 patients with T1D (3 with diabetic neuropathy), and 28 patients with T2D (10 with diabetic neuropathy). Results were subsequently correlated with clinical and electrophysiological data.

RESULTS: The sciatic nerve's MTR was lower in patients with T2D (0.211 ± 0.07, mean ± standard deviation) compared to patients with T1D (T1D 0.285 ± 0.03; p = 0.015) and HC (0.269 ± 0.05; p = 0.039). In patients with T1D, sciatic MTR correlated positively with tibial nerve conduction velocity (NCV; r = 0.71; p = 0.021) and negatively with hemoglobin A1c (r =  - 0.63; p < 0.050). In patients with T2D, we found negative correlations of sciatic nerve's MTR peroneal NCV (r =  - 0.44; p = 0.031) which remained significant after partial correlation analysis controlled for age and body mass index (r = 0.51; p = 0.016).

CONCLUSIONS: Lower MTR values of the sciatic nerve in T2D compared to T1D and HC and diametrical correlations of MTR values with NCV in T1D and T2D indicate that there are different macromolecular changes and pathophysiological pathways underlying the development of neuropathic nerve damage in T1D and T2D.

TRIAL REGISTRATION: https://classic.

CLINICALTRIALS: gov/ct2/show/NCT03022721 . 16 January 2017.

RELEVANCE STATEMENT: Magnetization transfer ratio imaging may serve as a non-invasive imaging method to monitor the diseases progress and to encode the pathophysiology of nerve damage in patients with type 1 and type 2 diabetes.

KEY POINTS: • Magnetization transfer imaging detects distinct macromolecular nerve lesion patterns in diabetes patients. • Magnetization transfer ratio was lower in type 2 diabetes compared to type 1 diabetes. • Different pathophysiological mechanisms drive nerve damage in type 1 and 2 diabetes.}, } @article {pmid38190274, year = {2024}, author = {Mancin, P and Malerba, A and Doron, G and Ghisi, M and Cerea, S}, title = {"Can I Have More Than This?" The Role of Romantic Relationship Quality, Maximization Style, and Social Media Addiction in Relationship Obsessive Compulsive Disorder Symptoms.}, journal = {Cyberpsychology, behavior and social networking}, volume = {27}, number = {2}, pages = {119-126}, doi = {10.1089/cyber.2023.0348}, pmid = {38190274}, issn = {2152-2723}, mesh = {Humans ; Female ; Adolescent ; Young Adult ; Adult ; *Interpersonal Relations ; Internet Addiction Disorder ; *Obsessive-Compulsive Disorder/diagnosis ; Personal Satisfaction ; Regression Analysis ; }, abstract = {Relationship Obsessive Compulsive Disorder (ROCD) is a form of obsessive-compulsive disorder that manifests in the relationship domain, such as romantic relationships. Within romantic relationship, ROCD symptoms could be focused on flaws perceived on the relationship itself (ROCD relationship-centered) or on the partners' quality (ROCD partner-focused). These symptoms are associated with negative relationship outcomes, such as low relationship satisfaction. However, no studies have yet addressed the role of relationship quality in the context of ROCD. Furthermore, previous studies have shown the detrimental role of social media use and maximization style in obsessive-compulsive symptoms and the romantic relational domain; however, the associations with ROCD symptoms have not yet been explored. Thus, this study aimed to close this gap examining the associations between ROCD symptoms (relationship-centered and partner-focused) and relationship quality, social media addiction, and maximization style. A total of 211 participants currently involved in a romantic relationship (71.1 percent female, mean age = 30.4 ± 11.54 years) participated in the study. Multiple hierarchical regression analyses revealed that relationship quality, social media addiction, and maximization style emerged as being significantly associated with relationship-centered and partner-focused ROCD symptoms. The results highlighted potential risk factors for ROCD symptoms in romantic relationships, namely relationship quality, social media addiction, and maximization style. These psychological dimensions could be identified as possible targets in the assessment and treatment of ROCD symptoms.}, } @article {pmid38190207, year = {2024}, author = {Elshanbary, AA and Zaazouee, MS and Nourelden, AZ and Al-Kafarna, M and Matar, SG and Elsaeidy, AS and Ragab, KM and Elhady, MM and Albadrani, GM and Altyar, AE and Kensara, OA and Abdel-Daim, MM}, title = {Risk factors of diabetes and cancer-specific mortalities in patients with infiltrating ductal carcinoma of the breast: a population-based study.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {33}, number = {4}, pages = {321-333}, pmid = {38190207}, issn = {1473-5709}, mesh = {Humans ; Female ; *Breast Neoplasms/mortality/pathology/therapy ; Middle Aged ; Risk Factors ; *Carcinoma, Ductal, Breast/mortality/pathology/therapy/epidemiology ; *SEER Program/statistics & numerical data ; Aged ; Adult ; Diabetes Mellitus/mortality/epidemiology ; Prognosis ; United States/epidemiology ; Survival Rate ; Follow-Up Studies ; Neoplasm Staging ; }, abstract = {BACKGROUND AND AIMS: Breast cancer is considered one of the most common neoplasms worldwide. Diabetes (DM) increases mortality among postmenopausal patients with breast cancer. Our study aims to identify the risk factors of DM-specific mortality and infiltrating ductal carcinoma (IDC) mortality in patients with IDC of the breast.

MATERIALS AND METHODS: Data of IDC patients were obtained from the Surveillance, Epidemiology, and End Results database from 1975 to 2016. Independent variables included age, race, marital status, the primary site of IDC, breast subtype, the disease stage, grade, chemotherapy, radiation, and surgery. Kaplan-Meier, Cox and Binary regression tests were used to analyze the data using SPSS software.

RESULTS: A total of 673 533 IDC patients were analyzed. Of them, 4224 died due to DM and 116 822 died due to IDC. Factors that increase the risk of overall, IDC-specific, and DM-specific mortalities include older age, black race, widowed, uninsured, regional and distant stages, grade II and III, and no treatment with chemotherapy or radiotherapy or surgery. Additionally, the IDC mortality increased with separated status, all primary sites, all breast subtypes, and stage IV.

CONCLUSION: In patients with IDC, controlling DM besides cancer is recommended to reduce the mortality risk. Old, black, widowed, uninsured, regional and distant stages, grade II and III, and no treatment are common risk factors for DM- and IDC-mortality.}, } @article {pmid38187107, year = {2024}, author = {Kassem, M and Kamr, A and Wright, CB and Sobolewski, AP}, title = {Efficacy of the Radiofrequency Identification Technique in Breast Cancer Patients: A Single Institution Retrospective Study.}, journal = {European journal of breast health}, volume = {20}, number = {1}, pages = {52-56}, pmid = {38187107}, issn = {2587-0831}, abstract = {OBJECTIVE: Breast conserving surgery is an excellent option in the treatment of breast cancer. To achieve a good result with this modality, a surgeon needs to identify and excise the tumor with adequate margins. The radiofrequency identification (RFID) technique is a wireless localization technique used for intraoperative breast lesion identification. We assessed the efficacy and outcomes of the RFID technique in breast cancer patients at our institution.

MATERIALS AND METHODS: This is a single institution, retrospective study (BSMH 22-02X-MWH) of 73 patients. We analyzed the medical records of women with biopsy-proven breast cancer from June 2020 to August 2022; participants received surgical care at Mercy Health West Hospital. Data collected included demographics, clinicopathological characteristics, and surgical procedure. The primary objective was to determine the safety and efficacy of RFID. The secondary objective was to assess the impact of obesity and breast density on the RFID outcomes.

RESULTS: A total of 73 female patients met the eligibility criteria with stage I (59%) and grade 1 (51%) breast cancer with mean age of at diagnosis of 66.8 years and mean body mass index of 31.4 kg/m2. Patients had invasive ductal carcinoma (61%), hormonal positive (56%), and human epidermal growth factor receptor 2 negative (68%) disease. All RFID tags were placed under image guidance with 100% accuracy of placement with no evidence of migration or procedure revision. Ninety percent of patients had free surgical margins and only seven patients needed margin re-excision with successful removal of the lesion and the tag.

CONCLUSION: RFID localization technique is a safe, effective and reliable procedure that results in favorable patient outcomes and quality of life.}, } @article {pmid38185614, year = {2024}, author = {Leung, D and Castellani, D and Nicoletti, R and Dilme, RV and Sierra, JM and Serni, S and Franzese, C and Chiacchio, G and Galosi, AB and Mazzucchelli, R and Palagonia, E and Dell'Oglio, P and Galfano, A and Bocciardi, AM and Zhao, X and Ng, CF and Lee, HY and Sakamoto, S and Vasdev, N and Rivas, JG and Campi, R and Teoh, JY}, title = {The Oncological and Functional Prognostic Value of Unconventional Histology of Prostate Cancer in Localized Disease Treated with Robotic Radical Prostatectomy: An International Multicenter 5-Year Cohort Study.}, journal = {European urology oncology}, volume = {7}, number = {3}, pages = {581-588}, doi = {10.1016/j.euo.2023.12.006}, pmid = {38185614}, issn = {2588-9311}, mesh = {Humans ; Male ; *Prostatic Neoplasms/surgery/pathology/radiotherapy ; *Prostatectomy/methods ; *Robotic Surgical Procedures ; Retrospective Studies ; Middle Aged ; Aged ; Prognosis ; Cohort Studies ; Treatment Outcome ; Time Factors ; Internationality ; }, abstract = {BACKGROUND AND OBJECTIVE: The impact of prostate cancer of unconventional histology (UH) on oncological and functional outcomes after robot-assisted radical prostatectomy (RARP) and adjuvant radiotherapy (aRT) receipt is unclear. We compared the impact of cribriform pattern (CP), ductal adenocarcinoma (DAC), and intraductal carcinoma (IDC) in comparison to pure adenocarcinoma (AC) on short- to mid-term oncological and functional results and receipt of aRT after RARP.

METHODS: We retrospectively collected data for a large international cohort of men with localized prostate cancer treated with RARP between 2016 and 2020. The primary outcomes were biochemical recurrence (BCR)-free survival, erectile and continence function. aRT receipt was a secondary outcome. Kaplan-Meier survival and Cox regression analyses were performed.

KEY FINDINGS AND LIMITATIONS: A total of 3935 patients were included. At median follow-up of 2.8 yr, the rates for BCR incidence (AC 10.7% vs IDC 17%; p < 0.001) and aRT receipt (AC 4.5% vs DAC 6.3% [p = 0.003] vs IDC 11.2% [p < 0.001]) were higher with UH. The 5-yr BCR-free survival rate was significantly poorer for UH groups, with hazard ratios of 1.67 (95% confidence interval [CI] 1.16-2.40; p = 0.005) for DAC, 5.22 (95% CI 3.41-8.01; p < 0.001) for IDC, and 3.45 (95% CI 2.29-5.20; p < 0.001) for CP in comparison to AC. Logistic regression analysis revealed that the presence of UH doubled the risk of new-onset erectile dysfunction at 1 yr, in comparison to AC (grade group 1-3), with hazard ratios of 2.13 (p < 0.001) for DAC, 2.14 (p < 0.001) for IDC, and 2.01 (p = 0.011) for CP. Moreover, CP, but not IDC or DAC, was associated with a significantly higher risk of incontinence (odds ratio 1.97; p < 0.001). The study is limited by the lack of central histopathological review and relatively short follow-up.

In a large cohort, UH presence was associated with worse short- to mid-term oncological outcomes after RARP. IDC independently predicted a higher rate of aRT receipt. At 1-yr follow-up after RP, patients with UH had three times higher risk of erectile dysfunction post RARP; CP was associated with a twofold higher incontinence rate.

PATIENT SUMMARY: Among patients with prostate cancer who undergo robot-assisted surgery to remove the prostate, those with less common types of prostate cancer have worse results for cancer control, erection, and urinary continence and a higher probability of receiving additional radiotherapy after surgery.}, } @article {pmid38180699, year = {2024}, author = {Nakagawa, S and Miyashita, M and Maeda, I and Goda, A and Tada, H and Amari, M and Kojima, Y and Tsugawa, K and Ohi, Y and Sagara, Y and Sato, M and Ebata, A and Harada-Shoji, N and Suzuki, T and Nakanishi, M and Ohta, T and Ishida, T}, title = {Potential role of Fbxo22 in resistance to endocrine therapy in breast cancer with invasive lobular carcinoma.}, journal = {Breast cancer research and treatment}, volume = {204}, number = {3}, pages = {453-463}, pmid = {38180699}, issn = {1573-7217}, mesh = {Female ; Humans ; *Breast Neoplasms/drug therapy/genetics/metabolism ; *Carcinoma, Lobular/pathology ; Selective Estrogen Receptor Modulators/therapeutic use ; *Carcinoma, Ductal, Breast/pathology ; Treatment Outcome ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is distinct from invasive ductal carcinoma (IDC) in terms of their hormonal microenvironments that may require different therapeutic strategies. We previously reported that selective estrogen receptor modulator (SERM) function requires F-box protein 22 (Fbxo22). Here, we investigated the role of Fbxo22 as a potential biomarker contributing to the resistance to endocrine therapy in ILC.

METHODS: A total of 302 breast cancer (BC) patients including 150 ILC were recruited in the study. Fbxo22 expression and clinical information were analyzed to elucidate whether Fbxo22 negativity could be a prognostic factor or there were any correlations among clinical variables and SERM efficacy.

RESULTS: Fbxo22 negativity was significantly higher in ILC compared with IDC (58.0% vs. 27.0%, P < 0.001) and higher in postmenopausal patients than premenopausal patients (64.1% vs. 48.2%, P = 0.041). In the ILC cohort, Fbxo22-negative patients had poorer overall survival (OS) than Fbxo22-positive patients, with 10-year OS rates of 77.4% vs. 93.6% (P = 0.055). All patients treated with SERMs, Fbxo22 negativity resulted in a poorer outcome, with 10-year OS rates of 81.3% vs. 92.3% (P = 0.032). In multivariate analysis regarding recurrence-free survival (RFS) in ILC patients, Fbxo22 status was independently predictive of survival as well as lymph node metastasis.

CONCLUSION: Fbxo22 negativity significantly impacts on survival in BC patients with IDC and ILC, and the disadvantage was enhanced among ILC postmenopausal women or patients treated with SERMs. The findings suggest that different therapeutic strategies might be needed according to the different histopathological types when considering adjuvant endocrine therapy.}, } @article {pmid38177130, year = {2024}, author = {Krishnaswamy, D and Bontempi, D and Thiriveedhi, VK and Punzo, D and Clunie, D and Bridge, CP and Aerts, HJWL and Kikinis, R and Fedorov, A}, title = {Enrichment of lung cancer computed tomography collections with AI-derived annotations.}, journal = {Scientific data}, volume = {11}, number = {1}, pages = {25}, pmid = {38177130}, issn = {2052-4463}, support = {HHSN261201500003C/CA/NCI NIH HHS/United States ; HHSN261201500003I/CA/NCI NIH HHS/United States ; T32 EB025823/EB/NIBIB NIH HHS/United States ; }, mesh = {Humans ; Artificial Intelligence ; *Carcinoma, Non-Small-Cell Lung/diagnostic imaging ; Lung/diagnostic imaging ; *Lung Neoplasms/diagnostic imaging ; Tomography, X-Ray Computed ; }, abstract = {Public imaging datasets are critical for the development and evaluation of automated tools in cancer imaging. Unfortunately, many do not include annotations or image-derived features, complicating downstream analysis. Artificial intelligence-based annotation tools have been shown to achieve acceptable performance and can be used to automatically annotate large datasets. As part of the effort to enrich public data available within NCI Imaging Data Commons (IDC), here we introduce AI-generated annotations for two collections containing computed tomography images of the chest, NSCLC-Radiomics, and a subset of the National Lung Screening Trial. Using publicly available AI algorithms, we derived volumetric annotations of thoracic organs-at-risk, their corresponding radiomics features, and slice-level annotations of anatomical landmarks and regions. The resulting annotations are publicly available within IDC, where the DICOM format is used to harmonize the data and achieve FAIR (Findable, Accessible, Interoperable, Reusable) data principles. The annotations are accompanied by cloud-enabled notebooks demonstrating their use. This study reinforces the need for large, publicly accessible curated datasets and demonstrates how AI can aid in cancer imaging.}, } @article {pmid38170222, year = {2024}, author = {Li, QY and Guo, Q and Luo, WM and Luo, XY and Ji, YM and Xu, LQ and Guo, JL and Shi, RS and Li, F and Lin, CY and Zhang, J and Ke, D}, title = {Overexpression of MTFR1 promotes cancer progression and drug-resistance on cisplatin and is related to the immune microenvironment in lung adenocarcinoma.}, journal = {Aging}, volume = {16}, number = {1}, pages = {66-88}, pmid = {38170222}, issn = {1945-4589}, mesh = {Humans ; Cisplatin/pharmacology/therapeutic use ; *Lung Neoplasms/drug therapy/genetics/pathology ; Proto-Oncogene Proteins c-akt/metabolism ; *Adenocarcinoma of Lung/drug therapy/genetics/pathology ; Drug Resistance, Neoplasm/genetics ; Cell Proliferation/genetics ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; Tumor Microenvironment/genetics ; }, abstract = {OBJECTIVE: The roles of MTFR1 in the drug resistance of lung adenocarcinoma (LAC) to cisplatin remain unexplored. In this study, the expression, clinical values and mechanisms of MTFR1 were explored, and the relationship between MTFR1 expression and immune microenvironment was investigated in LAC using bioinformatics analysis, cell experiments, and meta-analysis.

METHODS: MTFR1 expression and clinical values, and the relationship between MTFR1 expression and immunity were explored, through bioinformatics analysis. The effects of MTFR1 on the growth, migration and cisplatin sensitivity of LAC cells were identified using cell counting kit-8, wound healing and Transwell experiments. Additionally, the mechanisms of drug resistance of LAC cells involving MTFR1 were investigated using western blotting.

RESULTS: MTFR1 was elevated in LAC tissues. MTFR1 overexpression was associated with sex, age, primary therapy outcome, smoking, T stage, unfavourable prognosis and diagnostic value and considered an independent risk factor for an unfavourable prognosis in patients with LAC. MTFR1 co-expressed genes involved in the cell cycle, oocyte meiosis, DNA replication and others. Moreover, interfering with MTFR1 expression inhibited the proliferation, migration and invasion of A549 and A549/DDP cells and promoted cell sensitivity to cisplatin, which was related to the inhibition of p-AKT, p-P38 and p-ERK protein expression. MTFR1 overexpression was associated with stromal, immune and estimate scores along with natural killer cells, pDC, iDC and others in LAC.

CONCLUSIONS: MTFR1 overexpression was related to the unfavourable prognosis, diagnostic value and immunity in LAC. MTFR1 also participated in cell growth and migration and promoted the drug resistance of LAC cells to cisplatin via the p-AKT and p-ERK/P38 signalling pathways.}, } @article {pmid38157332, year = {2023}, author = {Shinohara, T and Asoda, T and Nakano, Y and Yamada, H and Fujimori, Y}, title = {Germline BRCA2 Pathogenic Variant in Primary Breast Cancer of a Down Syndrome Individual.}, journal = {The American journal of case reports}, volume = {24}, number = {}, pages = {e942208}, pmid = {38157332}, issn = {1941-5923}, mesh = {Female ; Humans ; Adult ; *Breast Neoplasms/pathology ; Mastectomy ; *Down Syndrome/complications/surgery ; Biomarkers, Tumor ; *Carcinoma, Ductal/surgery ; Germ Cells/pathology ; BRCA2 Protein/genetics ; }, abstract = {BACKGROUND Down syndrome (DS) is the most common genetic disorder, and individuals with DS are known to have a low risk for solid tumors, including breast cancer. In contrast, Breast Cancer Susceptibility Gene (BRCA) pathogenic variant can cause breast cancer. We report a case of primary breast cancer harboring a BRCA2 pathogenic variant in a 35-year-old woman with DS. CASE REPORT A 35-year-old woman with DS presented with a palpable 2-cm mass in the upper-inner quadrant of the left breast. A biopsy confirmed an invasive ductal carcinoma of the breast. Her clinical diagnosis was cT2, N0, M0, cStageIIA. A left modified radical mastectomy with axillary node dissection was performed. Her final pathological diagnosis was invasive ductal carcinoma (T2, pN1, M0, stageIIB), positive estrogen receptors, negative progesterone receptors, negative human epidermal receptor-2 status. She was started on adjuvant hormonal therapy. Unfortunately, 23 months after the operation, multiple metastases were detected. Testing for a BRCA pathogenic variant was performed, and a BRCA2 pathogenic variant was detected. Olaparib was orally administered, and the levels of tumor markers rapidly declined; however, the levels of the tumor markers started to increase again 5 months after the initiation of olaparib. Subsequently, she developed bilateral carcinomatous lymphangiomatosis and died 59 months after the operation. CONCLUSIONS This report highlights a rare case of primary breast cancer harboring a germline BRCA2 pathogenic variant in an individual with DS. Our study highlights the importance of genetic testing as part of breast cancer management in these patients.}, } @article {pmid38152369, year = {2023}, author = {Wang, Z and Hua, L and Liu, X and Chen, X and Xue, G}, title = {A hematological parameter-based model for distinguishing non-puerperal mastitis from invasive ductal carcinoma.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1295656}, pmid = {38152369}, issn = {2234-943X}, abstract = {PURPOSE: Non-puerperal mastitis (NPM) accounts for approximately 4-5% of all benign breast lesions. Ultrasound is the preferred method for screening breast diseases; however, similarities in imaging results can make it challenging to distinguish NPM from invasive ductal carcinoma (IDC). Our objective was to identify convenient and objective hematological markers to distinguish NPM from IDC.

METHODS: We recruited 89 patients with NPM, 88 with IDC, and 86 with fibroadenoma (FA), and compared their laboratory data at the time of admission. LASSO regression, univariate logistic regression, and multivariate logistic regression were used to screen the parameters for construction of diagnostic models. Receiver operating characteristic curves, calibration curves, and decision curves were constructed to evaluate the accuracy of this model.

RESULTS: We found significant differences in routine laboratory data between patients with NPM and IDC, and these indicators were candidate biomarkers for distinguishing between the two diseases. Additionally, we evaluated the ability of some classic hematological markers reported in previous studies to differentiate between NPM and IDC, and the results showed that these indicators are not ideal biomarkers. Furthermore, through rigorous LASSO and logistic regression, we selected age, white blood cell count, and thrombin time to construct a differential diagnostic model that exhibited a high level of discrimination, with an area under the curve of 0.912 in the training set and with 0.851 in the validation set. Furthermore, using the same selection method, we constructed a differential diagnostic model for NPM and FA, which also demonstrated good performance with an area under the curve of 0.862 in the training set and with 0.854 in the validation set. Both of these two models achieved AUCs higher than the AUCs of models built using machine learning methods such as random forest, decision tree, and SVM in both the training and validation sets.

CONCLUSION: Certain laboratory parameters on admission differed significantly between the NPM and IDC groups, and the constructed model was designated as a differential diagnostic marker. Our analysis showed that it has acceptable efficiency in distinguishing NPM from IDC and may be employed as an auxiliary diagnostic tool.}, } @article {pmid38151327, year = {2024}, author = {Kos, Z and Nielsen, TO and Laenkholm, AV}, title = {Breast Cancer Histopathology in the Age of Molecular Oncology.}, journal = {Cold Spring Harbor perspectives in medicine}, volume = {14}, number = {6}, pages = {}, pmid = {38151327}, issn = {2157-1422}, mesh = {Humans ; *Breast Neoplasms/pathology/genetics ; Female ; *Biomarkers, Tumor/genetics ; Prognosis ; Carcinoma, Ductal, Breast/pathology/genetics ; }, abstract = {For more than a century, microscopic histology has been the cornerstone for cancer diagnosis, and breast carcinoma is no exception. In recent years, clinical biomarkers, gene expression profiles, and other molecular tests have shown increasing utility for identifying the key biological features that guide prognosis and treatment of breast cancer. Indeed, the most common histologic pattern-invasive ductal carcinoma of no special type-provides relatively little guidance to management beyond triggering grading, biomarker testing, and clinical staging. However, many less common histologic patterns can be recognized by trained pathologists, which in many cases can be linked to characteristic biomarker and gene expression patterns, underlying mutations, prognosis, and therapy. Herein we describe more than a dozen such histomorphologic subtypes (including lobular, metaplastic, salivary analog, and several good prognosis special types of breast cancer) in the context of their molecular and clinical features.}, } @article {pmid38147544, year = {2024}, author = {Hasan-Aslih, S and Idan, O and Willer, R and Halperin, E}, title = {Disadvantaged group members are prouder of their group when using the language of the dominant group compared to their native language.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {1}, pages = {e2307736120}, pmid = {38147544}, issn = {1091-6490}, support = {335607//EC | European Research Council (ERC)/ ; }, mesh = {Humans ; *Language ; *Self Concept ; Surveys and Questionnaires ; Emotions ; Vulnerable Populations ; }, abstract = {In ethnically and linguistically diverse societies, disadvantaged groups often face pressures to acquire and speak the advantaged group's language to achieve social inclusion and economic mobility. This work investigates how using the advantaged group's language affects disadvantaged group members' in-group pride and collective self-esteem, relative to using their native language. Across six experimental studies involving Palestinian citizens of Israel (total N = 1,348), we test two competing hypotheses: Disadvantaged group members may experience greater in-group pride when using a) their native language, due to its emotional significance (the nativity hypothesis), or b) the language of the advantaged group, due to activation of habituated compensatory responses to dominance relations (the identity enhancement hypothesis). We found that respondents reported significantly higher in-group pride when responding to a Hebrew survey when compared to performing the same activity in Arabic (Studies 1a and 1b), regardless of whether the researchers administering the survey were identified as Jewish or Arab (Studies 2a and 2b). Study 3 replicated this effect while employing the "bogus pipeline" technique, suggesting the pride expression was authentic, not merely driven by social desirability. Finally, Study 4 (pre-registered) examined additional measures of positive regard for the in-group, finding that participants described their group more positively in an attribute selection task, and reported greater collective self-esteem, when surveyed in Hebrew, rather than in Arabic. Taken together, these findings suggest that language use influences disadvantaged group members' perceptions and feelings concerning their group when those languages are associated with relative position in an intergroup hierarchy.}, } @article {pmid38145712, year = {2024}, author = {Bessell, E and Markovic, TP and Caterson, ID and Hendy, C and Burk, J and Picone, T and Fuller, NR}, title = {Cost-effectiveness analysis of recruitment strategies in a large diabetes prevention trial conducted across two sites in Sydney, Australia.}, journal = {Contemporary clinical trials}, volume = {137}, number = {}, pages = {107421}, doi = {10.1016/j.cct.2023.107421}, pmid = {38145712}, issn = {1559-2030}, mesh = {Adult ; Humans ; *Cost-Effectiveness Analysis ; Patient Selection ; Research Design ; *Diabetes Mellitus ; Australia ; Cost-Benefit Analysis ; }, abstract = {BACKGROUND: Diabetes prevention trials require large samples and community-based recruitment, which can be protracted and expensive. We analysed the cost-effectiveness of recruitment strategies used in a randomised placebo-controlled supplement trial in adults with prediabetes and overweight or obesity conducted in Sydney, Australia.

METHODS: Recruitment strategies included advertising through local radio stations and newspapers, television news coverage, online advertising and editorials, advertising in and referral from primary care settings, university- and hospital-based advertising, and attending or hosting local events. For each strategy, the number of expressions of interest, screenings booked, and randomised participants were collated. The percentage contribution from each strategy, overall cost, and cost per participant were calculated.

RESULTS: Of 4498 expressions of interest, 551 (12%) were eligible for onsite screening and 401 (9%) were randomised. Recruitment costs totalled AU$218,501, averaging AU$545 per participant. The recruitment strategy was recorded for 49% who expressed interest in the trial, and for 75% randomised into the trial. From these data, advertising on local radio stations was the most cost-effective strategy, contributing 46% of participants at AU$286 per participant, then advertising in and referral from primary care settings (57 participants [19%], AU$1438 per participant). The least cost-effective strategy was television news coverage, which was not targeted to the Sydney-based audience, contributing only six participants (AU$10,000 per participant).

CONCLUSION: Radio advertising and recruitment through healthcare were the most effective recruitment strategies in this trial. Recruitment strategies should be location-specific and appropriate for the target population, prioritising low-effort high-yield strategies. Trial investigators should seek opportunities for free advertising.}, } @article {pmid38141236, year = {2023}, author = {Thai, JN and Sevrukov, AB and Ward, RC and Monticciolo, DL}, title = {Cryoablation Therapy for Early-Stage Breast Cancer: Evidence and Rationale.}, journal = {Journal of breast imaging}, volume = {5}, number = {6}, pages = {646-657}, doi = {10.1093/jbi/wbad064}, pmid = {38141236}, issn = {2631-6129}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery ; *Cryosurgery/adverse effects ; Treatment Outcome ; Mammography ; Mastectomy, Segmental ; }, abstract = {Recent advances in breast cancer research and treatment propel a paradigm shift toward less aggressive and less invasive treatment for some early-stage breast cancer. Select patients with small, low-risk tumors may benefit from a less aggressive approach with de-escalated local therapy. Cryoablation of breast cancer is an emerging nonsurgical treatment alternative to breast-conserving surgery. Advantages of cryoablation over surgery include the use of local anesthesia, faster recovery, improved cosmesis, and cost savings. Proper patient selection and meticulous technique are keys to achieving successful clinical outcomes. The best candidates for cryoablation have unifocal invasive ductal carcinoma tumors that are low grade, hormone receptor positive, and ≤1.5 cm in size. In this review, we outline the current evidence, patient selection criteria, procedural technique, pre- and postablation imaging, and the advantages and limitations of cryoablation therapy.}, } @article {pmid38131316, year = {2024}, author = {Özden, A and Dalgıç, B and Demir, M and Hazırolan, G and Uzun, Ö and Metan, G}, title = {Impact of a hospital sepsis management protocol on the selection of empirical antibiotics in infectious disease consultations.}, journal = {Journal of chemotherapy (Florence, Italy)}, volume = {36}, number = {3}, pages = {190-197}, doi = {10.1080/1120009X.2023.2296146}, pmid = {38131316}, issn = {1973-9478}, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; Anti-Bacterial Agents/therapeutic use ; *Bacteremia/drug therapy ; beta-Lactamases ; Carbapenems ; *Communicable Diseases/drug therapy ; Escherichia coli ; *Escherichia coli Infections/drug therapy ; Hospitals ; *Klebsiella Infections/microbiology ; Piperacillin, Tazobactam Drug Combination/therapeutic use ; Referral and Consultation ; Retrospective Studies ; *Sepsis/drug therapy ; Clinical Trials as Topic ; }, abstract = {It is well-established that Infectious Diseases consultation (IDC) enhances the prognosis of bloodstream infections. However, it is unclear if adoption of an institutional sepsis protocol would lead to any further improvement in a setting where IDC and infectious diseases approval (IDA) - available throughout 7 days/24 hours -are mandatory for administering broad spectrum antibiotics. We aimed to evaluate the influence of the institutional sepsis protocol developed by Department of Infectious Diseases and Clinical Microbiology on the selection of appropriate empirical antibiotics by IDC through focusing on patients who had bloodstream infections caused by Extended-spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae, which poses a therapeutic challenge. One hundred and fifty-three adult patients (58 patients in the pre-protocol period and 95 patients in the post-protocol period), who received empirical antibiotic treatment for ESBL-producing E. coli and K. pneumoniae, in whom at least one systemic antibiotic was started either on the day blood cultures were drawn or not later than 24 hours were included in the study, retrospectively. The primary outcome was whether the empirical treatment regimen included a carbapenem that was accepted as the appropriate treatment based on the results of the MERINO trial. Secondary outcomes included empirical treatment based on pre-defined risk factors suggesting multidrug resistance (MDR), 30-day inpatient mortality, and appropriate antibacterial treatment according to antimicrobial susceptibility test (AST) results. The median age (Interquartile range) was 61 (48-70.5) years and 76 (49.7%) out of 153 patients were male. The patients in the post-protocol period were older compared to the pre-protocol period (54 years vs 64 years, p = 0.045). The Charlson Comorbidity Index was higher during the post-protocol period compared to the pre-protocol period (4 vs 5, p=0.038). At least one risk factor for MDR bacteria infection was present in 147 (96.1%) of the 153 patients. While the rate of risk factors for MDR bacteria infections did not differ significantly between the pre-protocol and post-protocol periods, the post-protocol period showed a significantly higher level of appropriate antibiotic treatment according to the presence of MDR risk factors compared to the pre-protocol period (44.8% vs 64.2%, p=0.019). There was a significant increase in the use of carbapenems in the post-protocol period compared to the pre-protocol period (34.5% vs. 56.8%, p=0.007). When the subgroup of patients who were likely to have infection caused by ESBL-producing bacteria is taken into consideration, the carbapenem use was more frequent in the post-protocol period (37.8% vs 68.9%, p=0.002). The rate of appropriate empirical treatment according to AST was not statistically different between pre-protocol and post-protocol period. The 30-day mortality rates were similar in both periods (24.1% vs 31.5, p=0.33). However, the rate of susceptibility to piperacillin-tazobactam was statistically higher in the pre-protocol period (82.6% vs 46.2%, p=0.016) when 39.7% of the patients received piperacillin-tazobactam as the empirical treatment. This study highlights the significance of using a structured protocol to attain appropriate empirical treatment for patients suspected of sepsis, even in a setting where IDC is readily available.}, } @article {pmid38125060, year = {2023}, author = {Rafiq, MT and Abdul Hamid, MS and Hafiz, E}, title = {Effectiveness of lower limb rehabilitation protocol using mobile health on quality of life, functional strength, and functional capacity among knee osteoarthritis patients who are overweight and obese: A randomized-controlled trial.}, journal = {Archives of rheumatology}, volume = {38}, number = {4}, pages = {590-601}, pmid = {38125060}, issn = {2618-6500}, abstract = {OBJECTIVES: This study aims to investigate the effectiveness of the lower limb rehabilitation protocol (LLRP) using mobile health (mHealth) on quality of life (QoL), functional strength, and functional capacity among knee OA patients who were overweight and obese.

PATIENTS AND METHODS: Between August 2019 and November 2020, a total of 96 patients (42 males, 54 females; mean age; 52.9±4.8 years; range, 40 to 60 years) were randomized into either the rehabilitation group with mobile health (RGw-mHealth) receiving reminders by using mHealth to carry on the strengthening exercises of LLRP and instructions of daily care (IDC), the rehabilitation group without mobile health (RGwo-mHealth) following the strengthening exercises of LLRP and instructions of daily care (IDC) and control group (CG) only following the IDC for duration of 12 weeks. The reminders for using mHealth were provided two times a day for three days a week. Primary outcome measures were QoL assessed by the Western Ontario and McMaster Universities Osteoarthritis Index summary score, and functional strength by five-repetition sit-to-stand test. Secondary outcome measure was functional capacity assessed by the Gait Speed Test. The assessments of QoL, functional strength, and functional capacity were taken at baseline and post-test after 12 weeks of intervention.

RESULTS: After 12 weeks of intervention, the patients in all three groups had a statistically significant improvement in QoL within groups (p<0.05). Patients in the RGw-mHealth and RGwo-mHealth had a statistically significant improvement in functional strength and walking gait speed within groups (p<0.05). The pairwise between-group comparisons (Bonferroni post-hoc test) of the mean changes in QoL, functional strength, and functional capacity at post-test assessments revealed that patients in the RGw-mHealth had a statistically significant greater mean change in QoL, functional strength and functional capacity relative to both the RGwo-mHealth and CG (p<0.001).

CONCLUSION: The improvement in QoL, functional strength, and functional capacity was greater among patients in the RGw-mHealth compared to the RGwo-mHealth or CG.}, } @article {pmid38114301, year = {2024}, author = {Khazaeli, M and Maruthi, VK and See, S and Ondracek, T and Gerami, P}, title = {Melanocyte colonization and pigmentation of breast carcinoma: A case report.}, journal = {Journal of cutaneous pathology}, volume = {51}, number = {4}, pages = {280-283}, doi = {10.1111/cup.14564}, pmid = {38114301}, issn = {1600-0560}, mesh = {Humans ; Female ; *Paget's Disease, Mammary/pathology ; Diagnosis, Differential ; *Breast Neoplasms/pathology ; Melanocytes/pathology ; *Melanoma/diagnosis/pathology ; *Pigmentation Disorders/pathology ; Pigmentation ; }, abstract = {Pigmented mammary Paget disease is a rare variant of mammary Paget disease that is often clinically misdiagnosed as a melanocytic lesion of the skin or nipple-areolar complex. Careful morphological assessment, along with the performance of adequate immunohistochemical stains, will help in achieving the right diagnosis and avoiding misdiagnosis of the entity as malignant melanoma. We report a rare case of pigmented mammary Paget disease with concomitant colonization of the underlying invasive ductal carcinoma by melanocytes mimicking melanoma.}, } @article {pmid38112318, year = {2024}, author = {Brings, S and Mier, W and Beijer, B and Kliemank, E and Herzig, S and Szendroedi, J and Nawroth, PP and Fleming, T}, title = {Non-cross-linking advanced glycation end products affect prohormone processing.}, journal = {The Biochemical journal}, volume = {481}, number = {1}, pages = {33-44}, doi = {10.1042/BCJ20230321}, pmid = {38112318}, issn = {1470-8728}, mesh = {Humans ; *Glycation End Products, Advanced ; Pyruvaldehyde/metabolism ; Proinsulin ; *Diabetes Mellitus ; Peptides/chemistry ; Endopeptidases ; }, abstract = {Advanced glycation end products (AGEs) are non-enzymatic post-translational modifications of amino acids and are associated with diabetic complications. One proposed pathomechanism is the impaired processing of AGE-modified proteins or peptides including prohormones. Two approaches were applied to investigate whether substrate modification with AGEs affects the processing of substrates like prohormones to the active hormones. First, we employed solid-phase peptide synthesis to generate unmodified as well as AGE-modified protease substrates. Activity of proteases towards these substrates was quantified. Second, we tested the effect of AGE-modified proinsulin on the processing to insulin. Proteases showed the expected activity towards the unmodified peptide substrates containing arginine or lysine at the C-terminal cleavage site. Indeed, modification with Nε-carboxymethyllysine (CML) or methylglyoxal-hydroimidazolone 1 (MG-H1) affected all proteases tested. Cysteine cathepsins displayed a reduction in activity by ∼50% towards CML and MG-H1 modified substrates. The specific proteases trypsin, proprotein convertases subtilisin-kexins (PCSKs) type proteases, and carboxypeptidase E (CPE) were completely inactive towards modified substrates. Proinsulin incubation with methylglyoxal at physiological concentrations for 24 h resulted in the formation of MG-modified proinsulin. The formation of insulin was reduced by up to 80% in a concentration-dependent manner. Here, we demonstrate the inhibitory effect of substrate-AGE modifications on proteases. The finding that PCSKs and CPE, which are essential for prohormone processing, are inactive towards modified substrates could point to a yet unrecognized pathomechanism resulting from AGE modification relevant for the etiopathogenesis of diabetes and the development of obesity.}, } @article {pmid38104283, year = {2023}, author = {Maman, A and Senol, O}, title = {Evaluating Alterations in Breast Cancer Patients after Recovery Via A PET/CT-Assisted Metabolomics Approach.}, journal = {Puerto Rico health sciences journal}, volume = {42}, number = {4}, pages = {276-282}, pmid = {38104283}, issn = {2373-6011}, mesh = {Humans ; Female ; *Positron Emission Tomography Computed Tomography ; *Breast Neoplasms/pathology ; Metabolome ; Metabolomics/methods ; Biomarkers ; }, abstract = {OBJECTIVE: Breast cancer is a mortal disease that causes many deaths, especially in women. Improved therapies could contribute positively to survival rates. Metabolomics is an important tool for monitoring the alterations of several metabolites in clinical cases. This study aimed to develop a metabolomics model to observe (via mass spectroscopy) metabolic alterations in patients who suffered from breast cancer (BC), both before and after their recovery.

MATERIALS AND METHODS: Grades 1 and 2 invasive ductal carcinoma patients were evaluated based on their positron emission tomography/computed tomography results. Fourteen patients who had fully recovered from BC were subjected to metabolomics analysis. Plasma samples were extracted and analyzed via quadrupole time-of-flight mass tandem spectroscopy. A chemometrics analysis was performed in order to determine the statistically significant metabolites. All the metabolites were annotated via the mummichog algorithm.

RESULTS AND DISCUSSION: According to the data analysis, glucose, ornithine, phenyalanine, some vitamins, and metabolites in the fatty acid metabolism were statistically altered after recovery of each patient.

CONCLUSION: Untargeted metabolomics studies can be used to understand the etiopathogenesis of breast cancer, finding new biomarkers and alterations of metabolic pathways. After the tumor burden was removed, homeostasis was restored and the concentration of several metabolites began to normalize. This study elucidated the effects of breast cancer at the molecular level.}, } @article {pmid38100925, year = {2024}, author = {Li, HM and Huang, TY and Chang, TH and Wen, TN}, title = {Paget's disease of the nipple with underlying occult invasive carcinoma detected by magnetic resonance imaging and second-look ultrasound: Case report.}, journal = {International journal of surgery case reports}, volume = {114}, number = {}, pages = {109139}, pmid = {38100925}, issn = {2210-2612}, abstract = {INTRODUCTION: Paget's disease of the nipple (PDN) is a rare and often misdiagnosed condition characterized by the infiltration of adenocarcinoma cells into the nipple epidermis. It poses substantial diagnostic and therapeutic challenges due to its similarity to benign dermatological conditions and its association with in situ or invasive carcinoma.

CASE PRESENTATION: This report details the case of a 47-year-old woman with persistent nipple itching, rash, and occasional bloody discharge. No abnormalities were seen on the mammogram and ultrasound scans; punch biopsy was performed to confirm PDN. A small lesion missed by other imaging methods was detected via breast magnetic resonance imaging (MRI). A second-look ultrasound with needle localization enabled precise surgery. The pathology report after breast-conserving surgery (BCS) revealed invasive ductal carcinoma with no metastasis in the sentinel lymph node biopsy.

DISCUSSION: PDN often mimics benign skin conditions, leading to delayed diagnosis. Furthermore, timely identification is crucial as PDN is frequently associated with underlying breast malignancies. Additional imaging, such as breast MRI, is essential for comprehensive evaluation, as it can reveal hidden lesions previously undetected by conventional mammography and ultrasound. A second-look ultrasound guided needle placement for tumor localization, enhancing surgical precision, aesthetics, and reducing patient harm. Surgical management, including mastectomy, BCS with radiotherapy, and oncoplastic surgery, offers suitable options without affecting recurrence or survival in selected patients.

CONCLUSION: This case emphasizes the importance of employing additional imaging tools, such as breast MRI and second-look ultrasound for the early detection and surgical management of PDN.}, } @article {pmid38098206, year = {2024}, author = {Li, J and Wu, Y and Tian, Z and Shu, L and Wu, S and Wu, Z}, title = {Application Value of Ultrasound Elastography Combined With Contrast-Enhanced Ultrasound (CEUS) Quantitative Analysis in Differentiation of Nodular Fibrocystic Changes of the Breast From Invasive Ductal Carcinoma.}, journal = {Ultrasonic imaging}, volume = {46}, number = {2}, pages = {102-109}, doi = {10.1177/01617346231217087}, pmid = {38098206}, issn = {1096-0910}, mesh = {Humans ; *Elasticity Imaging Techniques/methods ; Contrast Media ; Ultrasonography/methods ; Breast/diagnostic imaging ; Diagnosis, Differential ; *Carcinoma, Ductal ; Sensitivity and Specificity ; }, abstract = {This study aimed to compare the value of ultrasound elastography combined with contrast-enhanced ultrasound (CEUS) quantitative analysis in the differentiation of nodular fibrocystic breast change (FBC) from breast invasive ductal carcinoma (BIDC). We selected 50 patients each with nodular FBC and BIDC, who were admitted to the Affiliated Hospital of Zunyi Medical University from January 2018 to December 2021. Their ultrasonic elastic images and CEUS videos were collected, their ultrasound elastography scores and the ratio of strain rate (SR) of the lesions were determined, and the exported DICOM format videos of CEUS were quantitatively analyzed using VueBox software to obtain quantitative perfusion parameters. The differences between the ultrasound elastography score and SR while comparing nodular FBC and BIDC cases were statistically significant (p < .05). The sensitivity, specificity, and accuracy of ultrasound elastography scores in the differential diagnoses of nodular FBC and BIDC were 74%, 88%, and 81%, respectively. Additionally, the sensitivity, specificity, and accuracy of SR in the differential diagnosis of nodular FBC and BIDC were 94%, 78%, and 86%, respectively. Statistically significant differences were observed in the CEUS quantitative perfusion parameters PE, AUC (WiAUC, WoAUC, WiWoAUC), and WiPI in both nodular FBC and BIDC according to the VueBox software (p < .05). The sensitivity, specificity, and accuracy of CEUS quantitative analysis in the differential diagnoses of nodular FBC and BIDC were 66%, 82%, and 74%, respectively. Using the pathological findings as the gold standard, ROC curves were established, and the area under the curve (AUC) of the CEUS quantitative analysis, elasticity score, SR, and ultrasound elastography combined with CEUS quantitative analysis were 0.731, 0.838, and 0.892, as well as 0.945, respectively. Ultrasound elasticity scoring, SR and CEUS quantitative analysis have certain application value for differentiating nodular FBC cases from BIDC; however, ultrasound elasticity imaging combined with CEUS quantitative analysis can help in improving the differential diagnostic efficacy of nodular FBC cases from BIDC.}, } @article {pmid38097248, year = {2023}, author = {Yin, L and Yin, AH and Pu, CC}, title = {Clinical characteristics and prognosis of primary small cell carcinoma of the breast: a propensity score-matched, population-based study.}, journal = {BMJ open}, volume = {13}, number = {12}, pages = {e073841}, pmid = {38097248}, issn = {2044-6055}, mesh = {Humans ; Male ; Cohort Studies ; Retrospective Studies ; Propensity Score ; *Carcinoma, Small Cell/epidemiology/therapy ; Prognosis ; Nomograms ; }, abstract = {OBJECTIVE: The purpose of this study was to describe the clinicopathological characteristics and prognosis of primary small cell carcinoma of the breast (PSCCB) and compare PSCCB with breast invasive ductal carcinoma (IDC).

DESIGN: A retrospective cohort study.

SETTING: Data of patients with PSCCB and breast IDC were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016.

PARTICIPANTS: Eighty-three patients with PSCCB and 410 699 patients with breast IDC were enrolled in the present cohort study.

MATERIALS AND METHODS: Patients with PSCCB and breast IDC were identified from the SEER database between 2004 and 2016. The clinicopathological characteristics and survival of patients with PSCCB and IDC were compared. Propensity score matching (PSM) analysis was performed to adjust for differences in baseline characteristics when comparing overall survival (OS) and cancer-specific survival (CSS). Moreover, OS-/CSS-specific nomograms were established to predict the prognosis of PSCCB.

RESULTS: Compared with IDC, PSCCB was significantly correlated with older age, male, higher pathological grade, higher TNM (tumour, node, metastases) stage, a higher proportion of triple-negative breast cancer, a lower proportion of ER/PR positivity and significantly worse clinical outcome. The median OS and CSS of patients with PSCCB were 23.0 m (95%CI 13.0 to 56.0) and 28.0 m (95%CI 18.0 to 66.0), respectively. The 5-year OS and CSS rates in the PSCCB group were 36.1% and 42.4%, respectively. In the matched cohort after PSM analysis, patients with PSCCB had significantly worse OS and CSS than IDC patients. Multivariate Cox regression analysis demonstrated that T stage and administration of chemotherapy were independent prognostic factors for both OS and CSS in patients with PSCCB. The C-index for OS-/CSS-specific nomogram was 0.75 (95%CI 0.66 to 0.85)/0.79 (95%CI 0.69 to 0.89), respectively. The calibration curve in the ROC analysis indicated that the predicted value was consistent with the actual observation value. Decision curve analysis suggested that the nomogram model has a significant positive net benefit from the risk of death and are better than the traditional TNM staging system.

CONCLUSION: PSCCB has distinct clinicopathological characteristics, and patients with PSCCB have significantly worse clinical outcomes than those with IDC.}, } @article {pmid38093163, year = {2023}, author = {Yi, S and Zhang, C and Li, M and Qu, T and Wang, J}, title = {Machine learning and experiments identifies SPINK1 as a candidate diagnostic and prognostic biomarker for hepatocellular carcinoma.}, journal = {Discover oncology}, volume = {14}, number = {1}, pages = {231}, pmid = {38093163}, issn = {2730-6011}, abstract = {Machine learning techniques have been widely used in predicting disease prognosis, including cancer prognosis. One of the major challenges in cancer prognosis is to accurately classify cancer types and stages to optimize early screening and detection, and machine learning techniques have proven to be very useful in this regard. In this study, we aimed at identifying critical genes for diagnosis and outcomes of hepatocellular carcinoma (HCC) patients using machine learning. The HCC expression dataset was downloaded from GSE65372 datasets and TCGA datasets. Differentially expressed genes (DEGs) were identified between 39 HCC and 15 normal samples. For the purpose of locating potential biomarkers, the LASSO and the SVM-RFE assays were performed. The ssGSEA method was used to analyze the TCGA to determine whether there was an association between SPINK1 and tumor immune infiltrates. RT-PCR was applied to examine the expression of SPINK1 in HCC specimens and cells. A series of functional assays were applied to examine the function of SPINK1 knockdown on the proliferation of HCC cells. In this study, 103 DEGs were obtained. Based on LASSO and SVM-RFE analysis, we identified nine critical diagnostic genes, including C10orf113, SPINK1, CNTLN, NRG3, HIST1H2AI, GPRIN3, SCTR, C2orf40 and PITX1. Importantly, we confirmed SPINK1 as a prognostic gene in HCC. Multivariate analysis confirmed that SPINK1 was an independent prognostic factor for overall survivals of HCC patients. We also found that SPINK1 level was positively associated with Macrophages, B cells, TFH, T cells, Th2 cells, iDC, NK CD56bright cells, Th1 cells, aDC, while negatively associated with Tcm and Eosinophils. Finally, we demonstrated that SPINK1 expression was distinctly increased in HCC specimens and cells. Functionally, silence of SPINK1 distinctly suppressed the proliferation of HCC cells via regulating Wnt/β-catenin pathway. The evidence provided suggested that SPINK1 may possess oncogenic properties by inducing dysregulated immune infiltration in HCC. Additionally, SPINK1 was identified as a novel biomarker and therapeutic target for HCC.}, } @article {pmid38091153, year = {2024}, author = {Schwartz, CJ and Khorsandi, N and Blanco, A and Mukhtar, RA and Chen, YY and Krings, G}, title = {Clinicopathologic and genetic analysis of invasive breast carcinomas in women with germline CHEK2 variants.}, journal = {Breast cancer research and treatment}, volume = {204}, number = {1}, pages = {171-179}, pmid = {38091153}, issn = {1573-7217}, mesh = {Humans ; Female ; Adult ; Middle Aged ; Aged ; *Breast Neoplasms/genetics/pathology ; Checkpoint Kinase 2/genetics ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Germ Cells ; Carrier Proteins/genetics ; }, abstract = {PURPOSE: Germline pathogenic variants in checkpoint kinase 2 (CHEK2) are associated with a moderately increased risk of breast cancer (BC). The spectrum of clinicopathologic features and genetics of these tumors has not been fully established.

METHODS: We characterized the histopathologic and clinicopathologic features of 44 CHEK2-associated BCs from 35 women, and assessed responses to neoadjuvant chemotherapy. A subset of cases (n = 23) was additionally analyzed using targeted next-generation DNA sequencing (NGS).

RESULTS: Most (94%, 33/35) patients were heterozygous carriers for germline CHEK2 variants, and 40% had the c.1100delC allele. Two patients were homozygous, and five had additional germline pathogenic variants in ATM (2), PALB2 (1), RAD50 (1), or MUTYH (1). CHEK2-associated BCs occurred in younger women (median age 45 years, range 25-75) and were often multifocal (20%) or bilateral (11%). Most (86%, 38/44) were invasive ductal carcinomas of no special type (IDC-NST). Almost all (95%, 41/43) BCs were ER + (79% ER + HER2-, 16% ER + HER2 + , 5% ER-HER2 +), and most (69%) were luminal B. Nottingham grade, proliferation index, and results of multiparametric molecular testing were heterogeneous. Biallelic CHEK2 alteration with loss of heterozygosity was identified in most BCs (57%, 13/23) by NGS. Additional recurrent alterations included GATA3 (26%), PIK3CA (226%), CCND1 (22%), FGFR1 (22%), ERBB2 (17%), ZNF703 (17%), TP53 (9%), and PPM1D (9%), among others. Responses to neoadjuvant chemotherapy were variable, but few patients (21%, 3/14) achieved pathologic complete response. Most patients (85%) were without evidence of disease at time of study (n = 34). Five patients (15%) developed distant metastasis, and one (3%) died (mean follow-up 50 months).

CONCLUSION: Almost all CHEK2-associated BCs were ER + IDC-NST, with most classified as luminal B with or without HER2 overexpression. NGS supported the luminal-like phenotype and confirmed CHEK2 as an oncogenic driver in the majority of cases. Responses to neoadjuvant chemotherapy were variable but mostly incomplete.}, } @article {pmid38090235, year = {2023}, author = {Adedokun, KA and Oluogun, WA and Oyenike, MA and Imodoye, SO and Yunus, LA and Lasisi, SA and Bello, IO and Kamorudeen, RT and Adekola, SA}, title = {Expression Patterns of ER, PR, HER-2/neu and p53 in Association with Nottingham Tumour Grade in Breast Cancer Patients.}, journal = {Sultan Qaboos University medical journal}, volume = {23}, number = {4}, pages = {526-533}, pmid = {38090235}, issn = {2075-0528}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology ; Receptors, Progesterone/metabolism ; Tumor Suppressor Protein p53 ; Erb-b2 Receptor Tyrosine Kinases/genetics/metabolism ; Hormones ; }, abstract = {OBJECTIVES: Recent molecular studies show that breast cancer (BC) is a heterogeneous disease, and several molecular changes may accumulate over time to influence treatment response. As a result, employing reliable molecular biomarkers to monitor these modifications may help deliver personalised treatment. However, this may be unrealistic in the resource-limited parts of the world. Thus, this study aimed to investigate the expression pattern of hormone receptors and p53 tumour suppressor using immunohistochemistry (IHC) in BC compared to the traditional tumour grade.

METHODS: In total, 205 cases were investigated, and the Modified Bloom-Richardson score system was adopted in grading the tumours. The tissue sections of the cases were stained with specific primary antibodies at dilutions of 1:60 for oestrogen receptors (ER) and progesterone receptors (PR), 1:350 for the human epidermal growth factor (HER-2/neu) and 1:50 for p53.

RESULTS: Invasive ductal carcinoma of no-specific type (n = 190, 92.7%) was predominant and grade II tumour (n = 146, 71.2%) was the most frequent. Hormone receptors ER (n = 127) and PR (n = 145) had 62.0% and 70.7% positive cases, respectively; 34.1% (n = 70) were positive for HER-2/neu, while 76.1% (n = 156) were positive for p53. Significant associations between Nottingham grade and expression patterns of ER (P <0.01), PR (P <0.001), HER-2/neu (P <0.001) and p53 (P = 0.001) were observed.

CONCLUSION: Nottingham grade had a high degree of concordance with the patterns of expression of hormone receptors, HER-2/neu and p53, suggesting that it may play an important role in connection with the predictive and prognostic biomarkers for BC.}, } @article {pmid38089951, year = {2023}, author = {Tong, CW and Cohen-Hallaleh, R}, title = {Goldilocks Mastectomy: The Middle Road Option for Obese Breast Cancer Patients.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e50362}, pmid = {38089951}, issn = {2168-8184}, abstract = {Breast cancer is the predominant cancer affecting females in Australia. With the rising obesity rates, the number of obese breast cancer patients is also rising. Full complex breast reconstruction is known to carry significant risk of complications in obese patients, hence we sought to utilize Goldilocks mastectomy as an alternative middle-ground option between standard mastectomy and complex breast reconstruction. A 63-year-old obese female presented with left nipple inversion. Ultrasonography revealed a 9.7 mm dilated retroareolar duct within the left breast, indicating lobular carcinoma. Subsequent biopsy analysis revealed estrogen/progesterone receptor (ER/PR)-positive cancer with equivocal human epidermal growth factor receptor 2 (HER2) status and a Ki67 index of 10%. Concurrently, a discrete area of conspicuous breast tissue prominence displayed characteristics of invasive ductal carcinoma with similar receptor status but a reduced Ki67 index of less than 5%. Traditional breast reconstruction options were unfavorable due to obesity, prompting consideration of a tailored Goldilocks mastectomy. The procedure was uncomplicated, and follow-up assessments revealed commendable wound healing, alongside the restoration of symmetrical breast contours. Conclusion: This study highlights the significance of Goldilocks mastectomy as an invaluable technique in the comprehensive management of breast cancer, particularly for obese patients characterized by a body mass index (BMI) exceeding 35 and substantial medical comorbidities.}, } @article {pmid38083560, year = {2023}, author = {Cheng, C and Foxworthy, GE and Fridman, GY}, title = {A Cuff Lead for Delivering Ionic Direct Current (iDC) to Block Neural Activities of Sciatic Nerve.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2023}, number = {}, pages = {1-4}, pmid = {38083560}, issn = {2694-0604}, support = {R01 NS110893/NS/NINDS NIH HHS/United States ; }, mesh = {Rats ; Animals ; *Sciatic Nerve/physiology ; Electrodes ; Neurons ; *Nerve Tissue ; Silicones ; }, abstract = {Direct current (DC) applied extracellularly can block action potential (AP) propagation in a neuron. This suppression paradigm has been proposed as a possible treatment for blocking nociceptive pain. However, the application of DC is limited in duration due to the charge injection constraint imposed by the evolution of electrochemical reactions at the metal electrode. To prolong the application of DC, a microfluidic lead filled with conductive electrolyte can be used to separate the metal electrode from the target nerve. Here, we describe a tripolar nerve cuff lead fabricated with biocompatible silicone to block the APs in the rat sciatic nerve. This lead has a self-curling silicone membrane to wrap around sciatic nerve for secured mechanical attachment and electrical isolation between the nerve and the surrounding muscle. In-vivo testing showed that delivering 1.4mA DC via the cuff lead blocked the nerve activity and reduced the evoked compound action potential (eCAP) to 30% of its unblocked response.}, } @article {pmid38076316, year = {2023}, author = {Qureshi, A and Gollamudi, S and Qureshi, S and Sondhi, N and Nabi, S and Genato, R and Xiao, P and Asarian, A}, title = {The phenomenon of spontaneous tumor regression in breast cancer.}, journal = {Journal of surgical case reports}, volume = {2023}, number = {12}, pages = {rjad651}, pmid = {38076316}, issn = {2042-8812}, abstract = {Spontaneous tumor regression is an increasingly prevalent phenomenon of partial or complete disappearance of primary tumor tissue or associated metastases in the absence of therapeutic intervention. Cases of spontaneous regression have been established in malignant tumors, such as testicular germ cell tumor, renal cell cancer, melanoma, basal cell carcinoma, neuroblastoma, colon cancer, breast cancer, as well as metastases. Breast cancer has increasingly been reported to have a higher rate of spontaneous regression than previously thought. Immunologic response is cited as the forefront of spontaneous regression phenomenon, with the focus on immunologic cell death. This report brings awareness to a case of spontaneous regression observed in invasive ductal carcinoma of the breast and how disruption of the tumor microenvironment can take a variable course even in malignant disease.}, } @article {pmid38076287, year = {2023}, author = {Tractenberg, RE and Groah, SL and Frost, JK and Yumoto, F and Rounds, AK and Ljungberg, IH}, title = {Urinary Symptoms Among People With Neurogenic Lower Urinary Tract Dysfunction (NLUTD) Vary by Bladder Management.}, journal = {Topics in spinal cord injury rehabilitation}, volume = {29}, number = {3}, pages = {31-43}, pmid = {38076287}, issn = {1945-5763}, mesh = {Humans ; Urinary Bladder ; *Urinary Bladder, Neurogenic/therapy/diagnosis ; *Spinal Cord Injuries/complications ; Catheters, Indwelling ; Pain/complications ; }, abstract = {OBJECTIVES: To determine whether assessment and decision-making around urinary symptoms in people with neurogenic lower urinary tract dysfunction (NLUTD) should depend on bladder management.

METHODS: Three surveys of urinary symptoms associated with NLUTD (USQNBs) were designed specific to bladder management method for those who manage their bladders with indwelling catheter (IDC), intermittent catheter (IC), or voiding (V). Each was deployed one time to a national sample. Subject matter experts qualitatively assessed the wording of validated items to identify potential duplicates. Clustering by unsupervised structural learning was used to analyze duplicates. Each item was classified into mutually exclusive and exhaustive categories: clinically actionable ("fever"), bladder-specific ("suprapubic pain"), urine quality ("cloudy urine"), or constitutional ("leg pain").

RESULTS: A core of 10 "NLUTD urinary symptoms" contains three clinically actionable, bladder-specific, and urine quality items plus one constitutional item. There are 9 (IDC), 11 (IC), and 8 (V) items unique to these instruments. One decision-making protocol applies to all instruments.

CONCLUSION: Ten urinary symptoms in NLUTD are independent of bladder management, whereas a similar number depend on bladder management. We conclude that assessment of urinary symptoms for persons with NLUTD should be specific to bladder management method, like the USQNBs are.}, } @article {pmid38075206, year = {2024}, author = {Sakurai, K and Yamada, S and Ito, R and Ochiai, M and Ando, T and Sakai, Y and Kato, T and Ito, H}, title = {Chromogenic in situ hybridization reveals specific expression pattern of long non-coding RNA DRAIC in formalin-fixed paraffin-embedded specimen.}, journal = {Non-coding RNA research}, volume = {9}, number = {1}, pages = {76-83}, pmid = {38075206}, issn = {2468-0540}, abstract = {Long non-coding RNA (lncRNA) plays an important role in the regulation of gene expression in normal and cancer cells. We previously discovered a novel tumor-suppressive lncRNA, DRAIC, in prostate cancer cells. Subsequent studies have demonstrated that DRAIC is dysregulated in various malignancies and exhibits a tumor-suppressive or pro-oncogenic function. However, details regarding its expression pattern in normal and cancerous tissues remain largely unknown. In this study, we performed chromogenic in situ hybridization (CISH) using RNAscope technology to assess DRAIC expression in formalin-fixed paraffin-embedded (FFPE) specimens. In the neuroendocrine-differentiated cancer cell line VMRC-LCD, CISH revealed a diffuse localization of DRAIC in the cytoplasm as well as specific accumulation in the nuclear compartment. DRAIC expression was comprehensively analyzed using tissue microarrays containing 89 normal and 155 tumor tissue samples. DRAIC was weakly expressed in normal epithelial cells of the colon, bronchiole, kidney, prostate, and testis. Conversely, DRAIC was moderately to highly expressed in some cancer tissues, including prostate adenocarcinoma, invasive ductal carcinoma of the breast, neuroendocrine carcinoma of the esophagus, lung adenocarcinoma, and small cell lung carcinoma. While DRAIC knockdown did not affect VMRC-LCD cellular viability and invasive ability, gene expression related to the neuroendocrine and cancer-related pathways was altered. Our expression analysis revealed the specific expression pattern of DRAIC in normal and cancerous FFPE tissues. The results presented here may lead to the elucidation of additional novel functions of DRAIC.}, } @article {pmid38071886, year = {2024}, author = {Ismail, Y and Zakaria, AS and Allam, R and Götte, M and Ibrahim, SA and Hassan, H}, title = {Compartmental Syndecan-1 (CD138) expression as a novel prognostic marker in triple-negative metaplastic breast cancer.}, journal = {Pathology, research and practice}, volume = {253}, number = {}, pages = {154994}, doi = {10.1016/j.prp.2023.154994}, pmid = {38071886}, issn = {1618-0631}, mesh = {Humans ; Female ; *Triple Negative Breast Neoplasms/pathology ; *Breast Neoplasms/pathology ; Prognosis ; Retrospective Studies ; Syndecan-1/metabolism ; Disease-Free Survival ; *Carcinoma, Ductal, Breast/pathology ; }, abstract = {BACKGROUND: Metaplastic breast cancer (MpBC) is rare, aggressive, and mostly triple-negative (TN) subtype of BC. We aimed to investigate the potential prognostic significance of Syndecan-1 (SDC1/CD138) expression in this unique tumor.

METHODS: Archived charts of 50 TNBC patients [21 MpBC and 29 invasive ductal carcinoma (IDC)] were retrospectively evaluated. Corresponding paraffin blocks were used for immunohistochemical (IHC) staining of SDC1. Compartmental (epithelial membranous, stromal, and cytoplasmic) staining scores were expressed in quartiles (Q) and correlated with disease-free survival (DFS) and overall survival (OS).

RESULTS: The median follow-up period was 54.6 months (range: 2.2-112.7). MpBC patients showed significantly worse DFS and OS than IDC (p = 0.007 and 0.004, respectively). MpBC demonstrated significantly higher Q4 stromal and membranous SDC1 compared to IDC (p = 0.016 and 0.021, respectively), whereas IDC exhibited significantly higher cytoplasmic Q4 SDC1 than MpBC (p = 0.015). Stromal Q4 SDC1 expression was found to be an independent factor associated with MpBC relative to IDC (OR: 6.7, 95% CI: 1.24-36.90; p = 0.028). Stromal Q4 SDC1 expression was also an independent prognostic parameter for worse DFS and OS compared to Q1-3 in the whole cohort (HR: 4.2, 95% CI: 1.6-10.5; p = 0.003 and HR: 5.8; 95% CI: 2.2-15.3; p < 0.001, respectively). In MpBC, cytoplasmic Q1-3 SDC1 expression was an independent prognostic indicator for worse OS compared with their IDC counterparts (HR: 2.837, 95% CI: 1.048-7.682; p = 0.04).

CONCLUSION: This study suggests, for the first time, that differential expression and localization of SDC1 may contribute to the pathogenesis and prognosis of TN-MpBC. Therefore, targeting SDC1 (CD138) could emerge as a novel therapeutic approach for this devastating disease.}, } @article {pmid38070191, year = {2024}, author = {Mouabbi, JA and Qaio, W and Shen, Y and Raghavendra, AS and Tripathy, D and Layman, RM}, title = {Efficacy of Single-Agent Chemotherapy in Endocrine Therapy-Refractory Metastatic Invasive Lobular Carcinoma.}, journal = {The oncologist}, volume = {29}, number = {3}, pages = {213-218}, pmid = {38070191}, issn = {1549-490X}, support = {MIRA RP170067//Cancer Prevention and Research Institute of Texas/ ; //NIH/ ; //NCI/ ; }, mesh = {Humans ; Female ; *Carcinoma, Lobular/pathology ; Prospective Studies ; Erb-b2 Receptor Tyrosine Kinases/genetics/therapeutic use ; *Breast Neoplasms/pathology ; Capecitabine/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; }, abstract = {BACKGROUND: Hormone receptor (HR)-positive, HER2-negative metastatic invasive lobular breast cancer (mILC) is distinct from invasive ductal cancer (IDC) in clinicopathologic and molecular characteristics, impacting its response to systemic therapy. While endocrine therapy (ET) combined with targeted therapies has shown efficacy in ET-sensitive mILC, data on chemotherapy in ET-refractory mILC remain limited. We investigated the efficacy of single-agent capecitabine (CAP) versus taxanes (TAX) in ET-refractory HR+ HER2-negative patients with mILC.

MATERIALS AND METHODS: Using data from the MD Anderson prospectively collected breast cancer database, we identified patients with HR+ HER2-negative mILC who received prior ET and first-time chemotherapy in the metastatic setting. We compared outcomes between 173 CAP-treated and 96 TAX-treated patients.

RESULTS: CAP-treated patients had significantly better median progression-free survival (PFS) than TAX-treated patients (8.8 vs 5.0 months, HR 0.63, P < .001). Overall survival (OS) did not differ significantly between the groups (42.7 vs 36.6 months for CAP vs TAX, respectively, HR 0.84, P = .241). Multivariate analyses for PFS and OS revealed better outcomes in subjects with fewer metastatic sites and those exposed to more lines of ET. Additionally, Black patients showed worse OS outcomes compared to White patients (HR 2.46; P = .001).

CONCLUSION: In ET-refractory HR+ HER2-negative mILC, single-agent CAP demonstrated superior PFS compared to TAX. Our findings highlight the potential benefit of CAP in this patient subset, warranting further investigation through prospective trials.}, } @article {pmid38067216, year = {2023}, author = {Bernhardt, M and Kristiansen, G}, title = {Molecular Alterations in Intraductal Carcinoma of the Prostate.}, journal = {Cancers}, volume = {15}, number = {23}, pages = {}, pmid = {38067216}, issn = {2072-6694}, abstract = {Intraductal carcinoma of the prostate is most commonly associated with high-grade invasive prostate cancer. However, isolated IDC-P without adjacent cancer or high-grade cancer is also well known. Common genetic alterations present in IDC-P with adjacent high-grade prostate cancer are those described in high-grade tumors, such as PTEN loss (69-84%). In addition, the rate of LOH involving TP53 and RB1 is significantly higher. IDC-P is common in the TCGA molecular subset of SPOP mutant cancers, and the presence of SPOP mutations are more likely in IDC-P bearing tumors. IDC-P without adjacent high-grade cancers are by far less common. They are less likely to have PTEN loss (47%) and rarely harbor an ERG fusion (7%). Molecular alterations that may predispose a person to the development of IDC-P include the loss of BRCA2 and PTEN as well as mutations in SPOP. However, the causative nature of these genetic alterations is yet to be validated.}, } @article {pmid38065742, year = {2024}, author = {Su, H and Lin, X and Huo, J and Zhang, F}, title = {Multiple distant metastases after surgery for ductal carcinoma in situ of the parotid gland: A case report.}, journal = {Asian journal of surgery}, volume = {47}, number = {3}, pages = {1481-1482}, doi = {10.1016/j.asjsur.2023.11.140}, pmid = {38065742}, issn = {0219-3108}, mesh = {Humans ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Parotid Gland/surgery/pathology ; Lymphatic Metastasis/pathology ; }, } @article {pmid38059175, year = {2023}, author = {Zhou, S and Wang, J and Li, M and Yang, Y and Zhang, H and Chen, D}, title = {Bilateral and synchronous male breast cancer: a case report.}, journal = {International journal of clinical and experimental pathology}, volume = {16}, number = {11}, pages = {352-356}, pmid = {38059175}, issn = {1936-2625}, abstract = {Genetic mutational characterization of synchronous bilateral male breast cancer (BC) has been poorly reported due to its rarity. Herein, we present a 55-year-old male patient who was diagnosed with bilateral breast cancer (BBC) and harbored different gene mutations. The diagnosis of synchronous bilateral breast cancer (SBBC) was made using ultrasonography, magnetic resonance imaging (MRI), mammography and core-needle biopsy. Subsequently, bilateral modified radical mastectomies were performed, and histopathologic examination revealed invasive ductal carcinoma. To further investigate the genetic profile of the patient, the biopsy tissue from both breasts and a blood sample were subjected to targeted next generation sequencing (NGS). The genomic profile of the left breast (LB) sample revealed two copy number variations (CNVs), amplification of MCL1 and DAXX, while the right breast (RB) sample showed no obvious mutation. We are reporting this case along with its clinicopathologic findings and genetic investigations, since SBBS occurs extremely rarely, especially in men. The heterogeneity in gene mutations observed in this case may suggest a different pathogenesis and the need for different therapy strategies.}, } @article {pmid38049608, year = {2024}, author = {Maggi, G and Giacobbe, C and Vitale, C and Amboni, M and Obeso, I and Santangelo, G}, title = {Theory of mind in mild cognitive impairment and Parkinson's disease: The role of memory impairment.}, journal = {Cognitive, affective & behavioral neuroscience}, volume = {24}, number = {1}, pages = {156-170}, pmid = {38049608}, issn = {1531-135X}, mesh = {Humans ; *Parkinson Disease/complications/psychology ; *Theory of Mind ; *Cognitive Dysfunction/etiology/psychology ; Executive Function ; *Cognition Disorders ; Memory Disorders ; Neuropsychological Tests ; }, abstract = {BACKGROUND: Social cognition is impaired in Parkinson's disease (PD). Whether social cognitive impairment (iSC) is a by-product of the underlying cognitive deficits in PD or a process independent of cognitive status is unknown. To this end, the present study was designed to investigate the weight of specific cognitive deficits in social cognition, considering different mild cognitive impairment subtypes of PD (PD-MCI).

METHODS: Fifty-eight PD patients underwent a neuropsychological battery assessing executive functions, memory, language, and visuospatial domains, together with social cognitive tests focused on theory of mind (ToM). Patients were divided into subgroups according to their clinical cognitive status: amnestic PD-MCI (PD-aMCI, n = 18), non-amnestic PD-MCI (PD-naMCI, n = 16), and cognitively unimpaired (PD-CU, n = 24). Composite scores for cognitive and social domains were computed to perform mediation analyses.

RESULTS: Memory and language impairments mediated the effect of executive functioning in social cognitive deficits in PD patients. Dividing by MCI subgroups, iSC occurred more frequently in PD-aMCI (77.8%) than in PD-naMCI (18.8%) and PD-CU (8.3%). Moreover, PD-aMCI performed worse than PD-CU in all social cognitive measures, whereas PD-naMCI performed worse than PD-CU in only one subtype of the affective and cognitive ToM tests.

CONCLUSIONS: Our findings suggest that ToM impairment in PD can be explained by memory dysfunction that mediates executive control. ToM downsides in the amnesic forms of PD-MCI may suggest that subtle changes in social cognition could partly explain future transitions into dementia. Hence, the evaluation of social cognition in PD is critical to characterize a possible behavioral marker of cognitive decline.}, } @article {pmid38047107, year = {2023}, author = {Zhang, W and Nowotny, H and Theodoropoulou, M and Simon, J and Hemmer, CM and Bidlingmaier, M and Auer, MK and Reincke, M and Uhlenhaut, H and Reisch, N}, title = {E47 as a novel glucocorticoid-dependent gene mediating lipid metabolism in patients with endogenous glucocorticoid excess.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1249863}, pmid = {38047107}, issn = {1664-2392}, mesh = {Animals ; Female ; Humans ; Mice ; Adrenocorticotropic Hormone/metabolism ; Cholesterol ; *Cushing Syndrome ; Dexamethasone/pharmacology ; *Glucocorticoids/pharmacology ; Hydrocortisone ; Lipid Metabolism/genetics ; Prospective Studies ; RNA, Messenger/metabolism ; Basic Helix-Loop-Helix Proteins ; }, abstract = {PURPOSE: E47 has been identified as a modulating transcription factor of glucocorticoid receptor target genes, its loss protecting mice from metabolic adverse effects of glucocorticoids. We aimed to analyze the role of E47 in patients with endogenous glucocorticoid excess [Cushing's syndrome (CS)] and its association with disorders of lipid and glucose metabolism.

METHODS: This is a prospective cohort study including 120 female patients with CS (ACTH-dependent = 79; ACTH-independent = 41) and 26 healthy female controls. Morning whole blood samples after an overnight fast were used to determine E47 mRNA expression levels in patients with overt CS before and 6-12 months after curative surgery. Expression levels were correlated with the clinical phenotype of the patients. Control subjects underwent ACTH stimulation tests and dexamethasone suppression tests to analyze short-term regulation of E47.

RESULTS: E47 gene expression showed significant differences in patient cohorts with overt CS vs. patients in remission (p = 0.0474) and in direct intraindividual comparisons pre- vs. post-surgery (p = 0.0353). ACTH stimulation of controls resulted in a significant decrease of E47 mRNA expression 30 min after i.v. injection compared to baseline measurements. Administration of 1 mg of dexamethasone overnight in controls did not change E47 mRNA expression. E47 gene expression showed a positive correlation with total serum cholesterol (p = 0.0036), low-density lipoprotein cholesterol (p = 0.0157), and waist-arm ratio (p = 0.0138) in patients with CS in remission.

CONCLUSION: E47 is a GC-dependent gene that is upregulated in GC excess potentially aiming at reducing metabolic glucocorticoid side effects such as dyslipidemia.}, } @article {pmid38046940, year = {2023}, author = {van Veen, FEE and Scheepe, JR and Blok, BFM}, title = {Regional variation in urinary catheter use in the Netherlands from 2012 to 2021: a population-based cohort.}, journal = {Therapeutic advances in urology}, volume = {15}, number = {}, pages = {17562872231215181}, pmid = {38046940}, issn = {1756-2872}, abstract = {OBJECTIVES: Our aim was to evaluate trends and regional differences in the use of indwelling and intermittent urinary catheters in the community setting in the Netherlands from 2012 to 2021.

DESIGN AND METHODS: For this population-based cohort study, data on catheter use was collected from the Drug and Medical Devices Information System of the National Healthcare Institute of the Netherlands. This database contains information on the Dutch insured population, which was 100% of the total population in 2018. Users were divided into 12 provinces according to the Nomenclature of Territorial Units for Statistics codes. The number of catheter users was adjusted for the total population of the provinces by sex and age, and was expressed by users per 100,000 people. Negative binomial regression (NBR) was used to test for differences in clean intermittent catheter (CIC) and indwelling catheter (IDC) users across Dutch provinces.

RESULTS: Between 2012 and 2021, IDC users increased by 44.6% from 41,619 to 60,172, and CIC users increased by 27.3% from 34,204 to 43,528. The greatest increases were mainly observed among IDC users over 85 years old and male CIC users over 65 years old. NBR showed significant differences for IDC and CIC users between the 12 provinces. CIC incidence was higher in Drenthe and Groningen (Northern Netherlands) compared to Zuid-Holland (Southern Netherlands). IDC incidence was higher in seven provinces dispersed throughout the Netherlands compared to Noord-Holland.

CONCLUSION: CIC and IDC users have continued to increase in recent years; this was especially observed among older men. In addition, there were regional differences in the number of CIC and IDC users; CIC was more prominent in the northern region of the Netherlands, and IDC varied between multiple provinces. Practice variation in urinary catheterization may result from patient population differences or healthcare provider preferences and their alignment with guidelines.}, } @article {pmid38046902, year = {2023}, author = {Naeimzadeh, Y and Ilbeigi, S and Dastsooz, H and Rafiee Monjezi, M and Mansoori, Y and Tabei, SMB}, title = {Protooncogenic Role of ARHGAP11A and ARHGAP11B in Invasive Ductal Carcinoma: Two Promising Breast Cancer Biomarkers.}, journal = {BioMed research international}, volume = {2023}, number = {}, pages = {8236853}, pmid = {38046902}, issn = {2314-6141}, mesh = {Female ; Humans ; *Breast Neoplasms/pathology ; Biomarkers, Tumor/genetics ; *Carcinoma, Ductal, Breast/pathology ; Breast/pathology ; GTPase-Activating Proteins/genetics/metabolism ; }, abstract = {Invasive duct carcinoma (IDC) is one of the most common types of breast cancer (BC) in women worldwide, with a high risk of malignancy, metastasis, recurrence, and death. So far, molecular patterns among IDC cases have not been fully defined. However, extensive evidence has shown that dysregulated Rho family small GTPases (Rho GTPases) including Rho GTPase activating proteins (RhoGAPs) have important roles in the invasive features of IDCs. In the current study, we analyzed the expression levels of two RhoGAP genes, ARHGAP11A and ARHGAP11B, in The Cancer Genome Atlas (TCGA) breast cancer (BRCA) and also our 51 IDC tumors compared to their matched normal tissues using quantitative polymerase chain reaction (qPCR). Our TCGA data analysis revealed higher expression of ARHGAP11A and ARHGAP11B in various cancers comprising BCs. Also, we found correlations between these genes and other genes in TCGA-BRCA. Moreover, our methylation analysis showed that their promotor methylation had a negative correlation with their overexpression. QPCR revealed their significant upregulation in our tumor samples. Furthermore, we found that the expression level of ARHGAP11A was considerably lower in women who were breastfeeding. Moreover, it had overexpression in cases who had regular menstrual cycles and early age (younger than 14) at menarche. However, ARHGAP11B had a higher expression in HER2-positive tumors versus HER2-positive and ER-positive tumors. Our study found possible protooncogenic roles for these genes and their involvement in IDC pathogenesis and malignancy. Therefore, they can be considered novel prognostic and diagnostic biomarkers for IDC.}, } @article {pmid38046195, year = {2023}, author = {Andrianto, A and Sudiana, IK and Suprabawati, DGA and Notobroto, HB}, title = {Immune system and tumor microenvironment in early-stage breast cancer: different mechanisms for early recurrence after mastectomy and chemotherapy on ductal and lobular types.}, journal = {F1000Research}, volume = {12}, number = {}, pages = {841}, pmid = {38046195}, issn = {2046-1402}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/surgery/pathology ; Mastectomy ; Matrix Metalloproteinase 1 ; Vimentin ; Tumor Microenvironment ; Cross-Sectional Studies ; *Carcinoma, Ductal, Breast/drug therapy/surgery/pathology ; Retrospective Studies ; *Carcinoma, Lobular/drug therapy/surgery/pathology ; Immune System ; }, abstract = {Background: The most common type of breast cancer is the ductal type (IDC), followed by lobular type (ILC). Surgery is the main therapy for early-stage breast cancer. Adjuvant chemotherapy might be given to those at high risk of recurrence. Recurrence is still possible after mastectomy and chemotherapy and most often occurs in the first two years. We aimed to determine the mechanisms in early local recurrence in both types. Methods: We used an observational method with a cross-sectional study design. The samples were patients with early-stage IDC and ILC, who underwent modified radical mastectomy (MRM) and got adjuvant chemotherapy with taxan and anthracycline base, and experienced recurrence in the first two years after surgery. The materials in this study were paraffin blocks from surgical specimens; we examined vimentin, α-SMA and MMP1, PDGF and CD95 by immunohistochemistry (IHC). Data analysis was done using OpenEpi 3.0.1 and EZR. We used pathway analysis with linear regression. Results: There were 25 samples with local recurrence and 25 samples without recurrence in the ductal type group. The lobular type group consisted of six subjects without recurrence and seven with recurrence. There were significant differences in the expression of vimentin (p=0.000 and 0.021, respectively), PDGF (p=0.000 and 0.002) and CD95 (p=0.000 and 0.045) in ductal and lobular cancer types, respectively. MMP1 (p=0.000) and α-SMA (p=0.000) only showed a significant difference in the ductal type. The pathway analysis showed that in the ductal type, the mechanism of recurrence was enabled by two factors: α-SMA and CD95. Meanwhile, for the lobular type, the recurrence mechanism was through the CD95 pathway. Conclusions: Local recurrence in early-stage IDC and ILC had different mechanisms. These findings are expected to make cancer treatment in both types more focused and efficient.}, } @article {pmid38028581, year = {2023}, author = {Tateishi, K and Kiyoi, M and Miyasaka, M and Kawaji, M and Nakanishi, H and Furuta, Y and Nishimatsu, M and Takahashi, Y and Nishikawa, M and Nishimura, Y}, title = {HER2-Positive Metaplastic Breast Cancer with Resistance to Neoadjuvant Chemotherapy: Case Report.}, journal = {Case reports in oncology}, volume = {16}, number = {1}, pages = {1482-1488}, pmid = {38028581}, issn = {1662-6575}, abstract = {INTRODUCTION: Metaplastic breast carcinoma (MBC) is a rare histologic subtype of breast carcinoma, which is usually negative for estrogen receptor, progesterone receptor, and HER2. HER2-positive MBC is therefore extremely rare. Most MBCs have poor response to chemotherapy. HER2-targeted neoadjuvant chemotherapy (NAC) is widely performed and has high efficacy in treating HER2-positive breast cancer. We report an atypical case of HER2-positive breast cancer that had poor response to NAC and was diagnosed with MBC after the surgery.

CASE PRESENTATION: A 73-year-old woman noticed a mass in her right breast and visited our hospital. The mass was diagnosed as hormone receptor-negative, HER2-positive invasive ductal carcinoma, T2N0M0 stage IIA. She received HER2-targeted NAC comprising trastuzumab + pertuzumab + docetaxel. Despite three courses, we observed disease progression. The next NAC regimen was composed of two courses of epirubicin + cyclophosphamide, but the cancer continued to grow. She stopped receiving NAC and underwent a unilateral mastectomy and sentinel lymph node biopsy. Although the preoperative pathological result of core needle biopsy specimen showed invasive ductal carcinoma, the postoperative pathological result of the surgical specimen was MBC.

CONCLUSION: In this case, when the patient had undergone three courses of trastuzumab + pertuzumab + docetaxel, it would have been appropriate to review the result of the core needle biopsy with pathologists or to perform vacuum-assisted breast biopsy. This case suggests the importance of considering the possibility of special histologic subtypes such as MBC when a tumor with the diagnosis of invasive ductal carcinoma is resistant to NAC.}, } @article {pmid38027836, year = {2023}, author = {Gorelik, M and Szepsenwol, O and Doron, G}, title = {Promoting couples' resilience to relationship obsessive compulsive disorder (ROCD) symptoms using a CBT-based mobile application: A randomized controlled trial.}, journal = {Heliyon}, volume = {9}, number = {11}, pages = {e21673}, pmid = {38027836}, issn = {2405-8440}, abstract = {Relationship Obsessive Compulsive Disorder (ROCD) is a disabling form of obsessive-compulsive disorder (OCD) centering on interpersonal relationships. Previous findings suggest ROCD symptoms are particularly detrimental to romantic relationships. In this randomized controlled trial (RCT), we assessed influence a CBT-based mobile application used by both partners on resilience to ROCD symptoms, cognitions, and relationship dissatisfaction. The app consists of brief, daily exercises targeting OCD symptoms, related cognitions and attachment insecurities. Heterosexual couples (Ncouples = 103; Mage = 26.15) were randomly assigned to individually use a mobile application for 15 days (n = 49 couples) or to a control group (n = 54 couples). All participants completed questionnaires at baseline (T1), 15 days from baseline (T2), and 45 days from baseline (T3). All couples also underwent an ROCD resilience task at T2. Intention-to-treat analyses revealed that, in contrast to the control group, couples who used the app exhibited enhanced resilience in the resilience task, as well as measures of ROCD symptoms, cognitions, and relationship dissatisfaction. These observed effects persisted even at the 1-month follow-up. Concurrent use of brief mobile delivered cognitive training by both romantic partners may foster resilience in romantic couples.}, } @article {pmid38026906, year = {2023}, author = {Günay, S and Gökçek, B and Kandemir, Ö and Akan, A and Yalçın, O}, title = {Long-term results of breast cancer patients who received IOERT as boost during BCS: A single-institution retrospective analysis.}, journal = {Turkish journal of surgery}, volume = {39}, number = {2}, pages = {115-120}, pmid = {38026906}, issn = {2564-6850}, abstract = {OBJECTIVES: Intraoperative electron radiotherapy (IOERT) applied as boost to the tumor bed during breast conserving surgery is advantageous in terms of local recurrence in breast cancer patients. In addition, it has other advantages over the adjuvant boost RT such as no risk of tumor bed change, ease of sequencing radiotherapy chemotherapy, and reduced workload of the radiotherapy clinic. This study aimed to evaluate the long-term results of our patients who were treated with this method in our institution and are still being followed up.

MATERIAL AND METHODS: One hundred and three patients enrolled in this study received IOERT equivalent to 10 Gy as boost during BCS and were subsequently given adjuvant WBI according to the biological subtype of the tumor systemic therapy. These patients were analyzed using their files and hospital records. Patients were evaluated for overall survival, local recurrence, distant metastasis, and cosmetic outcome (using LENT-SOMA scale).

RESULTS: Median age was 53,5 (27-74), mean follow-up time was 75 (48-106) months. Mean pathological tumor size was 18 mm (4-30), 90 of the patients had invasive ductal carcinoma, eight of them were lobular and five of them had mixed histological structure. Ninety-three of the patients presented histological grade II, 15 grade III; 74 patients were luminal A-like, 15 luminal B-like, eight HER2 positive and six triple negative breast cancer. According to the LENT-SOMA scale, 35 had grade 0, 42 each had grade I, 23 had grade II, and two had grade III. All patients underwent whole breast irradiation after surgery, 81 received chemotherapy and 90 endocrine therapy. There was one local recurrence, distant recurrence was seen in four patients and one patient died of non-breast cancer causes. Overall survival was %99, and event free survival %96.

CONCLUSION: IOERT for breast cancer treatment during BCS is a safe option with low chronic toxicity and the cosmetic outcome gets better over time.}, } @article {pmid38024932, year = {2023}, author = {Srivastava, NK and Singh, S and Mohanty, D and Hussain, N}, title = {Clinicopathological profile of breast cancer from Chhattisgarh India: A single-center hospital-based study.}, journal = {Journal of family medicine and primary care}, volume = {12}, number = {9}, pages = {1923-1930}, pmid = {38024932}, issn = {2249-4863}, abstract = {BACKGROUND: Global breast cancer incidence is increasing at an annual rate of 3·1%. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%). However, the data from different parts of India are still lacking and the study was conducted to assess the burden of disease at tertiary referral centers in central India.

MATERIAL AND METHODS: Retrospective record analysis (June 2013-June 2017) of data from outdoor clinics and pathology reports. The patients aged <15 yrs, nonresidence of Chhattisgarh, and diagnosed outside the study period were excluded. The triple assessment was used to diagnose all breast lumps (sensitivity 99%).

RESULTS: Eighty patients were diagnosed having breast carcinoma. The mean age for breast cancer was 39 ± 3.028 years (ranged 31-50 years). Twenty patients had locally advanced breast carcinoma. The predominant religion was Hindu 55.00%. The referral pathway to seek medical care for breast cancer was via a gynecologist in 40% (32/80). Familial breast cancers were in 0.03% (3/80) of patients. None breast cancer patients have previous histology-proven benign breast disease. The mean size of the breast cancer lump was 3.56 cm (ranged 1.0-11.0 cm). Overlying skin ulceration (n = 2), skin infiltration/peau-d'- orange (n = 2), skin tethering (n = 4), and bloody nipple discharge were found in one patient. Breast cancer was diagnosed during lactation (postnatal period) in one patient. The maximum number of patients have tumor size >5 cm (72.6%). Immunohistochemistry and pathological analysis was done on core biopsy (n = 20) and surgical procedure (n = 60). Modified radical mastectomy was done in 52, breast conservative surgery with Sentinal Lymph node biopsy and axillary lymph node dissection in 6, and toilet mastectomy in two patients. The predominant tumors were solid (n = 79/80), with both solid and cystic types (1/80). The solid and cystic lesion on FNAC was of C3b type, and an excision biopsy revealed medullary carcinoma of the breast. Invasive ductal carcinoma-no special type (IDC-NST) was observed to be the most common histopathologic type (n = 70/80), followed by medullary carcinoma (n = 2), metaplastic carcinoma (n = 1), papillary carcinoma (n = 4), Paget disease with DCIS (n = 1), mucinous carcinoma (n = 1), invasive lobular carcinoma (n = 1). One male patient with breast cancer and two female patient having bilateral breast cancer also have IDC-NST.Scarff Bloom Richardson Grade was predominantly graded 2 in 46.25% (37/80) of breast cancer patients (Grade 1 = 9, Grade 2 = 37, Grade 3 = 34). Lymphovascular (LVI) and perineural invasion (PNI) were predominantly without LVI and PVI. (Lymphovascular present and perineural invasion present = 4, Lymphovascular present and perineural invasion absent = 32, Lymphovascular absent and perineural invasion absent = 42, Lymphovascular absent and perineural invasion present = 2). Histological examination of axillary lymph nodes showed the presence of malignant cells in all. Triple-negative breast carcinoma was 26.58% (21/79). Most breast cancer presented at stage II A = 37.5% (30/80) and II B = 28.7% (23/80) of the AJCC staging system.

CONCLUSION: The clinico-epidemio and histological profile of breast cancer in Chhattisgarh is similar to other parts of India. Scarff Bloom Richardson Grade was predominantly grade 2 in 46.25% (37/80) contrary to Grade III (70%) in other series from India.}, } @article {pmid38024052, year = {2023}, author = {Prabhu, SD and Rai, HS and Nayak, R and Naik, R and Jayasheelan, S}, title = {Study of the Immunohistochemical Expression of p63 in Benign Lesions and Carcinoma of the Breast at a Tertiary Hospital in South India.}, journal = {Cureus}, volume = {15}, number = {11}, pages = {e48557}, pmid = {38024052}, issn = {2168-8184}, abstract = {BACKGROUND: Invasive breast carcinoma is among the most common female cancers worldwide, causing high morbidity and mortality. Considerable disagreement in the interpretation of diagnostically challenging breast lesions based on histology alone has been documented. One of the essential histopathological findings that help distinguish benign from malignant lesions is the presence of the myoepithelial cell layer. Myoepithelial markers such as tumor protein 63 (p63) help distinguish invasive carcinoma from benign proliferations. p63 antibody is superior to other myoepithelial markers as it selectively stains the nuclei and is negative in stromal cells.

OBJECTIVE: To study the expression of p63 in various histological subtypes and grades of breast carcinomas.

METHODS: After routine hematoxylin and eosin stain, 65 cases of breast lesions were subjected to immunohistochemistry for p63 antigen using Novacastra ready-to-use monoclonal antibody p6. All cases were analyzed for p63 expression, and its staining arrangement was interpreted.

RESULTS: In all benign lesions, immunoreactivity was noted in the myoepithelial cells, forming a continuous layer surrounding the luminal epithelial cells. The benign papillary lesions showed p63 staining in the fibrovascular core of the papillary fronds and at the periphery. A few single myoepithelial cells stained by p63 were also seen scattered discontinuously in ductal carcinoma in situ (DCIS). All invasive carcinomas and encapsulated papillary carcinomas were completely devoid of peripheral p63 staining of myoepithelial cells.

CONCLUSION: p63 is a specific nuclear marker of myoepithelial cells in the breast and can, therefore, aid in distinguishing invasive ductal carcinoma from DCIS or rare questionable hyperplastic lesions. They also play a significant role in distinguishing various papillary lesions of the breast and, hence, can be incorporated into routine reporting for definitive diagnosis and accurate treatment.}, } @article {pmid38024024, year = {2023}, author = {Ishikawa, Y and Umezawa, R and Yamamoto, T and Takahashi, N and Takeda, K and Suzuki, Y and Kishida, K and Teramura, S and Ito, K and Jingu, K}, title = {Pre-treatment Evaluation of Patients Eligible for Whole Brain Radiation Therapy: The Risk of Hippocampal Metastases in a Retrospective Study of 248 Cases at a Single Institution.}, journal = {Cureus}, volume = {15}, number = {11}, pages = {e49170}, pmid = {38024024}, issn = {2168-8184}, abstract = {Whole brain radiation therapy (WBRT) is effective for multiple brain metastases (BMs) but may impair neurocognitive function (NCF). The incidence of hippocampal metastasis (HM) is low, and the factors associated with the occurrence of HM remain unclear. This study aimed to assess the occurrence of limbic system metastasis (LSM), including HM, and to analyze the risk of HM. We retrospectively analyzed 248 patients who underwent three-dimensional conformal radiation therapy for BMs between May 2008 and October 2015. Gadolinium-enhanced brain MRI or CT scans were used for diagnosis. Statistical analysis involved assessing clinical factors, including age, gender, primary tumor, number of BMs, and maximum metastasis diameter, in relation to the presence of HMs using logistic regression and receiver operating characteristic (ROC) curve analysis. The median age at treatment was 62 years (range: 11-83 years). Primary lesion sites included the lung (n = 150; 60.5%), breast (n = 45; 18.1%), gastrointestinal tract (n = 18; 7.3%), and bone and soft tissue (n = 2; 0.8%). Histological cancer types included adenocarcinoma (n = 113; 45.6%), squamous cell carcinoma (n = 26; 10.5%), small cell carcinoma (n = 28; 11.3%), invasive ductal carcinoma (n = 35; 14.1%), sarcoma (n = 3; 1.2%), and others (n = 43; 17.3%). MRI or CT scans of the 248 patients were analyzed, indicating a total count of 2,163 brain metastases (median: five metastases per patient). HMs were identified in 18 (7.3%) patients. The most common location for LSMs was the cingulum/cingulate gyrus in 26 (10.5%) patients. In univariate and multivariate analyses, patients with 15 or fewer BMs had a significantly lower incidence of HMs (odds ratio (OR), 0.018 (95% confidence interval (CI), 0.030-0.24)) (p < 0.0001). A maximal tumor size of less than 2 cm significantly increased the incidence of HMs (OR, 13.8 (95%CI, 1.80-105.3)) (p = 0.0003). The presence of cingulum/cingulate gyrus metastases also demonstrated a significant increase in the incidence of HMs (OR, 9.42 (95%CI, 3.30-26.84)) (p < 0.0001). The present study has uncovered a novel association between a high number of metastases in the cingulate gyrus and the development of HMs. Patients with BMs eligible for WBRT with metastases in the cingulate gyrus may be at risk of developing HM.}, } @article {pmid38022397, year = {2023}, author = {Zhu, XD and Yu, JH and Ai, FL and Wang, Y and Lv, W and Yu, GL and Cao, XK and Lin, J}, title = {Construction and Validation of a Novel Nomogram for Predicting the Risk of Metastasis in a Luminal B Type Invasive Ductal Carcinoma Population.}, journal = {World journal of oncology}, volume = {14}, number = {6}, pages = {476-487}, pmid = {38022397}, issn = {1920-454X}, abstract = {BACKGROUND: Postoperative distant metastasis is the main cause of death in breast cancer patients. We aimed to construct a nomogram to predict the risk of metastasis of luminal B type invasive ductal carcinoma.

METHODS: We applied the data of 364 luminal B type breast cancer patients between 2008 and 2013. Patients were categorized into modeling group and validation group randomly (1:1). The breast cancer metastasis nomogram was developed from the logistic regression model using clinicopathological variables. The area under the receiver-operating characteristic curve (AUC) was calculated in modeling group and validation group to evaluate the predictive accuracy of the nomogram.

RESULTS: The multivariate logistic regression analysis showed that tumor size, No. of the positive level 1 axillary lymph nodes, human epidermal growth factor receptor 2 (HER2) status and Ki67 index were the independent predictors of the breast cancer metastasis. The AUC values of the modeling group and the validation group were 0.855 and 0.818, respectively. The nomogram had a well-fitted calibration curve. The positive and negative predictive values were 49.3% and 92.7% in the modeling group, and 47.9% and 91.0% in the validation group. Patients who had a score of 60 or more were thought to have a high risk of breast cancer metastasis.

CONCLUSIONS: The nomogram has a great predictive accuracy of predicting the risk of breast cancer metastasis. If patients had a score of 60 or more, necessary measures, like more standard treatment methods and higher treatment adherence of patients, are needed to take to lower the risk of metastasis and improve the prognosis.}, } @article {pmid38022128, year = {2023}, author = {Singh, I and Krasney, L and Civatte, W and Parrish, W}, title = {Treatment of Epiphyseal Metastasis to the Proximal Humerus Secondary to Breast Carcinoma: A Case Report.}, journal = {Cureus}, volume = {15}, number = {10}, pages = {e47564}, pmid = {38022128}, issn = {2168-8184}, abstract = {Metastasis to the bone is a known risk of breast cancer, with the humerus being the most common upper extremity site of metastases, with most lesions located at the humeral diaphysis. We present a unique case of proximal humeral metastasis involving the epiphysis secondary to primary invasive ductal carcinoma in a middle-aged Caucasian female. It is important to have a high degree of suspicion for metastasis when musculoskeletal pain occurs in breast cancer patients, as it may be masked by common, degenerative conditions about the shoulder girdle. When humeral metastases involve the epiphysis, treatment options are complicated by its location, which jeopardizes the integrity of articular cartilage and the function of the shoulder girdle. External beam irradiation provides pain control in a non-invasive manner, sans surgical risks. Surgical intervention will vary depending on the characteristics of the bony lesion, but the use of endoprosthetics has emerged as the most effective option for restoring range of motion and pain control with acceptable rates of implant survival.}, } @article {pmid38020289, year = {2023}, author = {Koi, Y and Yamamoto, Y and Fukunaga, S and Kajitani, K and Ohara, M and Daimaru, Y and Tahara, H and Tamada, R}, title = {Assessment of the expression of microRNAs‑221‑3p, ‑146a‑5p, ‑16‑5p and BCL2 in oncocytic carcinoma of the breast: A case report.}, journal = {Oncology letters}, volume = {26}, number = {6}, pages = {535}, pmid = {38020289}, issn = {1792-1082}, abstract = {Oncocytic carcinoma of the breast is rare and its molecular profiles remain poorly understood. MicroRNAs (miRNAs/miRs) have been identified as contributors to carcinogenesis at the post-transcriptional level; thus, an aberrant expression of miRNAs has attracted attention as a potential biomarker of numerous diseases, including cancer. The present study reports the case of a 76-year-old woman diagnosed with oncocytic carcinoma of the breast. Considering the distinctive feature of oncocytic carcinoma of the breast, which is the presence of granular eosinophilic cytoplasm containing numerous mitochondria, the present study hypothesized that the expression of mitochondria-related miRNAs could be altered in oncocytic carcinomas. Aberrant expression levels of the miRNAs previously reported as mitochondria-related miRNAs, such as miR-221-3p, -146a-5p and -16-5p, were revealed in tissue from specimens of oncocytic carcinoma of the breast, compared with that of a more typical type of invasive ductal carcinoma of the breast. The present study highlights the changes in miRNA expression in oncocytic carcinoma of the breast, suggesting its potential as a biomarker for diagnosis.}, } @article {pmid38019287, year = {2024}, author = {Mooshage, CM and Tsilingiris, D and Schimpfle, L and Seebauer, L and Eldesouky, O and Aziz-Safaie, T and Hohmann, A and Herzig, S and Szendroedi, J and Nawroth, P and Heiland, S and Bendszus, M and Kurz, FT and Kopf, S and Jende, JME and Kender, Z}, title = {A diminished sciatic nerve structural integrity is associated with distinct peripheral sensory phenotypes in individuals with type 2 diabetes.}, journal = {Diabetologia}, volume = {67}, number = {2}, pages = {275-289}, pmid = {38019287}, issn = {1432-0428}, support = {SFB 1158//Deutsche Forschungsgemeinschaft/ ; SFB1118//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Diabetes Mellitus, Type 2 ; Diffusion Tensor Imaging/methods ; Cross-Sectional Studies ; Sciatic Nerve ; *Diabetic Neuropathies ; Phenotype ; }, abstract = {AIMS/HYPOTHESIS: Quantitative sensory testing (QST) allows the identification of individuals with rapid progression of diabetic sensorimotor polyneuropathy (DSPN) based on certain sensory phenotypes. Hence, the aim of this study was to investigate the relationship of these phenotypes with the structural integrity of the sciatic nerve among individuals with type 2 diabetes.

METHODS: Seventy-six individuals with type 2 diabetes took part in this cross-sectional study and underwent QST of the right foot and high-resolution magnetic resonance neurography including diffusion tensor imaging of the right distal sciatic nerve to determine the sciatic nerve fractional anisotropy (FA) and cross-sectional area (CSA), both of which serve as markers of structural integrity of peripheral nerves. Participants were then assigned to four sensory phenotypes (participants with type 2 diabetes and healthy sensory profile [HSP], thermal hyperalgesia [TH], mechanical hyperalgesia [MH], sensory loss [SL]) by a standardised sorting algorithm based on QST.

RESULTS: Objective neurological deficits showed a gradual increase across HSP, TH, MH and SL groups, being higher in MH compared with HSP and in SL compared with HSP and TH. The number of participants categorised as HSP, TH, MH and SL was 16, 24, 17 and 19, respectively. There was a gradual decrease of the sciatic nerve's FA (HSP 0.444, TH 0.437, MH 0.395, SL 0.382; p=0.005) and increase of CSA (HSP 21.7, TH 21.5, MH 25.9, SL 25.8 mm[2]; p=0.011) across the four phenotypes. Further, MH and SL were associated with a lower sciatic FA (MH unstandardised regression coefficient [B]=-0.048 [95% CI -0.091, -0.006], p=0.027; SL B=-0.062 [95% CI -0.103, -0.020], p=0.004) and CSA (MH β=4.3 [95% CI 0.5, 8.0], p=0.028; SL B=4.0 [95% CI 0.4, 7.7], p=0.032) in a multivariable regression analysis. The sciatic FA correlated negatively with the sciatic CSA (r=-0.35, p=0.002) and markers of microvascular damage (high-sensitivity troponin T, urine albumin/creatinine ratio).

CONCLUSIONS/INTERPRETATION: The most severe sensory phenotypes of DSPN (MH and SL) showed diminishing sciatic nerve structural integrity indexed by lower FA, likely representing progressive axonal loss, as well as increasing CSA of the sciatic nerve, which cannot be detected in individuals with TH. Individuals with type 2 diabetes may experience a predefined cascade of nerve fibre damage in the course of the disease, from healthy to TH, to MH and finally SL, while structural changes in the proximal nerve seem to precede the sensory loss of peripheral nerves and indicate potential targets for the prevention of end-stage DSPN.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03022721.}, } @article {pmid38012767, year = {2023}, author = {Deguchi, S and Iwakami, A and Tujigiwa, M and Otake, H and Mano, Y and Yamamoto, N and Nakazawa, Y and Misra, M and Nagai, N}, title = {Recovery from indomethacin-induced gastrointestinal bleeding by treatment with teprenone.}, journal = {Journal of pharmaceutical health care and sciences}, volume = {9}, number = {1}, pages = {44}, pmid = {38012767}, issn = {2055-0294}, abstract = {BACKGROUND: Gastrointestinal injuries caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is a serious side effect in patients with rheumatoid arthritis (RA). However, effective therapeutic strategies have yet to be established. In this study, we investigated the therapeutic effects of teprenone (TEP), a gastric mucosal protective drug, on NSAID-induced gastrointestinal injuries in rats with RA (AA rats).

METHODS: Gastrointestinal injury was induced by oral administration of indomethacin (IMC), a typical NSAID. TEP was orally administered after IMC-induced gastrointestinal bleeding, and the stomach, jejunum, and ileum were excised.

RESULTS: On day 14 of IMC administration, lesion areas in the stomach, jejunum, and ileum were significantly larger in AA rats than in normal rats. When TEP was orally administered to AA rats, the lesion areas in the stomach, jejunum, and ileum significantly decreased compared with those in control rats (IMC-induced AA rats). Therefore, we measured NOS2 mRNA and NO levels, which were significantly decreased in rats with IMC-induced AA after treatment with TEP.

CONCLUSIONS: These results suggest that the oral administration of TEP may be useful for the treatment of NSAID-induced gastrointestinal injuries in patients with RA.}, } @article {pmid38008819, year = {2023}, author = {Jalilian, E and Abolhasani-Zadeh, F and Afgar, A and Samoudi, A and Zeinalynezhad, H and Langroudi, L}, title = {Neutralizing tumor-related inflammation and reprogramming of cancer-associated fibroblasts by Curcumin in breast cancer therapy.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {20770}, pmid = {38008819}, issn = {2045-2322}, support = {IR.KMU.REC.1398.326//Kerman University of Medical Sciences/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/genetics ; *Cancer-Associated Fibroblasts/metabolism ; *Curcumin/pharmacology/therapeutic use/metabolism ; Cyclooxygenase 2/metabolism ; Dinoprostone/metabolism ; Fibroblasts/metabolism ; Inflammation/pathology ; Cell Line, Tumor ; Tumor Microenvironment ; }, abstract = {Tumor-associated inflammation plays a vital role in cancer progression. Among the various stromal cells, cancer-associated fibroblasts are promising targets for cancer therapy. Several reports have indicated potent anti-inflammatory effects attributed to Curcumin. This study aimed to investigate whether inhibiting the inflammatory function of cancer-associated fibroblasts (CAFs) with Curcumin can restore anticancer immune responses. CAFs were isolated from breast cancer tissues, treated with Curcumin, and co-cultured with patients' PBMCs to evaluate gene expression and cytokine production alterations. Blood and breast tumor tissue samples were obtained from 12 breast cancer patients with stage II/III invasive ductal carcinoma. Fibroblast Activation Protein (FAP) + CAFs were extracted from tumor tissue, treated with 10 μM Curcumin, and co-cultured with corresponding PBMCs. The expression of smooth muscle actin-alpha (α-SMA), Cyclooxygenase-2(COX-2), production of PGE2, and immune cell cytokines were evaluated using Real-Time PCR and ELISA, respectively. Analyzes showed that treatment with Curcumin decreased the expression of genes α-SMA and COX-2 and the production of PGE2 in CAFs. In PBMCs co-cultured with Curcumin-treated CAFs, the expression of FoxP3 decreased along with the production of TGF-β, IL-10, and IL-4. An increase in IFN-γ production was observed that followed by increased T-bet expression. According to our results, Curcumin could reprogram the pro-tumor phenotype of CAFs and increase the anti-tumor phenotype in PBMCs. Thus, CAFs, as a component of the tumor microenvironment, are a suitable target for combination immunotherapies of breast cancer.}, } @article {pmid38007642, year = {2024}, author = {Zeng, YH and Yang, YP and Liu, LJ and Xie, J and Dai, HX and Zhou, HL and Huang, X and Huang, RL and Liu, EQ and Deng, YJ and Li, HJ and Wu, JJ and Zhang, GL and Liao, ML and Xu, XH}, title = {The discriminatory diagnostic value of multimodal ultrasound combined with blood cell analysis for granulomatous lobular mastitis and invasive ductal carcinoma of the breast.}, journal = {Clinical hemorheology and microcirculation}, volume = {86}, number = {4}, pages = {481-493}, doi = {10.3233/CH-231999}, pmid = {38007642}, issn = {1875-8622}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/diagnostic imaging/pathology ; Adult ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Granulomatous Mastitis/diagnostic imaging/pathology ; Aged ; Ultrasonography, Mammary/methods ; Ultrasonography/methods ; }, abstract = {OBJECTIVE: To explore the discriminatory diagnostic value of multimodal ultrasound(US) combined with blood cell analysis (BCA) for Granulomatous Lobular Mastitis (GLM) and Invasive Ductal Carcinoma (IDC) of the breast.

METHODS: A total of 157 breast disease patients were collected and divided into two groups based on postoperative pathological results: the GLM group (57 cases with 57 lesions) and the IDC group (100 cases with 100 lesions). Differences in multimodal ultrasound features and the presence of BCA were compared between the two groups. The receiver operating characteristic (ROC) curve was used to calculate the optimal cutoff values, sensitivity, specificity, 95% confidence interval (CI), and the area under the curve (AUC) for patient age, lesion size, lesion resistive index (RI), and white blood cell (WBC) count in BCA. Sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, and AUC were calculated for different diagnostic methods.

RESULTS: There were statistically significant differences (P < 0.05) observed between GLM and IDC patients in terms of age, breast pain, the factors in Conventional US (lesion size, RI, nipple delineation, solitary/multiple lesions, margin, liquefaction area, growth direction, microcalcifications, posterior echogenicity and abnormal axillary lymph nodes), the factors in CEUS (contrast agent enhancement intensity, enhancement pattern, enhancement range, and crab-like enhancement) and the factors in BCA (white blood cells, neutrophils, lymphocytes and monocytes). ROC curve analysis results showed that the optimal cutoff values for distinguishing GLM from IDC were 40.5 years for age, 7.15 cm for lesion size, 0.655 for lesion RI, and 10.525*109/L for white blood cells. The diagnostic accuracy of conventional US combined with CEUS (US-CEUS) was the highest (97.45%). The diagnostic performance AUCs for US-CEUS, CEUS, and US were 0.965, 0.921 and 0.832, respectively.

CONCLUSION: Multifactorial analysis of multimodal ultrasound features and BCA had high clinical application value in the differential diagnosis of GLM and IDC.}, } @article {pmid38007533, year = {2024}, author = {Wang, X and Zhou, L and Qi, L and Zhang, Y and Yin, H and Gan, Y and Gao, X and Cai, Y}, title = {High GLUT1 membrane expression and low PSMA membrane expression in Ductal Adenocarcinoma and Intraductal Carcinoma of the prostate.}, journal = {Prostate cancer and prostatic diseases}, volume = {27}, number = {4}, pages = {720-727}, pmid = {38007533}, issn = {1476-5608}, support = {82273121//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2022JJ20096//Natural Science Foundation of Hunan Province (Hunan Provincial Natural Science Foundation)/ ; }, mesh = {Humans ; Male ; *Prostatic Neoplasms/metabolism/pathology/surgery ; *Glucose Transporter Type 1/metabolism ; Aged ; Middle Aged ; *Biomarkers, Tumor/metabolism ; *Carcinoma, Ductal/metabolism/pathology/surgery ; *Antigens, Surface/metabolism ; Glutamate Carboxypeptidase II/metabolism ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Positron Emission Tomography Computed Tomography ; Prostatectomy ; Prognosis ; Neoplasm Grading ; }, abstract = {BACKGROUND: Both Ductal Adenocarcinoma (DAC) and Intraductal Carcinoma (IDC) of the prostate are generally associated with aggressive clinical behavior and poor prognosis, which were linked with discordant FDG positivity and low Prostate-Specific Membrane Antigen (PSMA) expression. A recent study only cited a DAC patient with low [68]Ga-PSMA-11 PET/CT uptake but high [18]F-FDG PET/CT uptake, however, there is lack of directly compared articles nor large data sets. Hence, the objective of this study was to investigate the expression of PSMA and GLUT1 in DAC and IDC-P patients.

METHODS: The study was conducted on 87 DAC or/and IDC-P patients without any treatment and 97 PAC patients with a Gleason score ≥8 of prostate biopsies and prostatectomy samples between August 2017 and August 2022. We performed immunohistochemical staining and scoring of various cancer component samples from the patients to reflect the protein expression levels of PSMA and GLUT1.

RESULTS: PSMA expression in PAC was significantly higher than in DAC/IDC-P (141.2 vs 78.6, p < 0.001). There was no significant difference in PSMA expression between DAC/IDC-P and adjacent PAC (78.6 vs 93.4, p = 0.166). GLUT1 expression was higher in DAC/IDC-P than in adjacent PAC (68.6 vs 51.3, p = 0.007), but was still lower than that in pure PAC (68.6 vs 93.1, p = 0.0014). It is worth noting that GLUT1 membrane expression in DAC/IDC-P was significantly increased than in pure PAC (13.0 vs 6.6, p = 0.025), and in PAC adjacent to DAC/IDC-P (13.0 vs 2.0, p < 0.001).

CONCLUSIONS: In DAC/IDC-P tissues, PSMA expression is low, while GLUT1 expression, especially GLUT1 membrane expression is high. These findings imply that DAC/IDC-P may have higher glucose metabolic and raise interest in targeting membrane GLUT1 as a novel anticancer strategy for DAC/IDC-P and other prostate cancer with high glucose metabolism.}, } @article {pmid38007354, year = {2024}, author = {Miyajima, K and Sato, S and Uchida, N and Suzuki, H and Iwatani, K and Imai, Y and Aikawa, K and Yanagisawa, T and Kimura, S and Tashiro, K and Tsuzuki, S and Honda, M and Koike, Y and Miki, J and Miki, K and Shimomura, T and Yuen, S and Yamada, Y and Aoki, M and Takahashi, H and Urabe, F and Kimura, T}, title = {Clinical Significance of Intraductal Carcinoma of the Prostate After High-Dose Brachytherapy With External Beam Radiation Therapy: A Single Institution Series and an Updated Meta-Analysis.}, journal = {Clinical genitourinary cancer}, volume = {22}, number = {2}, pages = {149-156.e1}, doi = {10.1016/j.clgc.2023.10.005}, pmid = {38007354}, issn = {1938-0682}, mesh = {Male ; Humans ; *Brachytherapy/adverse effects ; Prostate/pathology ; Retrospective Studies ; *Carcinoma, Intraductal, Noninfiltrating/etiology ; Clinical Relevance ; *Prostatic Neoplasms/pathology ; }, abstract = {BACKGROUND: We compared oncological outcomes between prostate cancer (PCa) patients with and without intraductal carcinoma of the prostate (IDC-P) after high-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT).

METHODS: We performed a retrospective analysis of 138 patients with clinically high-risk, very high-risk, or locally advanced PCa who received HDR-BT with EBRT. Of these, 70 (50.7 %) patients were diagnosed with IDC-P; 68 (49.3 %) patients with acinar adenocarcinoma of prostate. The oncological outcomes, including biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS), were assessed using Kaplan-Meier curves. Additionally, Cox proportional hazards models were used to identify significant prognostic indicators or biochemical recurrence (BCR). Meta-analysis of existing literatures was performed to evaluate the risk of BCR in patients with IDC-P after radiation therapy, compared to those without IDC-P.

RESULTS: Kaplan-Meier curves demonstrated significantly inferior BCRFS and CPFS in patients with IDC-P. Multivariate analysis revealed that IDC-P and Grade Group 5 status were associated with increased BCR risk. in our meta-analysis, IDC-P was associated with BCR (HR = 2.13, P = .003).

CONCLUSION: Amongst the patients who received HDR-BT, patients with IDC-P displayed significantly more rapid disease progression, compared with patients who did not have IDC-P.}, } @article {pmid38001579, year = {2023}, author = {Surintrspanont, J and Zhou, M}, title = {Intraductal Carcinoma of the Prostate: To Grade or Not to Grade.}, journal = {Cancers}, volume = {15}, number = {22}, pages = {}, pmid = {38001579}, issn = {2072-6694}, abstract = {Intraductal carcinoma of the prostate (IDC-P) is a distinct tumor type characterized by an expansile growth of atypical glandular epithelial cells within pre-existing prostate glands and ducts and has significant implications on clinical outcomes and patient management. There is an agreement that isolated IDC-P should not be graded, and IDC-P should be reported with a comment on its clinical significance. However, whether IDC-P should be factored into Grade Group (GG) in the presence of concurrent prostate cancer (PCa) has been debated vigorously. The contradicting opinions were promulgated when the Genitourinary Pathology Society (GUPS) and the International Society of Urological Pathologists (ISUP) published their recommendations for this issue. When IDC-P is present with PCa, the ISUP recommends incorporating it in the GG for the entire case, whereas the GUPS recommends excluding it from the final GG. Consequently, pathologists and clinicians are faced with the conundrum of conflicting recommendations. In this review article, the authors evaluate the magnitude of discrepant GG between the two grading methods, explore the rationales behind the differing views of the two urological societies, present the current reporting practices for IDC-P, and propose a provisional and pragmatic guide to alleviate the dilemma of which recommendation to follow.}, } @article {pmid38000681, year = {2024}, author = {Boyraz, B and Ly, A}, title = {Spectrum of histopathologic findings in risk-reducing bilateral prophylactic mastectomy in patients with and without BRCA mutations.}, journal = {Human pathology}, volume = {151}, number = {}, pages = {105534}, doi = {10.1016/j.humpath.2023.11.010}, pmid = {38000681}, issn = {1532-8392}, mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; Biomarkers, Tumor/genetics ; *BRCA1 Protein/genetics ; *BRCA2 Protein/genetics ; *Breast Neoplasms/genetics/pathology/prevention & control/surgery ; Carcinoma, Ductal, Breast/genetics/pathology/prevention & control/surgery ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/surgery/prevention & control ; Genetic Predisposition to Disease ; *Germ-Line Mutation ; Phenotype ; *Prophylactic Mastectomy ; PTEN Phosphohydrolase/genetics ; Risk Factors ; }, abstract = {Many germline mutations have been implicated in breast cancer pathogenesis and despite several studies on occult atypical lesions in prophylactic mastectomy specimens from patients with BRCA1/2 mutations, there are very limited data on other genes associated with increased breast cancer risk and the distribution of lesions in patients with hereditary breast cancer. We identified 207 patients who underwent bilateral prophylactic mastectomy due to germline mutations in BRCA1/2, PALB2, CHEK2, ATM, CDH1, PTEN, BARD1, or strong family history between 2015 and 2023. Patients with biopsy-proven past or current invasive breast carcinoma or carcinoma in-situ preoperatively were excluded. In addition to multiple benign lesions, the following atypical lesions were identified: flat epithelial atypia (16.9%), atypical ductal hyperplasia (14.0%), lobular neoplasia (14.0%), ductal carcinoma in-situ (4.3%), invasive ductal carcinoma (0.4%). Both low-grade and high-grade pathway lesions were identified in this cohort, and in a subset of patients, they co-occurred. The frequency of atypical lesions identified in patients with strong family history were comparable to those with proven germline mutation. PTEN immunohistochemistry showed loss of expression in ductal carcinoma in-situ and tubular adenomas in PTEN-mutant patients. Overall, findings from this cohort support the benefit of prophylactic mastectomy in patients with germline mutations and/or strong family history. Additionally, this is the first demonstration that PTEN immunohistochemistry may be helpful in identifying germline mutations in patients with atypical or neoplastic proliferations.}, } @article {pmid37999984, year = {2023}, author = {Fedorov, A and Longabaugh, WJR and Pot, D and Clunie, DA and Pieper, SD and Gibbs, DL and Bridge, C and Herrmann, MD and Homeyer, A and Lewis, R and Aerts, HJWL and Krishnaswamy, D and Thiriveedhi, VK and Ciausu, C and Schacherer, DP and Bontempi, D and Pihl, T and Wagner, U and Farahani, K and Kim, E and Kikinis, R}, title = {National Cancer Institute Imaging Data Commons: Toward Transparency, Reproducibility, and Scalability in Imaging Artificial Intelligence.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {43}, number = {12}, pages = {e230180}, pmid = {37999984}, issn = {1527-1323}, support = {HHSN261201500003C/CA/NCI NIH HHS/United States ; HHSN261201500003I/CA/NCI NIH HHS/United States ; }, mesh = {United States ; Humans ; *Artificial Intelligence ; National Cancer Institute (U.S.) ; Reproducibility of Results ; Diagnostic Imaging ; Multiomics ; *Neoplasms/diagnostic imaging ; }, abstract = {The remarkable advances of artificial intelligence (AI) technology are revolutionizing established approaches to the acquisition, interpretation, and analysis of biomedical imaging data. Development, validation, and continuous refinement of AI tools requires easy access to large high-quality annotated datasets, which are both representative and diverse. The National Cancer Institute (NCI) Imaging Data Commons (IDC) hosts large and diverse publicly available cancer image data collections. By harmonizing all data based on industry standards and colocalizing it with analysis and exploration resources, the IDC aims to facilitate the development, validation, and clinical translation of AI tools and address the well-documented challenges of establishing reproducible and transparent AI processing pipelines. Balanced use of established commercial products with open-source solutions, interconnected by standard interfaces, provides value and performance, while preserving sufficient agility to address the evolving needs of the research community. Emphasis on the development of tools, use cases to demonstrate the utility of uniform data representation, and cloud-based analysis aim to ease adoption and help define best practices. Integration with other data in the broader NCI Cancer Research Data Commons infrastructure opens opportunities for multiomics studies incorporating imaging data to further empower the research community to accelerate breakthroughs in cancer detection, diagnosis, and treatment. Published under a CC BY 4.0 license.}, } @article {pmid37999848, year = {2023}, author = {Tahir, S and Zahid, M and Hanif, MA and Javed, MY}, title = {g-C3N4/graphene oxide/SnFe2O4 ternary composite for the effective sunlight-driven photocatalytic degradation of methylene blue.}, journal = {Environmental science and pollution research international}, volume = {30}, number = {60}, pages = {125540-125558}, doi = {10.1007/s11356-023-31096-1}, pmid = {37999848}, issn = {1614-7499}, mesh = {Humans ; *Methylene Blue/chemistry ; Hydrogen Peroxide ; *Graphite/chemistry ; Sunlight ; Catalysis ; }, abstract = {A broadly used dye, methylene blue (MB), adversely impacts human health and water resources, which triggers efficient methods for its elimination. Semiconductor-based heterogeneous photocatalysis is an environmentally friendly approach that effectively degrades organic pollutants. The purpose of the current work is to elucidate and validate the application of a promising g-C3N4/GO/SnFe2O4 (CGS) composite for the environmental remediation of methylene blue dye. The ternary CGS composite has been synthesized using a solvothermal approach. The fabricated composites were analyzed through FTIR, XRD, SEM/EDX, UV-VIS spectroscopy, TEM, and XPS. The photoactivity of composites and affecting parameters (pH, H2O2 dosage, composite amount, initial dye concentration, and irradiation time) were observed in sunlight illumination. The optimal conditions for photocatalytic degradation were pH = 5, photocatalyst dosage = 30 mg/100 mL, H2O2 dosage = 6 mM, and initial dye concentration (IDC) of 10 ppm employing ternary CGS composite, and MB dye was degraded effectively within 1 h. Ninety-eight percent degradation efficacy was attained by employing ternary CGS composite under the optimized conditions. Scavenging analysis suggested that [•]OH radicals were the key reactive oxygen species (ROS) responsible for the photodegradation of MB dye. Furthermore, the CGS nanocomposite exhibited outstanding recyclability of 84% after five consecutive runs, demonstrating its potential for use in practical applications, particularly pollutant removal.}, } @article {pmid37996840, year = {2023}, author = {Yang, X and Tang, T and Zhou, T}, title = {Clinicopathological characteristics and prognosis of metaplastic breast cancer versus triple-negative invasive ductal carcinoma: a retrospective analysis.}, journal = {World journal of surgical oncology}, volume = {21}, number = {1}, pages = {364}, pmid = {37996840}, issn = {1477-7819}, mesh = {Humans ; Female ; *Breast Neoplasms ; Retrospective Studies ; *Carcinoma, Ductal, Breast/therapy ; Prognosis ; Disease-Free Survival ; }, abstract = {BACKGROUND: Metaplastic breast cancer(MBC) is a specific pathological type of invasive breast cancer. There are few studies related to MBC due to its rarity. This study aimed to analyse the differences in clinicopathological characteristics and prognosis between Metaplastic breast cancer and triple-negative invasive ductal carcinoma (TN-IDC).

METHODS: We retrospectively compared the clinicopathological characteristics of patients diagnosed with MBC and TN-IDC at the Fourth Hospital of Hebei Medical University between 2011 and 2020 in a 1:2 ratio. The log-rank test was used to compare the two groups' disease-free survival (DFS) and overall survival (OS). For MBCs, we performed univariate and multivariate analyses using the Cox proportional hazards model to determine the characteristics that impacted OS and DFS.

RESULTS: A total of 81 patients with MBC and 162 patients with TN-IDC were included in this study. At initial diagnosis, MBC patients had larger tumour diameters(P = 0.03) and fewer positive lymph nodes (P = 0.04). Patients with MBC were more likely to have organ metastases after surgery (P = 0.03). Despite receiving the same treatment, MBC patients had worse DFS (HR = 1.66, 95%CI 0.90-3.08, P = 0.11) and OS (HR = 1.98, 95% CI 1.03-3.81, P = 0.04), and OS was statistically significant. Positive lymph nodes at initial diagnosis were associated with worse DFS (HR = 3.98, 95%CI 1.05-15.12, P = 0.04) and OS (HR = 3.70, 95%CI 1.03-13.34, P = 0.04) for patients with MBC. The efficacy of platinum-based agents is insensitive for MBC patients receiving chemotherapy. In addition, patients treated with preoperative chemotherapy had worse DFS compared to patients treated with postoperative chemotherapy (HR = 3.51, 95%CI 1.05-11.75, P = 0.04).

CONCLUSIONS: The clinicopathological characteristics and prognosis of MBC and TN-IDC differ in many ways. Further studies are required to determine suitable treatment guidelines for patients with MBC.}, } @article {pmid37995519, year = {2023}, author = {Antolín Novoa, S and Escrivá-de-Romaní, S and Tolosa Ortega, P and Oliva Fernández, L and López López, R and López González, A and de la Morena Barrio, P and Echavarria Díaz-Guardamino, I and Alés Martinez, JE and Garate, Z and González-Cortijo, L}, title = {Real world data on the demographic and clinicopathological profile and management of patients with early-stage HER2-positive breast cancer and residual disease treated with adjuvant trastuzumab emtansine (KARMA study).}, journal = {Cancer treatment and research communications}, volume = {37}, number = {}, pages = {100772}, doi = {10.1016/j.ctarc.2023.100772}, pmid = {37995519}, issn = {2468-2942}, mesh = {Humans ; Female ; Ado-Trastuzumab Emtansine/therapeutic use ; *Breast Neoplasms/pathology ; Retrospective Studies ; Erb-b2 Receptor Tyrosine Kinases ; *Maytansine/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Demography ; }, abstract = {INTRODUCTION: Trastuzumab emtansine (T-DM1) significantly improves invasive disease-free survival and reduces the risk of recurrence in patients with HER2-positive early breast cancer (EBC) with residual disease (RD). The KARMA study aimed to describe the characteristics and management of these patients in clinical practice in Spain.

MATERIAL AND METHODS: We conducted a multicentre retrospective study in patients with HER2-positive EBC with RD following neoadjuvant treatment (NeoT) and who had received ≥1 dose of T-DM1 as adjuvant treatment. The primary endpoint was the evaluation of sociodemographic and clinicopathological characteristics of these patients.

RESULTS: A total of 114 patients were included (March-July 2020). At diagnosis, most tumours were infiltrating ductal carcinoma (IDC) (93.9 %), grade 2 (56.1 %), and hormone receptor (HR)-positive (79.8 %). Over 75 % of patients had disease in operable clinical stages (T1-3 N0-1). In the neoadjuvant setting, 86.8 % of patients received trastuzumab plus pertuzumab, and 23.6 % achieved radiological complete response. Breast-conserving surgery was performed in 55.8 % of patients. Surgical specimens showed that 89.5 % of patients had IDC, 49.1 % grade 2, 84.1 % HR-positive, and 8.3 % HER2-negative disease. Most patients had RD classified as RCB-II and Miller/Payne grade 3/4. Grade 3 treatment-related adverse events (trAEs) occurred in 5.3 % of patients. No grade 4/5 AEs occurred. Over 95 % of patients were free of invasive-disease during T-DM1 adjuvant treatment.

CONCLUSION: The KARMA study describes the characteristics of patients with HER2-positive EBC with RD after NeoT and the real-life management of a T-DM1 adjuvant regimen, which showed a manageable safety profile in line with the KATHERINE trial data.}, } @article {pmid37993928, year = {2023}, author = {Göker, M and Denys, H and Hendrix, A and De Wever, O and Van de Vijver, K and Braems, G}, title = {Histologic tumor type as a determinant of survival in hormone receptor-positive, HER2-negative, pT1-3 invasive ductal and lobular breast cancer.}, journal = {Breast cancer research : BCR}, volume = {25}, number = {1}, pages = {146}, pmid = {37993928}, issn = {1465-542X}, mesh = {Humans ; Female ; *Carcinoma, Lobular/pathology ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; Treatment Outcome ; Proportional Hazards Models ; Prognosis ; Retrospective Studies ; }, abstract = {PURPOSE: The aim of the study was to compare the difference in survival between invasive ductal (IDC) and lobular carcinoma (ILC).

METHODS: Data of patients (n = 1843) with a hormone receptor-positive, HER2-negative, pT1-3 IDC or ILC cancer without distant metastasis, treated at the Ghent University Hospital over the time period 2001-2015, were analyzed.

RESULTS: ILC represented 13.9% of the tumors, had a higher percentage of pT3 and pN3 stages than IDC, lymphovascular space invasion (LVSI) was less present and Ki-67 was mostly low. 73.9% of ILCs were grade 2, whereas IDC had more grade 1 and grade 3 tumors. Kaplan-Meier curves and log-rank testing showed a significant worse DFS for ILC with pN ≥ 1 than for their IDC counterpart. In a multivariable Cox regression analysis the histologic tumor type, ductal or lobular, was a determinant of DFS over 120 months (IDC as reference; hazard ratio for ILC 1.77, 95% CI 1.08-2.90) just as the ER Allred score (hazard ratio 0.84, 95% CI 0.78-0.91), LVSI (hazard ratio 1.75, 95% CI 1.12-2.74) and pN3 (hazard ratio 2.29, 95% CI 1.03-5.09). Determinants of OS over ten years were age (hazard ratio 1.05, 95% CI 1.02-1.07), LVSI (hazard ratio 3.62, 95% CI 1.92-6.82) and the ER Allred score (hazard ratio 0.80, 95% CI 0.73-0.89).

CONCLUSION: The histologic tumor type, ductal or lobular, determines DFS in hormone receptor-positive, HER2-negative, pT1-3 breast cancer besides the ER Allred score, LVSI and pN3.}, } @article {pmid37993544, year = {2023}, author = {Voon, W and Hum, YC and Tee, YK and Yap, WS and Nisar, H and Mokayed, H and Gupta, N and Lai, KW}, title = {Evaluating the effectiveness of stain normalization techniques in automated grading of invasive ductal carcinoma histopathological images.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {20518}, pmid = {37993544}, issn = {2045-2322}, support = {IPSR/RMC/UTARRF/2022-C1/H01//Universiti Tunku Abdul Rahman Research Fund/ ; IPSR/RMC/UTARRF/2022-C1/H01//Universiti Tunku Abdul Rahman Research Fund/ ; IPSR/RMC/UTARRF/2022-C1/H01//Universiti Tunku Abdul Rahman Research Fund/ ; IPSR/RMC/UTARRF/2022-C1/H01//Universiti Tunku Abdul Rahman Research Fund/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology ; Breast/pathology ; Neural Networks, Computer ; Staining and Labeling ; *Carcinoma, Ductal ; *Carcinoma, Ductal, Breast/pathology ; }, abstract = {Debates persist regarding the impact of Stain Normalization (SN) on recent breast cancer histopathological studies. While some studies propose no influence on classification outcomes, others argue for improvement. This study aims to assess the efficacy of SN in breast cancer histopathological classification, specifically focusing on Invasive Ductal Carcinoma (IDC) grading using Convolutional Neural Networks (CNNs). The null hypothesis asserts that SN has no effect on the accuracy of CNN-based IDC grading, while the alternative hypothesis suggests the contrary. We evaluated six SN techniques, with five templates selected as target images for the conventional SN techniques. We also utilized seven ImageNet pre-trained CNNs for IDC grading. The performance of models trained with and without SN was compared to discern the influence of SN on classification outcomes. The analysis unveiled a p-value of 0.11, indicating no statistically significant difference in Balanced Accuracy Scores between models trained with StainGAN-normalized images, achieving a score of 0.9196 (the best-performing SN technique), and models trained with non-normalized images, which scored 0.9308. As a result, we did not reject the null hypothesis, indicating that we found no evidence to support a significant discrepancy in effectiveness between stain-normalized and non-normalized datasets for IDC grading tasks. This study demonstrates that SN has a limited impact on IDC grading, challenging the assumption of performance enhancement through SN.}, } @article {pmid37993256, year = {2023}, author = {Wang, H and Ma, X and Li, S and Ni, X}, title = {SEL1L3 as a link molecular between renal cell carcinoma and atherosclerosis based on bioinformatics analysis and experimental verification.}, journal = {Aging}, volume = {15}, number = {22}, pages = {13150-13162}, pmid = {37993256}, issn = {1945-4589}, mesh = {Humans ; Biomarkers, Tumor/genetics ; *Carcinoma, Renal Cell/genetics/pathology ; Computational Biology/methods ; Gene Expression Profiling/methods ; Gene Regulatory Networks ; *Kidney Neoplasms/genetics ; Transcription Factors/genetics ; Proteins ; }, abstract = {BACKGROUND: Renal cancer, the most common type of kidney cancer, develops in the renal tubular epithelium. Atherosclerosis of the aorta is the primary cause of atherosclerosis. However, the underlying mechanisms remain unclear.

METHODS: The renal clear cell carcinoma RNA sequence profile was obtained from The Cancer Genome Atlas (TCGA) database, and the atherosclerosis datasets GSE28829 and GSE43292 based on GPL570 and GPL6244 was obtained from the Gene Expression Omnibus (GEO) database. The difference and hub genes were identified by the Limma protein-protein interaction (PPI) network in R software. Functional enrichment, survival, and immunoinfiltration analyses were performed. The role of SEL1L3 in the ErbB/PI3K/mTOR signaling pathway, apoptosis, invasion, cell cycle, and inflammation was analyzed using western blotting.

RESULTS: 764 DEGs were identified from TCGA Kidney Renal Clear Cell Carcinoma (KIRC) dataset. A total of 344 and 117 DEGs were screened from the GSE14762 and GSE53757 datasets, respectively. Functional enrichment analysis results primarily indicated enrichment in the transporter complex, DNA-binding transcription activator activity, morphogenesis of the embryonic epithelium, stem cell proliferation, adrenal overactivity and so on. Fifteen common DEGs overlapped among the three datasets. The PPI network revealed that SEL1L3 was the core gene. Survival analysis showed that lower SEL1L3 expression levels led to a worse prognosis. Immune cell infiltration analysis showed that SEL1L3 expression was significantly correlated with antibody-drug conjugates (aDC), B cells, eosinophils, interstitial dendritic cells (iDC), macrophages, and more.

CONCLUSIONS: SEL1L3 plays an important role in renal clear cell carcinoma and atherosclerosis and may be a potential link between them.}, } @article {pmid37992687, year = {2023}, author = {d'Aquino, AI and Maikawa, CL and Nguyen, LT and Lu, K and Hall, IA and Jons, CK and Kasse, CM and Yan, J and Prossnitz, AN and Chang, E and Baker, SW and Hovgaard, L and Steensgaard, DB and Andersen, HB and Simonsen, L and Appel, EA}, title = {Use of a biomimetic hydrogel depot technology for sustained delivery of GLP-1 receptor agonists reduces burden of diabetes management.}, journal = {Cell reports. Medicine}, volume = {4}, number = {11}, pages = {101292}, pmid = {37992687}, issn = {2666-3791}, support = {P30 DK116074/DK/NIDDK NIH HHS/United States ; R01 AI154989/AI/NIAID NIH HHS/United States ; R01 DK119254/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Animals ; Rats ; *Diabetes Mellitus, Type 2/drug therapy ; Hypoglycemic Agents/pharmacology/therapeutic use ; Hydrogels/therapeutic use ; Biomimetics ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide-1 Receptor Agonists ; }, abstract = {Glucagon-like peptide-1 (GLP-1) is an incretin hormone and neurotransmitter secreted from intestinal L cells in response to nutrients to stimulate insulin and block glucagon secretion in a glucose-dependent manner. Long-acting GLP-1 receptor agonists (GLP-1 RAs) have become central to treating type 2 diabetes (T2D); however, these therapies are burdensome, as they must be taken daily or weekly. Technological innovations that enable less frequent administrations would reduce patient burden and increase patient compliance. Herein, we leverage an injectable hydrogel depot technology to develop a GLP-1 RA drug product capable of months-long GLP-1 RA delivery. Using a rat model of T2D, we confirm that one injection of hydrogel-based therapy sustains exposure of GLP-1 RA over 42 days, corresponding to a once-every-4-months therapy in humans. Hydrogel therapy maintains management of blood glucose and weight comparable to daily injections of a leading GLP-1 RA drug. This long-acting GLP-1 RA treatment is a promising therapy for more effective T2D management.}, } @article {pmid37991026, year = {2024}, author = {Su, HZ and Huang, M and Li, ZY and Tu, JH and Hong, LC and Zhang, ZB and Zhang, XD}, title = {Ultrasound characteristics of breast fibromatosis mimicking carcinoma.}, journal = {Journal of clinical ultrasound : JCU}, volume = {52}, number = {2}, pages = {144-151}, doi = {10.1002/jcu.23613}, pmid = {37991026}, issn = {1097-0096}, support = {2022J011366//Natural Science Foundation of Fujian Province/ ; 3502Z20214ZD1010//Science and Technology Foundation of Xiamen, China/ ; }, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/pathology ; *Breast Neoplasms/diagnostic imaging/pathology ; Breast/diagnostic imaging/pathology ; Ultrasonography ; Lymph Nodes/pathology ; Retrospective Studies ; }, abstract = {PURPOSE: To explore the value of ultrasound (US) characteristics in diagnosing breast fibromatosis (BF) and evaluate their differences from breast carcinoma.

METHODS: A total of 121 patients with BF (n = 24, 29 lesions) or invasive ductal carcinoma (IDC) (n = 97, 102 lesions) of the breast were included. Their clinical and US findings were recorded and analyzed.

RESULTS: The mean age of BF was younger than that of IDC (28.75 ± 5.55 vs. 50.19 ± 9.87, p < 0.001). The mean size of the BF was smaller than that of IDC (2.09 ± 0.91 vs. 2.71 ± 1.20, p = 0.011). Compared to IDC, BF had more frequency of posterior echo attenuation (p < 0.001), less frequency of peripheral hyperechoic halo (p = 0.002), calcification (p = 0.001), US reported axillary lymph node positive (p = 0.025), and grade 2-3 vascularity (p < 0.001). The Breast Imaging Reporting and Data System categorized BF at a lower level than IDC (p < 0.001). After adjusting for age, the peripheral hyperechoic halo, posterior echo feature, and vascularity could independently identify the differences between these two entities.

CONCLUSION: Some differences were observed between BF and IDC in terms of patient age, lesion size, and US characteristics.}, } @article {pmid37978324, year = {2023}, author = {Stead, Z and Capuano, R and Di Natale, C and Pain, A}, title = {The volatilome signatures of Plasmodium falciparum parasites during the intraerythrocytic development cycle in vitro under exposure to artemisinin drug.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {20167}, pmid = {37978324}, issn = {2045-2322}, support = {BAS/1/1020-01-01//KAUST faculty baseline fund/ ; BAS/1/1020-01-01//KAUST faculty baseline fund/ ; Giunta Regionale n. G10795//Regione Lazio/ ; Giunta Regionale n. G10795//Regione Lazio/ ; }, mesh = {Humans ; Animals ; Plasmodium falciparum ; *Parasites ; *Antimalarials/pharmacology/therapeutic use ; *Volatile Organic Compounds/pharmacology ; Drug Resistance ; *Artemisinins/pharmacology/therapeutic use ; *Malaria, Falciparum/drug therapy/parasitology ; *Malaria/drug therapy ; Protozoan Proteins/pharmacology ; }, abstract = {Volatile organic compounds (VOCs) comprise a diverse range of metabolites with high vapour pressure and low boiling points. Although they have received attention, they are a largely unexplored part of the metabolome. Previous studies have shown that malaria infections produce characteristic, definitive, and detectable volatile signatures. Many transcriptional and metabolic differences are observed at different stages of the parasite Intraerythrocytic Developmental Cycle (IDC) as well as when artemisinin-resistant parasites are put under drug pressure. This prompted our research to characterize whether these responses are reflected at a volatile level in malaria during the IDC stages using gas chromatography-mass spectrometry. We investigated whether the resistant P. falciparum parasites would produce their own characteristic volatilome profile compared to near-isogenic wild-type parasite in vitro; firstly at three different stages of the IDC and secondly in the presence or absence of artemisinin drug treatment. Finally, we explored the VOC profiles from two media environments (Human serum and Albumax) of recently lab-adapted field parasite isolates, from Southeast Asia and West/East Africa, compared to long-term lab-adapted parasites. Recognizable differences were observed between IDC stages, with schizonts having the largest difference between wild type and resistant parasites, and with cyclohexanol and 2,5,5-trimethylheptane only present for resistant schizonts. Artemisinin treatment had little effect on the resistant parasite VOC profile, whilst for the wild type parasites compounds ethylbenzene and nonanal were greatly affected. Lastly, differing culturing conditions had an observable impact on parasite VOC profile and clustering patterns of parasites were specific to geographic origin. The results presented here provide the foundation for future studies on VOC based characterization of P. falciparum strains differing in abilities to tolerate artemisinin.}, } @article {pmid37973797, year = {2023}, author = {Abdallah, N and Marion, JM and Tauber, C and Carlier, T and Hatt, M and Chauvet, P}, title = {Enhancing histopathological image classification of invasive ductal carcinoma using hybrid harmonization techniques.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {20014}, pmid = {37973797}, issn = {2045-2322}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Databases, Factual ; *Carcinoma, Ductal ; }, abstract = {This study aims to develop a robust pipeline for classifying invasive ductal carcinomas and benign tumors in histopathological images, addressing variability within and between centers. We specifically tackle the challenge of detecting atypical data and variability between common clusters within the same database. Our feature engineering-based pipeline comprises a feature extraction step, followed by multiple harmonization techniques to rectify intra- and inter-center batch effects resulting from image acquisition variability and diverse patient clinical characteristics. These harmonization steps facilitate the construction of more robust and efficient models. We assess the proposed pipeline's performance on two public breast cancer databases, BreaKHIS and IDCDB, utilizing recall, precision, and accuracy metrics. Our pipeline outperforms recent models, achieving 90-95% accuracy in classifying benign and malignant tumors. We demonstrate the advantage of harmonization for classifying patches from different databases. Our top model scored 94.7% for IDCDB and 95.2% for BreaKHis, surpassing existing feature engineering-based models (92.1% for IDCDB and 87.7% for BreaKHIS) and attaining comparable performance to deep learning models. The proposed feature-engineering-based pipeline effectively classifies malignant and benign tumors while addressing variability within and between centers through the incorporation of various harmonization techniques. Our findings reveal that harmonizing variabilities between patches from different batches directly impacts the learning and testing performance of classification models. This pipeline has the potential to enhance breast cancer diagnosis and treatment and may be applicable to other diseases.}, } @article {pmid37970339, year = {2023}, author = {Qu, J and Li, C and Liu, M and Wang, Y and Sun, S and Feng, Z and Wu, F and Zhang, S and Zhao, X}, title = {A novel web-based prognostic nomogram and the features influencing the curative effect of chemotherapy and radiotherapy for Paget's disease with invasive ductal carcinoma.}, journal = {American journal of cancer research}, volume = {13}, number = {10}, pages = {4508-4530}, pmid = {37970339}, issn = {2156-6976}, abstract = {Paget's disease (PD) of the breast is a rare underlying malignant tumor. Approximately 50% to 60% of patients with mammary PD are concurrently diagnosed with invasive ductal carcinoma (PD-IDC), a condition associated with a worse prognosis than IDC without PD. Thus far, there has been a lack of an accurate and efficient prognostic model for PD-IDC, and the factors influencing the effectiveness of chemotherapy and radiotherapy for these patients remain unknown. In this study, we developed a web-based nomogram based on the data from the Surveillance Epidemiology and End Results (SEER) database. We subjected the model to a series of validation methods, including area under the curve (AUC) values, receiver operating characteristic curve (ROC) analysis, calibration curves, and decision curve analysis (DCA). Our results demonstrated that our model exhibited high discrimination, accuracy, and clinical applicability in predicting the overall survival (OS) of patients with PD-IDC (testing set: three- and five-year AUCs, 0.831 and 0.841, respectively). To further validate our nomogram, we used external data from both our institution and sister hospitals (external data: three- and five-year AUCs, 0.892 and 0.914, respectively). Multivariable Cox regression analysis identified several independent unfavorable prognostic factors for the OS of patients with PD-IDC, including increasing age, high grade, widowed status, higher T stages, and the presence of bone metastases. Furthermore, propensity score matching (PSM)-adjusted analysis was conducted, revealing that chemotherapy did not significantly improve the survival of patients with PD-IDC across molecular subtypes, except for those in the grade III/IV group, where it improved both OS and breast cancer-specific survival (BCSS). Additionally, our findings indicated that only patients with PD-IDC with T4 and N3 stages benefited from radiotherapy, leading to improvements in both OS and BCSS. In conclusion, we have comprehensively analyzed the clinical characteristics and prognosis of patients with PD-IDC, culminating in the development of a user-friendly web-based nomogram for predicting their survival. Our predictive model is not only highly accurate but also offers simplicity, making it accessible for healthcare providers and patients. Furthermore, our stratified analysis highlights that the pathological grade, rather than the molecular subtype, plays a pivotal role in determining the efficacy of chemotherapy in improving the prognosis for patients with PD-IDC, while radiotherapy confers survival benefits to patients with PD-IDC in T4 and N3 stages.}, } @article {pmid37969442, year = {2023}, author = {Bai, J and Li, Y and Cai, L}, title = {Clinical implications of forkhead box M1, cyclooxygenase-2, and glucose-regulated protein 78 in breast invasive ductal carcinoma.}, journal = {World journal of clinical cases}, volume = {11}, number = {30}, pages = {7284-7293}, pmid = {37969442}, issn = {2307-8960}, abstract = {BACKGROUND: Breast infiltrating ductal carcinoma (BIDC) represents the largest heterotypic tumor group, and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.

AIM: To analyze the expression profiles and clinical implications of forkhead box M1 (FOXM1), cyclooxygenase-2 (COX-2), and glucose-regulated protein 78 (GRP78) in BIDC.

METHODS: A total of 65 BIDC patients and 70 healthy controls who presented to our hospital between August 2019 and May 2021 were selected for analysis. The peripheral blood FOXM1, COX-2, and GRP78 levels in both groups were measured and the association between their expression profiles in BIDC was examined. Additionally, we investigated the diagnostic value of FOXM1, COX-2, and GRP78 in patients with BIDC and their correlations with clinicopathological features. Furthermore, BIDC patients were followed for 1 year to identify factors influencing patient prognosis.

RESULTS: The levels of FOXM1, COX-2, and GRP78 were significantly higher in BIDC patients compared to healthy controls (P < 0.05), and a positive correlation was observed among them (P < 0.05). Receiver operating characteristic analysis demonstrated that FOXM1, COX-2, and GRP78 had excellent diagnostic value in predicting the occurrence of BIDC (P < 0.05). Subsequently, we found significant differences in FOXM1, COX-2, and GRP78 levels among patients with different histological grades and metastasis statuses (with vs without) (P < 0.05). Cox analysis revealed that FOXM1, COX-2, GRP78, increased histological grade, and the presence of tumor metastasis were independent risk factors for prognostic death in BIDC (P < 0.001).

CONCLUSION: FOXM1, COX-2, and GRP78 exhibit abnormally high expression in BIDC, promoting malignant tumor development and closely correlating with prognosis. These findings hold significant research implications for the future diagnosis and treatment of BIDC.}, } @article {pmid37957878, year = {2023}, author = {Zhang, Y and Xin, Y and Zhang, N and Hu, X and Peng, B and Zhang, S and Yuan, Y}, title = {Breast Edema of Early-stage Invasive Ductal Carcinoma: Correlation with Axillary Lymph Node Metastasis and Clinical-pathological Characteristics.}, journal = {Current medical imaging}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115734056243245231024082647}, pmid = {37957878}, issn = {1573-4056}, abstract = {OBJECTIVE: This study aimed to evaluate the association of different patterns of breast edema and clinical-pathological features and axillary lymph node (ALN) status in early invasive ductal carcinoma (IDC) for simple and readily available assessment and to guide surgeons to perform sentinel lymph node biopsy for selected patients.

MATERIALS AND METHODS: This retrospective analysis involved 207 individuals with clinical T1-T2 stage IDC. The clinical-pathological features of the patients were compared with different breast edema and ALN statuses. Independent risk factors for ALN metastasis were verified using multivariate logistic regression analysis.

RESULTS: ALN metastasis was confirmed in 100 of 207 patients (48.3%) with early-stage IDC. Significant differences were found between different ALN states for tumour size, clinical T stage, and breast edema (P <0.05). The clinical T2 stage (odds ratio-1.882, p=0.043) and moderate to severe edema (odds ratio-10.869, p=0.004) were independent risk factors for ALN metastasis. Moreover, better prognostic factors, including smaller tumour size, lower Ki-67 index and histologic grade, luminal A subtype, and lower incidence of lymph node metastasis, were more frequently found in patients with no breast edema (p<0.05).

CONCLUSION: Breast edema can be considered a promising feature to improve the predictive performance of pathological ALN status in patients with early-stage breast cancer and thus may contribute to preoperative treatment planning.}, } @article {pmid37957665, year = {2023}, author = {G K, AV and Gogoi, G and Kachappilly, MC and Rangarajan, A and Pandya, HJ}, title = {Label-free multimodal electro-thermo-mechanical (ETM) phenotyping as a novel biomarker to differentiate between normal, benign, and cancerous breast biopsy tissues.}, journal = {Journal of biological engineering}, volume = {17}, number = {1}, pages = {68}, pmid = {37957665}, issn = {1754-1611}, support = {BIRAC SRISTI PMU-2020/001//Biotechnology Industry Research Assistance Council/ ; CRG/2019/004963//Science and Engineering Research Board/ ; CRG/2019/004963//Science and Engineering Research Board/ ; 17X(3)/Ad-hoc/81/2022-ITR//Indian Council of Medical Research/ ; 17X(3)/Ad-hoc/81/2022-ITR//Indian Council of Medical Research/ ; SP-DSTO-0019//Department of Science and Technology, Ministry of Science and Technology, India/ ; }, abstract = {BACKGROUND: Technologies for quick and label-free diagnosis of malignancies from breast tissues have the potential to be a significant adjunct to routine diagnostics. The biophysical phenotypes of breast tissues, such as its electrical, thermal, and mechanical properties (ETM), have the potential to serve as novel markers to differentiate between normal, benign, and malignant tissue.

RESULTS: We report a system-of-biochips (SoB) integrated into a semi-automated mechatronic system that can characterize breast biopsy tissues using electro-thermo-mechanical sensing. The SoB, fabricated on silicon using microfabrication techniques, can measure the electrical impedance (Z), thermal conductivity (K), mechanical stiffness (k), and viscoelastic stress relaxation (%R) of the samples. The key sensing elements of the biochips include interdigitated electrodes, resistance temperature detectors, microheaters, and a micromachined diaphragm with piezoresistive bridges. Multi-modal ETM measurements performed on formalin-fixed tumour and adjacent normal breast biopsy samples from N = 14 subjects were able to differentiate between invasive ductal carcinoma (malignant), fibroadenoma (benign), and adjacent normal (healthy) tissues with a root mean square error of 0.2419 using a Gaussian process classifier. Carcinoma tissues were observed to have the highest mean impedance (110018.8 ± 20293.8 Ω) and stiffness (0.076 ± 0.009 kNm[-1]) and the lowest thermal conductivity (0.189 ± 0.019 Wm[-1] K[-1]) amongst the three groups, while the fibroadenoma samples had the highest percentage relaxation in normalized load (47.8 ± 5.12%).

CONCLUSIONS: The work presents a novel strategy to characterize the multi-modal biophysical phenotype of breast biopsy tissues to aid in cancer diagnosis from small-sized tumour samples. The methodology envisions to supplement the existing technology gap in the analysis of breast tissue samples in the pathology laboratories to aid the diagnostic workflow.}, } @article {pmid37950182, year = {2023}, author = {Haghpanah, S and Hosseini-Bensenjan, M and Ramzi, M and Khosravizadegan, Z and Rezaianzadeh, A}, title = {Investigating the trends of incidence rates of breast cancer in Southern Iran: a population based survey.}, journal = {BMC women's health}, volume = {23}, number = {1}, pages = {589}, pmid = {37950182}, issn = {1472-6874}, mesh = {Male ; Humans ; Female ; *Breast Neoplasms/epidemiology ; Incidence ; Iran/epidemiology ; Retrospective Studies ; Registries ; }, abstract = {BACKGROUND: The overall incidence of breast cancer is different all over the world and even within a nation. The present study aims to investigate the stratum-specific incidence trends of breast cancer in southern Iran.

METHODS: In this retrospective cohort study, the data of Fars Population-Based Cancer Registry was used during 2001-2018. New cancer cases with ICD-O-3 codes C50.0 to C50.9 were categorized based on age group, morphology, and topography. Age-specific incidence rates of breast cancer were calculated during 2001-2018. Annual overall and truncated age-standardized incidence rates and their 95% Confidence Intervals (CIs) were also calculated. Afterward, the Annual Percentage Changes (APCs) of the age-specific and age-standardized incidence rates of breast cancer during 2001-2018 were calculated using Joinpoint regression software.

RESULTS: An increasing trend was observed in the incidence of breast cancer among women during 2001-2018 (APC of age-standardized incidence rates: 9.5 (95% CI: 7.5, 11.5)).However, the trend was increasing less during the recent years. The APC of age-standardized rates decreased from 15.03 (95% CI: 10.4, 19.8) in 2007 to 6.15(95% CI: 4.0, 8.4) in 2018. The most common morphology of breast cancer was invasive ductal carcinoma (77.3% in females and 75.1% in males) and its trend was similar to the general trend of different types of breast cancer. The most common site of breast cancer was the upper outer quadrant. Most breast cancer cases were female and males accounted for 2.45% of the cases. Among females, 40-55 was the most prevalent age group.

CONCLUSION: The incidence of breast cancer among women living in southern Iran showed an increasing trend from 2001 to 2018. However, the rate of increase exhibited a milder slope during the more recent years. Based on the higher prevalence of breast cancer in the 40-55 age group observed in the present study, it offers valuable insight into the potential reduction of the breast cancer screening age from 50 to 40 years for healthy Iranian women. However, before implementing such a policy change, it is crucial to conduct additional studies that specifically examine the cost-effectiveness, as well as the potential benefits and risks associated with this alteration.}, } @article {pmid37949797, year = {2024}, author = {Aguado, JM and Navarro, D and Montoto, C and Yébenes, M and de Castro-Orós, I}, title = {Incidence of refractory CMV infection with or without antiviral resistance in Spain: A systematic literature review.}, journal = {Transplantation reviews (Orlando, Fla.)}, volume = {38}, number = {1}, pages = {100804}, doi = {10.1016/j.trre.2023.100804}, pmid = {37949797}, issn = {1557-9816}, mesh = {Humans ; Antiviral Agents/pharmacology/therapeutic use ; *Cytomegalovirus Infections/drug therapy/epidemiology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Incidence ; Organ Transplantation/adverse effects ; Spain/epidemiology ; Transplant Recipients ; }, abstract = {INTRODUCTION: Solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) recipients are susceptible to cytomegalovirus (CMV) infection. The incidence of refractoriness to antivirals, with or without resistance, is unclear. The purpose of this review was to describe the epidemiology of refractory CMV infection in Spain to understand the current unmet needs.

METHODS: PubMed, EMBASE, Cochrane and MEDES were searched systematically for relevant articles. We included randomized controlled trials and observational studies published during the period from January 1990 to June 2021.

RESULTS: From 212 screened records, we selected 19 papers including 1973 transplant recipients. Refractory infection ranged from 3 to 10% in studies with SOT recipients. The incidence of CMV resistance ranged from 1% to 36% in these patients. The incidence of CMV refractory infection in HSCT recipients ranged from 11 to 50%, while values for resistant infection ranged from 0% to 21%.

CONCLUSION: The wide range of definitions and values observed does not allow us to establish the true incidence of refractory CMV infection with or without resistances in SOT and HSCT patients in Spain. This review highlights the gap between clinical practice and clinical trials' definitions which needed to be updated to be easier followed in current clinical practice.}, } @article {pmid37941541, year = {2023}, author = {Bhimani, F and McEvoy, M and Gupta, A and Pastoriza, J and Shihabi, A and Basavatia, A and Tomé, WA and Fox, J and Mehta, K and Feldman, S}, title = {Case Report: Bilateral targeted intraoperative radiotherapy: a safe and effective alternative for synchronous bilateral breast cancer.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1276766}, pmid = {37941541}, issn = {2234-943X}, abstract = {BACKGROUND: The incidence of bilateral breast cancer (BBC) ranges from 1.4% to 11.8%. BBC irradiation is a challenge in current clinical practice due to the large target volume that must be irradiated while minimizing the dose to critical organs. Supine or prone breast techniques can be used, with the latter providing better organ sparing; both, however, result in lengthy treatment times. The use of Intra-operative radiotherapy (IORT) in breast cancer patients who choose breast conservation has been highlighted in previous studies, but there is a scarcity of literature analyzing the utility and applicability of IORT in BBC. This case series aims to highlight the applicability of administering bilateral IORT in patients with BBC.

CASE REPORTS: Five patients with bilateral early-stage breast cancer (or DCIS) were treated with breast-conserving surgery followed by bilateral IORT. Of the 10 breast cancers, 8 were diagnosed as either DCIS or IDC, while the other 2 were diagnosed as invasive lobular carcinoma and invasive carcinoma, respectively. During surgery, all patients received bilateral IORT. Furthermore, 1 patient received external beam radiation therapy after her final pathology revealed grade 3 DCIS. The IORT procedure was well tolerated by all five patients, and all patients received aromatase inhibitors as adjuvant therapy. Additionally, none of these patients showed evidence of disease after a 36-month median follow-up.

CONCLUSION: Our findings demonstrate the successful use of IORT for BCS in patients with BBC. Furthermore, none of the patients in our study experienced any complications, suggesting the feasibility of the use of IORT in BBC. Considering the benefits of improved patient compliance and a reduced number of multiple visits, IORT may serve as an excellent patient-centered alternative for BBC. Future studies are recommended to reinforce the applicability of IORT in patients with BBC.}, } @article {pmid37938845, year = {2023}, author = {Yoon, TI and Jeong, J and Lee, S and Ryu, JM and Lee, YJ and Lee, JY and Hwang, KT and Kim, H and Kim, S and Lee, SB and Ko, BS and Lee, JW and Son, BH and Metzger, O and Kim, HJ}, title = {Survival Outcomes in Premenopausal Patients With Invasive Lobular Carcinoma.}, journal = {JAMA network open}, volume = {6}, number = {11}, pages = {e2342270}, pmid = {37938845}, issn = {2574-3805}, mesh = {Humans ; Female ; *Carcinoma, Lobular/therapy ; *Carcinoma, Ductal, Breast/therapy ; Cohort Studies ; *Breast Neoplasms/epidemiology ; Prognosis ; }, abstract = {IMPORTANCE: The disparate prognostic implications between invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have been demonstrated. However, information on premenopausal patients remains insufficient.

OBJECTIVE: To examine long-term survival outcomes of ILC and IDC in premenopausal patients using national databases.

This cohort study used the Surveillance, Epidemiology, and End Results (SEER), Korean Breast Cancer Registry (KBCR), and Asan Medical Center Research (AMCR) databases to identify premenopausal patients with stage I to III ILC or IDC between January 1, 1990, and December 31, 2015. The median follow-up time was 90 (IQR, 40-151) months in the SEER database, 94 (IQR, 65-131) months in the KBCR database, and 120 (IQR, 86-164) months in the AMCR database. Data were analyzed from January 1 to May 31, 2023.

MAIN OUTCOMES AND MEASURES: The primary outcome was breast cancer-specific survival (BCSS), which was analyzed according to histological type, and the annual hazard rate was evaluated. Survival rates were analyzed using a log-rank test and a Cox proportional hazards regression model with time-varying coefficients. Multivariable analysis was performed by adjusting for tumor characteristics and treatment factors.

RESULTS: A total of 225 938 women diagnosed with IDC or ILC and younger than 50 years were identified. Mean (SD) age at diagnosis was 42.7 (5.3) years in the SEER database, 41.8 (5.5) years in the KBCR database, and 41.8 (5.5) years in the AMCR database. In terms of race (available for the SEER database only), 12.4% of patients were Black, 76.1% were White, 11.0% were of other race (including American Indian or Alaska Native, Asian, and Native Hawaiian or Other Pacific Islander), and 0.5% were of unknown race). Patients with ILC had better BCSS in the first 10 years after diagnosis than those with IDC (hazard ratios [HRs], 0.73 [95% CI, 0.68-0.78] in the SEER database, 1.20 [95% CI, 0.91-1.58] in the KBCR database, and 0.50 [95% CI, 0.29-0.86] in the AMCR database), although BCSS was worse after year 10 (HRs, 1.80 [95% CI, 1.59-2.02] in the SEER database, 2.79 [95% CI, 1.32-5.88] in the KBCR database, and 2.23 [95% CI, 1.04-4.79] in the AMCR database). Similar trends were observed for hormone receptor-positive tumors (HRs, 1.55 [95% CI, 1.37-1.75] in the SEER database, 2.27 [95% CI, 1.01-5.10] in the KBCR database, and 2.12 [95% CI, 0.98-4.60] in the AMCR database). Considering the annual hazard model of BCSS, IDC events tended to decline steadily after peaking 5 years before diagnosis. However, the annual peak event of BCSS was observed 5 years after diagnosis for ILC, which subsequently remained constant.

CONCLUSIONS AND RELEVANCE: These findings suggest that premenopausal women with ILC have worse BCSS estimates than those with IDC, which can be attributed to a higher late recurrence rate of ILC than that of IDC. Histological subtypes should be considered when determining the type and duration of endocrine therapy in premenopausal women.}, } @article {pmid37936612, year = {2023}, author = {Li, Y and Wei, XL and Pang, KK and Ni, PJ and Wu, M and Xiao, J and Zhang, LL and Zhang, FX}, title = {A comparative study on the features of breast sclerosing adenosis and invasive ductal carcinoma via ultrasound and establishment of a predictive nomogram.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1276524}, pmid = {37936612}, issn = {2234-943X}, abstract = {OBJECTIVE: To analyze the clinical and ultrasonic characteristics of breast sclerosing adenosis (SA) and invasive ductal carcinoma (IDC), and construct a predictive nomogram for SA.

MATERIALS AND METHODS: A total of 865 patients were recruited at the Second Hospital of Shandong University from January 2016 to November 2022. All patients underwent routine breast ultrasound examinations before surgery, and the diagnosis was confirmed by histopathological examination following the operation. Ultrasonic features were recorded using the Breast Imaging Data and Reporting System (BI-RADS). Of the 865 patients, 203 (252 nodules) were diagnosed as SA and 662 (731 nodules) as IDC. They were randomly divided into a training set and a validation set at a ratio of 6:4. Lastly, the difference in clinical characteristics and ultrasonic features were comparatively analyzed.

RESULT: There was a statistically significant difference in multiple clinical and ultrasonic features between SA and IDC (P<0.05). As age and lesion size increased, the probability of SA significantly decreased, with a cut-off value of 36 years old and 10 mm, respectively. In the logistic regression analysis of the training set, age, nodule size, menopausal status, clinical symptoms, palpability of lesions, margins, internal echo, color Doppler flow imaging (CDFI) grading, and resistance index (RI) were statistically significant (P<0.05). These indicators were included in the static and dynamic nomogram model, which showed high predictive performance, calibration and clinical value in both the training and validation sets.

CONCLUSION: SA should be suspected in asymptomatic young women, especially those younger than 36 years of age, who present with small-size lesions (especially less than 10 mm) with distinct margins, homogeneous internal echo, and lack of blood supply. The nomogram model can provide a more convenient tool for clinicians.}, } @article {pmid37933375, year = {2023}, author = {Mahoney, MT and Kubinak, N and Masi, A and Lok, C and Eanelli, TR}, title = {Mind the Gap: Recurrence of Oligometastatic Breast Invasive Ductal Carcinoma in the Sternal Gap of Two Tangential Photon Fields of Bilateral Whole Breast Irradiation a Decade Later.}, journal = {Cureus}, volume = {15}, number = {10}, pages = {e46601}, pmid = {37933375}, issn = {2168-8184}, abstract = {Despite bilateral breast cancer being a rare clinical entity compared to unilateral breast cancer, both share a treatment paradigm of breast-conserving therapy for limited disease and metastasis direct therapy for oligometastatic disease. We present a case of left breast invasive ductal carcinoma in the setting of original bilateral breast cancer, now with oligometastatic recurrence to the soft tissue of the sternum, notably in an area not previously irradiated, over a decade later.}, } @article {pmid37925055, year = {2024}, author = {Derakhshan, F and Da Cruz Paula, A and Selenica, P and da Silva, EM and Grabenstetter, A and Jalali, S and Gazzo, AM and Dopeso, H and Marra, A and Brown, DN and Ross, DS and Mandelker, D and Razavi, P and Chandarlapaty, S and Wen, HY and Brogi, E and Zhang, H and Weigelt, B and Pareja, F and Reis-Filho, JS}, title = {Nonlobular Invasive Breast Carcinomas with Biallelic Pathogenic CDH1 Somatic Alterations: A Histologic, Immunophenotypic, and Genomic Characterization.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {37}, number = {2}, pages = {100375}, pmid = {37925055}, issn = {1530-0285}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P50 CA247749/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Carcinoma, Lobular/pathology ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; Cadherins/genetics ; Genomics ; Antigens, CD/genetics ; }, abstract = {CDH1 encodes for E-cadherin, and its loss of function is the hallmark of invasive lobular carcinoma (ILC). Albeit vanishingly rare, biallelic CDH1 alterations may be found in nonlobular breast carcinomas (NL-BCs). We sought to determine the clinicopathologic characteristics and repertoire of genetic alterations of NL-BCs harboring CDH1 biallelic genetic alterations. Analysis of 5842 breast cancers (BCs) subjected to clinical tumor-normal sequencing with an FDA-cleared multigene panel was conducted to identify BCs with biallelic CDH1 pathogenic/likely pathogenic somatic mutations lacking lobular features. The genomic profiles of NL-BCs with CDH1 biallelic genetic alterations were compared with those of ILCs and invasive ductal carcinomas (IDCs), matched by clinicopathologic characteristics. Of the 896 CDH1-altered BCs, 889 samples were excluded based on the diagnosis of invasive mixed ductal/lobular carcinoma or ILC or the detection of monoallelic CDH1 alterations. Only 7 of the 5842 (0.11%) BCs harbored biallelic CDH1 alterations and lacked lobular features. Of these, 4/7 (57%) cases were ER-positive/HER2-negative, 1/7 (14%) was ER-positive/HER2-positive, and 2/7 (29%) were ER-negative/HER2-negative. In total, 5/7 (71%) were of Nottingham grade 2, and 2/7 (29%) were of grade 3. The NL-BCs with CDH1 biallelic genetic alterations included a mucinous carcinoma (n = 1), IDCs with focal nested growth (n = 2), IDC with solid papillary (n = 1) or apocrine (n = 2) features, and an IDC of no special type (NST; n = 1). E-cadherin expression, as detected by immunohistochemistry, was absent (3/5) or aberrant (discontinuous membranous/cytoplasmic/granular; 2/5). However, NL-BCs with CDH1 biallelic genetic alterations displayed recurrent genetic alterations, including TP53, PIK3CA (57%, 4/7; each), FGFR1, and NCOR1 (28%, 2/7, each) alterations. Compared with CDH1 wild-type IDC-NSTs, NL-BCs less frequently harbored GATA3 mutations (0% vs 47%, P = .03), but no significant differences were detected when compared with matched ILCs. Therefore, NL-BCs with CDH1 biallelic genetic alterations are vanishingly rare, predominantly comprise IDCs with special histologic features, and have genomic features akin to luminal B ER-positive BCs.}, } @article {pmid37922498, year = {2024}, author = {Maggi, G and Giacobbe, C and Iannotta, F and Santangelo, G and Vitale, C}, title = {Prevalence and clinical aspects of obstructive sleep apnea in Parkinson disease: A meta-analysis.}, journal = {European journal of neurology}, volume = {31}, number = {2}, pages = {e16109}, pmid = {37922498}, issn = {1468-1331}, mesh = {Humans ; Male ; *Parkinson Disease/complications/epidemiology ; Polysomnography ; Prevalence ; *REM Sleep Behavior Disorder/etiology/complications ; *Sleep Apnea, Obstructive/epidemiology/complications ; }, abstract = {BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) frequently occurs in Parkinson Disease (PD), probably caused by upper airway dysfunctions or shared pathogenetic mechanisms. OSA may precede PD diagnosis or worsen throughout its course, but its relationship with clinical features and dopaminergic medication remains unclear. This meta-analysis aimed to provide a reliable estimate of OSA prevalence in the PD population (PD-OSA) and to clarify its clinical associated factors to help clinicians in understanding the underlying pathophysiological mechanisms.

METHODS: A systematic literature search was performed up to April 2023 using the PubMed, Scopus, and PsycINFO databases. Articles were included if they provided data on PD patients with and without OSA. Pooled prevalence for PD-OSA was calculated using the proportions of PD participants diagnosed with OSA. Demographic and clinical features associated with PD-OSA were explored by comparing PD patients with and without OSA.

RESULTS: Seventeen studies were included in the meta-analysis. Pooled OSA prevalence was 45% of a total sample of 1448 PD patients and was associated with older age, male sex, higher body mass index (BMI), more severe motor disturbances and periodic limb movements, reduced risk of rapid eye movement sleep behavior disorder, intake of dopamine agonists, and worse excessive daytime sleepiness. No relationship emerged with cognitive functioning and neuropsychiatric manifestations.

CONCLUSIONS: OSA affects nearly half of PD patients as a secondary outcome of predisposing factors such as older age and higher BMI in addition to PD-related motor impairment. Future studies should focus on determining the impact of both clinical features and dopaminergic medication on the development of PD-OSA.}, } @article {pmid37921670, year = {2023}, author = {Kalra, R and Lim, B and Ellis, MJ and Kavuri, SM}, title = {The uncharted role of HER2 mutant alleles in breast cancer.}, journal = {Oncotarget}, volume = {14}, number = {}, pages = {904-907}, pmid = {37921670}, issn = {1949-2553}, support = {P50 CA186784/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/genetics ; Alleles ; Erb-b2 Receptor Tyrosine Kinases/genetics ; }, abstract = {Somatic HER2 mutations are a novel class of therapeutic targets across different cancer types. Treatment with the tyrosine kinase inhibitor (TKI) neratinib as a single agent continues to be evaluated in HER2-mutant metastatic disease. However, responses are heterogeneous, with frequent early progression. Herein, we discuss the under-explored effects of individual HER2 mutant alleles on therapeutic response, a role for HER2 mutation in metastatic propensity, and differences in patient outcomes in ER+ invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC). The preclinical efficacy of additional agents is also discussed, particularly the pan-HER inhibitor poziotinib.}, } @article {pmid37920380, year = {2023}, author = {Alshaibani, N and Chandramohan, JK and Khairi, SS and Al-Hashimi, F and Aljawder, AA}, title = {Invasive Cystic Hypersecretory Ductal Carcinoma of Breast: Challenges in Diagnosis and Management.}, journal = {Case reports in oncology}, volume = {16}, number = {1}, pages = {1259-1266}, pmid = {37920380}, issn = {1662-6575}, abstract = {Cystic hypersecretory lesions of the breast are a spectrum of conditions ranging from cystic hypersecretory hyperplasia with atypia and invasive cystic hypersecretory carcinoma (CHC). It is a subtype of ductal carcinoma of the breast. The tumour is very infrequent and hence, extensive literature is limited. This culminates in the fact that it does not feature as part of the WHO classification of breast tumours. However, a good knowledge about its distinct pathological features can avert misdiagnosis and help differentiate CHC from other conditions. Thus far, only 22 cases of invasive CHC have been reported, of which 3 were microinvasive. Only 7 cases of axillary lymph node metastasis have been documented. We report a case of invasive CHC of the breast that was metastatic to the axilla and refractory to neoadjuvant chemotherapy. Our case report aims to add to the literature on the disease, aiming to support large-scale studies in the future in order to elaborate on its clinical and biological characteristics.}, } @article {pmid37919558, year = {2024}, author = {Avatefi, M and HadavandSiri, F and Nazari, SSH and Akbari, ME}, title = {Risk factors of developing contralateral breast cancer after first primary breast cancer treatment.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {7}, number = {1}, pages = {e1927}, pmid = {37919558}, issn = {2573-8348}, mesh = {Female ; Humans ; *Breast Neoplasms/diagnosis/epidemiology/therapy ; Retrospective Studies ; *Neoplasms, Second Primary/diagnosis/epidemiology/etiology ; Risk Factors ; Proportional Hazards Models ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide. Increased survival of primary BC (PBC) has increased contralateral breast cancer (CBC) and become a health problem.

AIMS: This study aimed to determine the effect of disease-free interval (DFI), risk factors and PBC characteristics on the progression of CBC within primary BC survivors.

METHODS AND RESULTS: This retrospective study identified 5003 women diagnosed with breast cancer between 2000 and 2020 in the cancer research center. The study included 145 CBC and 4858 PBC survivors, with CBC diagnosed at least 6 months after the detection of primary BC. ER+, PR+, and HER2+ were reported in 72.13%, 66.67%, and 30% of CBC patients. Invasive ductal carcinoma (IDC) BC was reported in 69.57% of patients, and 81.90% and 83.64% of the patients were treated with adjuvant chemotherapy and external radiotherapy. The Kaplan-Meier method indicated that the median time interval between PBC and CBC was 3.92 years, and the 5-year DFI was 97%. The Cox proportional hazard regression model indicated that although more than half of the participants had no family history of BC (69.57%), women 60 years and older were negatively associated with CBC.

CONCLUSION: This study provides the first investigation of CBC and DFI risk factors among PBC survivors in Iran. Age was found to be negatively associated with CBC development particularly after the age of 60, indicating the necessity of tracking CBC survivors carefully in this age group.}, } @article {pmid37914605, year = {2024}, author = {Shuman, E and Goldenberg, A and Saguy, T and Halperin, E and van Zomeren, M}, title = {When Are Social Protests Effective?.}, journal = {Trends in cognitive sciences}, volume = {28}, number = {3}, pages = {252-263}, doi = {10.1016/j.tics.2023.10.003}, pmid = {37914605}, issn = {1879-307X}, abstract = {Around the world, people engage in social protests aimed at addressing major societal problems. Certain protests have led to significant progress, yet other protests have resulted in little demonstrable change. We introduce a framework for evaluating the effectiveness of social protest made up of three components: (i) what types of action are being considered; (ii) what target audience is being affected; and (iii) what outcomes are being evaluated? We then review relevant research to suggest how the framework can help synthesize conflicting findings in the literature. This synthesis points to two key conclusions: that nonviolent protests are effective at mobilizing sympathizers to support the cause, whereas more disruptive protests can motivate support for policy change among resistant individuals.}, } @article {pmid37910521, year = {2023}, author = {Imamichi, T and Chen, Q and Sowrirajan, B and Yang, J and Laverdure, S and Marquez, M and Mele, AR and Watkins, C and Adelsberger, JW and Higgins, J and Sui, H}, title = {Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, autophagy, and YB-1 independent manner.}, journal = {PloS one}, volume = {18}, number = {11}, pages = {e0287829}, pmid = {37910521}, issn = {1932-6203}, support = {HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Interleukin-27 ; *HIV Infections ; Virus Internalization ; *HIV-1 ; Interleukins/metabolism ; Monocytes ; Autophagy/genetics ; DNA/metabolism ; Dendritic Cells/metabolism ; Virus Replication ; Spectrin/metabolism ; }, abstract = {Interleukin (IL)-27, a member of the IL-12 family of cytokines, induces human immunodeficiency virus (HIV)-resistant monocyte-derived macrophages and T cells. This resistance is mediated via the downregulation of spectrin beta, non-erythrocytic 1 (SPTBN1), induction of autophagy, or suppression of the acetylation of Y-box binding protein-1 (YB-1); however, the role of IL-27 administration during the induction of immature monocyte-derived dendritic cells (iDC) is poorly investigated. In the current study, we investigated the function of IL-27-induced iDC (27DC) on HIV infection. 27DC inhibited HIV infection by 95 ± 3% without significant changes in the expression of CD4, CCR5, and SPTBN1 expression, autophagy induction and acetylation of YB-1 compared to iDC. An HIV proviral DNA copy number assay displayed that 27DC suppressed reverse transcriptase (RT) reaction without influencing the virus entry. A DNA microarray analysis was performed to identify the differentially expressed genes between 27DC and iDC. Compared to iDC, 51 genes were differentially expressed in 27DC, with more than 3-fold changes in four independent donors. Cross-reference analysis with the reported 2,214 HIV regulatory host genes identified nine genes as potential interests: Ankyrin repeat domain 22, Guanylate binding protein (GBP)-1, -2, -4, -5, Stabilin 1, Serpin family G member 1 (SERPING1), Interferon alpha inducible protein 6, and Interferon-induced protein with tetratricopeptide repeats 3. A knock-down study using si-RNA failed to determine a key factor associated with the anti-HIV activity due to the induction of robust amounts of off-target effects. Overexpression of each protein in cells had no impact on HIV infection. Thus, we could not define the mechanism of the anti-HIV effect in 27DC. However, our findings indicated that IL-27 differentiates monocytes into HIV-resistant DC, and the inhibitory mechanism differs from IL-27-induced HIV-resistant macrophages and T cells.}, } @article {pmid37908910, year = {2023}, author = {Malik, M and Yasmin, S and Kumar, A and Hassan, Y and Rizvi, Y and Iffat, }, title = {Can Artificial Intelligence Beat Humans in Detecting Breast Malignancy on Mammograms?.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e46208}, pmid = {37908910}, issn = {2168-8184}, abstract = {BACKGROUND: The study was aimed at identifying how useful Computer-Aided Detection (CAD) could be in reducing false-negative reporting in mammography and early detection of breast cancer at an early stage as the best protection is early detection.

MATERIALS AND METHODS: This retrospective study was conducted in a tertiary care setup of Atomic Energy Cancer Hospital, Nuclear Medicine, Oncology and Radiotherapy Institute (AECH-NORI), where 33 patients with suspicious findings on mammography and subsequent biopsy-proven malignancy were included. The findings of mammography including the lesion type, breast parenchymal density, and sensitivity of CAD detection, as well as the final biopsy results, were recorded. A second group of 40 normal screening mammograms was also included who had no symptoms, had Breast Imaging-Reporting and Data System category I(BI-RADS I) mammograms, and had no pathology identified on correlative sonomammography as well.

RESULTS: A total of 35 masses, 11 pleomorphic clusters of microcalcification, five clustered foci of macrocalcification, and nine lesions with pleomorphic clusters of microcalcification and two with pleomorphic clusters of microcalcification only were included. The CAD system was able to identify 26 masses (74%), eight lesions with pleomorphic clusters of microcalcification (72%), five foci of macrocalcification (100%), six lesions with pleomorphic clusters of microcalcification (66%), and two pleomorphic clusters of microcalcification without formed mass (100%). The overall sensitivity of the CAD system was 75.8%. CAD was able to identify 13 out of 16 masses with invasive ductal carcinoma (81.3%), eight out of nine lesions proven as invasive ductal carcinoma with ductal carcinoma in situ (DCIS) (88.9%), two out of five masses with invasive lobular carcinoma (40%), four out of four masses with invasive mammary carcinoma (100%), and zero out of one lesion identified as medullary carcinoma (0%). There was 100% detection for pleomorphic clusters of microcalcification without formed mass with CAD marking two out of two mammograms.

CONCLUSION: CAD performed better with combined lesions, accurately marked pleomorphic clusters of microcalcification, and identified small lesions in predominant fibrofatty parenchymal density but was not reliable in dense breast, areas of asymmetric increased density, summation artifacts, edematous breast parenchyma, and retroareolar lesions. It also performed poorly with ill-defined lesions of invasive lobular carcinoma. Human intelligence hence beats CAD for the diagnosis of breast malignancy in mammograms as per our experience.}, } @article {pmid37900827, year = {2023}, author = {Heng, YJ and Zhang, KJ and Valero, MG and Baker, GM and Fein-Zachary, VJ and Irwig, MS and Wulf, GM}, title = {Invasive Ductal Carcinoma of the Breast in a Transgender Man: A Case Report.}, journal = {Case reports in oncology}, volume = {16}, number = {1}, pages = {811-817}, pmid = {37900827}, issn = {1662-6575}, support = {P50 CA168504/CA/NCI NIH HHS/United States ; R01 CA226776/CA/NCI NIH HHS/United States ; R21 CA267088/CA/NCI NIH HHS/United States ; }, abstract = {There is limited literature about breast cancer in the transgender population. Very little is known about how gender-affirming hormone therapy affects their breast cancer risk. On the other end, for those diagnosed with breast cancer, there are no clinical guidelines to manage their breast cancer, specifically, how to manage their gender-affirming hormone therapy during breast cancer treatment. Here, we report a 52-year-old transman diagnosed with a grade 2 invasive ductal carcinoma (ER+/PR+/HER2-), and ductal carcinoma in situ (DCIS) of intermediate grade. We discussed his risk factors as well as treatment options.}, } @article {pmid37900789, year = {2023}, author = {Mostafa, S and Habib, MB and Ahmed, N and Sawaf, B and Sadik, N and Abdulhadi, AM}, title = {Large Ascites in a Cirrhotic Patient Reveal an Isolated and Late Metastasis of Ductal Breast Cancer: A Case Study.}, journal = {Case reports in oncology}, volume = {16}, number = {1}, pages = {585-590}, pmid = {37900789}, issn = {1662-6575}, abstract = {Breast cancer is the most prevalent cancer in women worldwide, and its prevalence has increased since the introduction of screening programs. Most cases are discovered at an early stage; however, despite effective treatment, some cases progress to metastasis. The most common breast cancer metastatic locations are the bone, liver, and lungs. Ascites malignant due to peritoneal involvement is a rare manifestation of metastatic breast cancer. After 8 years of well-controlled breast cancer, we report a 54-year-old woman who presents with malignant ascites and is known to have cirrhosis of the liver.}, } @article {pmid37897648, year = {2024}, author = {Zhao, YY and Ge, HJ and Yang, WT and Shao, ZM and Hao, S}, title = {Secretory breast carcinoma: clinicopathological features and prognosis of 52 patients.}, journal = {Breast cancer research and treatment}, volume = {203}, number = {3}, pages = {543-551}, pmid = {37897648}, issn = {1573-7217}, support = {82203789//National Natural Science Foundation of China/ ; 82102683//National Natural Science Foundation of China/ ; }, mesh = {Male ; Humans ; Female ; Middle Aged ; *Breast Neoplasms/diagnosis/genetics/therapy ; *Carcinoma, Ductal, Breast/pathology ; In Situ Hybridization, Fluorescence ; China ; Prognosis ; *Triple Negative Breast Neoplasms/pathology ; *Carcinoma ; }, abstract = {PURPOSE: Secretory breast carcinoma is a rare histological subtype of invasive breast cancer and considered with an indolent clinical behavior. This study was conducted to analyze the clinicopathological features of patients with secretory breast carcinoma (SBC), explore the outcome, and compare the prognostic difference with invasive ductal breast carcinoma (IDC). METHODS AND MATERIALS: Patients with SBC diagnosed between 2006 and 2017 from Fudan University Shanghai Cancer Center were included in the study, excluding patients with previous malignant tumor history and incomplete clinical data or follow-up records. Peculiar clinicopathological and immunohistochemical features of the cases were fully described. Clinical data of 4979 cases of IDC were also evaluated during this period. After propensity score matching, prognostic analysis of SBCs and IDCs was calculated by Kaplan-Meier method and landmark analysis method.

RESULTS: The data of 52 patients diagnosed with SBC were identified from the pathological files. Among them, 47 patients were women, and 5 were men. The median age of the 52 SBCs was 46 years (mean, 48.1 years; range, 10-80 years). The tumor sizes ranged from 0.3 to 6.8 cm, with a mean of 3.5 cm. Eight patients (15.4%) had positive axillary lymph node involvement. The molecular classification was mostly triple-negative breast cancer (65.4%). Fluorescence in situ hybridization confirmed the presence of ETV6::NTRK3 rearrangement in 16 of 18 cases (88.9%). Furthermore, Kaplan-Meier survival analysis and landmark analysis demonstrated that there were no statistically significant differences in DFS and OS between SBC and IDC patients.

CONCLUSION: Although SBCs are generally associated with a favorable prognosis, our work exhibited that the clinicopathological features of SBC were partly different from former understandings, indicating that therapeutic procedure should be prudent. Further studies are necessary to fully identify the clinical behavior and predictive markers to improve diagnosis and management in this unique subtype of breast cancer.}, } @article {pmid37890687, year = {2024}, author = {Liao, H and Wang, H and Zheng, R and Yu, Y and Zhang, Y and Lv, L and Zhang, B and Chen, J}, title = {LncRNA CARMN suppresses EMT through inhibiting transcription of MMP2 activated by DHX9 in breast cancer.}, journal = {Cellular signalling}, volume = {113}, number = {}, pages = {110943}, doi = {10.1016/j.cellsig.2023.110943}, pmid = {37890687}, issn = {1873-3913}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *RNA, Long Noncoding/genetics/metabolism ; Matrix Metalloproteinase 2/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Epithelial Cells/metabolism ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; *MicroRNAs/genetics ; Neoplasm Proteins/genetics/metabolism ; DEAD-box RNA Helicases/genetics/metabolism ; }, abstract = {Long non-coding RNAs (lncRNAs) have been shown to drive cancer progression. However, the function of lncRNAs and the underlying mechanism in early-stage breast cancer(BC) have rarely been investigated. Datasets of pre-invasive ductal carcinoma in situ (DCIS), invasive ductal BC (IDC) and normal breast tissue from TCGA and GEO databases were used to conduct bioinformatics analysis. LncRNA CARMN was identified as a tumor suppressor in early-stage BC and related to a better prognosis. CARMN over-expression inhibited MMP2 mediated migration and EMT in BC. Further analysis showed that CARMN was located in the nucleus and functioned as an enhancer RNA (eRNA) in mammary epithelial cell. Mechanically, CARMN binding protein DHX9 was identified by RNA pull-down and mass spectrometry (MS) assays and it also bound to the MMP2 promoter to activate its transcription. As a decoy, CARMN competitively bound to DHX9 and blocked MMP2 transcriptional activation, thereby inhibiting metastasis and EMT of BC cells. These findings reveal the important role of CARMN as a tumor suppressor in the metastasis and a potential biomarker for progression in early-stage BC.}, } @article {pmid37879875, year = {2023}, author = {Wang, HY and Li, SJ and Zhang, AL and Ni, XC}, title = {[Identification of lymph node metastasis related genes in prostate cancer using weighted gene co-expression network analysis].}, journal = {Zhonghua yi xue za zhi}, volume = {103}, number = {40}, pages = {3204-3210}, doi = {10.3760/cma.j.cn112137-20230531-00902}, pmid = {37879875}, issn = {0376-2491}, mesh = {Male ; Humans ; Lymphatic Metastasis ; *Nomograms ; *Prostatic Neoplasms/genetics/pathology ; Neoplasm Grading ; Risk Factors ; }, abstract = {Objective: To explore the molecular markers related to lymph node metastasis of prostate cancer (PCa) based on bioinformatics technology and carry out clinical verification. Methods: The differentially expressed genes of PCa with lymph node metastasis were screened from geo data, and the hub genes of the gene co expression network were constructed. The hub genes were incorporated into the support vector machine model to evaluate its prediction efficiency. The hub genes were verified in the TCGA data set and analyzed for immune infiltration. The clinical data of 80 patients with prostate cancer in the Fourth Hospital of Hebei Medical University from January 2019 to December 2022 were collected. The logistic risk model was used to evaluate the prediction efficiency of hub gene metastasis. Results: Five hub genes (GSK3B, TP53, PSMC6, SUMO1, PIK3CA) were identified, and the support vector machine model constructed by them had good diagnostic value (the accuracy rate was 83.87%). TCGA validation results showed that only PSMC6 was significantly differentially expressed in PCa tissues with lymph node metastasis (P<0.001). The results of immune infiltration analysis showed that the expression of PSMC6 was significantly correlated with 9 kinds of immune cells (B cells, DC, IDC, etc.). Clinical information analysis showed that the expression of PSMC6 was significantly correlated with lymph node metastasis, PSA value, T stage and Gleason score (P<0.01). Univariate logistic results showed that T stage (OR=3.230, 95%CI:1.192-8.757, P=0.021), Gleason score (OR=4.627, 95%CI:2.212-9.677, P<0.001), PSMC6 (OR=25.235, 95%CI:5.326-119.560, P<0.001) could be used as predictors of lymph node metastasis. Multivariate logistic analysis showed that PSMC6 (OR=16.537, 95%CI:2.928-93.393, P=0.001) could be used as an independent risk factor for predicting lymph node metastasis. Conclusion: PSMC6 may be used as a potential molecular marker for judging lymph node metastasis in patients with PCa.}, } @article {pmid37874803, year = {2023}, author = {Coskunpinar, E and Tiryakioglu, DZ and Abaci, N and Tukenmez, M and Pence, S}, title = {Investigation of the miR-637 and miR-523-5p as candidate biomarkers in breast cancer.}, journal = {Bratislavske lekarske listy}, volume = {124}, number = {11}, pages = {814-820}, doi = {10.4149/BLL_2023_125}, pmid = {37874803}, issn = {0006-9248}, mesh = {Humans ; Female ; *Fibroadenoma/diagnosis/genetics ; *Breast Neoplasms/diagnosis/genetics/pathology ; *MicroRNAs/metabolism ; Biomarkers ; *Carcinoma, Ductal ; Biomarkers, Tumor/genetics ; Gene Expression Profiling ; }, abstract = {OBJECTIVES: The distinction of benign lesions from malign tumors is crucial for the diagnosis and treatment of breast cancers.

BACKGROUND: The aim of this study was to investigate the use of miRNAs as plasma biomarkers for the discrimination of malign and benign breast tumors.

METHODS: Whole blood samples obtained from 40 individuals in 3 groups designated as invasive ductal carcinoma group, fibroadenoma group and healthy controls were included in this study. The expression levels of 372 miRNAs were determined using RT-PCR.  Results: The comparison of fibroadenoma group with healthy controls revealed an upregulation of thirty miRNAs and downregulation of twenty-nine miRNAs. The comparison of invasive ductal carcinoma (IDC) group with controls has shown that eight miRNAs were upregulated while eleven miRNAs were downregulated. When comparing IDC and fibroadenoma groups, 15 miRNAs were found to be upregulated, while 10 miRNAs were downregulated. Further analysis of these miRNAs aimed to determine their power in distinguishing  IDCs from fibroadenomas. Among the miRNAs analyzed, seven miRNAs have shown sufficient discriminative power, of which three miRNAs, namely miR-637, miR-523-5p and miR-490-3p, have shown a significantly high discriminative power.

CONCLUSIONS: Circulating miR-637 and miR-523-5p combination maybe used to discriminate between invasive ductal carcinomas and fibroadenomas. (Tab. 9, Fig. 4, Ref. 30).}, } @article {pmid37874736, year = {2025}, author = {Munro-Kramer, ML and Loder, C and Kalpakjian, C and Martin, KE and Hess, A and Smith, E and Parrish, D and Ernst, S}, title = {Creating a tool to understand university students' experiences regarding inappropriate, disrespectful, and coercive (IDC) healthcare interactions.}, journal = {Journal of American college health : J of ACH}, volume = {73}, number = {5}, pages = {2226-2235}, doi = {10.1080/07448481.2023.2272190}, pmid = {37874736}, issn = {1940-3208}, mesh = {Humans ; *Students/psychology/statistics & numerical data ; Female ; Male ; Universities/organization & administration ; *Coercion ; Adult ; Qualitative Research ; Focus Groups ; Young Adult ; Surveys and Questionnaires ; *Professional-Patient Relations ; Adolescent ; }, abstract = {Objective: The purpose of this study was to develop a survey tool to capture inappropriate, disrespectful, and coercive (IDC) interactions with healthcare providers among a diverse sample of university students. Participants: Participants were university students at one large Midwestern public university. Methods: An exploratory qualitative approach was used to create a survey tool to capture IDC interactions. Results: In Phase I, 9 focus group discussions (FGDs) and 3 individual interviews were conducted with a total of 38 participants. In Phase II, 18 participants completed cognitive interviews. Themes across all FGDs included: (1) communication; (2) respect for identity; (3) institutional practices; (4) power imbalances; and (5) lack of patient education and empowerment. Queer participants discussed unique considerations of how queer identity influences one's IDC healthcare experiences. Conclusions: This study resulted in the development of a 64-70 item tool, the IDC Survey, to measure the prevalence and characteristics of IDC healthcare interactions.}, } @article {pmid37873952, year = {2024}, author = {Patel, K and Rao, DM and Sundersingh, S and Velusami, S and Rajkumar, T and Nair, B and Pandey, A and Chatterjee, A and Mani, S and Gowda, H}, title = {MicroRNA Expression Profile in Early-Stage Breast Cancers.}, journal = {MicroRNA (Shariqah, United Arab Emirates)}, volume = {13}, number = {1}, pages = {71-81}, pmid = {37873952}, issn = {2211-5374}, support = {BT/PR8152/AGR/36/739/2013//Department of Biotechnology, Govt. of India/ ; }, mesh = {Humans ; Female ; *MicroRNAs/genetics ; *Breast Neoplasms/genetics/pathology/mortality ; *Gene Expression Regulation, Neoplastic/genetics ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology ; Middle Aged ; Neoplasm Staging ; Gene Expression Profiling ; Biomarkers, Tumor/genetics ; Transcriptome/genetics ; }, abstract = {BACKGROUND: Breast cancer is one of the leading causes of cancer deaths in women. Early diagnosis offers the best hope for a cure. Ductal carcinoma in situ is considered a precursor of invasive ductal carcinoma of the breast. In this study, we carried out microRNA sequencing from 7 ductal carcinoma in situ (DCIS), 6 infiltrating ductal carcinomas (IDC Stage IIA) with paired normal, and 5 unpaired normal breast tissue samples.

METHODS: We have deployed miRge for microRNA analysis, DESeq for differential expression analysis, and Cytoscape for competing endogenous RNA network investigation.

RESULTS: Here, we identified 76 miRNAs that were differentially expressed in DCIS and IDC. Additionally, we provide preliminary evidence of miR-365b-3p and miR-7-1-3p being overexpressed, and miR-6507-5p, miR-487b-3p, and miR-654-3p being downregulated in DCIS relative to normal breast tissue. We also identified a miRNA miR-766-3p that was overexpressed in earlystage IDCs. The overexpression of miR-301a-3p in DCIS and IDC was confirmed in 32 independent breast cancer tissue samples.

CONCLUSION: Higher expression of miR-301a-3p is associated with poor overall survival in The Cancer Genome Atlas Breast Cancer (TCGA-BRCA) dataset, indicating that it may be associated with DCIS at high risk of progressing to IDC and warrants deeper investigation.}, } @article {pmid37872454, year = {2024}, author = {Lohani, KR and Hoskin, TL and Day, CN and Yasir, S and Boughey, JC and Degnim, AC}, title = {Lobular-Like Features and Outcomes of Mixed Invasive Ductolobular Breast Cancer (MIDLC): Insights from 54,403 Stage I-III MIDLC Patients.}, journal = {Annals of surgical oncology}, volume = {31}, number = {2}, pages = {936-946}, pmid = {37872454}, issn = {1534-4681}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery/drug therapy ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/pathology ; Mastectomy ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; }, abstract = {BACKGROUND: Mixed invasive ductolobular breast cancer (MIDLC) is a rare histological subtype of breast cancer (BC), with components of both invasive ductal cancer (IDC) and invasive lobular cancer (ILC). Its clinicopathological features and outcomes have not been well characterized.

METHOD: The National Cancer Database 2010-2017 was reviewed to identify women with stage I-III BCs. Univariate analysis was performed using Chi-square or Wilcoxon rank-sum tests and multivariable analysis with logistic regression to predict surgical decisions. Survival was assessed using multivariable Cox proportional hazards regression analysis.

RESULTS: We identified 955,828 women with stage I-III BCs (5.7% MIDLC, 10.3% ILC, and 84.0% IDC). MIDLC was more like ILC than IDC in terms of multicentricity (14.2% MIDLC, 13.0% ILC, 10.0% IDC), hormone receptor positivity (96.6% MIDLC, 98.2% ILC, 81.2% IDC), and use of neoadjuvant chemotherapy (NAC; 5.8% MIDLC, 5.2% ILC, 10.8% IDC). 744,607 women underwent upfront surgery. The mastectomy rates were 42.3% for MIDLC, 46.5% for ILC, and 33.3% for IDC (all p < 0.001). With 5.5 years of median follow-up, the adjusted overall survival in the upfront surgery hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) biological subgroup was better in MIDLC (hazard ratio 0.88, p < 0.001) and ILC (hazard ratio 0.91, p < 0.001) than in IDC. Like ILC, MIDLC also had a lower pathological complete response to NAC than IDC (12.3% MIDLC, 7.3% ILC, 28.6% IDC).

CONCLUSIONS: MIDLC displays a mixed pattern of characteristics favoring features of ILC compared with IDC, with favorable 5-year overall survival compared with IDC within the HR+/HER2- subtype who underwent upfront surgery.}, } @article {pmid37871884, year = {2024}, author = {Grendarova, P and Roumeliotis, M and Quirk, S and Phan, T and Liu, HW and Craighead, P and Lesiuk, M and Pinilla, J and Long, K and Olivotto, IA}, title = {Accelerated Partial Breast Irradiation Using 5 Daily Fractions: A Prospective, Phase 2, Multicenter Trial of Cosmetic Outcomes and Toxicity-ACCEL Final Results.}, journal = {International journal of radiation oncology, biology, physics}, volume = {118}, number = {4}, pages = {1041-1048}, doi = {10.1016/j.ijrobp.2023.10.016}, pmid = {37871884}, issn = {1879-355X}, mesh = {Female ; Humans ; Prospective Studies ; Breast/radiation effects ; Mastectomy, Segmental/methods ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; *Breast Neoplasms/radiotherapy/surgery ; Treatment Outcome ; }, abstract = {PURPOSE: This study investigated the cosmetic degradation and toxicity for an accelerated partial breast irradiation (APBI) prescription delivered in 5 fractions over 1 week and compared the outcomes with those of whole breast irradiation (WBI).

METHODS AND MATERIALS: The trial was a multicenter, single-arm, phase 2 prospective cohort study. Eligible women 50 years of age or older with estrogen receptor-positive and human epidermal growth factor receptor 2-negative invasive ductal carcinoma or ductal carcinoma in situ after breast-conserving surgery received 27 Gy in 5 daily fractions of APBI. The primary endpoint was noninferiority of 2-year cosmesis using the RAPID trial's WBI arm as the control arm. A global consensus cosmetic score using a European Organisation for Research and Treatment of Cancer rating scale score of excellent, good, fair, or poor for each patient at baseline and 2 years was generated by a panel of 5 radiation oncologists using photographs of treated and untreated breasts.

RESULTS: From 2016 to 2019, 298 eligible women were enrolled. By the 2-year follow-up, 76 patients had been lost or withdrawn and 3 had died, resulting in 219 patients available for complete, 2-year photographic cosmetic evaluation. The median follow-up for all participants was 4.7 years (IQR, 3.8-5.5 years). No patient had a fair or poor cosmetic score at the 2-year evaluation. Cosmesis was better or unchanged for 97% of patients and worse for 3% (excellent to good), and no cosmetic failures occurred. The confidence intervals were 0.88 (0.86-0.90) and 1.00 (0.99-1.00) for the RAPID and ACCEL trials, respectively.

CONCLUSIONS: Cosmetic degradation with 5 daily treatments of the ACCEL trial's APBI intervention is noninferior to the WBI arm of the RAPID trial.}, } @article {pmid37870280, year = {2023}, author = {Aydos, U and Ateş, SG and Kurukahvecioğlu, O and Akdemir, ÜÖ and Uyar Göçün, P and Atay, LÖ}, title = {Relationship Between Metabolic Activity, Cellularity, Histopathological Features of Primary Tumors and Distant Metastatic Potential in Breast Cancer.}, journal = {Molecular imaging and radionuclide therapy}, volume = {32}, number = {3}, pages = {195-205}, pmid = {37870280}, issn = {2146-1414}, abstract = {OBJECTIVES: The aim of this study was to evaluate the relationship between the types of distant metastatic spread, histopathological features, and imaging features of primary tumor on positron emission tomography/magnetic resonance imaging (PET/MRI) for primary staging in newly diagnosed breast invasive ductal carcinoma (IDC) patients.

METHODS: Data from 289 female patients were retrospectively evaluated. Maximum standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and minimum apparent diffusion coefficient (ADCmin) values of primary tumors were obtained from PET/MRI. The patients were grouped as non-metastatic, oligometastatic (1-5 metastatic lesions) and multimetastatic (>5 metastatic lesions) disease according to the number of distant metastases, and divided into two groups as isolated bone metastasis (IBM) and mixed/soft tissue metastasis (M-SM) groups according to the sites of metastatic spread.

RESULTS: Metabolic parameters had higher values and ADCmin had lower values in the multimetastatic and oligometastatic groups than in the non-metastatic group. MTV was the only parameter that showed significant difference between the multimetastatic and oligometastatic groups. MTV and TLG were significantly higher in the M-SM group than in the IBM group. [18]F-fluorodeoxyglucose PET parameters had significantly higher values in grade 3, hormone receptor negative, human epidermal growth factor receptor 2 positive, triple negative, and highly proliferative (Ki-67 ≥14%) tumors. The prediction models that included imaging parameters to predict the presence of distant metastasis had higher discriminatory powers than the prediction models that included only histopathological parameters.

CONCLUSION: Primary tumors with higher metabolic-glycolytic activity and higher cellularity were more aggressive and had higher metastatic potential in breast IDC. Compared with histopathological parameters alone, the combination of imaging parameters and histopathological features of primary tumors may help to better understand tumor biology and behavior.}, } @article {pmid37869933, year = {2024}, author = {Bódis, K and Breuer, S and Crepzia-Pevzner, A and Zaharia, OP and Schön, M and Saatmann, N and Altenhofen, D and Springer, C and Szendroedi, J and Wagner, R and Al-Hasani, H and Roden, M and Pesta, D and Chadt, A and , }, title = {Impact of physical fitness and exercise training on subcutaneous adipose tissue beiging markers in humans with and without diabetes and a high-fat diet-fed mouse model.}, journal = {Diabetes, obesity & metabolism}, volume = {26}, number = {1}, pages = {339-350}, doi = {10.1111/dom.15322}, pmid = {37869933}, issn = {1463-1326}, support = {CH1659//Deutschen Diabetes Stiftung AllgemeineProjektförderung/ ; //EFSD/Novo Nordisk Programme for Diabetes Research/ ; //European Funds for Regional Development/ ; //German Center for Diabetes Research/ ; //German Federal Ministry of Education and Research/ ; //German Federal Ministry of Health/ ; 236177352//German Research Foundation/ ; //Ministry of Culture and Science of the state North Rhine-Westphalia/ ; //Schmutzler Stiftung/ ; }, mesh = {Humans ; Mice ; Animals ; *Diet, High-Fat ; Motor Activity ; *Diabetes Mellitus, Type 2/metabolism ; Subcutaneous Fat/metabolism ; Adipose Tissue, White/metabolism ; Adipose Tissue ; Physical Fitness ; Glucose/metabolism ; }, abstract = {AIMS: Exercise training induces white adipose tissue (WAT) beiging and improves glucose homeostasis and mitochondrial function in rodents. This could be relevant for type 2 diabetes in humans, but the effect of physical fitness on beiging of subcutaneous WAT (scWAT) remains unclear. This translational study investigates if beiging of scWAT associates with physical fitness in healthy humans and recent-onset type 2 diabetes and if a voluntary running wheel intervention is sufficient to induce beiging in mice.

MATERIALS AND METHODS: Gene expression levels of established beiging markers were measured in scWAT biopsies of humans with (n = 28) or without type 2 diabetes (n = 28), stratified by spiroergometry into low (L-FIT; n = 14 each) and high physical fitness (H-FIT; n = 14 each). High-fat diet-fed FVB/N mice underwent voluntary wheel running, treadmill training or no training (n = 8 each group). Following the training intervention, mitochondrial respiration and content of scWAT were assessed by high-resolution respirometry and citrate synthase activity, respectively.

RESULTS: Secreted CD137 antigen (Tnfrsf9/Cd137) expression was three-fold higher in glucose-tolerant H-FIT than in L-FIT, but not different between H-FIT and L-FIT with type 2 diabetes. In mice, both training modalities increased Cd137 expression and enhanced mitochondrial content without changing respiration in scWAT. Treadmill but not voluntary wheel running led to improved whole-body insulin sensitivity.

CONCLUSIONS: Higher physical fitness and different exercise interventions associated with higher gene expression levels of the beiging marker CD137 in healthy humans and mice on a high-fat diet. Humans with recent-onset type 2 diabetes show an impaired adipose tissue-specific response to physical activity.}, } @article {pmid37869296, year = {2023}, author = {Chen, W and Liu, F and Wang, R and Qi, M and Zhang, J and Liu, X and Song, S}, title = {End-to-end deep learning radiomics: development and validation of a novel attention-based aggregate convolutional neural network to distinguish breast diffuse large B-cell lymphoma from breast invasive ductal carcinoma.}, journal = {Quantitative imaging in medicine and surgery}, volume = {13}, number = {10}, pages = {6598-6614}, pmid = {37869296}, issn = {2223-4292}, abstract = {BACKGROUND: Apart from invasive pathological examination, there is no effective method to differentiate breast diffuse large B-cell lymphoma (DLBCL) from breast invasive ductal carcinoma (IDC). In this study, we aimed to develop and validate an effective deep learning radiomics model to discriminate between DLBCL and IDC.

METHODS: A total of 324 breast nodules from 236 patients with baseline [18]F-fluorodeoxyglucose ([18]F-FDG) positron emission tomography/computed tomography (PET/CT) were retrospectively analyzed. After grouping breast DLBCL and breast IDC patients, external and internal datasets were divided according to the data collected by different centers. Preprocessing was then used to process the original PET/CT images and an attention-based aggregate convolutional neural network (AACNN) model was designed. The AACNN model was trained using patches of CT or PET tumor images and optimized with an improved loss function. The final ensemble predictive model was built using distance weight voting. Finally, the model performance was evaluated and statistically verified.

RESULTS: A total of 249 breast nodules from Fudan University Shanghai Cancer Center (FUSCC) and 75 breast nodules from Shanghai Proton and Heavy Ion Center (SPHIC) were selected as internal and external datasets, respectively. On the internal testing, our method yielded an area under the curve (AUC), accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and harmonic mean of precision and sensitivity (F1) of 0.886, 83.0%, 80.9%, 85.0%, 84.8%, 81.2%, and 0.828, respectively. Meanwhile on the external testing, the results were 0.788, 71.6%, 61.4%, 84.7%, 84.0%, 62.6%, and 0.709, respectively.

CONCLUSIONS: Our study outlines a deep learning radiomics method which can automatically, noninvasively, and accurately differentiate breast DLBCL from breast IDC, which will be more in line with the needs and strategies of precision medicine, individualized diagnosis, and treatment.}, } @article {pmid37856936, year = {2023}, author = {Mansour, O and Kazem, A and El Wakil, A}, title = {Assessment of breast cytoarchitecture and its associated axillary lymph node status under normal and pathological conditions in Egyptian women.}, journal = {Tissue & cell}, volume = {85}, number = {}, pages = {102244}, doi = {10.1016/j.tice.2023.102244}, pmid = {37856936}, issn = {1532-3072}, mesh = {Female ; Humans ; *Carcinoma, Ductal, Breast ; Egypt ; Retrospective Studies ; *Breast Neoplasms/pathology ; Lymph Nodes/metabolism/pathology ; }, abstract = {OBJECTIVE: Herein, we compare the features of neoplastic cancer cells in invasive ductal carcinoma (IDC) grade II and III patients to their corresponding normal cells both in breast and axillary lymph node (ALN) tissues.

METHODS: A retrospective cohort of 70 female breast cancer patients enrolled between 2018 and 2020 at Medical Research Institute, Alexandria University, Egypt, was analyzed for clinicopathological features presentation. Fresh tiny pieces of breast tissue and its associated ALN tissues were then processed to investigate the morphological appearance by scanning electron microscopy. Moreover, the histological architecture of tissue sections stained with hematoxylin and eosin was studied by light microscope, while the characterization of the ultrastructure features of breast and ALN tissues was analyzed by transmission electron microscopy.

RESULTS: Clinicopathological presentation of patients revealed that the Egyptian female breast cancer population adhered to the global trends of breast cancer disease with elevated incidence rate among postmenopausal women (61.3%), high frequency of IDC (95.7%), and increased ALN metastasis (65.7%). The percentage of estrogen receptor alpha (ERα) and human epidermal growth factor receptor 2 (HER2) expression, as key indicators for carcinogenesis and disease progression was 87.1% and 55.8%, respectively. The present study points to the observed discrepancies among the investigated variables in the diagnostic separation between IDC grade II and grade III. Ductal epithelial cells organization, nuclei size and irregularity, chromatin amount and uniformity, mitochondrial abundance and dysfunction were differentially manifested in IDC grades. Moreover, aberrations in the cellular organelles like lysosomes, endoplasmic reticulum, and lipid droplets vary according to the grade of IDC and the aggressiveness of the invasive breast cancer.

CONCLUSIONS: To sum up, this study emphasizes the importance of accurate specimen evaluation for treatment choice and decision.}, } @article {pmid37855288, year = {2024}, author = {Mohammed, BT and Uzodi, N and Gotimukul, A and Kokebie, R}, title = {Case Report of MPO+ ANCA Vasculitis with Pauci-immune GN Associated with Invasive Ductal Carcinoma of the Breast.}, journal = {Current rheumatology reviews}, volume = {20}, number = {2}, pages = {213-218}, doi = {10.2174/0115733971246438230924163114}, pmid = {37855288}, issn = {1875-6360}, mesh = {Female ; Humans ; Aged ; Antibodies, Antineutrophil Cytoplasmic ; *Glomerulonephritis ; Abscess ; *Breast Neoplasms/complications ; Mastectomy ; *Vasculitis ; Peroxidase ; *Carcinoma, Ductal ; }, abstract = {BACKGROUND: Malignancy-associated vasculitis usually presents in the form of polyarteritis nodosa or leukocytoclastic vasculitis. However, ANCA vasculitis associated with malignancy is rare. Here, we present a case of MPO+ ANCA vasculitis with pauci-immune GN associated with invasive ductal carcinoma of the breast.

CASE PRESENTATION: A 66-year-old female with a history of rheumatoid arthritis, Hashimoto's thyroiditis, and psoriasis presented with multiple joint pain, body aches, petechial rash, paresthesia and numbness, and deranged renal function a month after diagnosis of localized left breast invasive ductal carcinoma. Renal biopsy showed crescentic pauci-immune glomerulonephritis, and serology was positive for Perinuclear Antineutrophil Cytoplasmic Antibody (P-ANCA) and myeloperoxidase (MPO). The disease course was complicated by diverticulitis with peritonitis and intraperitoneal abscess collection, which required laparoscopic peritoneal lavage and additional interventional radiology-guided drainage of the abscess. We treated the patient successfully with steroids, rituximab, and mastectomy for left breast malignant lesions, resulting in the resolution of symptoms, normalization of inflammatory markers, and ANCA seroconversion.

CONCLUSION: Treating ANCA-associated Vasculitis (AAV) in surgical emergencies like bowel perforation can be challenging. Individualized treatment strategy tailored to patients' acute needs is crucial. In this case, we considered malignancy-associated vasculitis and pursued treatment that fit the patient's clinical situation in a multidisciplinary approach.}, } @article {pmid37848693, year = {2024}, author = {Özdemir, A and Güven, M and Binici, S and Uygur, S and Toktaş, O}, title = {Impact of 18F-FDG PET/CT in the management decisions of breast cancer board on early-stage breast cancer.}, journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {26}, number = {5}, pages = {1139-1146}, pmid = {37848693}, issn = {1699-3055}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/therapy ; Positron Emission Tomography Computed Tomography/methods ; Fluorodeoxyglucose F18 ; Retrospective Studies ; Neoplasm Staging ; Positron-Emission Tomography/methods ; Radiopharmaceuticals ; }, abstract = {PURPOSE: Breast cancer is the most common malignancy accounting for 11.7% of all cancer cases, with a rising incidence rate. Various diagnostic methods, including 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT), play a crucial role in breast cancer diagnosis and staging. However, the unnecessary use of advanced imaging techniques such as PET/CT in early-stage breast cancer can have negative effects on both economics and patients. We aimed to investigate the impact of PET/CT on the management decisions of early-stage breast cancer patients by the breast cancer tumor board.

METHODS: A retrospective analysis was performed on a cohort of 81 patients with early-stage breast cancer who were evaluated by breast cancer tumor board from January 2015 to December 2020. Demographic, clinical, and radiographic data, along with surgical procedures and treatment options, were documented and analyzed.

RESULTS: The results showed that 18F-FDG PET/CT had a moderate impact on treatment decisions of breast cancer tumor board, as only treatment decisions were changed in 14,86% of the patients. The surgical procedure decision of breast cancer tumor board changed in 12.35% of patients, while 87.65% of patients had consistent decisions before and after PET/CT. Pathological assessments revealed invasive ductal carcinoma as the most prevalent tumor type, and molecular subtypes were predominantly luminal B. PET/CT use had limited impact on surgical procedures and did not significantly alter treatment decisions of breast cancer tumor board in this early-stage breast cancer cohort.

CONCLUSIONS: In conclusion, this study highlights the importance of adherence to the guidelines and appropriate use of PET/CT in early-stage breast cancer management. PET/CT should be reserved for cases where it is clinically warranted, considering the potential economic burden and minimal impact on treatment decisions of breast cancer tumor board in this patient population.}, } @article {pmid37847513, year = {2024}, author = {Zhao, J and Xu, N and Zhu, S and Nie, L and Zhang, M and Zheng, L and Cai, D and Sun, X and Chen, J and Dai, J and Ni, Y and Wang, Z and Zhang, X and Liang, J and Chen, Y and Hu, X and Pan, X and Yin, X and Liu, H and Zhao, F and Zhang, B and Chen, H and Miao, J and Qin, C and Zhao, X and Yao, J and Liu, Z and Liao, B and Wei, Q and Li, X and Liu, J and Gao, AC and Huang, H and Shen, P and Chen, N and Zeng, H and Sun, G}, title = {Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.}, journal = {Cancer research}, volume = {84}, number = {1}, pages = {154-167}, doi = {10.1158/0008-5472.CAN-23-1176}, pmid = {37847513}, issn = {1538-7445}, support = {82203110//National Natural Science Foundation of China/ ; 82172785//National Natural Science Foundation of China/ ; 81974398//National Natural Science Foundation of China/ ; ZYJC21020//1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University/ ; 2021YFS0119//Science and Technology Support Program of Sichuan Province/ ; 2022-12M-C&T-B-098//Clinical and Translational Medicine Research Project, Chinese Academy of Mediccal Sciences/ ; mnzl202002//Beijing Bethune Charitable Foundation/ ; mnzl202007//Beijing Bethune Charitable Foundation/ ; 2023HXBH024//Postdoctoral Research and Development Fund of West China Hospital of Sichuan University/ ; }, mesh = {Male ; Humans ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Prostate/pathology ; *Adenocarcinoma/genetics/pathology ; *Prostatic Neoplasms/pathology ; Genomics ; Neoplasm Grading ; }, abstract = {UNLABELLED: Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally coexists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared with concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathologic heterogeneity between IDC-P and PAC. Compared with coexisting PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 patients with metastatic prostate cancer revealed that IDC-P carriers with lower risk International Society of Urological Pathology (ISUP) grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P.

SIGNIFICANCE: The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.}, } @article {pmid37835856, year = {2023}, author = {Khalid, A and Mehmood, A and Alabrah, A and Alkhamees, BF and Amin, F and AlSalman, H and Choi, GS}, title = {Breast Cancer Detection and Prevention Using Machine Learning.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {19}, pages = {}, pmid = {37835856}, issn = {2075-4418}, abstract = {Breast cancer is a common cause of female mortality in developing countries. Early detection and treatment are crucial for successful outcomes. Breast cancer develops from breast cells and is considered a leading cause of death in women. This disease is classified into two subtypes: invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS). The advancements in artificial intelligence (AI) and machine learning (ML) techniques have made it possible to develop more accurate and reliable models for diagnosing and treating this disease. From the literature, it is evident that the incorporation of MRI and convolutional neural networks (CNNs) is helpful in breast cancer detection and prevention. In addition, the detection strategies have shown promise in identifying cancerous cells. The CNN Improvements for Breast Cancer Classification (CNNI-BCC) model helps doctors spot breast cancer using a trained deep learning neural network system to categorize breast cancer subtypes. However, they require significant computing power for imaging methods and preprocessing. Therefore, in this research, we proposed an efficient deep learning model that is capable of recognizing breast cancer in computerized mammograms of varying densities. Our research relied on three distinct modules for feature selection: the removal of low-variance features, univariate feature selection, and recursive feature elimination. The craniocaudally and medial-lateral views of mammograms are incorporated. We tested it with a large dataset of 3002 merged pictures gathered from 1501 individuals who had digital mammography performed between February 2007 and May 2015. In this paper, we applied six different categorization models for the diagnosis of breast cancer, including the random forest (RF), decision tree (DT), k-nearest neighbors (KNN), logistic regression (LR), support vector classifier (SVC), and linear support vector classifier (linear SVC). The simulation results prove that our proposed model is highly efficient, as it requires less computational power and is highly accurate.}, } @article {pmid37835373, year = {2023}, author = {Porter, BA and Frerich, C and Lainé, M and Clark, AB and Durdana, I and Lee, J and Taya, M and Sahoo, S and Greene, GL and Bennett, L and Conzen, SD}, title = {Glucocorticoid Receptor Activation in Lobular Breast Cancer Is Associated with Reduced Cell Proliferation and Promotion of Metastases.}, journal = {Cancers}, volume = {15}, number = {19}, pages = {}, pmid = {37835373}, issn = {2072-6694}, support = {P30 CA014599/CA/NCI NIH HHS/United States ; P30 CA142543/CA/NCI NIH HHS/United States ; }, abstract = {Estrogen receptor-positive (ER+) invasive lobular breast cancer (ILC) comprises about ~15% of breast cancer. ILC's unique genotypic (loss of wild type E-cadherin expression) and phenotypic (small individual round cancer cells that grow in discontinuous nests) are thought to contribute to a distinctive pattern of metastases to serosal membranes. Unlike invasive ductal carcinoma (IDC), ILC metastases often intercalate into the mesothelial layer of the peritoneum and other serosal surfaces. While ER activity is a known driver of ILC proliferation, very little is known about how additional nuclear receptors contribute to ILC's distinctive biology. In ER+ IDC, we showed previously that glucocorticoid receptor (GR) activity inhibits pro-proliferative gene expression and cell proliferation. Here we examined ER+ ILC models and found that GR activation similarly reduces S-phase entry gene expression and ILC proliferation. While slowing tumor growth rate, our data also suggest that GR activation results in an enhanced metastatic phenotype through increasing integrin-encoding gene expression, extracellular matrix protein adhesion, and mesothelial cell clearance. Moreover, in an intraductal mouse mammary gland model of ILC, we found that GR expression is associated with increased bone metastases despite slowed primary mammary tumor growth. Taken together, our findings suggest GR-mediated gene expression may contribute to the unusual characteristics of ILC biology.}, } @article {pmid37833450, year = {2024}, author = {Rothschild, HT and Clelland, EN and Abel, MK and Chien, AJ and Shui, AM and Esserman, L and Khan, SA and Mukhtar, RA}, title = {The impact of histologic subtype on primary site surgery in the management of metastatic lobular versus ductal breast cancer: a population based study from the National Cancer Database (NCDB).}, journal = {Breast cancer research and treatment}, volume = {203}, number = {2}, pages = {245-256}, pmid = {37833450}, issn = {1573-7217}, support = {K08 CA256047/CA/NCI NIH HHS/United States ; TL1 TR001871/TR/NCATS NIH HHS/United States ; K08CA256047/CA/NCI NIH HHS/United States ; TL1 TR 001871/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Female ; *Breast Neoplasms/surgery/drug therapy ; *Carcinoma, Lobular/surgery/drug therapy ; Mastectomy ; *Carcinoma, Ductal, Breast/surgery/drug therapy ; Mastectomy, Segmental ; }, abstract = {PURPOSE: Primary site surgery for metastatic breast cancer improves local control but does not impact overall survival. Whether histologic subtype influences patient selection for surgery is unknown. Given differences in surgical management between early-stage lobular versus ductal disease, we evaluated the impact of histology on primary site surgery in patients with metastatic breast cancer.

METHODS: The National Cancer Database (NCDB, 2010-2016) was queried for patients with stage IV HR-positive, HER2-negative invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). We compared clinicopathologic features, primary site surgery rates, and outcomes by histologic subtype. Multivariable Cox proportional hazard models with and without propensity score matching were used for overall survival (OS) analyses.

RESULTS: In 25,294 patients, primary site surgery was slightly but significantly less common in the 6,123 patients with ILC compared to the 19,171 patients with IDC (26.9% versus 28.8%, p = 0.004). Those with ILC were less likely to receive chemotherapy (41.3% versus 47.4%, p < 0.0001) or radiotherapy (29.1% versus 37.9%, p < 0.0001), and had shorter OS. While mastectomy rates were similar, those with ILC who underwent lumpectomy had significantly higher positive margin rates (ILC 15.7% versus IDC 11.2%, p = 0.025). In both groups, the odds of undergoing surgery decreased over time, and were higher in younger patients with T2/T3 tumors and higher nodal burden.

CONCLUSION: Lobular histology is associated with less primary site surgery, higher positive margin rates, less radiotherapy and chemotherapy, and shorter OS compared to those with HR-positive HER2-negative IDC. These findings support the need for ILC-specific data and treatment approaches in the setting of metastatic disease.}, } @article {pmid37833434, year = {2023}, author = {Yu, Q and Wan, D and Fu, R and Li, F and Zhang, Y}, title = {Overexpression of TPL2 may be a predictor of good prognosis in patients with breast invasive ductal carcinoma.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {17346}, pmid = {37833434}, issn = {2045-2322}, mesh = {Female ; Humans ; Breast/pathology ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Prognosis ; Proto-Oncogene Proteins ; MAP Kinase Kinase Kinases ; }, abstract = {The objective of this study was to investigate the clinical significance and roles of tumor progression locus 2 (TPL2) and peptidyl-prolyl cis-trans isomerase 1 (Pin1) in the occurrence and development of breast invasive ductal carcinoma (IDC). Immunohistochemistry was used to detect the expression of TPL2 and Pin1 in human breast tissues, which included normal breast tissues (Normal), tissues with fibrocystic changes (FCC), ductal carcinoma in situ (DCIS), and IDC. The roles of TPL2 and Pin1 in the occurrence and development of IDC, as well as the correlation between their expression levels and clinicopathological parameters, were analyzed. Compared with Normal and FCC groups, the overexpression of TPL2 and Pin1 was significantly increased in DCIS and IDC groups (DCIS vs Normal: P = 0.002/P < 0.001; IDC vs Normal: P = 0.007/P = 0.003; DCIS vs. FCC: P = 0.008/P = 0.004; IDC vs. FCC: P = 0.04/P = 0.043). The expression levels of TPL2 and Pin1 were positively correlated in DCIS and IDC groups (P = 0.001, P = 0.011). In the IDC group, the Ki67 level in the TPL2 overexpression group was significantly lower than that in the TPL2 low expression group (P = 0.02). The TPL2 overexpression rate was significantly higher in IDC with histological grades 1-2 than that in IDC with histological grade 3 (P = 0.029). The TPL2 overexpression rate in IDC with tumor-node-metastasis (TNM) stage I was significantly higher than that in IDC with TNM stages II-III (P = 0.035). We conclude that TPL2 and Pin1 may synergistically promote the occurrence and development of IDC, but TPL2 overexpression may be an early molecular event in IDC development. TPL2 overexpression is significantly related with IDC with lower malignancy or earlier TNM stage, suggesting that the prognosis of IDC patients with TPL2 overexpression may be better and TPL2 overexpression may be a predictor of good prognosis in IDC.}, } @article {pmid37832430, year = {2023}, author = {Schacherer, DP and Herrmann, MD and Clunie, DA and Höfener, H and Clifford, W and Longabaugh, WJR and Pieper, S and Kikinis, R and Fedorov, A and Homeyer, A}, title = {The NCI Imaging Data Commons as a platform for reproducible research in computational pathology.}, journal = {Computer methods and programs in biomedicine}, volume = {242}, number = {}, pages = {107839}, pmid = {37832430}, issn = {1872-7565}, support = {HHSN261201500003C/CA/NCI NIH HHS/United States ; HHSN261201500003I/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Software ; Reproducibility of Results ; Cloud Computing ; Diagnostic Imaging ; *Lung Neoplasms/diagnostic imaging ; }, abstract = {BACKGROUND AND OBJECTIVES: Reproducibility is a major challenge in developing machine learning (ML)-based solutions in computational pathology (CompPath). The NCI Imaging Data Commons (IDC) provides >120 cancer image collections according to the FAIR principles and is designed to be used with cloud ML services. Here, we explore its potential to facilitate reproducibility in CompPath research.

METHODS: Using the IDC, we implemented two experiments in which a representative ML-based method for classifying lung tumor tissue was trained and/or evaluated on different datasets. To assess reproducibility, the experiments were run multiple times with separate but identically configured instances of common ML services.

RESULTS: The results of different runs of the same experiment were reproducible to a large extent. However, we observed occasional, small variations in AUC values, indicating a practical limit to reproducibility.

CONCLUSIONS: We conclude that the IDC facilitates approaching the reproducibility limit of CompPath research (i) by enabling researchers to reuse exactly the same datasets and (ii) by integrating with cloud ML services so that experiments can be run in identically configured computing environments.}, } @article {pmid37830404, year = {2024}, author = {Melli, G and Caccico, L and Micheli, E and Bulli, F and Doron, G}, title = {Pathological narcissism and relationship obsessive-compulsive disorder (ROCD) symptoms: Exploring the role of vulnerable narcissism.}, journal = {Journal of clinical psychology}, volume = {80}, number = {1}, pages = {144-157}, doi = {10.1002/jclp.23601}, pmid = {37830404}, issn = {1097-4679}, mesh = {Humans ; *Narcissism ; *Obsessive-Compulsive Disorder ; Emotions ; Surveys and Questionnaires ; Self Report ; }, abstract = {OBJECTIVE: Relationship obsessive-compulsive disorder (ROCD) symptoms, which include obsessive preoccupation, doubts, and compulsive behaviors focusing on the suitability of the relationship and/or partner, have been receiving increasing clinical, theoretical, and empirical attention. This clinical variant of OCD is associated with significant functional, personal, and dyadic consequences. ROCD symptoms have also been linked to several cognitive vulnerability factors, such as maladaptive relationship catastrophization. However, little is known about the connection between ROCD symptoms and specific personality traits. In this study, we examine whether vulnerable narcissistic personality traits may constitute a general vulnerability factor for ROCD symptoms. Specifically, we assess whether partner value self-contingencies moderate the association between vulnerable narcissistic traits and obsessive preoccupation with a romantic partner's perceived flaws.

METHOD: A total of 310 individuals self-reporting ROCD symptoms completed questionnaires assessing narcissistic personality traits, ROCD symptoms and cognitions, and partner value self-contingencies.

RESULTS: Vulnerable narcissistic traits were uniquely associated with ROCD symptoms over and above ROCD-related cognitions. Self-worth contingent on the partner's perceived value partially mediated the effect of vulnerable narcissistic traits on ROCD symptoms.

CONCLUSION: Results supported the role of vulnerable narcissistic traits and domain-relevant self-vulnerabilities on obsessive preoccupation with romantic partners' perceived flaws. Further research is needed to explore the susceptibility of vulnerable individuals to the development and maintenance of ROCD symptoms.}, } @article {pmid37828835, year = {2023}, author = {Yang, SY and Zhang, J and Yang, ZQ and Duan, JJ and Zhang, Y and Li, MK and Wang, L and Ye, CM and Nie, JY}, title = {Advanced hormone receptor-positive/human epidermal growth factor receptor 2-positive invasive ductal carcinoma with cecal metastasis: A case report.}, journal = {Science progress}, volume = {106}, number = {4}, pages = {368504231201043}, pmid = {37828835}, issn = {2047-7163}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology ; *Breast Neoplasms/metabolism ; Erb-b2 Receptor Tyrosine Kinases/genetics/metabolism ; }, abstract = {The incidence of gastrointestinal metastases from breast cancer (BC) is low. We report a special case of Luminal B (Hormone Receptor positive [HR+]/Human Epidermal Growth Factor receptor 2-positive [HER-2+]) BC. The patient presented with asymptomatic brain metastases two years after radical surgery for modified breast cancer and developed right lower abdominal pain during relief therapy. Electronic gastroenteroscopy revealed inflammatory changes in the cecal mucosa. These changes were confirmed on pathology to be cecal metastasis from BC. The patient's condition was stabilised after treatment with an antibody-drug conjugate (ADC). For patients with BC who develop appendicitis-like symptoms after treatment for invasive ductal carcinoma of the breast, clinicians should be fully aware that the possibility of cecal metastasis needs to be considered, despite the very low probability of occurrence.}, } @article {pmid37824772, year = {2023}, author = {Dieu Vuong, L and Ngoc Nguyen, Q}, title = {ABERRANT METHYLATION OF CANCER-RELATED GENES IN VIETNAMESE BREAST CANCER PATIENTS: ASSOCIATIONS WITH CLINICOPATHOLOGICAL FEATURES.}, journal = {Experimental oncology}, volume = {45}, number = {2}, pages = {195-202}, doi = {10.15407/exp-oncology.2023.02.195}, pmid = {37824772}, issn = {2312-8852}, mesh = {Aged ; Female ; Humans ; *Breast Neoplasms/genetics/pathology ; DNA Methylation ; ErbB Receptors/genetics ; Promoter Regions, Genetic ; Southeast Asian People ; Epigenomics ; Vietnam ; BRCA1 Protein ; DNA Modification Methylases ; Tumor Suppressor Proteins ; DNA Repair Enzymes ; Glutathione S-Transferase pi ; }, abstract = {BACKGROUND: Epigenetic alteration is one of the most common molecular changes identified in the progression of breast cancer (BC).

AIM: To study the frequency and relation between methylation of BRCA1, MLH1, MGMT, GSTP1, APC, RASSF1A, p16, WIF, and EGFR and the clinicopathological features in Vietnamese BC patients.

MATERIALS AND METHODS: Methylation-specific polymerase chain reaction (MS-PCR) and SPSS 20.0 software were utilized in order to identify methylated frequency as well as evaluate its relationship with the patient's clinical features.

RESULTS: In 162 BC cases, the methylation rates of the selected genes were 53.7%, 22.8%, 38.9%, 34.6%, 29.0%, 46.3%, 20.4%, 18.5%, and 28.4% respectively. In 32 cases of benign breast diseases (BBD) - 12.5%, 15.6%, 6.3%, 3.1%, 12.5%, 21.9%, 3.1%, 15.6% and 3.1%. BC samples displayed higher BRCA1, MGMT, GSTP1, APC, RASSF1A, WIF1, and p16 methylation levels than BBD samples (p < 0.001). Hypermethylation of BRCA1, GSTP1, and RASSF1A was predominant in the invasive ductal carcinoma, while hypermethylation of BRCA1, GSTP1, RASSF1A, WIF-1, and p16 was found to significantly correlate with lymph node metastasis (p < 0.05). Hypermethylation of BRCA1, MGMT, and GSTP1 was more common in stage III (p < 0.05) than in stages I/II, whereas MLH1 methylation was predominant in stage I and APC methylation was less common in stage III (p = 0.03). In addition, methylation of RASSF1A and EGFR was more frequent in younger patients (p < 0.01) than in elder patients.

CONCLUSION: These data suggest that a gene panel (BRCA1/MGMT/GSTP1) can be used to support the diagnosis and screening of Vietnamese patients' BC with a sensitivity of 70%, and a specificity of 85%.}, } @article {pmid37821332, year = {2024}, author = {Ghuman, N and Ambinder, EB and Oluyemi, ET and Sutton, E and Myers, KS}, title = {Clinical and Imaging Features of MRI Screen-Detected Breast Cancer.}, journal = {Clinical breast cancer}, volume = {24}, number = {1}, pages = {45-52}, pmid = {37821332}, issn = {1938-0666}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/epidemiology ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/epidemiology ; Breast/pathology ; Mammography ; Magnetic Resonance Imaging/methods ; Retrospective Studies ; }, abstract = {BACKGROUND: Supplemental screening with breast MRI is recommended annually for patients who have greater than 20% lifetime risk for breast cancer. While there is robust data regarding features of mammographic screen-detected breast cancers, there is limited data regarding MRI-screen-detected cancers.

PATIENTS AND METHODS: Screening breast MRIs performed between August 1, 2016 and July 30, 2022 identified 50 screen-detected breast cancers in 47 patients. Clinical and imaging features of all eligible cancers were recorded.

RESULTS: During the study period, 50 MRI-screen detected cancers were identified in 47 patients. The majority of MRI-screen detected cancers (32/50, 64%) were invasive. Pathology revealed ductal carcinoma in situ (DCIS) in 36% (18/50), invasive ductal carcinoma (IDC) in 52% (26/50), invasive lobular carcinoma in 10% (5/50), and angiosarcoma in 2% (1/50). The majority of patients (43/47, 91%) were stage 0 or 1 at diagnosis and there were no breast cancer-related deaths during the follow-up periods. Cancers presented as masses in 50% (25/50), nonmass enhancement in 48% (25/50), and a focus in 2% (1/50). DCIS was more likely to present as nonmass enhancement (94.4%, 17/18), whereas invasive cancers were more likely to present as masses (75%, 24/32) (P < .001). All cancers that were stage 2 at diagnosis were detected either on a baseline exam or more than 4 years since the prior MRI exam.

CONCLUSION: MRI screen-detected breast cancers were most often invasive cancers. Cancers detected by MRI screening had an excellent prognosis in our study population. Invasive cancers most commonly presented as a mass.}, } @article {pmid37812297, year = {2024}, author = {Tsai, HY and Kao, YW and Wang, JC and Tsai, TY and Chung, WS and Hsu, JS and Hou, MF and Weng, SF}, title = {Multitask deep learning on mammography to predict extensive intraductal component in invasive breast cancer.}, journal = {European radiology}, volume = {34}, number = {4}, pages = {2593-2604}, pmid = {37812297}, issn = {1432-1084}, support = {SI-10911//Kaohsiung Medical University Chung-Ho Memorial Hospital/ ; SI-11008//Kaohsiung Medical University Chung-Ho Memorial Hospital/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *Deep Learning ; Mammography/methods ; Breast/diagnostic imaging ; *Calcinosis ; }, abstract = {OBJECTIVES: To develop a multitask deep learning (DL) algorithm to automatically classify mammography imaging findings and predict the existence of extensive intraductal component (EIC) in invasive breast cancer.

METHODS: Mammograms with invasive breast cancers from 2010 to 2019 were downloaded for two radiologists performing image segmentation and imaging findings annotation. Images were randomly split into training, validation, and test datasets. A multitask approach was performed on the EfficientNet-B0 neural network mainly to predict EIC and classify imaging findings. Three more models were trained for comparison, including a single-task model (predicting EIC), a two-task model (predicting EIC and cell receptor status), and a three-task model (combining the abovementioned tasks). Additionally, these models were trained in a subgroup of invasive ductal carcinoma. The DeLong test was used to examine the difference in model performance.

RESULTS: This study enrolled 1459 breast cancers on 3076 images. The EIC-positive rate was 29.0%. The three-task model was the best DL model with an area under the curve (AUC) of EIC prediction of 0.758 and 0.775 at the image and breast (patient) levels, respectively. Mass was the most accurately classified imaging finding (AUC = 0.915), followed by calcifications and mass with calcifications (AUC = 0.878 and 0.824, respectively). Cell receptor status prediction was less accurate (AUC = 0.625-0.653). The multitask approach improves the model training compared to the single-task model, but without significant effects.

CONCLUSIONS: A mammography-based multitask DL model can perform simultaneous imaging finding classification and EIC prediction.

CLINICAL RELEVANCE STATEMENT: The study results demonstrated the potential of deep learning to extract more information from mammography for clinical decision-making.

KEY POINTS: • Extensive intraductal component (EIC) is an independent risk factor of local tumor recurrence after breast-conserving surgery. • A mammography-based deep learning model was trained to predict extensive intraductal component close to radiologists' reading. • The developed multitask deep learning model could perform simultaneous imaging finding classification and extensive intraductal component prediction.}, } @article {pmid37811173, year = {2023}, author = {Parashar, S and Arora, J and Mittal, A}, title = {Bright Is Not Always Better: A Pictorial Review of Hyperechoic Malignant Breast Masses.}, journal = {The Indian journal of radiology & imaging}, volume = {33}, number = {4}, pages = {532-540}, pmid = {37811173}, issn = {0971-3026}, abstract = {Hyperechogenic breast lesions are a relatively rare finding at breast ultrasonography and are traditionally thought to be benign. However, hyperechogenicity on the ultrasound alone does not provide enough evidence to rule out malignancy completely. We herein reported a short series of nine cases of echogenic malignant breast lesions, which include invasive ductal carcinoma, ductal carcinoma in situ, invasive lobular carcinoma, angiosarcoma, lymphoma, and metastasis to the breast. Echogenic breast lesions should be carefully evaluated and properly categorized based on any other suspicious sonographic characteristics and must be correlated with mammographic findings and clinical history to lower the threshold for biopsy and avoid delay in diagnosis. Hyperechogenicity should not be considered as a characteristically benign feature and should not supersede the less specifically benign features of the same lesion on the other examination.}, } @article {pmid37811111, year = {2023}, author = {Mansour, M and Zahra, O and Nabulsi, D and Alhamwi, A and Chahin, M and Alani, WR and Yousef, D and Kanbour, I and Kurdi, B and Mohammad Deeb, A}, title = {Ectopic primary ductal breast carcinoma of the vulva: a case report and literature review.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {10}, pages = {5138-5144}, pmid = {37811111}, issn = {2049-0801}, abstract = {BACKGROUND: Ectopic breast tissue (EBT) is normally found along the rudimentary mammary line, which is located from the axilla to the inguinal region and disappears during embryogenesis. Up to 6% of females around the world suffer from EBT. EBT cancer is rare, with only a few reports in the literature. The diagnosis, and treatment of these rare cases can be very difficult and complex.

CASE PRESENTATION: The authors report an interesting case of a 74-year-old female patient with a vulvar lump located on the mons pubis associated with ulceration, pain, and size increase. The histopathological study demonstrated an invasive ductal carcinoma grade 2 arising from EBT in the vulva. Within 4 months of follow-up, the patient's condition was stable.

Throughout this paper, the authors aim to highlight the diagnostic and therapeutic challenges since there are no current guidelines for treatment for such cases. Furthermore, this article describes this rare disease and includes surgical details, difficulties, diagnostic methods, and treatment options.}, } @article {pmid37811031, year = {2023}, author = {Rhoul, C and Kharkhach, A and Aabdi, H and Atmani, A and Mhand, M and Seghrouchni, N and Amal, B and Bouhout, T and Serji, B and El Harroudi, T}, title = {Radiation-induced angiosarcoma of the breast: a case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {10}, pages = {5047-5050}, pmid = {37811031}, issn = {2049-0801}, abstract = {INTRODUCTION: Breast angiosarcoma is a rare, aggressive tumour affecting adult women. It can occur in two forms, primary form and secondary forms or radiation-induced breast angiosarcoma affecting patients with history of breast or chest radiotherapy.

CASE PRESENTATION: The authors report a new case of breast angiosarcoma in 52-year-old women, with history of invasive ductal carcinoma, and reporting a discoloration of her breast skin. The patient did undergo a mastectomy of right breast and adjuvant chemotherapy.

CONCLUSION/DISCUSSION: Surgery with total excision associated or not to adjuvant chemotherapy remains the treatment of choice in breast angiosarcoma.}, } @article {pmid37807773, year = {2023}, author = {Gozalishvilli-Boncheva, A and Gonzalez-Espinoza, IR and Castro-Ponce, A and Bravo-Gutiérrez, OA and Juárez-Salazar, G and Montes-de-Oca-Moreda, RI and Aguirre-Flores, E and Coyotl-Huexotl, M and Orozco-Luis, J and Chiquillo-Domínguez, M and Garibay-Díaz, JC and Aranda-Claussen, JE and Ponce-de-León, EA and Sánchez-Sosa, S and Sabaté-Fernández, M and García-Reyna, JC and Cordero-Vargas, C and González-Blanco, MJ and Aguilar-Priego, JM and Sánchez-Fernández, NJ and Cortés-García, CA and González-Lozada, LE and Miguel-Cruz, E and Ceja-Utrera, FJ and Hernández-Garcia, MS and Piña-Vazquez, M and Aguilar-Jiménez, C}, title = {Observational analysis of clinical and pathological characteristics and their prognostic impact in Mexican patients with breast cancer: A multi-center study.}, journal = {Breast disease}, volume = {42}, number = {1}, pages = {305-313}, doi = {10.3233/BD-230025}, pmid = {37807773}, issn = {1558-1551}, mesh = {Adult ; Female ; Humans ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; Mexico/epidemiology ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Young Adult ; Middle Aged ; Aged ; Aged, 80 and over ; }, abstract = {Breast cancer is the most incidental and deadly neoplasm worldwide; in Mexico, very few epidemiologic reports have analyzed the pathological features and its impact on their clinical outcome. Here, we studied the relation between pathological features and the clinical presentation at diagnosis and their impact on the overall and progression-free survival of patients with breast cancer. For this purpose, we collected 199 clinical records of female patients, aged at least 18 years old (y/o), with breast cancer diagnosis confirmed by biopsy. We excluded patients with incomplete or conflicting clinical records. Afterward, we performed an analysis of overall and progression-free survival and associated risks. Our results showed an average age at diagnosis of 52 y/o (24-85), the most common features were: upper outer quadrant tumor (32%), invasive ductal carcinoma (76.8%), moderately differentiated (44.3%), early clinical stages (40.8%), asymptomatic patients (47.8%), luminal A subtype (47.8%). Median overall survival was not reached, but median progression-free survival was 32.2 months (29.75-34.64, CI 95%) associated risk were: clinical stage (p < 0.0001) symptomatic presentation (p = 0.009) and histologic grade (p = 0.02). Therefore, we concluded that symptom presence at diagnosis impacts progression-free survival, and palpable symptoms are related to an increased risk for mortality.}, } @article {pmid37800299, year = {2023}, author = {Takashima, Y and Terasawa, R and Hirata, A and Morita, S and Kimura, K and Iwamoto, M and Hayashi, M}, title = {[A Case of COVID-19 Infection during Postoperative Chemotherapy for Breast Cancer Treated with Antibody Cocktail Therapy to Prevent Disease Aggravation].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {9}, pages = {1009-1011}, pmid = {37800299}, issn = {0385-0684}, mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/drug therapy/surgery/pathology ; Capecitabine/therapeutic use ; Combined Antibody Therapeutics ; *COVID-19 ; COVID-19 Drug Treatment ; Mastectomy ; }, abstract = {The outbreak of COVID-19 has caused a global pandemic, and it has been reported that patients with cancer are at high risk of developing complications from the disease. However, we believe that prolonged interruption of chemotherapy due to extended COVID-19 treatment is not desirable, given the intensity of cancer treatment. We report a case of COVID-19 infection during postoperative chemotherapy for breast cancer, in which antibody cocktail therapy prevented disease aggravation and delayed breast cancer treatment. The patient is a 45-year-old woman who came to our hospital with a complaint of a right mammary mass. The mass was diagnosed as invasive ductal carcinoma with an ER and PR of 0%, a HER2 score of 1+, and a Ki-67 of 90%. After preoperative chemotherapy, she underwent a right mastectomy and axillary dissection. The pathology result showed non-pCR. The administration of capecitabine was started as adjuvant therapy. On day 8 of cycle 3, she developed a fever in the 39℃ range, and on the next day, a COVID-19 POC gene test confirmed that the patient was positive for infection. On the same day, neutralizing antibody drugs(casirivimab and imdevimab)were administered as antibody cocktail therapy. Two days after treatment(day 11), a blood test showed Grade 3 neutropenia, but there was no recurrence of fever or evidence of pneumonia. After 2 weeks, capecitabine was resumed, and the patient was able to complete 8 cycles of capecitabine therapy without any major complications.}, } @article {pmid37798148, year = {2024}, author = {Aitken, GL and Samuels, S and Gannon, CJ and Llaguna, OH}, title = {Influence of contralateral prophylactic mastectomy on textbook outcome attainment at time of mastectomy.}, journal = {American journal of surgery}, volume = {227}, number = {}, pages = {111-116}, doi = {10.1016/j.amjsurg.2023.09.050}, pmid = {37798148}, issn = {1879-1883}, mesh = {Humans ; Female ; Mastectomy ; *Prophylactic Mastectomy ; *Breast Neoplasms/surgery ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/pathology ; }, abstract = {INTRODUCTION: The objective of this study was to determine the incidence of textbook oncologic outcome (TOO) and its impact on overall survival (OS) among patients with invasive ductal carcinoma (IDC) following modified radical mastectomy (MRM) versus MRM with contralateral prophylactic mastectomy (MRM + CPM).

METHODS: The 2004-2017 National Cancer Database was queried for patients with IDC who underwent MRM and MRM ​+ ​CPM. TOO was defined as: resection with negative margins, adequate lymphadenectomy, length of stay ≤50th percentile, and no 30-day readmission or mortality.

RESULTS: 87,573 patients were identified, of which 14.3% underwent MRM ​+ ​CPM. Logistic regression models revealed that MRM ​+ ​CPM is independently associated with a reduced likelihood of achieving TOO (AOR ​= ​0.71; P ​< ​0.001). MRM patients who achieved TOO had a higher median OS compared to those who did not (164.6 vs.142.2 months, P ​< ​0.001).

CONCLUSIONS: MRM ​+ ​CPM is associated with a lower incidence of TOO attainment compared to MRM.}, } @article {pmid37792368, year = {2023}, author = {Martelli, G and Barretta, F and Vernieri, C and Folli, S and Pruneri, G and Segattini, S and Trapani, A and Carolla, C and Spatti, G and Miceli, R and Ferraris, C}, title = {Prophylactic Salpingo-Oophorectomy and Survival After BRCA1/2 Breast Cancer Resection.}, journal = {JAMA surgery}, volume = {158}, number = {12}, pages = {1275-1284}, pmid = {37792368}, issn = {2168-6262}, mesh = {Female ; Humans ; Adult ; *Breast Neoplasms/genetics/prevention & control/surgery ; Salpingo-oophorectomy ; BRCA1 Protein/genetics ; Mastectomy ; Retrospective Studies ; BRCA2 Protein/genetics ; Genes, BRCA1 ; Neoplasm Recurrence, Local/genetics ; Ovariectomy ; *Ovarian Neoplasms/genetics/prevention & control ; Mutation ; }, abstract = {IMPORTANCE: Few studies have investigated whether prophylactic salpingo-oophorectomy (PSO) for patients with previously resected breast cancer who carry pathogenic germline BRCA1 or BRCA2 variants is associated with a reduced risk of cancer-specific death.

OBJECTIVE: To assess the association of PSO and prophylactic mastectomy (PM) with prognosis after quadrantectomy or mastectomy as primary treatment for patients with BRCA1 or BRCA2 breast cancer.

This retrospective cohort study was performed in a single-institution, tertiary referral center. Consecutive patients with invasive breast cancer treated surgically between 1972 and 2019 were recruited and followed up prospectively after they were found to carry the BRCA1 or BRCA2 gene variant. The data analysis was performed between April 2022 and July 2023.

EXPOSURE: Following breast surgery, some patients underwent PSO, PM, or both, whereas others did not.

MAIN OUTCOMES AND MEASURES: The primary study end point was overall survival as measured by the Kaplan-Meier method. Secondary end points were crude cumulative incidence of breast cancer-specific mortality, ipsilateral breast tumor recurrence (IBTR), contralateral breast cancer, ovarian cancer, and ovarian cancer-specific mortality.

RESULTS: Of 480 patients included in the cohort (median age at initial surgery, 40.0 years; IQR, 34.0-46.0 years), PSO was associated with a significantly reduced risk of death (hazard ratio [HR], 0.40; 95% CI, 0.25-0.64; P < .001). This reduction was most evident for patients carrying the BRCA1 variant (HR, 0.35; 95% CI, 0.20-0.63; P = .001), those with triple-negative disease (HR, 0.21; 95% CI, 0.09-0.46; P = .002), and those with invasive ductal carcinoma (HR, 0.51; 95% CI, 0.31-0.84; P = .008). Prophylactic salpingo-oophorectomy was not associated with risk of contralateral breast cancer or IBTR. Initial or delayed PM was associated with a reduced risk of IBTR but not with overall survival or breast cancer-specific mortality.

CONCLUSIONS: The study findings suggest that PSO should be offered to all patients with BRCA1/2 breast cancer who undergo surgery with curative intent to reduce risk of death. In particular, PSO should be offered to patients with the BRCA1 variant at the time of breast surgery.}, } @article {pmid37790038, year = {2023}, author = {Bahadure, SD and Noman, O and Jaiswal, N and Bandre, G and Akulwar, A}, title = {Incidental Finding of Invasive Ductal Carcinoma on Mastectomy in the Case of Lymphocytic Mastitis: A Case Report.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e44545}, pmid = {37790038}, issn = {2168-8184}, abstract = {A rare inflammatory breast disorder called lymphocytic mastitis is characterized by lymphocyte infiltrates in the mammary parenchyma. Due to their rarity, incidental observations of invasive ductal carcinoma in lymphocytic mastitis present diagnostic and management challenges. We present a case of a 52-year-old female with a history of painfully swollen breasts for three months who underwent a core needle biopsy, consistent with lymphocytic mastitis on histopathology. Due to persistent and worsening symptoms, a mastectomy was performed. During the examination, an incidental finding of infiltrating ductal carcinoma was identified in the mastectomy specimen. This unexpected discovery led to further investigations and altered the patient's treatment plan. The detection of invasive ductal carcinoma in the presence of lymphocytic mastitis highlights the importance of continuous surveillance and thorough examination. In the circumstances of lymphocytic mastitis, it is vital to take the likelihood of concurrent malignancy into account, especially when symptoms persist or reappear after appropriate management. This case report seeks to raise awareness among physicians of this exceptional association and drive further research that will explain its pathophysiology while enhancing management strategies.}, } @article {pmid37787287, year = {2023}, author = {Chaudhary, D and Balhara, K and Mandal, S and Mallya, V and Tomar, R and Khurana, N and Bains, L}, title = {Metaplastic breast carcinoma: Analysis of clinical and pathologic features, a five-year study.}, journal = {Journal of cancer research and therapeutics}, volume = {19}, number = {5}, pages = {1226-1230}, doi = {10.4103/jcrt.jcrt_1229_21}, pmid = {37787287}, issn = {1998-4138}, mesh = {Adult ; Female ; Humans ; Breast/surgery/pathology ; *Breast Neoplasms/diagnosis/surgery/pathology ; *Carcinoma, Squamous Cell/pathology ; Mastectomy ; Metaplasia/pathology ; Retrospective Studies ; }, abstract = {BACKGROUND: Metaplastic carcinoma breast (MCB) is a rare tumor comprising of both glandular and non-glandular patterns with epithelial and or mesenchymal components. Due to their varied clinicomorphological features, diagnosis has been challenging.

AIM: To study the clinicopathological and histomorphology of cases of metaplastic carcinoma breast diagnosed in a tertiary care hospital along with literature review.

MATERIALS AND METHODS: This is a retrospective study including data of 11 patients who were diagnosed with MCB either on trucut or mastectomy specimens conducted between January 2014 and December 2018.

RESULTS: The study includes 11 patients, out of which 10 were diagnosed on mastectomy while one on trucut specimen. All the patients were women with the mean age of presentation being 43.8 years. The most common presentation was palpable breast lump with mean tumor size of 7.3 cm in greatest dimension. Skin involvement was seen in 36.3% of cases. While eight cases (72.7%) were classified as epithelial, three (27.2%) were classified as mixed. Amongst epithelial variety, in eight cases, squamous component was seen along with infiltrating ductal carcinoma (IDC) while one was pure squamous type. In mixed variety, one case showed spindled areas along with squamous areas and areas of IDC. Other two showed focal sarcomatous and cartilaginous areas in one and angiosarcomatous, bone and cartilage formation admixed with areas of IDC in other case.

CONCLUSION: MCB are rare breast tumors with aggressive course and are characterized by their large size and rapid growth rate. Recently, there has been an upsurge in the cases of MCB due to increase in recognition of this entity. It has to be distinguished from other tumors by the pathologists so as to guide proper treatment.}, } @article {pmid37783506, year = {2023}, author = {Bola, Ł and Vetter, P and Wenger, M and Amedi, A}, title = {Decoding Reach Direction in Early "Visual" Cortex of Congenitally Blind Individuals.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {43}, number = {46}, pages = {7868-7878}, pmid = {37783506}, issn = {1529-2401}, mesh = {Male ; Female ; Humans ; *Visual Perception ; Brain ; *Visual Cortex/diagnostic imaging ; Brain Mapping ; Blindness ; Magnetic Resonance Imaging ; }, abstract = {Motor actions, such as reaching or grasping, can be decoded from fMRI activity of early visual cortex (EVC) in sighted humans. This effect can depend on vision or visual imagery, or alternatively, could be driven by mechanisms independent of visual experience. Here, we show that the actions of reaching in different directions can be reliably decoded from fMRI activity of EVC in congenitally blind humans (both sexes). Thus, neither visual experience nor visual imagery is necessary for EVC to represent action-related information. We also demonstrate that, within EVC of blind humans, the accuracy of reach direction decoding is highest in areas typically representing foveal vision and gradually decreases in areas typically representing peripheral vision. We propose that this might indicate the existence of a predictive, hard-wired mechanism of aligning action and visual spaces. This mechanism might send action-related information primarily to the high-resolution foveal visual areas, which are critical for guiding and online correction of motor actions. Finally, we show that, beyond EVC, the decoding of reach direction in blind humans is most accurate in dorsal stream areas known to be critical for visuo-spatial and visuo-motor integration in the sighted. Thus, these areas can develop space and action representations even in the lifelong absence of vision. Overall, our findings in congenitally blind humans match previous research on the action system in the sighted, and suggest that the development of action representations in the human brain might be largely independent of visual experience.SIGNIFICANCE STATEMENT Early visual cortex (EVC) was traditionally thought to process only visual signals from the retina. Recent studies proved this account incomplete, and showed EVC involvement in many activities not directly related to incoming visual information, such as memory, sound, or action processing. Is EVC involved in these activities because of visual imagery? Here, we show robust reach direction representation in EVC of humans born blind. This demonstrates that EVC can represent actions independently of vision and visual imagery. Beyond EVC, we found that reach direction representation in blind humans is strongest in dorsal brain areas, critical for action processing in the sighted. This suggests that the development of action representations in the human brain is largely independent of visual experience.}, } @article {pmid37781368, year = {2023}, author = {Wang, W and Truong, K and Ye, C and Sharma, S and He, H and Liu, L and Wen, M and Misra, A and Zhou, P and Kimata, JT}, title = {Engineered CD4 T cells expressing a membrane anchored viral inhibitor restrict HIV-1 through cis and trans mechanisms.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1167965}, pmid = {37781368}, issn = {1664-3224}, support = {S10 OD028480/OD/NIH HHS/United States ; R33 AI116167/AI/NIAID NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; R21 AI116167/AI/NIAID NIH HHS/United States ; S10 RR024574/RR/NCRR NIH HHS/United States ; R01 AI106574/AI/NIAID NIH HHS/United States ; P30 AI161943/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *HIV-1 ; CD4-Positive T-Lymphocytes ; *HIV Infections ; HIV Antibodies ; Cell Line ; *HIV Seropositivity ; *Single-Chain Antibodies/pharmacology ; }, abstract = {HIV-1 infection of target cells can occur through either cell-free virions or cell-cell transmission in a virological synapse, with the latter mechanism of infection reported to be 100- to 1,000-fold more efficient. Neutralizing antibodies and entry inhibitors effectively block cell-free HIV-1, but with few exceptions, they display much less inhibitory activity against cell-mediated HIV-1 transmission. Previously, we showed that engineering HIV-1 target cells by genetically linking single-chain variable fragments (scFvs) of antibodies to glycosyl phosphatidylinositol (GPI) potently blocks infection by cell-free virions and cell-mediated infection by immature dendritic cell (iDC)-captured HIV-1. Expression of scFvs on CD4[+] cell lines by transduction with X5 derived anti-HIV-1 Env antibody linked to a GPI attachment signal directs GPI-anchored scFvs into lipid rafts of the plasma membrane. In this study, we further characterize the effect of GPI-scFv X5 on cell-cell HIV-1 transmission from DCs to target cells. We report that expression of GPI-scFv X5 in transduced CD4[+] cell lines and human primary CD4[+] T cells potently restricts viral replication in iDC- or mDC-captured HIV-1 in trans. Using live-cell imaging, we observed that when GPI-GFP or GPI-scFv X5 transduced T cells are co-cultured with iDCs, GPI-anchored proteins enrich in contact zones and subsequently migrate from T cells into DCs, suggesting that transferred GPI-scFv X5 interferes with HIV-1 infection of iDCs. We conclude that GPI-scFv X5 on the surface of transduced CD4[+] T cells not only potently blocks cell-mediated infection by DCs, but it transfers from transduced cells to the surface of iDCs and neutralizes HIV-1 replication in iDCs. Our findings have important implications for HIV-1 antibody-based immunotherapies as they demonstrate a viral inhibitory effect that extends beyond the transduced CD4+ T cells to iDCs which can enhance HIV-1 replication.}, } @article {pmid37776183, year = {2024}, author = {Liraz Zaltsman, S and Sharabi, S and Guez, D and Daniels, D and Cooper, I and Shemesh, C and Atrakchi, D and Ravid, O and Omesi, L and Rand, D and Livny, A and Schnaider Beeri, M and Friedman-Levi, Y and Shohami, E and Mardor, Y and Last, D}, title = {Application of Delayed Contrast Extravasation Magnetic Resonance Imaging for Depicting Subtle Blood-Brain Barrier Disruption in a Traumatic Brain Injury Model.}, journal = {Journal of neurotrauma}, volume = {41}, number = {3-4}, pages = {430-446}, doi = {10.1089/neu.2023.0048}, pmid = {37776183}, issn = {1557-9042}, mesh = {Male ; Animals ; Mice ; *Blood-Brain Barrier/diagnostic imaging ; Mice, Inbred C57BL ; Brain/blood supply ; Magnetic Resonance Imaging/methods ; *Brain Injuries, Traumatic/diagnostic imaging ; }, abstract = {The blood-brain barrier (BBB) is composed of brain microvasculature that provides selective transport of solutes from the systemic circulation into the central nervous system to protect the brain and spinal microenvironment. Damage to the BBB in the acute phase after traumatic brain injury (TBI) is recognized as a major underlying mechanism leading to secondary long-term damage. Because of the lack of technological ability to detect subtle BBB disruption (BBBd) in the chronic phase, however, the presence of chronic BBBd is disputable. Thus, the dynamics and course of long-term BBBd post-TBI remains elusive. Thirty C57BL/6 male mice subjected to TBI using our weight drop closed head injury model and 19 naïve controls were scanned by magnetic resonance imaging (MRI) up to 540 days after injury. The BBB maps were calculated from delayed contrast extravasation MRI (DCM) with high spatial resolution and high sensitivity to subtle BBBd, enabling depiction and quantification of BBB permeability. At each time point, 2-6 animals were sacrificed and their brains were extracted, sectioned, and stained for BBB biomarkers including: blood microvessel coverage by astrocyte using GFAP, AQP4, ZO-1 gaps, and IgG leakage. We found that DCM provided depiction of subtle yet significant BBBd up to 1.5 years after TBI, with significantly higher sensitivity than standard contrast-enhanced T1-weighted and T2-weighted MRI (BBBd volumes main effect DCM/T1/T2 p < 0.0001 F(2,70) = 107.3, time point p < 0.0001 F(2,133, 18.66) = 23.53). In 33% of the cases, both in the acute and chronic stages, there was no detectable enhancement on standard T1-MRI, nor detectable hyperintensities on T2-MRI, whereas DCM showed significant BBBd volumes. The BBBd values of TBI mice at the chronic stage were found significantly higher compared with age matched naïve animals at 30, 60, and 540 days. The calculated BBB maps were histologically validated by determining significant correlation between the calculated levels of disruption and a diverse set of histopathological parameters obtained from different brain regions, presenting different components of the BBB. Cumulative evidence from recent years points to BBBd as a central component of the pathophysiology of TBI. Therefore, it is expected that routine use of highly sensitive non-invasive techniques to measure BBBd, such as DCM with advanced analysis methods, may enhance our understanding of the changes in BBB function after TBI. Application of the DCM technology to other CNS disorders, as well as to normal aging, may shed light on the involvement of chronic subtle BBBd in these conditions.}, } @article {pmid37771380, year = {2023}, author = {Asare, B and White, MJ and Rossi, J}, title = {Metaplastic carcinoma with osteosarcomatous differentiation in the breast: Case report.}, journal = {Radiology case reports}, volume = {18}, number = {12}, pages = {4272-4280}, pmid = {37771380}, issn = {1930-0433}, abstract = {Metaplastic breast carcinoma is rare and may present as a highly aggressive subtype of breast cancer. In this case report of metastatic metaplastic breast carcinoma with osteosarcomatous differentiation in a female patient previously treated for invasive ductal carcinoma, we describe the new presentation of a palpable mass with associated calcifications on imaging near the site of prior partial mastectomy. This article will detail the clinical presentation, imaging findings, histopathology, and clinical course following treatment of our case. Knowledge of the clinical and imaging presentation of this rare subtype, which can present with benign features on mammography and ultrasound, can facilitate timely diagnosis as treatment paradigms evolve.}, } @article {pmid37769530, year = {2023}, author = {Siregar, KB and Al Anas, M}, title = {Unveiling bone metastasis: Exploring histological subtypes of breast cancer in Indonesia's tertiary referral hospital.}, journal = {Cancer treatment and research communications}, volume = {37}, number = {}, pages = {100764}, doi = {10.1016/j.ctarc.2023.100764}, pmid = {37769530}, issn = {2468-2942}, mesh = {Humans ; Female ; Adult ; Middle Aged ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/secondary ; *Carcinoma, Ductal, Breast/secondary ; Retrospective Studies ; Indonesia/epidemiology ; Tertiary Care Centers ; *Bone Neoplasms ; }, abstract = {INTRODUCTION: The histological grade of a tumor is an important prognostic indicator in both primary breast cancer and metastatic. We aimed to show the distribution of bone metastasis locations across different histological subtypes of breast cancer and how they relate to each.

METHODS: The cohort retrospective study comprised 65 patients diagnosed with bone-only metastatic breast cancer, all female. The secondary statistics for 2014 to 2022 were derived from breast cancer registration data collected to determine the relationships between patterns of bone metastases sites and histopathological grading in various histological categories.

RESULTS: The average age was 44.28±9.80 years (25-62 years), with 38 patients (58.5%) diagnosed with Invasive Ductal Carcinoma (IDC) and 27 patients (41.5%) with Invasive Lobular Carcinoma (ILC). Grade III were found in 34 patients (50.8%), Grade II in 31 patients (47.7%) and Grade I in one patient (1.5%). The most common sites of bone metastases are costae, followed by femur, vertebrae and pelvic. Vertebrae and costae metastasis are significantly correlated with histological grading and breast cancer pathology (p: 0.027 and 0.033, respectively).

CONCLUSION: There is a considerable difference between vertebrae and costae metastasis in terms of histological grading and breast cancer pathology which indicates the higher grade contains a greater variety of bone metastases sites.}, } @article {pmid37761331, year = {2023}, author = {Al-Refai, R and Bendari, A and Morrar, D and Sham, S and Kataw, L and Garajayev, A and Hajiyeva, S}, title = {Immunohistochemical Staining Characteristics of Low-Grade Invasive Ductal Carcinoma Using the ADH5 Cocktail (CK5/14, P63, and CK7/18): A Potential Interpretative Pitfall.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {18}, pages = {}, pmid = {37761331}, issn = {2075-4418}, abstract = {Background: In our practice, the antibody cocktail ADH5 (CK5/14, p63, and CK7/18) helps with diagnostic challenges, such as identifying microinvasion and foci of invasive carcinoma, differentiating atypical ductal hyperplasia from hyperplasia of the usual type, and distinguishing basal phenotypes in triple-negative carcinomas. However, the ADH5 cocktail does have pitfalls and caveats. Methods: We describe our experience with the ADH5 cocktail of antibodies in breast pathology. Institutional knowledge and a literature search form our data sources. Results: We analyzed 44 cases. Four out of a total of 44 cases (9.1%)-two tubular carcinomas and two low-grade invasive breast carcinomas of no special type (ductal) with tubular features-showed an expected pattern of staining for ADH5 with a loss of brown (P63, CK5/14) staining around invasive glands and diffuse red (CK7/18) expression. Forty out of 44 (90.9%) cases showed an unexpected staining pattern (mixture of cytoplasmic brown and red). All 44 cases (100%) showed negative myoepithelial staining around invasive foci when separately stained for P63 and SMMH (Smooth Muscle Myosin Heavy). Conclusions: The unexpected staining pattern of ADH5 in low-grade invasive ductal carcinomas can be challenging to interpret in these lesions with low-grade cytology. The occurrence can cause confusion among users who employ multiplex stains, and it is important for users to be aware of this potential pitfall.}, } @article {pmid37749321, year = {2023}, author = {Taylor, J and Uhl, L and Moll, I and Hasan, SS and Wiedmann, L and Morgenstern, J and Giaimo, BD and Friedrich, T and Alsina-Sanchis, E and De Angelis Rigotti, F and Mülfarth, R and Kaltenbach, S and Schenk, D and Nickel, F and Fleming, T and Sprinzak, D and Mogler, C and Korff, T and Billeter, AT and Müller-Stich, BP and Berriel Diaz, M and Borggrefe, T and Herzig, S and Rohm, M and Rodriguez-Vita, J and Fischer, A}, title = {Endothelial Notch1 signaling in white adipose tissue promotes cancer cachexia.}, journal = {Nature cancer}, volume = {4}, number = {11}, pages = {1544-1560}, pmid = {37749321}, issn = {2662-1347}, support = {394046768 - SFB1366//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB1118-A04/S01//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; BO 1639/9-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, mesh = {Animals ; Humans ; Male ; Mice ; *Adipose Tissue, White/pathology ; *Cachexia/pathology ; *Neoplasms/complications ; Signal Transduction ; Tretinoin ; *Receptor, Notch1/metabolism ; }, abstract = {Cachexia is a major cause of morbidity and mortality in individuals with cancer and is characterized by weight loss due to adipose and muscle tissue wasting. Hallmarks of white adipose tissue (WAT) remodeling, which often precedes weight loss, are impaired lipid storage, inflammation and eventually fibrosis. Tissue wasting occurs in response to tumor-secreted factors. Considering that the continuous endothelium in WAT is the first line of contact with circulating factors, we postulated whether the endothelium itself may orchestrate tissue remodeling. Here, we show using human and mouse cancer models that during precachexia, tumors overactivate Notch1 signaling in distant WAT endothelium. Sustained endothelial Notch1 signaling induces a WAT wasting phenotype in male mice through excessive retinoic acid production. Pharmacological blockade of retinoic acid signaling was sufficient to inhibit WAT wasting in a mouse cancer cachexia model. This demonstrates that cancer manipulates the endothelium at distant sites to mediate WAT wasting by altering angiocrine signals.}, } @article {pmid37747019, year = {2023}, author = {Choi, JH and Yu, J and Jung, M and Jekal, J and Kim, KS and Jung, SU}, title = {Prognostic significance of TP53 and PIK3CA mutations analyzed by next-generation sequencing in breast cancer.}, journal = {Medicine}, volume = {102}, number = {38}, pages = {e35267}, pmid = {37747019}, issn = {1536-5964}, mesh = {Humans ; Female ; Adult ; Middle Aged ; *Breast Neoplasms/genetics ; Prognosis ; Mastectomy ; High-Throughput Nucleotide Sequencing ; Class I Phosphatidylinositol 3-Kinases/genetics ; Tumor Suppressor Protein p53/genetics ; }, abstract = {Breast cancer is one of the most prevalent malignant tumors affecting women globally. It is a heterogeneous disease characterized by mutations in several genes. Several gene panels have been applied to assess the risk of breast cancer and determine the appropriate treatment. As a powerful tool, Next-generation sequencing (NGS) has been widely utilized in cancer research due to its advantages, including high speed, high throughput, and high accuracy. In this study, we aim to analyze the correlation between somatic mutations in breast cancer, analyzed using NGS, and the prognosis of patients. Between May 2018 and May 2019, a total of 313 patients with breast cancer underwent surgical treatment, which included total mastectomy and breast-conserving surgery. Among these patients, 265 were diagnosed with invasive ductal carcinoma. In this study, we analyzed the NGS results, clinicopathological characteristics, and their correlation with prognosis. Using a gene panel, we examined 143 somatic mutations in solid cancers. Notably, the study population included patients who had received neoadjuvant chemotherapy. The mean age of the patients was 53.1 (±10.28) years, and the median follow-up time was 48 months (range, 8-54). Among the 265 patients, 68 had received prior systemic therapy. Of these, 203 underwent breast-conserving surgery, and 62 underwent a mastectomy. Various somatic mutations were observed in NGS, with the most frequent mutation being PIK3CA mutations, which accounted for 44% of all mutations. TP53 mutations were the second most frequent, and ERBB2 mutations were the third most frequent. TP53 mutations were associated with poor disease-free survival (P = .027), while PIK3CA mutations were associated with better disease-free survival (P = .035) than PIK3CA wild-type. In our study, we identified various somatic mutations in breast cancer. Particularly, we found that TP53 and PIK3CA mutations are potentially associated with the prognosis of breast cancer. These findings suggest that the presence of specific mutations may have implications for predicting the prognosis of breast cancer. Further research and validation are needed to gain a deeper understanding of the role of these mutations and their mechanisms in prognosis prediction.}, } @article {pmid37745509, year = {2023}, author = {Stindt, KR and McClean, MN}, title = {Tuning Interdomain Conjugation Toward in situ Population Modification in Yeast.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.09.12.557379}, pmid = {37745509}, issn = {2692-8205}, abstract = {The ability to modify and control natural and engineered microbiomes is essential for biotechnology and biomedicine. Fungi are critical members of most microbiomes, yet technology for modifying the fungal members of a microbiome has lagged far behind that for bacteria. Interdomain conjugation (IDC) is a promising approach, as DNA transfer from bacterial cells to yeast enables in situ modification. While such genetic transfers have been known to naturally occur in a wide range of eukaryotes, and are thought to contribute to their evolution, IDC has been understudied as a technique to control fungal or fungal-bacterial consortia. One major obstacle to widespread use of IDC is its limited efficiency. In this work, we utilize interactions between genetically tractable Escherichia coli and Saccharomyces cerevisiae to control the incidence of IDC. We test the landscape of population interactions between the bacterial donors and yeast recipients to find that bacterial commensalism leads to maximized IDC, both in culture and in mixed colonies. We demonstrate the capacity of cell-to-cell binding via mannoproteins to assist both IDC incidence and bacterial commensalism in culture, and model how these tunable controls can predictably yield a range of IDC outcomes. Further, we demonstrate that these lessons can be utilized to lastingly alter a recipient yeast population, by both "rescuing" a poor-growing recipient population and collapsing a stable population via a novel IDC-mediated CRISPR/Cas9 system.}, } @article {pmid37743485, year = {2023}, author = {Pourriahi, R and Omranipour, R and Alipour, S and Hajimaghsoudi, L and Mashoori, N and Kenary, AY and Motamedi, M and Tavakol, M and Mohammadzadeh, M and Hessamiazar, S and Shabani, S and Mahmoodi, F and Goodarzi, MM and Eslami, B}, title = {Clinical characteristics of breast cancer patients admitted to academic surgical wards in Tehran, Iran: an analytical cross-sectional study.}, journal = {BMC women's health}, volume = {23}, number = {1}, pages = {511}, pmid = {37743485}, issn = {1472-6874}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/diagnosis/epidemiology ; Iran/epidemiology ; Cross-Sectional Studies ; Hospitalization ; Palpation ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women. Knowledge of the clinical characteristics of BC in a population may be informative for disease prediction or diagnosis and for developing screening and diagnostic guidelines. This study aimed to evaluate the clinical characteristics of female patients with BC who were admitted to academic surgical wards in Tehran, Iran.

METHODS: In this cross-sectional study, demographic information and clinical characteristics of Iranian females with BC who had undergone breast surgery from 2017-2021 in four academic Breast Surgery Units were extracted from medical files and recorded via a pre-designed checklist.

RESULTS: A total of 1476 patients with a mean age of 48.03 (± 11.46) years were enrolled. Among them, 10.4% were aged less than 35. In younger patients, Triple-negative and Her2-enriched subtypes of BC were significantly higher compared to older ones. Overall, 85.7% of tumors were invasive ductal carcinoma, 43.3% were grade 2, 41.4% were located in the UOQ, and 65.2% had presented with mass palpation. The mean pathologic tumor size was 28.94 mm, and the most common subtype was luminal B.

CONCLUSIONS: Many characteristics of breast cancer in this study were similar to other countries and previous studies in Iran. However, a higher proportion of young BC compared with Western countries, and even with older studies in Iran, suggest a trend toward lower age for BC in recent years. These results indicate the need for preventive measures and screening in Iranian women at a younger age.}, } @article {pmid37738898, year = {2023}, author = {Peng, L and He, X and Peng, X and Li, Z and Zhang, L}, title = {STGNNks: Identifying cell types in spatial transcriptomics data based on graph neural network, denoising auto-encoder, and k-sums clustering.}, journal = {Computers in biology and medicine}, volume = {166}, number = {}, pages = {107440}, doi = {10.1016/j.compbiomed.2023.107440}, pmid = {37738898}, issn = {1879-0534}, mesh = {Humans ; Cluster Analysis ; *Transcriptome/genetics ; *Neural Networks, Computer ; Algorithms ; Gene Expression Profiling/methods ; Breast Neoplasms/genetics/pathology/metabolism ; }, abstract = {BACKGROUND: Spatial transcriptomics technologies fully utilize spatial location information, tissue morphological features, and transcriptional profiles. Integrating these data can greatly advance our understanding about cell biology in the morphological background.

METHODS: We developed an innovative spatial clustering method called STGNNks by combining graph neural network, denoising auto-encoder, and k-sums clustering. First, spatial resolved transcriptomics data are preprocessed and a hybrid adjacency matrix is constructed. Next, gene expressions and spatial context are integrated to learn spots' embedding features by a deep graph infomax-based graph convolutional network. Third, the learned features are mapped to a low-dimensional space through a zero-inflated negative binomial (ZINB)-based denoising auto-encoder. Fourth, a k-sums clustering algorithm is developed to identify spatial domains by combining k-means clustering and the ratio-cut clustering algorithms. Finally, it implements spatial trajectory inference, spatially variable gene identification, and differentially expressed gene detection based on the pseudo-space-time method on six 10x Genomics Visium datasets.

RESULTS: We compared our proposed STGNNks method with five other spatial clustering methods, CCST, Seurat, stLearn, Scanpy and SEDR. For the first time, four internal indicators in the area of machine learning, that is, silhouette coefficient, the Davies-Bouldin index, the Caliniski-Harabasz index, and the S_Dbw index, were used to measure the clustering performance of STGNNks with CCST, Seurat, stLearn, Scanpy and SEDR on five spatial transcriptomics datasets without labels (i.e., Adult Mouse Brain (FFPE), Adult Mouse Kidney (FFPE), Human Breast Cancer (Block A Section 2), Human Breast Cancer (FFPE), and Human Lymph Node). And two external indicators including adjusted Rand index (ARI) and normalized mutual information (NMI) were applied to evaluate the performance of the above six methods on Human Breast Cancer (Block A Section 1) with real labels. The comparison experiments elucidated that STGNNks obtained the smallest Davies-Bouldin and S_Dbw values and the largest Silhouette Coefficient, Caliniski-Harabasz, ARI and NMI, significantly outperforming the above five spatial transcriptomics analysis algorithms. Furthermore, we detected the top six spatially variable genes and the top five differentially expressed genes in each cluster on the above five unlabeled datasets. And the pseudo-space-time tree plot with hierarchical layout demonstrated a flow of Human Breast Cancer (Block A Section 1) progress in three clades branching from three invasive ductal carcinoma regions to multiple ductal carcinoma in situ sub-clusters.

CONCLUSION: We anticipate that STGNNks can efficiently improve spatial transcriptomics data analysis and further boost the diagnosis and therapy of related diseases. The codes are publicly available at https://github.com/plhhnu/STGNNks.}, } @article {pmid37738835, year = {2023}, author = {Coffey, K and Dixon, LB and Sevilimedu, V and Jochelson, MS and Sung, JS}, title = {Short-term follow-up of contrast-enhanced mammography lesions after negative breast MRI in women with elevated breast cancer risk.}, journal = {European journal of radiology}, volume = {168}, number = {}, pages = {111097}, doi = {10.1016/j.ejrad.2023.111097}, pmid = {37738835}, issn = {1872-7727}, mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/diagnostic imaging/epidemiology ; Retrospective Studies ; Follow-Up Studies ; *Triple Negative Breast Neoplasms ; Mammography/methods ; Magnetic Resonance Imaging/methods ; }, abstract = {PURPOSE: To determine the outcome of enhancing lesions detected on contrast-enhanced mammography (CEM) that had no correlate on magnetic resonance imaging (MRI) and underwent short-term follow-up CEM.

METHODS: In this retrospective single-center study, we identified patients with elevated breast cancer risk who had a CEM between 2014 and 2021 showing indeterminate enhancement on recombined images (BI-RADS 0, 3, 4) that had no correlate on subsequent MRI (performed within one month), and therefore underwent short-term follow-up CEM (performed within eight months). Medical records and imaging studies were reviewed to collect data on patient and lesion characteristics, and outcomes. Cancer incidence with 95% confidence interval (CI) was calculated.

RESULTS: This study included 71 women (median age 49 years) with 81 enhancing CEM lesions who underwent short-term follow-up CEM (median 6.2 months) after MRI reported no correlate. Of 81 lesions (median size = 0.7 cm), 73 (90%) were non-mass enhancement and 8 (10%) were enhancing masses. No sonographic correlate was identified for 75 lesions that had a same-day targeted ultrasound. Two cancers (2.5%, 95% CI 0.3-8.6) were diagnosed during the short-term follow-up period, one at 6-months (invasive ductal carcinoma) and one at 12-months (ductal carcinoma in situ). The remaining 79 lesions were benign at 6-month follow-up CEM and at one-year mammographic follow-up.

CONCLUSIONS: Follow-up CEM of MRI-occult lesions is prudent and may be reasonable to perform at one-year given the low incidence of cancer detected at six-months (one of 81) in our small study sample.}, } @article {pmid37737015, year = {2023}, author = {Sijnesael, T and Richard, F and Rätze, MA and Koorman, T and Bassey-Archibong, B and Rohof, C and Daniel, J and Desmedt, C and Derksen, PW}, title = {Canonical Kaiso target genes define a functional signature that associates with breast cancer survival and the invasive lobular carcinoma histological type.}, journal = {The Journal of pathology}, volume = {261}, number = {4}, pages = {477-489}, doi = {10.1002/path.6205}, pmid = {37737015}, issn = {1096-9896}, support = {2018NovPCC1297/BBC_/Breast Cancer Now/United Kingdom ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/metabolism ; Neoplasm Recurrence, Local ; Prognosis ; Cadherins/genetics/metabolism ; Transcription Factors/metabolism ; *Carcinoma, Ductal, Breast/pathology ; }, abstract = {Invasive lobular carcinoma (ILC) is a low- to intermediate-grade histological breast cancer type caused by mutational inactivation of E-cadherin function, resulting in the acquisition of anchorage independence (anoikis resistance). Most ILC cases express estrogen receptors, but options are limited in relapsed endocrine-refractory disease as ILC tends to be less responsive to standard chemotherapy. Moreover, ILC can relapse after >15 years, an event that currently cannot be predicted. E-cadherin inactivation leads to p120-catenin-dependent relief of the transcriptional repressor Kaiso (ZBTB33) and activation of canonical Kaiso target genes. Here, we examined whether an anchorage-independent and ILC-specific transcriptional program correlated with clinical parameters in breast cancer. Based on the presence of a canonical Kaiso-binding consensus sequence (cKBS) in the promoters of genes that are upregulated under anchorage-independent conditions, we defined an ILC-specific anoikis resistance transcriptome (ART). Converting the ART genes into human orthologs and adding published Kaiso target genes resulted in the Kaiso-specific ART (KART) 33-gene signature, used subsequently to study correlations with histological and clinical variables in primary breast cancer. Using publicly available data for ER[POS] Her2[NEG] breast cancer, we found that expression of KART was positively associated with the histological ILC breast cancer type (p < 2.7E-07). KART expression associated with younger patients in all invasive breast cancers and smaller tumors in invasive ductal carcinoma of no special type (IDC-NST) (<2 cm, p < 6.3E-10). We observed associations with favorable long-term prognosis in both ILC (hazard ratio [HR] = 0.51, 95% CI = 0.29-0.91, p < 3.4E-02) and IDC-NST (HR = 0.79, 95% CI = 0.66-0.93, p < 1.2E-04). Our analysis thus defines a new mRNA expression signature for human breast cancer based on canonical Kaiso target genes that are upregulated in E-cadherin deficient ILC. The KART signature may enable a deeper understanding of ILC biology and etiology. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.}, } @article {pmid37734568, year = {2023}, author = {Deberti, M and Goupille, C and Arbion, F and Vilde, A and Body, G and Ouldamer, L}, title = {Prognostic value of axillary lymph node metastases in invasive lobular breast carcinoma.}, journal = {Journal of gynecology obstetrics and human reproduction}, volume = {52}, number = {10}, pages = {102665}, doi = {10.1016/j.jogoh.2023.102665}, pmid = {37734568}, issn = {2468-7847}, mesh = {Humans ; Female ; Prognosis ; Lymphatic Metastasis/pathology ; *Carcinoma, Lobular/pathology ; Neoplasm Staging ; Disease-Free Survival ; Retrospective Studies ; Neoplasm Recurrence, Local/pathology ; Lymph Nodes/pathology ; *Breast Neoplasms/pathology ; Inflammation ; }, abstract = {BACKGROUND: Axillary lymph node involvement is a well-established prognostic factor for recurrence in breast cancer, specifically the number of nodes affected and the ratio of the number of affected nodes to the number of harvested nodes for non-specific invasive breast cancer (invasive ductal carcinoma). However, there is limited information on the impact of lymph node involvement in the case of invasive lobular carcinoma.

OBJECTIVES: our study aimed to evaluate the prognostic impact of lymph node involvement on overall survival and distant metastatic-free survival according to the number of nodes affected and the ratio of positive nodes (LNR) for patients managed for invasive lobular carcinoma.

METHODS: This is a monocentre, comparative, observational study of patients managed for invasive lobular carcinoma at the Gynaecology Department of the University Hospital Center of Tours between January 1, 2007 and December 31, 2018. The LNR cut-off values used were: low risk if LNR ≤ 0.2; intermediate risk if LNR > 0.2 and ≤ 0.65, and high risk for LNR >0.659.

RESULTS: Our study demonstrated a significant difference in overall survival and distant metastasis free survival (p < 0.0001). The 5-years Overall survival was 94 % for N0 patients, 92.4 % for low-risk patients, 85.6 % for intermediate-risk patients and 58.5 % for high-risk patients. The 5-year distant metastasis-free survival was 98.2 % for N0 patients, 95.9 % for low-risk patients, 80.1 % for intermediate-risk patients, and 60.3 % for high-risk patients. Multivariate analysis identified age, invasive lobular histologic type, presence of clinical inflammation, and intermediate and high risk classes of LNR ratio as independent factors affecting overall survival. For metastatic-free survival, the presence of clinical inflammation, the presence of LVSI and the low, intermediate, or high-risk classes of LNR ratio were identified as independent factors. However, age and invasive lobular histologic type did not appear to be independent factors affecting metastatic-free survival.

CONCLUSION: Our study highlights the significant prognostic impact of lymph node involvement in patients with invasive lobular carcinoma. The LNR ratio can be used as a reliable predictor of overall survival and metastatic-free survival in these patients.}, } @article {pmid37731440, year = {2023}, author = {Okubo, T and Minari, Y and Ikura, Y}, title = {Change in Main Histological Type of Invasive Breast Cancer From Ductal to Lobular Carcinoma by Neoadjuvant Chemotherapy.}, journal = {Cureus}, volume = {15}, number = {8}, pages = {e43816}, pmid = {37731440}, issn = {2168-8184}, abstract = {We present a case study of breast cancer initially diagnosed as invasive ductal carcinoma (IDC), which subsequently substituted into invasive lobular carcinoma (ILC) following neoadjuvant chemotherapy (NAC). A 61-year-old woman presented with a palpable breast lump, and histological examination through core needle biopsy (CNB) confirmed the presence of IDC. After a 6-month course of NAC, the patient achieved a clinically complete response (cCR) and underwent mastectomy. The surgical specimen showed no detectable tumor upon palpation, but microscopic analysis revealed a highly infiltrative growth of poorly-cohesive small atypical cells in the original tumor area. Immunohistochemical staining demonstrated that the tumor cells were negative for E-cadherin, leading to a diagnosis of ILC. To address the histological discrepancy before and after NAC, we re-evaluated the initial CNB using E-cadherin immunohistochemistry. While most tumor cells were E-cadherin positive, a small area displaying scirrhous subtype-like morphology exhibited E-cadherin negativity. Consequently, we revised the diagnosis to mixed IDC-ILC. The differential chemosensitivity between IDC and ILC may provide insight into this phenomenon.}, } @article {pmid37729354, year = {2023}, author = {Ferreira, CJDS and Caires, IQS and Costa Neto, WJBD and Almeida, SMV}, title = {Collagen content and C-X-C motif chemokine ligand 12 expression in neoplastic breast stroma.}, journal = {Revista da Associacao Medica Brasileira (1992)}, volume = {69}, number = {9}, pages = {e20221210}, pmid = {37729354}, issn = {1806-9282}, mesh = {Adolescent ; Adult ; Female ; Humans ; *Breast Neoplasms ; *Carcinoma, Ductal ; Collagen ; Ligands ; Mastectomy ; Receptors, Chemokine ; Retrospective Studies ; Tumor Microenvironment ; Chemokine CXCL12 ; }, abstract = {OBJECTIVE: This study aimed to evaluate the expression of C-X-C motif chemokine ligand 12 and its C-X-C chemokine receptor type 4, and the tumor-stroma ratio using collagen stromal content of breast cancer samples, correlating it with clinicopathological data.

METHODS: Through a retrospective cohort study, samples were obtained from female patients, over 18 years of age, with the disease in stages 1-4, who underwent mastectomy or lumpectomy. The biopsies were provided by the Oncology sector of the Hospital das Clínicas of Universidade Federal de Pernambuco, Recife city, in 2011-2014, including samples of invasive ductal carcinoma, ductal carcinoma in situ, or benign changes (fibroadenoma and hypertrophy), which were analyzed between 2020 and 2022 by immunohistochemistry for the expression of stromal cell characteristics. Collagen content was tested by Gomori staining and digital analysis of images.

RESULTS: Absence of stromal expression of C-X-C motif chemokine ligand 12 was associated with longer disease-free survival (disease-free survival=0.481), and expression of C-X-C chemokine receptor type 4 was associated with lower disease-free survival. An association was observed between clinicopathological variables and stromal expression of chemokines, that is, an association of stromal C-X-C motif chemokine ligand 12 with histological grade, angiolymphatic invasion, and an association between C-X-C chemokine receptor type 4 expression and histological grade. Analyses of digital pixels images of collagen and tumor cells showed a lower percentage of collagen in the invasive ductal carcinoma samples (39%), unlike samples without neoplasms (78%).

CONCLUSION: Low expression of C-X-C motif chemokine ligand 12 may be associated with a worse prognosis for breast cancer. Collagen staining analyzed using digital images represents an opportunity for clinical application and is indicative of the prognosis of the tumor microenvironment in breast carcinoma.}, } @article {pmid37724141, year = {2023}, author = {Rezaei, A and Shayan, N and Shirazinia, S and Mollazadeh, S and Ghiyasi-Moghaddam, N}, title = {The Prognostic Significance of P16 Immunohistochemical Expression Pattern in Women with Invasive Ductal Breast Carcinoma.}, journal = {Reports of biochemistry & molecular biology}, volume = {12}, number = {1}, pages = {83-91}, pmid = {37724141}, issn = {2322-3480}, abstract = {BACKGROUND: Breast cancer is the most common malignancy in women worldwide. The p16 protein is a cell cycle regulator and tumor suppressor implicated in several types of cancers. However, its relationship to breast cancer is still unknown. The present study aimed to assess the association of p16 protein expression with clinicopathological features in breast cancer.This study aimed to investigate the anti-cancer effects of different gum extracts on metabolic changes and their impact on gene expression in HT-29 cell.

METHODS: The study enrolled 100 patients with invasive ductal carcinoma. The samples were collected before any adjuvant chemotherapy, and p16 protein expression was determined using immunohistochemistry. Clinicopathological features were obtained from the patient's medical records.

RESULTS: Our findings demonstrated that p16 protein expression increased in estrogen receptor-positive tumor tissues (P< 0.01). However, no significant correlation was found between the p16 protein expression and the other clinicopathological features.

CONCLUSIONS: Our study demonstrated that p16 protein expression increased in ER-positive tumor tissue from patients with invasive ductal breast carcinoma. However, no correlation was found between the p16 protein expression and the other clinicopathological features.}, } @article {pmid37705411, year = {2023}, author = {McMurtry, V and Cleary, AS and Ruano, AL and Lomo, L and Gulbahce, HE}, title = {Metaplastic Breast Carcinoma: Clinicopathologic Features and Recurrence Score Results From a Population-based Database.}, journal = {American journal of clinical oncology}, volume = {46}, number = {12}, pages = {559-566}, doi = {10.1097/COC.0000000000001041}, pmid = {37705411}, issn = {1537-453X}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/genetics ; *Breast Neoplasms/genetics/epidemiology ; Proportional Hazards Models ; SEER Program ; Registries ; Prognosis ; }, abstract = {OBJECTIVES: Metaplastic breast carcinoma (MBC) is a rare, aggressive form of cancer comprising epithelial and mesenchymal elements. The purpose of this study was to use population-based data to review the clinicopathologic, molecular features, and outcomes of MBC.

METHODS: Surveillance, Epidemiology, and End Results Program (SEER) data were used to identify MBC and invasive ductal carcinoma (IDC), no special type (NOS) between 2004 and 2015. Results from Oncotype DX's 21-gene assay linked to SEER registries were included for hormone receptor (HR)-positive tumors. χ 2 analysis was performed to determine the differences between MBC and IDC. Kaplan-Meier curves and multivariate Cox proportional hazards models were used for breast cancer specific death (BCSD).

RESULTS: Compared with IDC, NOS (n=509,864), MBC (n=3876) were more likely to present at an older age, be black, have negative lymph nodes, be >2 cm, grade 3, and triple negative (TN). All subtypes [HR-positive/human epidermal growth receptor 2 (HER2)-negative, HR-positive/HER2-positive, HR-negative/HER2-positive, and TN] had higher BCSD than IDC, NOS. 22.3% of MBC cases were HR-positive. HR-positive MBCs tested for a recurrence score (RS) 65% were high-risk compared with 16.8% of IDC, NOS. Within the MBC cohort, no significant differences in BCSD were identified with respect to different molecular subtypes. In a fully adjusted model, TN or HER2-positive status did not adversely affect BCSD compared with HR-positive MBC.

CONCLUSIONS: All molecular subtypes of MBC had a poorer prognosis compared with IDC, NOS. The different molecular subtypes of MBC did not affect the BCSD. HR-positive MBC patients had a significantly higher high-risk RS than IDC, NOS patients.}, } @article {pmid37697863, year = {2023}, author = {Lu, D and Li, F and Zhao, C and Ye, Y and Zhang, X and Yang, P and Zhang, X}, title = {A Remineralizing and Antibacterial Coating for Arresting Caries.}, journal = {Journal of dental research}, volume = {102}, number = {12}, pages = {1315-1325}, doi = {10.1177/00220345231189992}, pmid = {37697863}, issn = {1544-0591}, mesh = {Humans ; *Dental Caries/prevention & control ; Dental Caries Susceptibility ; *Tooth Demineralization/prevention & control ; Dental Enamel ; Composite Resins ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Tooth Remineralization/methods ; }, abstract = {Dental caries is a dynamic disease induced by the unbalance between demineralization of dental hard tissues caused by biofilm and remineralization of them; however, although various effective remineralization methods have been well documented, it is a challenge to reestablish the balance by enhancing remineralization alone while ignoring the antibacterial therapy. Therefore, the integration of remineralizing and antibacterial technologies offers a promising strategy to halt natural caries progression in clinical practice. Here, the conception of interrupting dental caries (IDC) was proposed based on the development of dual-functional coating with remineralizing and antibacterial properties. In this study, bovine serum albumin (BSA) loaded octenidine (OCT) successfully to form a BSA-OCT composite. Subsequently, through fast amyloid-like aggregation, the phase-transited BSA-OCT (PTB-OCT) coating can be covered on teeth, resin composite, or sealant surfaces in 30 min by a simple smearing process. The PTB-OCT coating showed satisfactory effects in promoting the remineralization of demineralized enamel and dentin in vitro. Moreover, this coating also exerted significant acid-resistance stability and anti-biofilm properties. Equally importantly, this coating exhibited promising abilities in reducing the microleakage between the tooth and resin composite in vitro and preventing primary and secondary caries in vivo. In conclusion, this novel dual-functional PTB-OCT coating could reestablish the balance between demineralization and remineralization in the process of caries, thereby potentially preventing or arresting caries.}, } @article {pmid37697031, year = {2023}, author = {Onega, T and Abraham, L and Miglioretti, DL and Lee, CI and Henderson, LM and Kerlikowske, K and Tosteson, ANA and Weaver, D and Sprague, BL and Bowles, EJA and di Florio-Alexander, RM}, title = {Digital mammography and digital breast tomosynthesis for detecting invasive lobular and ductal carcinoma.}, journal = {Breast cancer research and treatment}, volume = {202}, number = {3}, pages = {505-514}, pmid = {37697031}, issn = {1573-7217}, support = {HHSN261201000140C/CA/NCI NIH HHS/United States ; U54CA163303/CA/NCI NIH HHS/United States ; N01 CN067009/CN/NCI NIH HHS/United States ; U01 CA086076/CA/NCI NIH HHS/United States ; P01 CA154292/CA/NCI NIH HHS/United States ; U54 CA163303/CA/NCI NIH HHS/United States ; HHSN261201300012I/CA/NCI NIH HHS/United States ; PCS-1504-30370/PCORI/Patient-Centered Outcomes Research Institute/United States ; HHSN261201000035I/CA/NCI NIH HHS/United States ; U58 DP003862/DP/NCCDPHP CDC HHS/United States ; HHSN261201000029C/CA/NCI NIH HHS/United States ; P01CA154292/CA/NCI NIH HHS/United States ; N01 PC035142/CA/NCI NIH HHS/United States ; R01 CA149365/CA/NCI NIH HHS/United States ; R50 CA211115/CA/NCI NIH HHS/United States ; HHSN261201000035C/PC/NCI NIH HHS/United States ; HHSN261201000034C/CA/NCI NIH HHS/United States ; N01 CN005230/CN/NCI NIH HHS/United States ; R01 HS018366/HS/AHRQ HHS/United States ; R50CA211115/CA/NCI NIH HHS/United States ; R01CA149365/CA/NCI NIH HHS/United States ; }, mesh = {Female ; Humans ; *Breast Neoplasms/pathology ; Early Detection of Cancer/methods ; Mammography/methods ; Breast Density ; *Carcinoma, Ductal, Breast/diagnostic imaging ; Mass Screening/methods ; Retrospective Studies ; }, abstract = {PURPOSE: Invasive lobular carcinoma (ILC) is a distinct histological subtype of breast cancer that can make early detection with mammography challenging. We compared imaging performance of digital breast tomosynthesis (DBT) to digital mammography (DM) for diagnoses of ILC, invasive ductal carcinoma (IDC), and invasive mixed carcinoma (IMC) in a screening population.

METHODS: We included screening exams (DM; n = 1,715,249 or DBT; n = 414,793) from 2011 to 2018 among 839,801 women in the Breast Cancer Surveillance Consortium. Examinations were followed for one year to ascertain incident ILC, IDC, or IMC. We measured cancer detection rate (CDR) and interval invasive cancer rate/1000 screening examinations for each histological subtype and stratified by breast density and modality. We calculated relative risk (RR) for DM vs. DBT using log-binomial models to adjust for the propensity of receiving DBT vs. DM.

RESULTS: Unadjusted CDR per 1000 mammograms of ILC overall was 0.33 (95%CI: 0.30-0.36) for DM; 0.45 (95%CI: 0.39-0.52) for DBT, and for women with dense breasts- 0.33 (95%CI: 0.29-0.37) for DM and 0.54 (95%CI: 0.43-0.66) for DBT. Similar results were noted for IDC and IMC. Adjusted models showed a significantly increased RR for cancer detection with DBT compared to DM among women with dense breasts for all three histologies (RR; 95%CI: ILC 1.53; 1.09-2.14, IDC 1.21; 1.02-1.44, IMC 1.76; 1.30-2.38), but no significant increase among women with non-dense breasts.

CONCLUSION: DBT was associated with higher CDR for ILC, IDC, and IMC for women with dense breasts. Early detection of ILC with DBT may improve outcomes for this distinct clinical entity.}, } @article {pmid37696743, year = {2024}, author = {Bernardino, RM and Sayyid, RK and Lajkosz, K and Al-Daqqaq, Z and Cockburn, JG and Chavarriaga, J and Abedi, S and Leão, R and Berlin, A and van der Kwast, T and Fleshner, NE}, title = {Limitations of Prostate Biopsy in Detection of Cribriform and Intraductal Prostate Cancer.}, journal = {European urology focus}, volume = {10}, number = {1}, pages = {146-153}, doi = {10.1016/j.euf.2023.08.010}, pmid = {37696743}, issn = {2405-4569}, mesh = {Male ; Humans ; *Prostate/pathology ; *Prostatic Neoplasms/diagnosis/surgery/pathology ; Prostatectomy/methods ; Prognosis ; Image-Guided Biopsy ; }, abstract = {BACKGROUND: The presence of cribriform morphology and intraductal carcinoma (IDC) in prostate biopsies and radical prostatectomy specimens is an adverse prognostic feature that can be used to guide treatment decisions.

OBJECTIVE: To assess how accurately biopsies can detect cribriform morphology and IDC cancer by examining matched biopsy and prostatectomy samples.

Patients who underwent radical prostatectomy at The Princess Margaret Cancer Centre between January 2015 and December 2022 and had cribriform morphology and/or IDC in the surgical specimen were included in the study.

We used detection sensitivity to evaluate the level of agreement between biopsy and prostatectomy samples regarding the presence of cribriform morphology and IDC.

RESULTS AND LIMITATIONS: Of the 287 men who underwent radical prostatectomy, 241 (84%) had cribriform morphology and 161 (56%) had IDC on final pathology. The sensitivity of prostate biopsy, using radical prostatectomy as the reference, was 42.4% (95% confidence interval [CI] 36-49%) for detection of cribriform morphology and 44.1% (95% CI 36-52%) for detection of IDC. The sensitivity of prostate biopsy for detection of either IDC or cribriform morphology was 52.5% (95% CI 47-58%). Among patients who underwent multiparametric magnetic resonance imaging-guided biopsies, the sensitivity was 54% (95% CI 39-68%) for detection of cribriform morphology and 37% (95% CI 19-58%) for detection of IDC.

CONCLUSIONS: Biopsy has low sensitivity for detecting cribriform morphology and IDC. These limitations should be incorporated into clinical decision-making. Biomarkers for better detection of these histological patterns are needed.

PATIENT SUMMARY: Prostate biopsy is not an accurate method for detecting two specific types of prostate cancer cells, called cribriform pattern and intraductal prostate cancer, which are associated with unfavorable prognosis.}, } @article {pmid37694008, year = {2023}, author = {Tanpure, VR and Palagiri, FB and Kolhe, KK and Wajekar, NA and Pathak, SS and Tanpure, AV and Kumar, A and Badiyani, BK}, title = {A Study to Assess Indian Patients' Expectations of Check-Up and Diagnosis or Discussion about Treatment at their Initial Orthodontic Visit.}, journal = {Journal of pharmacy & bioallied sciences}, volume = {15}, number = {Suppl 2}, pages = {S1253-S1256}, pmid = {37694008}, issn = {0976-4879}, abstract = {AIM: To access the patient's expectations of orthodontic treatment at the first visit.

MATERIALS AND METHODS: Three hundred new patients to the orthodontics department were included in the analysis. Their demographic details and their opinions on what they hoped to gain from orthodontic treatment were gleaned from their replies to a well-crafted questionnaire.

RESULTS: Most respondents were more concerned with the cosmetic results of orthodontic treatment than they were with the therapy's practical benefits. They hoped that after having their teeth straightened, they would feel more comfortable interacting with others and have a better overall appearance. In terms of improving one's job and making one's speaking simpler, the mean scores were the lowest. The female participants averaged higher marks than the male participants across all areas studied, with the greatest mark coming in the area of improved smiles.

CONCLUSION: An effective outcome from orthodontic therapy requires full patient participation. Before beginning treatment, it is important for the orthodontist and patient to have an agreement on the patient's reasonable expectations for the therapy's outcomes.}, } @article {pmid37688253, year = {2023}, author = {Yang, SY and Kang, DS and Lee, CY}, title = {Coloration on Bluish Alginate Films with Amorphous Heterogeneity Thereof.}, journal = {Polymers}, volume = {15}, number = {17}, pages = {}, pmid = {37688253}, issn = {2073-4360}, support = {2019R1I1A3A01060180//National Research Foundation of Korea/ ; 2021R1A5A1031868//National Research Foundation of Korea/ ; }, abstract = {Using sodium alginate (Alg) aqueous solution containing indigo carmine (IdC) at various concentrations we characterized the rippled surface pattern with micro-spacing on a flexible film as intriguing bluish Alg-IdC iridescence. The characterization was performed using Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, field emission scanning electron microscopy, atomic force microscopy, electron microscopy, differential scanning calorimetry, thermogravimetric analysis, X-ray diffraction analysis, and photoluminescence detection. The edge pattern on the film had a maximum depth of 825 nm, a peak-to-peak distance of 63.0 nm, and an average distance of 2.34 nm. The center of the pattern had a maximum depth of 343 nm and a peak-to-peak distance of 162 nm. The pattern spacing rippled irregularly, widening toward the center and narrowing toward the edges. The rippled nano-patterned areas effectively generated iridescence. The ultraviolet absorption spectra of the mixture in the 270 and 615 nm ranges were the same for both the iridescent and non-iridescent film surfaces. By adding Ag[+] ions to Alg-IdC, self-assembled microspheres were formed, and conductivity was improved. Cross-linked bluish materials were immediately formed by the addition of Ca[2+] ions, and the film was prepared by controlling their concentration. This flexible film can be used in applications such as eco-friendly camouflage, anti-counterfeiting, QR code materials for imaging/sensing, and smart hybrid displays.}, } @article {pmid37686673, year = {2023}, author = {Timbres, J and Kohut, K and Caneppele, M and Troy, M and Schmidt, MK and Roylance, R and Sawyer, E}, title = {DCIS and LCIS: Are the Risk Factors for Developing In Situ Breast Cancer Different?.}, journal = {Cancers}, volume = {15}, number = {17}, pages = {}, pmid = {37686673}, issn = {2072-6694}, abstract = {Ductal carcinoma in situ (DCIS) is widely accepted as a precursor of invasive ductal carcinoma (IDC). Lobular carcinoma in situ (LCIS) is considered a risk factor for invasive lobular carcinoma (ILC), and it is unclear whether LCIS is also a precursor. Therefore, it would be expected that similar risk factors predispose to both DCIS and IDC, but not necessarily LCIS and ILC. This study examined associations with risk factors using data from 3075 DCIS cases, 338 LCIS cases, and 1584 controls aged 35-60, recruited from the UK-based GLACIER and ICICLE case-control studies between 2007 and 2012. Analysis showed that breastfeeding in parous women was protective against DCIS and LCIS, which is consistent with research on invasive breast cancer (IBC). Additionally, long-term use of HRT in post-menopausal women increased the risk of DCIS and LCIS, with a stronger association in LCIS, similar to the association with ILC. Contrary to findings with IBC, parity and the number of births were not protective against DCIS or LCIS, while oral contraceptives showed an unexpected protective effect. These findings suggest both similarities and differences in risk factors for DCIS and LCIS compared to IBC and that there may be justification for increased breast surveillance in post-menopausal women taking long-term HRT.}, } @article {pmid37684268, year = {2023}, author = {Zhao, F and Zhang, T and Sun, X and Zhang, X and Chen, L and Wang, H and Li, J and Fan, P and Lai, L and Sui, T and Li, Z}, title = {A strategy for Cas13 miniaturization based on the structure and AlphaFold.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {5545}, pmid = {37684268}, issn = {2041-1723}, mesh = {*Dependovirus ; *Endonucleases ; Miniaturization ; RNA ; RNA Editing ; }, abstract = {The small size of the Cas nuclease fused with various effector domains enables a broad range of function. Although there are several ways of reducing the size of the Cas nuclease complex, no efficient or generalizable method has been demonstrated to achieve protein miniaturization. In this study, we establish an Interaction, Dynamics and Conservation (IDC) strategy for protein miniaturization and generate five compact variants of Cas13 with full RNA binding and cleavage activity comparable the wild-type enzymes based on a combination of IDC strategy and AlphaFold2. In addition, we construct an RNA base editor, mini-Vx, and a single AAV (adeno-associated virus) carrying a mini-RfxCas13d and crRNA expression cassette, which individually shows efficient conversion rate and RNA-knockdown activity. In summary, these findings highlight a feasible strategy for generating downsized CRISPR/Cas13 systems based on structure predicted by AlphaFold2, enabling targeted degradation of RNAs and RNA editing for basic research and therapeutic applications.}, } @article {pmid37683019, year = {2023}, author = {Moon, SY and Lim, KR and Son, JS}, title = {The role of infectious disease consultations in the management of patients with fever in a long-term care facility.}, journal = {PloS one}, volume = {18}, number = {9}, pages = {e0291421}, pmid = {37683019}, issn = {1932-6203}, mesh = {Humans ; Long-Term Care ; Retrospective Studies ; Nursing Homes ; Fever ; Referral and Consultation ; Tertiary Care Centers ; *Cardiomyopathy, Dilated ; *Communicable Diseases/therapy ; }, abstract = {BACKGROUND: Infectious disease (ID) clinicians can provide essential services for febrile patients in tertiary hospitals. The aim of this study was to evaluate the role of ID consultations (IDC) in managing hospitalized patients with infections in an oriental medical hospital (OMH), which serves as a long-term care facility. To our knowledge, this is the first study on the role of IDCs in managing patients in an OMH.

METHODS: This retrospective study was conducted in an OMH in Seoul, Korea, from June 2006 to June 2013.

RESULTS: Among the 465 cases of hospital-acquired fever, 141 (30.3%) were referred for ID. The most common cause of fever was infection in both groups. The peak body temperature of the patient was higher in IDC group (38.8±0.6°C vs. 38.6±0.5°C, p<0.001). Crude mortality at 30 days (14.6% vs. 7.8%, p = 0.043) and infection-attributable mortality (15.3% vs. 6.7%, p = 0.039) were higher in the No-IDC group. Multivariable analysis showed that infection as the focus of fever (adjusted Odd ratio [aOR] 3.49, 95% confidence interval (CI) 1.64-7.44), underlying cancer (aOR 10.32, 95% CI 4.34-24.51,), and multiorgan dysfunction syndrome (aOR 15.68, 95% CI 2.06-119.08) were associated with increased 30-day mortality. Multivariate analysis showed that in patients with infectious fever, appropriate antibiotic therapy (aOR 0.19, 95% CI 0.05-0.76) was the only factor associated with decreased infection-attributable mortality while underlying cancer (aOR 7.80, 95% CI 2.555-23.807) and severe sepsis or septic shock at the onset of fever (aOR 10.15, 95% CI 1.00-102.85) were associated with increased infection-attributable mortality.

CONCLUSION: Infection was the most common cause of fever in patients hospitalized for OMH. Infection as the focus of fever, underlying cancer, and MODS was associated with increased 30-day mortality in patients with nosocomial fever. Appropriate antibiotic therapy was associated with decreased infection-attributable mortality in patients with infectious fever.}, } @article {pmid37682691, year = {2023}, author = {Goh, SSN and Syn, NLX and Lim, CJE and Lee, RE and Samuel, M and Ng, CWQ}, title = {Oncologic outcomes after breast-conserving surgery with radiotherapy versus mastectomy in patients with Paget's disease of the breast: systematic review and meta-analysis.}, journal = {The British journal of surgery}, volume = {110}, number = {11}, pages = {1451-1457}, doi = {10.1093/bjs/znad199}, pmid = {37682691}, issn = {1365-2168}, abstract = {BACKGROUND: The conventional approach to treatment for Paget's disease of the breast has been mastectomy, but there is an increasing trend to consider breast-conserving surgery (BCS) followed by radiotherapy (RT) in these patients. This study aimed to provide an updated systematic review and meta-analysis comparing outcomes after BCS with RT versus mastectomy in the treatment of Paget's disease of the breast.

METHODS: Studies before May 2021 were included. Primary outcomes were overall survival and local recurrence. Separate analyses of Paget's disease associated with ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) were undertaken. Meta-regression was used to adjust for imbalance in the proportion of IDC among patients selected to undergo BCS versus mastectomy.

RESULTS: Overall survival in patients with Paget's disease who underwent BCS with RT was higher than for those who underwent mastectomy with pooled mortality hazard ratio (HR) of 0.68, (95% per cent c.i. 0.45 to 1.01). Patients with Paget's disease with DCIS had higher overall survival after BCS with or without RT versus mastectomy, with adjusted HR of 0.14 (0.10 to 0.20) and 0.28 (0.22 to 0.36), respectively. For patients with Paget's disease and IDC, overall survival was lower for BCS with or without RT versus mastectomy, with adjusted HR of 0.84 (0.57 to 1.25) and 1.64 (1.04 to 2.58), respectively. In Paget's disease and IDC, local recurrence risk was much higher for BCS with RT, RR 26.8 (1.60 to 456) versus without RT, RR 51.8 (6.80 to 391). In patients with Paget's disease and DCIS, risk of local recurrence versus mastectomy was lower for BCS with RT 0.72 (0.11 to 4.50) but slightly higher for BCS alone 1.38 (0.09 to 21.20).

CONCLUSION: BCS with RT may be a comparable treatment alternative to mastectomy for patients with Paget's disease with DCIS, and for selected patients with Paget's disease and IDC.}, } @article {pmid37681174, year = {2023}, author = {Wang, W and Ge, J and Ma, H and Lian, H and Cui, L and Zhao, Y and Li, Z and Wang, T and Zhang, R}, title = {Cladribine and cytarabine in children refractory high risk multisystem Langerhans cell histiocytosis.}, journal = {Heliyon}, volume = {9}, number = {9}, pages = {e19277}, pmid = {37681174}, issn = {2405-8440}, abstract = {There is no uniform regimen for refractory Langerhans cell histiocytosis (LCH). We retrospectively described patients with refractory multisystem and risk organ involvement LCH treated with the low-dose (Ara-c, 100 mg/m[2]/d × 5day; 2-CDA, 5 mg/m[2]/d × 5day) chemotherapy (LDC) and the intermediate-dose (Ara-c, 500 mg/m[2]/d × 5day; 2-CDA, 9 mg/m[2]/d × 5day) chemotherapy (IDC). 26 patients and 10 patients receiving the LDC and IDC regimen from January 2013 to December 2016 were included in the study. The overall response rate exhibited no significant difference between the LDC and IDC groups after four courses (76.9% vs 90%, P = 0.375) and eight courses (80.8% vs 100%, P = 0.135) of treatment. No statistical differences in the overall survival rate were observed between the two groups, but 5-year event-free survival rate of patients in the IDC group was higher than that in the LDC group at the median follow-up of 6.16 and 5.07 years (88.9% vs 52.9%, P = 0.033). The patients in the IDC group had more severe myelosuppression than those in the LDC group (grade 3/4 myelosuppression, 80% vs 19.2%, P = 0.001). The intermediate-dose regimen of 2CDA and Ara-c had a higher event-free survival rate and a similar overall survival rate compared with the low-dose regimen.}, } @article {pmid37673327, year = {2023}, author = {Mudeng, V and Farid, MN and Ayana, G and Choe, SW}, title = {Domain and Histopathology Adaptations-Based Classification for Malignancy Grading System.}, journal = {The American journal of pathology}, volume = {193}, number = {12}, pages = {2080-2098}, doi = {10.1016/j.ajpath.2023.07.007}, pmid = {37673327}, issn = {1525-2191}, mesh = {Humans ; Female ; *Neural Networks, Computer ; *Breast Neoplasms/pathology ; Breast/pathology ; Diagnosis, Computer-Assisted ; Biopsy ; }, abstract = {Accurate proliferation rate quantification can be used to devise an appropriate treatment for breast cancer. Pathologists use breast tissue biopsy glass slides stained with hematoxylin and eosin to obtain grading information. However, this manual evaluation may lead to high costs and be ineffective because diagnosis depends on the facility and the pathologists' insights and experiences. Convolutional neural network acts as a computer-based observer to improve clinicians' capacity in grading breast cancer. Therefore, this study proposes a novel scheme for automatic breast cancer malignancy grading from invasive ductal carcinoma. The proposed classifiers implement multistage transfer learning incorporating domain and histopathologic transformations. Domain adaptation using pretrained models, such as InceptionResNetV2, InceptionV3, NASNet-Large, ResNet50, ResNet101, VGG19, and Xception, was applied to classify the ×40 magnification BreaKHis data set into eight classes. Subsequently, InceptionV3 and Xception, which contain the domain and histopathology pretrained weights, were determined to be the best for this study and used to categorize the Databiox database into grades 1, 2, or 3. To provide a comprehensive report, this study offered a patchless automated grading system for magnification-dependent and magnification-independent classifications. With an overall accuracy (means ± SD) of 90.17% ± 3.08% to 97.67% ± 1.09% and an F1 score of 0.9013 to 0.9760 for magnification-dependent classification, the classifiers in this work achieved outstanding performance. The proposed approach could be used for breast cancer grading systems in clinical settings.}, } @article {pmid37671834, year = {2023}, author = {Giroud, M and Kotschi, S and Kwon, Y and Le Thuc, O and Hoffmann, A and Gil-Lozano, M and Karbiener, M and Higareda-Almaraz, JC and Khani, S and Tews, D and Fischer-Posovszky, P and Sun, W and Dong, H and Ghosh, A and Wolfrum, C and Wabitsch, M and Virtanen, KA and Blüher, M and Nielsen, S and Zeigerer, A and García-Cáceres, C and Scheideler, M and Herzig, S and Bartelt, A}, title = {The obesity-linked human lncRNA AATBC stimulates mitochondrial function in adipocytes.}, journal = {EMBO reports}, volume = {24}, number = {10}, pages = {e57600}, pmid = {37671834}, issn = {1469-3178}, support = {//Helmholtz Zentrum München (Helmholtz Centre Munich, German Research Center for Environmental Health)/ ; //Alexander von Humboldt-Stiftung (AvH)/ ; FI1700/7#x2010;1//Deutsche Forschungsgemeinschaft (DFG)/ ; TE912/2#x2010;2//Deutsche Forschungsgemeinschaft (DFG)/ ; TRR205//Deutsche Forschungsgemeinschaft (DFG)/ ; SFB1123//Deutsche Forschungsgemeinschaft (DFG)/ ; //Deutsches Zentrum für Herz-Kreislaufforschung (DZHK)/ ; //EC | H2020 | PRIORITY 'Excellent science' | H2020 European Research Council (ERC)/ ; }, abstract = {Adipocytes are critical regulators of metabolism and energy balance. While white adipocyte dysfunction is a hallmark of obesity-associated disorders, thermogenic adipocytes are linked to cardiometabolic health. As adipocytes dynamically adapt to environmental cues by functionally switching between white and thermogenic phenotypes, a molecular understanding of this plasticity could help improving metabolism. Here, we show that the lncRNA Apoptosis associated transcript in bladder cancer (AATBC) is a human-specific regulator of adipocyte plasticity. Comparing transcriptional profiles of human adipose tissues and cultured adipocytes we discovered that AATBC was enriched in thermogenic conditions. Using primary and immortalized human adipocytes we found that AATBC enhanced the thermogenic phenotype, which was linked to increased respiration and a more fragmented mitochondrial network. Expression of AATBC in adipose tissue of mice led to lower plasma leptin levels. Interestingly, this association was also present in human subjects, as AATBC in adipose tissue was inversely correlated with plasma leptin levels, BMI, and other measures of metabolic health. In conclusion, AATBC is a novel obesity-linked regulator of adipocyte plasticity and mitochondrial function in humans.}, } @article {pmid37668423, year = {2023}, author = {Amiri, A and Dietz, C and Rapp, A and Cardoso, MC and Stark, RW}, title = {The cyto-linker and scaffolding protein "plectin" mis-localization leads to softening of cancer cells.}, journal = {Nanoscale}, volume = {15}, number = {36}, pages = {15008-15026}, doi = {10.1039/d3nr02226a}, pmid = {37668423}, issn = {2040-3372}, mesh = {Humans ; *Carcinoma, Ductal/metabolism ; Cytoplasm/metabolism ; Cytoskeleton/metabolism ; Hydrolases/metabolism ; Microtubules/metabolism ; }, abstract = {Discovering tools to prevent cancer progression requires understanding the fundamental differences between normal and cancer cells. More than a decade ago, atomic force microscopy (AFM) revealed cancer cells' softer body compared to their healthy counterparts. Here, we investigated the mechanism underlying the softening of cancerous cells in comparison with their healthy counterparts based on AFM high resolution stiffness tomography and 3D confocal microscopy. We showed microtubules (MTs) network in invasive ductal carcinoma cell cytoskeleton is basally located and segmented for around 400 nm from the cell periphery. Additionally, the cytoskeleton scaffolding protein plectin exhibits a mis-localization from the cytoplasm to the surface of cells in the carcinoma which justifies the dissociation of the MT network from the cell's cortex. Furthermore, the assessment of MTs' persistence length using a worm-like-chain (WLC) model in high resolution AFM images showed lower persistence length of the single MTs in ductal carcinoma compared to that in the normal state. Overall, these tuned mechanics support the invasive cells to ascertain more flexibility under compressive forces in small deformations. These data provide new insights into the structural origins of cancer aids in progression.}, } @article {pmid37665386, year = {2024}, author = {Aiello, EN and D'Iorio, A and Solca, F and Torre, S and Bonetti, R and Scheveger, F and Colombo, E and Maranzano, A and Maderna, L and Morelli, C and Doretti, A and Amboni, M and Vitale, C and Verde, F and Ferrucci, R and Barbieri, S and Zirone, E and Priori, A and Pravettoni, G and Santangelo, G and Silani, V and Ticozzi, N and Ciammola, A and Poletti, B}, title = {Correction: Clinimetrics and feasibility of the Italian version of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease patients.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {131}, number = {9}, pages = {1143-1144}, doi = {10.1007/s00702-023-02690-x}, pmid = {37665386}, issn = {1435-1463}, } @article {pmid37664269, year = {2023}, author = {Haque, E and Mushtaq, AH and Alkhatib, R and Alhusaini, H and Suleman, K}, title = {An Unexpected Diagnosis of Second Primary Malignancy in a Breast Cancer Survivor: A Case Report.}, journal = {Cureus}, volume = {15}, number = {8}, pages = {e42819}, pmid = {37664269}, issn = {2168-8184}, abstract = {BACKGROUND: Breast cancer survival rates are increasing more than ever with the development of better diagnostic and therapeutic techniques. Survivors of breast cancer have an increased risk of developing second primary malignancies, which may be mistaken for breast cancer recurrence and lead to delayed diagnosis and poor prognosis.

CASE REPORT: We report a case of a 62-year-old female who presented with shortness of breath and bone pain. She had a history of left triple-positive invasive ductal carcinoma (T1N0M0) treated with bilateral skin-sparing mastectomy, adjuvant Taxotere, and trastuzumab-based therapy and then continued on trastuzumab and letrozole. She underwent imaging to explore the source of her symptoms at which new pulmonary nodules were discovered. During workup, she was found to have elevated tumor markers. They were initially suspected to be breast cancer recurrence metastases based on elevated tumor markers; however, further investigations confirmed that the nodules were a second primary lung adenocarcinoma with a different molecular profile. The patient had disease progression despite chemotherapy and eventually succumbed to her disease.

CONCLUSION: This case highlights the importance of considering second primary malignancies in breast cancer survivors and utilizing advanced diagnostic modalities to efficiently diagnose such cases.}, } @article {pmid37661085, year = {2023}, author = {Park, SY and Kim, HJ and Lee, J and Jeong, JY and Byun, J and Kim, WH and Park, B and Hong, J}, title = {A Radiation Induced Low-Grade Myofibroblastic Sarcoma in the Retropectoral Area After Breast Conserving Surgery: A Case Report.}, journal = {Journal of breast cancer}, volume = {26}, number = {4}, pages = {397-402}, pmid = {37661085}, issn = {1738-6756}, abstract = {Low-grade myofibroblastic sarcoma (LGMFS) is a rare type of sarcoma, and its manifestation as a radiotherapy (RT)-induced sarcoma following RT for breast cancer is even more unusual. To date, only one case of RT-induced mammary myofibroblastic sarcoma (MFS) has been reported. Here we present the case of a 49-year-old woman with LGMFS after undergoing breast-conserving surgery for invasive ductal carcinoma (IDC), and with a history of RT 16 years prior. Due to the rarity of this disease, previous studies have focused primarily on the pathological findings of MFS. In this report however, we present the clinical and radiological features of LGMFS in the retro pectoral area as a rare type of RT-induced sarcoma.}, } @article {pmid37652705, year = {2023}, author = {Li, X and Stitt, D and Lanzino, G and Giannini, C and Dubey, D and Carabenciov, ID}, title = {Teaching NeuroImage: Pachymeningitis and Aortitis as the Initial Presentation of Granulomatosis With Polyangiitis.}, journal = {Neurology}, volume = {101}, number = {21}, pages = {979-980}, pmid = {37652705}, issn = {1526-632X}, mesh = {Humans ; *Aortitis/complications/diagnostic imaging ; *Granulomatosis with Polyangiitis/complications/diagnostic imaging ; *Meningitis/complications/diagnostic imaging ; }, } @article {pmid37649292, year = {2023}, author = {Ramli Hamid, MT and Loi, KS and Chan, WY and Ab Mumin, N and Abdul Hamid, S and Izza Rozalli, F and Rahmat, K}, title = {Clinical usefulness of abbreviated mri protocol in breast cancer detection.}, journal = {Current medical imaging}, volume = {}, number = {}, pages = {}, doi = {10.2174/1573405620666230829150218}, pmid = {37649292}, issn = {1573-4056}, abstract = {BACKGROUND: The use of breast MRI for screening has increased over the past decade, mostly in women with a high risk of breast cancer. Abbreviated breast MRI (AB-MR) is introduced to make MRI a more accessible screening modality. AB-MR decreases scanning and reporting time and the overall cost of MRI.

OBJECTIVE: This study aims to evaluate the diagnostic efficacy of abbreviated MRI protocol in detecting breast cancer in screening and diagnostic populations, using histopathology as the reference standard.

MATERIALS AND METHODS: This is a single-centre retrospective cross-sectional study of 134 patients with 198 histologically proven breast lesions who underwent full diagnostic protocol contrast-enhanced breast MRI (FDP-MR) at the University Malaya Medical Centre (UMMC) from 1st January 2018 to 31st December 2019. AB-MR was pre-determined and evaluated with regard to the potential to detect and exclude malignancy from 3 readers of varying radiological experiences. The sensitivity of both AB-MR and FDP-MR were compared using the McNemar test, where both protocols' diagnostic performances were assessed via the receiver operating characteristic (ROC) curve. Inter-observer agreement was analysed using Fleiss Kappa.

RESULT: There were 134 patients with 198 lesions. The average age was 50.9 years old (range 27 - 80). A total of 121 (90%) MRIs were performed for diagnostic purposes. Screening accounted for 9.4% of the cases, 55.6% (n=110) lesions were benign, and 44.4% (n=88) were malignant. The commonest benign and malignant lesions were fibrocystic change (27.3%) and invasive ductal carcinoma (78.4%). The mean sensitivity, specificity, positive predictive value, and negative predictive value for AB-MR were 0.96, 0.57, 0.68 and 0.94, respectively. Both AB-MR and FDP-MR showed excellent diagnostic performance with AUC of 0.88 and 0.96, respectively. The general inter-observer agreement of all three readers for AB-MR was substantial (k=0.69), with fair agreement demonstrated between AB-MR and FDP-MR (k=0.36).

CONCLUSION: The study shows no evidence that the diagnostic efficacy of AB-MR is inferior to FDP-MR. AB-MR, with high sensitivity, has proven its capability in cancer detection and exclusion, especially for biologically aggressive cancers.}, } @article {pmid37648809, year = {2023}, author = {Miljanic, M and Nwachukwu, C and Rahimi, A}, title = {Definitive ablative stereotactic partial breast irradiation in early stage inoperable breast cancer.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {17}, pages = {15553-15559}, pmid = {37648809}, issn = {1432-1335}, mesh = {Female ; Humans ; Aged, 80 and over ; *Carcinoma, Non-Small-Cell Lung/pathology ; *Lung Neoplasms/pathology ; *Breast Neoplasms/surgery ; *Radiosurgery/methods ; Treatment Outcome ; }, abstract = {PURPOSE: This case series and literature review aims to investigate the efficacy and safety of definitive ablative radiation therapy as a treatment modality for non-operable patients with early stage breast cancer. We present two cases demonstrating the potential of this approach to achieve durable responses.

METHODS: We assessed the long-term response of two non-operable patients diagnosed with Stage II (cT2N0M) and Stage IA (T1bN0M0) invasive ductal carcinoma (IDC), who were deemed unfit for surgery due to significant co-morbid conditions. Definitive ablative radiation therapy was administered using stereotactic partial breast irradiation with ablative doses delivered in either a single fraction or two fractions. Serial imaging was conducted to assess treatment response and monitor adverse events.

RESULTS: Both patients exhibited notable treatment responses following definitive ablative radiation therapy. The first patient, an 84-year-old woman, experienced a 69% reduction in tumor size over a follow-up period exceeding 2 years. The second patient, an 87-year-old woman, achieved complete resolution of disease on imaging, with no signs of progression even 26 month post-treatment. Both patients tolerated the treatment well, without significant treatment-related adverse events.

CONCLUSIONS: Our case series suggests that definitive ablative radiation therapy may serve as a safe and effective treatment option for non-operable patients with early stage breast cancer. The observed durable treatment responses and minimal toxicity support the potential of this approach. Furthermore, a longer interval between ablative radiation therapy and surgery may enhance treatment response, potentially leading to increased complete pathologic response rates.}, } @article {pmid37637763, year = {2023}, author = {Abbasi, A and Ghaffarizadeh, F and Mojdeganlou, H}, title = {Prognostic Significance of Microvessel Density in Invasive Ductal Carcinoma of Breast.}, journal = {International journal of hematology-oncology and stem cell research}, volume = {17}, number = {2}, pages = {100-105}, pmid = {37637763}, issn = {2008-3009}, abstract = {Background: Breast cancer is the most common malignant tumor and cause of death in women. Factors that play role in tumor metastasis are lymph node involvement, lack of tumor differentiation and hormone receptor expression, high proliferation rate, and angiogenesis. In the present study, we tried to evaluate the microvessel density (MVD) using Immunohistochemistry for the CD34 marker to investigate the amount of angiogenesis in breast cancer and its relationship with other histopathological parameters and compare it with normal tissue. Materials and Methods: 58 paraffin-embedded samples of breast cancer were enrolled. All blocks were sectioned and stained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2(HER 2/neu), ki67, and CD34 by immunohistochemistry (IHC) method. Results: The mean age of patients in this study was 49.6 ± 10.6 years. Statistically, there was a significant relationship between the grade of the tumor (P = 0.01), absence of expression of estrogen receptor (P = 0.008), and progesterone receptor (P = 0.003) with MVD. Conclusion: Due to the association between MVD, tumor grade, and absence of ER and PR expression, this valuable marker can play an important role in the prediction of prognosis in breast cancer patients and can lead to new-targeted therapy in the future.}, } @article {pmid37635979, year = {2023}, author = {Barlier, A and Romanet, P and Pellegata, NS}, title = {Editorial: New insights into multiple endocrine neoplasia type 1.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1266148}, pmid = {37635979}, issn = {1664-2392}, mesh = {Humans ; *Multiple Endocrine Neoplasia Type 1/genetics ; }, } @article {pmid37624596, year = {2023}, author = {Liu, G and Kong, X and Dai, Q and Cheng, H and Wang, J and Gao, J and Wang, Y}, title = {Clinical Features and Prognoses of Patients With Breast Cancer Who Underwent Surgery.}, journal = {JAMA network open}, volume = {6}, number = {8}, pages = {e2331078}, pmid = {37624596}, issn = {2574-3805}, mesh = {Female ; Humans ; Middle Aged ; Asian People ; *Breast Neoplasms/surgery ; Cohort Studies ; Lymphatic Metastasis ; Mastectomy ; Prognosis ; Erb-b2 Receptor Tyrosine Kinases/chemistry ; }, abstract = {IMPORTANCE: Breast cancer (BC) remains a pervasive malignant neoplasm worldwide, with increasing incidence. However, there are a scarcity of studies examining the clinical characteristics and prognosis of Chinese patients with BC who have undergone surgery.

OBJECTIVE: To evaluate overall survival (OS) and disease-free survival (DFS) in patients with surgically treated BC in China, focusing on histopathology and surgical approach.

This cohort study included a retrospective review of the medical records of patients with unilateral BC who underwent surgery between January 2009 and September 2017, with a median follow-up time of 7.69 years. Clinical features were extracted from these records, and survival analysis was performed. Data analysis was conducted in March 2023.

MAIN OUTCOMES AND MEASURES: Patients' OS and DFS.

RESULTS: The study included 14 782 patients (14 724 [99.6%] female patients; mean [SD] age, 51.6 [10.9] years). Invasive ductal carcinoma (IDC) was the most prevalent type, observed in 12 671 patients (85.6%). Stages 0, I, II, III, and IV accounted for 6.4% (919 patients), 32.0% (4579 patients), 40.5% (5791 patients), 20.2% (2896 patients), and 0.9% (126 patients) of cases, respectively. Hormone receptor (HR) positivity was observed in 10 241 patients (75.1%), and 3665 (29.1%) tested positive for ERBB2 (formerly HER2/neu). The HR-negative-ERBB2-negative, HR-negative-ERBB2-positive, HR-positive-ERBB2-negative, and HR-positive-ERBB2-positive subtypes constituted 13.3% (1666 patients), 12.7% (1595 patients), 57.8% (7251 patients), and 16.2% (2034 patients) of cases, respectively. Breast-conserving surgery (BCS) was performed in 2884 patients (19.5%). The 5-year and 10-year OS rates were 92.9% (13 689 of 14 732) and 87.4% (3287 of 3760), while the 5-year and 10-year DFS rates were 89.0% (12 916 of 14 512) and 82.9% (3078 of 3713), respectively. Multivariate analysis found that for patients with IDC, age, BCS, invasive tumor size, tumor grade, lymphovascular invasion (LVI), the number of lymph node metastases (LNMs), distant metastasis, Ki67, and HR status were associated with OS, whereas invasive tumor size, tumor grade, LVI, the number of LNMs, HR status, and ERBB2 status were associated with DFS. After propensity score matching, BCS was equivalent to mastectomy with respect to survival in patients with IDC.

CONCLUSIONS AND RELEVANCE: This cohort study of patients with BC who underwent surgery in China provides valuable insights into the histopathological characteristics and survival outcomes of this population. The diverse histopathological features emphasize the necessity for customized treatment strategies. The relatively low BCS rate in the study population suggests the need for heightened awareness and adoption of this approach, considering its potential advantages for survival.}, } @article {pmid37621419, year = {2023}, author = {Dao, E and Gohla, G and Williams, P and Lovrics, P and Badr, F and Fang, Q and Farrell, TJ and Farquharson, MJ}, title = {Multivariate analysis of breast tissue using optical parameters extracted from a combined time-resolved fluorescence and diffuse reflectance system for tumor margin detection.}, journal = {Journal of biomedical optics}, volume = {28}, number = {8}, pages = {085001}, pmid = {37621419}, issn = {1560-2281}, mesh = {Humans ; Multivariate Analysis ; *Breast/diagnostic imaging ; Mastectomy, Segmental ; Obesity ; *Optical Devices ; Radiopharmaceuticals ; }, abstract = {SIGNIFICANCE: Breast conservation therapy is the preferred technique for treating primary breast cancers. However, breast tumor margins are hard to determine as tumor borders are often ill-defined. As such, there exists a need for a clinically compatible tumor margin detection system.

AIM: A combined time-resolved fluorescence and diffuse reflectance (TRF-DR) system has been developed to determine the optical properties of breast tissue. This study aims to improve tissue classification to aid in surgical decision making.

APPROACH: Normal and tumor breast tissue were collected from 80 patients with invasive ductal carcinoma and measured in the optical system. Optical parameters were extracted, and the tissue underwent histopathological examination. In total, 761 adipose, 77 fibroglandular, and 347 tumor spectra were analyzed. Principal component analysis and decision tree modeling were performed using only TRF optical parameters, only DR optical parameters, and using the combined datasets.

RESULTS: The classification modeling using TRF data alone resulted in a tumor margin detection sensitivity of 72.3% and specificity of 88.3%. Prediction modeling using DR data alone resulted in greater sensitivity and specificity of 80.4% and 94.0%, respectively. Combining both datasets resulted in the improved sensitivity and specificity of 85.6% and 95.3%, respectively. While both sensitivity and specificity improved with the combined modeling, further study of fibroglandular tissue could result in improved classification.

CONCLUSION: The combined TRF-DR system showed greater tissue classification capability than either technique alone. Further work studying more fibroglandular tissue and tissue of mixed composition would develop this system for intraoperative use for tumor margin detection.}, } @article {pmid37610487, year = {2023}, author = {Barker, VR and Naffouje, SA and Mallory, MA and Hoover, SA and Laronga, C}, title = {Surgical Management of the Axilla in HR+/HER2- Breast Cancer in the Z1071 Era: A Propensity Score-Matched Analysis of the National Cancer Database.}, journal = {Annals of surgical oncology}, volume = {30}, number = {13}, pages = {8371-8380}, pmid = {37610487}, issn = {1534-4681}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery ; Axilla/pathology ; Propensity Score ; Sentinel Lymph Node Biopsy ; Lymph Node Excision ; *Carcinoma, Ductal, Breast/pathology ; Neoadjuvant Therapy ; Lymph Nodes/pathology ; }, abstract = {BACKGROUND: Axillary management varies between sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) for patients with clinical N1 (cN1), hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)/neu-negative (HER2-), infiltrative ductal carcinoma (IDC) who achieve a complete clinical response (cCR) to neoadjuvant systemic therapy (NAST). This study sought to evaluate clinical practice patterns and survival outcomes of SLNB versus ALND in this patient subset.

METHODS: Patients with cN1, HR+/HER2-, unilateral IDC demonstrating a cCR to NAST were identified from the 2012-2017 National Cancer Database (NCDB) and stratified based on final axillary surgery management (SLNB vs ALND). After propensity score-matching, overall survival (OS) was compared using a Kaplan-Meier analysis, and significant OS predictors were identified using Cox regression.

RESULTS: Of the 1676 patients selected for this study, 593 (35.4%) underwent SLNB and 1083 (64.6%) underwent ALND. Use of SLNB increased by 28 % between 2012 and 2017. Among a total of 584 matched patients, 461 matched ypN0 patients, and 108 matched ypN+ patients, mean OS did not differ between SLNB and ALND (all patients [92.1 ± 0.8 vs 90.2 ± 1.0 months; p = 0.157], ypN0 patients [92.4 ± 0.8 vs 89.9 ± 0.9 months; p = 0.105], ypN+ patients [83.5 ± 2.3 vs 91.7 ± 2.7 months; p ± 0.963). Cox regression identified age, Charlson score, clinical T stage, and pathologic nodal status as significant predictors of OS.

CONCLUSION: The final surgical management strategy used for cN1, HR+/HER2- IDC patients who achieved a cCR to NAST did not have a significant impact on survival outcomes in this analysis. Potential opportunities for de-escalation of axillary management among this patient subset exist, and validation studies are needed.}, } @article {pmid37608749, year = {2023}, author = {Ito, T and Takahara, T and Taniguchi, N and Yamamoto, Y and Satou, A and Ohashi, A and Takahashi, E and Sassa, N and Tsuzuki, T}, title = {PTEN loss in intraductal carcinoma of the prostate has low incidence in Japanese patients.}, journal = {Pathology international}, volume = {73}, number = {11}, pages = {542-548}, doi = {10.1111/pin.13369}, pmid = {37608749}, issn = {1440-1827}, support = {21K06933//Japan Society for the Promotion of Science/ ; 21K15392//Japan Society for the Promotion of Science/ ; }, mesh = {Male ; Humans ; Prostate/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Incidence ; East Asian People ; *Prostatic Neoplasms/pathology ; PTEN Phosphohydrolase/genetics/metabolism ; }, abstract = {Clinical and genomic features of prostate cancer (PCa) vary considerably between Asian and Western populations. PTEN loss is the most frequent abnormality in intraductal carcinoma of the prostate (IDC-P) in Western populations. However, its prevalence and significance in Asian populations have not yet been well studied. In the present study, we evaluated PTEN expression in IDC-P in a Japanese population and its association with ERG expression. This study included 45 and 59 patients with PCa with and without IDC-P, respectively, who underwent radical prostatectomy. PTEN loss was observed in 10 patients with PCa with IDC-P (22%) and nine patients with PCa without IDC-P (17%). ERG expression was relatively frequent in patients with PCa with PTEN loss, although a significant difference was not observed. The co-occurrence of PTEN loss and ERG expression was observed in four patients with PCa with IDC-P and one without IDC-P. PTEN loss and ERG expression did not affect progression-free survival, regardless of the presence of IDC-P. The frequency of PTEN loss in IDC-P is lower in Asian patients than in Western patients. Our results indicate that mechanisms underlying IDC-P in Asian populations are different from those of Western populations.}, } @article {pmid37605516, year = {2023}, author = {Wang, Y and Liang, Y and Ye, F and Luo, D and Jin, Y and Li, Y and Zhao, W and Chen, B and Wang, L and Yang, Q}, title = {Histologic heterogeneity predicts patient prognosis of HER2-positive metastatic breast cancer: A retrospective study based on SEER database.}, journal = {Cancer medicine}, volume = {12}, number = {18}, pages = {18597-18610}, pmid = {37605516}, issn = {2045-7634}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Retrospective Studies ; *Carcinoma, Lobular/pathology ; Prognosis ; *Carcinoma, Ductal, Breast/pathology ; *Bone Neoplasms ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; }, abstract = {BACKGROUND: Human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) is a subtype of breast cancer with a worse prognosis. Little is known about the relationship between histology and prognosis among different distant metastasis sites (DMS). Our aims were to explore the prognostic value of histologic subtypes in different DMS and screen out specific subtypes with particular DMS that need more attention in HER2+ MBC.

METHODS: HER2+ MBC patient data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2014. Chi-squared tests were utilized to compare histologic subtypes in four DMS. The logistic regression analyses were used to control confounding factors. The log-rank tests were used to analyze the correlation of histologic subtype with disease-specific survival and overall survival. The survival data was analyzed using Kaplan-Meier methods.

RESULTS: A total of 1174 HER2+ MBC patients were involved. First, the distribution of histological subtypes varied across metastatic sites, and the proportions of metastatic sites in different histological subtypes were also different. Furthermore, different histological subtypes within specific DMS showed divergent prognoses, and the different outcomes were shown by distinct DMS for specific histological subtypes. Among them, lobular carcinoma (ILC) subtypes showed the worst prognosis in bone metastasis, and lung metastasis predicted the worst prognosis in infiltration duct and lobular carcinoma (IDC-ILC) subtypes. After further consideration of hormone receptor (HR) status, the IDC-ILC subtype with liver metastasis in HR+/HER2+ MBC patients and the ILC subtype with bone metastasis in HR-/HER2+ MBC patients proved to be noteworthy.

CONCLUSIONS: Histological subtypes are involved in determining the heterogeneity of HER2+ MBC patient prognosis, which is helpful to guide the prognosis prediction and monitoring of HER2+ breast cancer patients in clinics.}, } @article {pmid37602185, year = {2023}, author = {Amritanand, A and Arthur, A and Horo, S and Obed, P and Ramamurthy, P and Rebekah, G and Abraham, VJ and Paul, P}, title = {Comparative evaluation of diabetic retinopathy screening programs in regular ophthalmology clinics versus integrated diabetic clinics within rural health-care services.}, journal = {Oman journal of ophthalmology}, volume = {16}, number = {2}, pages = {237-243}, pmid = {37602185}, issn = {0974-620X}, abstract = {BACKGROUND: Robust integration of diabetic retinopathy (DR) screening within health systems is essential to prevent DR-related blindness. This, however, remains a challenge in the developing world. The aim of this study was to evaluate two models of DR screening programs within rural general health-care services.

MATERIALS AND METHODS: This was a retrospective observational study from two rural health centers. Demographic and clinical data of patients completing DR screening were analyzed. Patients were screened in regular ophthalmology clinics (ROC) or integrated diabetic clinics (IDC). Referral and treatment completion data were retrieved from the clinical charts at the base hospital.

RESULTS: A total of 2535 DR screenings were conducted for 2296 patients. The total population prevalence for any DR was 14.2% (95% confidence interval [CI]: 12.8%-15.6%) and vision-threatening DR (VTDR) was 4.7% (95% CI: 3.8%-5.6%). In the ROC and IDC groups, respectively, the prevalence of any DR was 20.4% and 8.2%, VTDR, 7.8% and 1.7%, and blindness, 1.4% and 0.4% (all P < 0.001). Referral completion rates were higher in the ROC group (44.8% vs. 25.2%, P < 0.001), while treatment completion in both was similar (69.6% vs. 70.6%). Referral and treatment completion rates for referable DR were 61.2% and 48.2%, and for VTDR, 62% and 38.8%, respectively. Only 11.45% of patients completed the repeat screening follow-up.

CONCLUSIONS: Patients attending IDCs had a significantly lower prevalence of any DR, VTDR, and blindness demonstrating the advantages of integrated diabetic care in a rural setting. However, referral uptake and DR treatment completion need strengthening.}, } @article {pmid37602036, year = {2023}, author = {Ayandipo, O and Ajagbe, O and Afolabi, A and Ogundiran, T and Orunmuyi, A and Soneye, O}, title = {Venous Thromboembolism in Hospitalized Patients With Surgical Breast Cancer: Risks and Outcomes.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e42096}, pmid = {37602036}, issn = {2168-8184}, abstract = {Background The Caprini risk assessment model has been validated in breast cancer surgery patients. However, its utility in our population has not been described. This study evaluated the benefits and risks of the Caprini risk stratification tool and the incidence of venous thromboembolism (VTE) in the 30-day postoperative period among surgical female patients with breast cancer who were hospitalized during their treatment. Methodology This is a retrospective review of prospectively collected data of all surgical patients with histologically confirmed breast cancer who were hospitalized between January and December 2018. Caprini score, treatment information, and 30-day outcome of prophylaxis were collated and analyzed using SPSS version 26 (IBM Corp., Armonk, NY, USA). Results A total of 167 female patients with breast cancer aged 19 to 75 years were hospitalized during the study period. All patients had invasive ductal carcinoma, and the majority (76.6%) were premenopausal. Two fatal VTE events occurred during hospitalization, giving a 30-day incidence of 1.2%. There was no adverse event from chemoprophylaxis. Conclusions VTE is rare in hospitalized surgical patients with breast cancer undergoing routine pharmacologic and mechanical prophylaxis. The Caprini tool can identify extremely low-risk patients who require no prophylaxis.}, } @article {pmid37601676, year = {2023}, author = {Liu, G and Xing, Z and Guo, C and Dai, Q and Cheng, H and Wang, X and Tang, Y and Wang, Y}, title = {Identifying clinicopathological risk factors for regional lymph node metastasis in Chinese patients with T1 breast cancer: a population-based study.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1217869}, pmid = {37601676}, issn = {2234-943X}, abstract = {OBJECTIVES: To analyze clinicopathological risk factors and regular pattern of regional lymph node metastasis (LNM) in Chinese patients with T1 breast cancer and the effect on overall survival (OS) and disease-free survival (DFS).

MATERIALS AND METHODS: Between 1999 and 2020, breast cancer patients meeting inclusion criteria of unilateral, no distant metastatic site, and T1 invasive ductal carcinoma were reviewed. Clinical pathology characteristics were retrieved from medical records. Survival analysis was performed using Kaplan-Meier methods and an adjusted Cox proportional hazards model.

RESULTS: We enrolled 11,407 eligible patients as a discovery cohort to explore risk factors for LNM and 3484 patients with stage T1N0 as a survival analysis cohort to identify the effect of those risk factors on OS and DFS. Compared with patients with N- status, patients with N+ status had a younger age, larger tumor size, higher Ki67 level, higher grade, higher HR+ and HER2+ percentages, and higher luminal B and HER2-positive subtype percentages. Logistic regression indicated that age was a protective factor and tumor size/higher grade/HR+ and HER2+ risk factors for LNM. Compared with limited LNM (N1) patients, extensive LNM (N2/3) patients had larger tumor sizes, higher Ki67 levels, higher grades, higher HR- and HER2+ percentages, and lower luminal A subtype percentages. Logistic regression indicated that HR+ was a protective factor and tumor size/higher grade/HER2+ risk factors for extensive LNM. Kaplan-Meier analysis indicated that grade was a predictor of both OS and DFS; HR was a predictor of OS but not DFS. Multivariate survival analysis using the Cox regression model demonstrated age and Ki67 level to be predictors of OS and grade and HER2 status of DFS in stage T1N0 patients.

CONCLUSION: In T1 breast cancer patients, there were several differences between N- and N+ patients, limited LNM and extensive LNM patients. Besides, HR+ plays a dual role in regional LNM. In patients without LNM, age and Ki67 level are predictors of OS, and grade and HER2 are predictors of DFS.}, } @article {pmid37596340, year = {2023}, author = {Aftab, A and Ahmad, B and Bashir, S and Rafique, S and Bashir, M and Ghani, T and Gul, A and Shah, AU and Khan, R and Sajini, AA}, title = {Comparative study of microscale and macroscale technique for encapsulation of Calotropis gigantea extract in metal-conjugated nanomatrices for invasive ductal carcinoma.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {13474}, pmid = {37596340}, issn = {2045-2322}, mesh = {Silver ; Antioxidants/pharmacology ; *Calotropis ; *Metal Nanoparticles ; Plant Extracts/pharmacology ; *Carcinoma, Ductal ; }, abstract = {The encapsulation of plant extract in nanomatrices has limitations due to its adhesion to walls, size control, high cost and long durations that results in low yield. Macroscale and microscale level techniques for development of micro/nanoparticles may impact the encapsulation of plant extract. This study aimed to evaluate the relative efficiency of microscale and macroscale techniques for encapsulation of plant extract, which is not compared yet. Keeping this in view, encapsulation of Calotropis gigantea leaves extract (CaG) was attained in silver-conjugated poliglusam nanomatrices (POL/Ag) to induce apoptosis in invasive ductal carcinoma (IDC) cells. The ethanolic CaG extract was prepared using percolation method and characterized by chemical tests for its active phytochemical compounds. The droplet-based microfluidic system was utilized as microscale encapsulation technique for CaG in nanomatrices at two different aqueous to oil flow rate ratios 1.0:1.5, and 1.0:3.0. Moreover, conventional batch system was utilized as macroscale encapsulation technique consisted of hot plate magnetic stirrer. The prepared nanomatrices were analysed for antioxidant activity using DPPH test and for cytotoxicity analysis using MCF-7 cells. The characteristic peaks of UV-Vis, FTIR and XRD spectrum confirmed the synthesis of CaG(POL/Ag) by both the encapsulation methods. However, microfluidic system was found to be more expedient because of attaining small and uniform sized silver nanoparticles (92 ± 19 nm) at high flow rate and achieving high encapsulation efficiency (80.25%) as compared to the conventional batch method (52.5%). CaG(POL/Ag) nanomatrices found to have significant antioxidant activity (p = 0.0014) against DPPH radical scavenging activity. The CaG(POL/Ag) of the smallest sized formulated by the microfluidic system has also shown the highest cytotoxicity (90%) as compared to batch method (70%) at 80 µg/mL. Our results indicate that the microscale technique using microfluidic system is a more efficient method to formulate size-controlled CaG(POL/Ag) nanomatrices and achieve high encapsulation of plant extract. Additionally, CaG(Pol/Ag) was found to be an efficient new combination for inducing potent (p < 0.0001) apoptosis in IDC cells. Therefore, CaG(Pol/Ag) can be further tested as an anti-cancer agent for in-vivo experiments.}, } @article {pmid37595905, year = {2023}, author = {Hu, J and Effiong, K and Liu, M and Xiao, X}, title = {Broad spectrum and species specificity of plant allelochemicals 1,2-benzenediol and 3-indoleacrylic acid against marine and freshwater harmful algae.}, journal = {The Science of the total environment}, volume = {898}, number = {}, pages = {166356}, doi = {10.1016/j.scitotenv.2023.166356}, pmid = {37595905}, issn = {1879-1026}, mesh = {*Pheromones/toxicity ; Species Specificity ; *Harmful Algal Bloom ; Fresh Water ; Indoles ; Catechols ; }, abstract = {Allelochemicals derived from plants have shown great potential in mitigating harmful algal blooms (HABs), although different algal species can respond differently to these chemicals. Therefore, we first investigated the allelopathic effects of two newly identified plant-derived allelochemicals, 1,2-benzenediol (1,2-BD) and 3-indoleacrylic acid (3-IDC), on six algal species. Then we further evaluated the allelopathic responses of two bloom-forming species, Microcystis aeruginosa FACHB-905 and Heterosigma akashiwo to 1,2-BD. Results showed that 1,2-BD had a broader antialgal spectrum than 3-IDC. Allelopathic response analysis indicated that 1,2-BD consistently and stably inhibit the growth of M. aeruginosa FACHB-905, with inhibitory mechanism being disruption of photosynthetic activity, overwhelming of the antioxidant system and activation of programmed cell death (PCD). H. akashiwo displayed resistance to 1,2-BD during exposure, and the growth inhibition was mainly attributed to PCD. Therefore, the species-specific allelopathic responses provide new insights for controlling HABs using 1,2-BD and 3-IDC.}, } @article {pmid37592911, year = {2023}, author = {Rosa, C and Singh, P and Chen, P and Sinha, A and Claës, A and Preiser, PR and Dedon, PC and Baumgarten, S and Scherf, A and Bryant, JM}, title = {Cohesin contributes to transcriptional repression of stage-specific genes in the human malaria parasite.}, journal = {EMBO reports}, volume = {24}, number = {10}, pages = {e57090}, pmid = {37592911}, issn = {1469-3178}, support = {MOE2018-T2-2-131//Academic Research Fund of the Ministry of Education, Singapore/ ; ANR-21-CE15-0010 PlasmoVarOrg//Agence Nationale de la Recherche (ANR)/ ; ANR-11-LABEX-0024-01 ParaFrap//Agence Nationale de la Recherche (ANR)/ ; //Alliance Française contre les Maladies Parasitaires (ParaFrap)/ ; PlasmoSilencing 670301//EC | ERC | HORIZON EUROPE European Research Council (ERC)/ ; PlasmoEpiRNA 947819//EC | ERC | HORIZON EUROPE European Research Council (ERC)/ ; EMBO ALTF 1444-2016//European Molecular Biology Organization (EMBO)/ ; EMBO ALTF 632-2018//European Molecular Biology Organization (EMBO)/ ; EMBO ALTF 180-2015//European Molecular Biology Organization (EMBO)/ ; //Institut Pasteur/ ; 6.11.18//Merlion Project/ ; //Ministry of Education, Singapore/ ; //National Research Foundation Singapore (NRF)/ ; }, abstract = {The complex life cycle of the human malaria parasite, Plasmodium falciparum, is driven by specific transcriptional programs, but it is unclear how most genes are activated or silenced at specific times. There is an association between transcription and spatial organization; however, the molecular mechanisms behind genome organization are unclear. While P. falciparum lacks key genome-organizing proteins found in metazoans, it has all core components of the cohesin complex. To investigate the role of cohesin in P. falciparum, we functionally characterize the cohesin subunit Structural Maintenance of Chromosomes protein 3 (SMC3). SMC3 knockdown during early stages of the intraerythrocytic developmental cycle (IDC) upregulates a subset of genes involved in erythrocyte egress and invasion, which are normally expressed at later stages. ChIP-seq analyses reveal that during the IDC, SMC3 enrichment at the promoter regions of these genes inversely correlates with gene expression and chromatin accessibility. These data suggest that SMC3 binding contributes to the repression of specific genes until their appropriate time of expression, revealing a new mode of stage-specific gene repression in P. falciparum.}, } @article {pmid37580403, year = {2023}, author = {Ishtiaq, A and Nasrullah, MA and Khan, JS and Malik, S and Tareen, U and Anees, M and Sultan, A and Murtaza, I}, title = {A cohort study investigating the role of Bisphenol A in the molecular pathogenesis of breast cancer.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {16}, pages = {14565-14575}, pmid = {37580403}, issn = {1432-1335}, support = {HEC//Higher Education Commision, Pakistan/ ; URF//Quaid-i-Azam University/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Tumor Suppressor Protein p53/metabolism ; Cohort Studies ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; *Carcinoma, Ductal, Breast/pathology ; Bisphenol A Compounds ; }, abstract = {BACKGROUND: Breast cancer is an abnormal division of breast cells. Bisphenol A (BPA), an environmental toxicant, is identified as an emerging risk factor for breast cancer development. However, to the best of our knowledge, no previous study has investigated the BPA levels in breast cancer patients in Pakistan. The present study sought to explore the role of BPA in tumor growth among the Pakistani population.

METHODS: The levels of BPA were analyzed in the serum samples of breast cancer patients and controls by using HPLC. To elucidate the role of BPA to initiate tumorigenic events in breast tissue different biochemical assays along with expression analysis of tumor markers were performed.

RESULTS: The level of BPA in the serum samples of breast cancer patients was significantly higher than control. Histological analysis of breast cancer tissue samples revealed distinct subtypes of tumor, such as ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). There was a significant increase in ROS level while a significant decrease in the levels of superoxide dismutase (SOD) and catalase (CAT) enzymes in malignant breast tissue samples as compared to control tissue samples. We found upregulated expression of p53, ZEB1 and WNT1 genes at mRNA level in malignant breast tissue samples by 17 folds, 328 folds and 35 folds, respectively. p53 protein expression in malignant breast tissue samples was also enhanced at the translational level.

CONCLUSION: Current findings suggest a relationship between BPA and the progression of breast cancer among the Pakistani population.}, } @article {pmid37579629, year = {2023}, author = {Bencherifi, Y and Watik, F and Lyafi, Y and Mostapha, B and Ennachit, M and Mohammed, EK}, title = {Mucinous carcinoma of the breast: Rare histological entity to know: About two cases and review of literature.}, journal = {International journal of surgery case reports}, volume = {110}, number = {}, pages = {108652}, pmid = {37579629}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Breast cancer is the first gynecological cancer in women, dominated by invasive ductal cancer . It is characterized by the presence of extracellular mucus, mucinous carcinoma represents one to 7 % of all invasive carcinomas and by a more favorable prognosis, Presentation of the case: We present two patients followed for an invasive mucinous carcinoma, CLINICAL DISCUSSION: Mucinous carcinoma of the breast is a rare entity. Therapeutic management does not differ from other histological types. It is based on surgery, chemotherapy and radiotherapy. Conservative treatment is recommended for T1, T2. Partial and accelerated irradiation of the breast is currently the most recommended after breast-conserving surgery.

CONCLUSION: Mucinous carcinoma is a rare histological entity with a favorable prognosis compared to other histological types. A benign-looking mass on imaging is not always reassuring, especially if it occurs in a woman over 60 years old. Since it can reveal colloid carcinoma.}, } @article {pmid37579325, year = {2023}, author = {Mooshage, CM and Tsilingiris, D and Schimpfle, L and Kender, Z and Aziz-Safaie, T and Hohmann, A and Szendroedi, J and Nawroth, P and Sturm, V and Heiland, S and Bendszus, M and Kopf, S and Kurz, FT and Jende, JME}, title = {Insulin Resistance Is Associated With Reduced Capillary Permeability of Thigh Muscles in Patients With Type 2 Diabetes.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {109}, number = {1}, pages = {e137-e144}, doi = {10.1210/clinem/dgad481}, pmid = {37579325}, issn = {1945-7197}, support = {//Novo Nordisk/ ; //Codman/ ; //Guerbet/ ; //Bayer/ ; //Novartis/ ; //Roche/ ; //Teva/ ; //Springer/ ; //Boehringer/ ; //Siemens/ ; }, mesh = {Humans ; Capillary Permeability ; Contrast Media ; *Diabetes Mellitus, Type 2 ; *Insulin Resistance ; *Insulins ; Magnetic Resonance Imaging/methods ; Muscle, Skeletal/diagnostic imaging ; Thigh ; }, abstract = {CONTEXT: Insulin-mediated microvascular permeability and blood flow of skeletal muscle appears to be altered in the condition of insulin resistance. Previous studies on this effect used invasive procedures in humans or animals.

OBJECTIVE: The aim of this study was to demonstrate the feasibility of a noninvasive assessment of human muscle microcirculation via dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) of skeletal muscle in patients with type 2 diabetes (T2D).

METHODS: A total of 56 participants (46 with T2D, 10 healthy controls [HC]) underwent DCE-MRI of the right thigh at 3 Tesla. The constant of the musculature's microvascular permeability (Ktrans), extravascular extracellular volume fraction (ve), and plasma volume fraction (vp) were calculated.

RESULTS: In T2D patients, skeletal muscle Ktrans was lower (HC 0.0677 ± 0.002 min-1, T2D 0.0664 ± 0.002 min-1; P = 0.042) while the homeostasis model assessment (HOMA) index was higher in patients with T2D compared to HC (HC 2.72 ± 2.2, T2D 6.11 ± 6.2; P = .011). In T2D, Ktrans correlated negatively with insulin (r = -0.39, P = .018) and HOMA index (r = -0.38, P = .020).

CONCLUSION: The results signify that skeletal muscle DCE-MRI can be employed as a noninvasive technique for the assessment of muscle microcirculation in T2D. Our findings suggest that microvascular permeability of skeletal muscle is lowered in patients with T2D and that a decrease in microvascular permeability is associated with insulin resistance. These results are of interest with regard to the impact of muscle perfusion on diabetic complications such as diabetic sarcopenia.}, } @article {pmid37560809, year = {2023}, author = {Alfaro, AJ and Dittner, C and Becker, J and Loft, A and Mhamane, A and Maida, A and Georgiadi, A and Tsokanos, FF and Klepac, K and Molocea, CE and El-Merahbi, R and Motzler, K and Geppert, J and Karikari, RA and Szendrödi, J and Feuchtinger, A and Hofmann, S and Karaca, S and Urlaub, H and Berriel Diaz, M and Melchior, F and Herzig, S}, title = {Fasting-sensitive SUMO-switch on Prox1 controls hepatic cholesterol metabolism.}, journal = {EMBO reports}, volume = {24}, number = {10}, pages = {e55981}, pmid = {37560809}, issn = {1469-3178}, support = {314061271//Deutsche Forschungsgemeinschaft (DFG)/ ; 329628492//Deutsche Forschungsgemeinschaft (DFG)/ ; A01//Deutsche Forschungsgemeinschaft (DFG)/ ; //Edith-Haberland-Wagner Stiftung/ ; 2020 EKSE.23//Else Köner-Fresenius-Stiftung (EKFS)/ ; ZT-0026//Helmholtz Gemeinschaft/ ; //DKFZ-ZMBH Alliance/ ; //Open Access funding enabled and organized by Projekt DEAL/ ; }, abstract = {Accumulation of excess nutrients hampers proper liver function and is linked to nonalcoholic fatty liver disease (NAFLD) in obesity. However, the signals responsible for an impaired adaptation of hepatocytes to obesogenic dietary cues remain still largely unknown. Post-translational modification by the small ubiquitin-like modifier (SUMO) allows for a dynamic regulation of numerous processes including transcriptional reprogramming. We demonstrate that specific SUMOylation of transcription factor Prox1 represents a nutrient-sensitive determinant of hepatic fasting metabolism. Prox1 is highly SUMOylated on lysine 556 in the liver of ad libitum and refed mice, while this modification is abolished upon fasting. In the context of diet-induced obesity, Prox1 SUMOylation becomes less sensitive to fasting cues. The hepatocyte-selective knock-in of a SUMOylation-deficient Prox1 mutant into mice fed a high-fat/high-fructose diet leads to a reduction of systemic cholesterol levels, associated with the induction of liver bile acid detoxifying pathways during fasting. The generation of tools to maintain the nutrient-sensitive SUMO-switch on Prox1 may thus contribute to the development of "fasting-based" approaches for the preservation of metabolic health.}, } @article {pmid37559588, year = {2023}, author = {Bai, X and Fang, C and Liu, B and Huagn, J and Chen, X and Xie, X and Zhang, Q and Liu, M and Liang, J and Guo, J and Song, L and Lan, X and Chen, L and Huang, S and Deng, W and Luo, Z and Du, C}, title = {Breast cancer metastases to the thyroid and stomach: A case report.}, journal = {Oncology letters}, volume = {26}, number = {3}, pages = {386}, pmid = {37559588}, issn = {1792-1082}, abstract = {The most common sites of metastasis for breast cancer are the soft tissues, bones, lungs, liver and brain; however, metastases to the gastrointestinal tract and thyroid gland from breast cancer rarely occur. The present study describes the case of a 30-year-old woman who developed gastric and thyroid metastases 5 years after her initial diagnosis of invasive ductal breast carcinoma. The initial pathological diagnosis when receiving modified radical mastectomy was invasive ductal carcinoma, and further immunohistochemical examination revealed the cancer to be estrogen receptor (-), progesterone receptor (-), human epidermal growth factor receptor 2 (HER2; ++) and Ki-67 (70%). Genetic testing indicated the HER2 amplification mutation, whereas BRCA1/2 testing was negative. A total of 21 months after surgery, during regular follow-up, the patient was revealed to have developed an enlarged lymph node in the left side of the neck and the first recurrence was confirmed. Approximately 5 years after surgery, the patient gradually developed multi-site metastasis, and developed metastases to the thyroid gland and stomach confirmed by pathology and imaging. Combined chemotherapy and targeted therapy were administered and exhibited good efficacy; however, the patient subsequently died due to heart failure. This case report describes the occurrence of gastric and thyroid metastases from breast cancer, and highlights the importance of distinguishing between metastatic and primary tumors. Distinguishing between a metastatic and primary tumor is crucial as treatment protocols vary significantly for these two types of tumors. For patients with a history of breast cancer it should first be considered whether they have metastasis of the primary disease or discomfort caused by treatment; however, the possibility of a second primary tumor cannot be ignored. If the patient has symptoms such as loss of appetite, nausea, vomiting, stomach pain and stomach discomfort, a gastroscopy should be performed in a timely manner.}, } @article {pmid37558640, year = {2023}, author = {Doi, K and Fujii, T and Hanamoto, M and Takamura, K and Nakada, T and Sato, Y and Ogura, K}, title = {[A Case of BRCA2 Mutation-Positive Intraductal Carcinoma of the Prostate].}, journal = {Hinyokika kiyo. Acta urologica Japonica}, volume = {69}, number = {7}, pages = {189-192}, doi = {10.14989/ActaUrolJap_69_7_189}, pmid = {37558640}, issn = {0018-1994}, mesh = {Male ; Humans ; Aged ; Prostate/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Prostate-Specific Antigen ; Hematuria ; *Prostatic Neoplasms/drug therapy/genetics/pathology ; Disease Progression ; Mutation ; *Prostatic Neoplasms, Castration-Resistant/drug therapy/genetics/pathology ; BRCA2 Protein/genetics ; Taxoids ; }, abstract = {A 75-year-old man presented with macroscopic hematuria and a high serum prostate-specific antigen (PSA) level. Macroscopic hematuria had subsided by the time of consultation. The PSA level was 38.590 ng/ml, which, along with rectal examination and magnetic resonance imaging findings, led to the suspicion of prostate cancer. Transrectal needle biopsy of the prostate revealed intraductal carcinoma of the prostate (IDC-P). Computed tomography and bone scintigraphy were performed, and the prostate cancer was classified as cT2cN0M0. After 6 months of combined androgen blockade therapy, a radical prostatectomy was performed; however, PSA levels continued to increase, and the patient was diagnosed with castration resistant prostate cancer. Multiple bone metastases appeared 5 months after the initiation of abiraterone therapy. Three courses of docetaxel and two courses of cabazitaxel were administered, but the disease progression continued. The IDC-P was found to be positive for the BRCA2 mutation by BRACAnalysis® performed at the start of cabazitaxel therapy. To our knowledge, no other cases of BRCA2 mutation positive IDC-P have been reported in Japan. After we started administration of Olaparib, the patient's PSA level was lowered and the disease progression stopped.}, } @article {pmid37558528, year = {2024}, author = {Downes, MR and Liu, KN and Yu, Y and Lajkosz, K and Kroon, LJ and Hollemans, E and Fleshner, N and Finelli, A and van Leenders, GJLH and Iczkowski, KA and van der Kwast, TH}, title = {Addition of Cribriform and Intraductal Carcinoma Presence to Prostate Biopsy Reporting Strengthens Pretreatment Risk Stratification Using CAPRA and NCCN Tools.}, journal = {Clinical genitourinary cancer}, volume = {22}, number = {1}, pages = {47-55}, doi = {10.1016/j.clgc.2023.07.013}, pmid = {37558528}, issn = {1938-0682}, mesh = {Male ; Humans ; Prostate/surgery/pathology ; *Carcinoma, Intraductal, Noninfiltrating/surgery/pathology ; Retrospective Studies ; Neoplasm Recurrence, Local/pathology ; *Prostatic Neoplasms/pathology ; Biopsy ; Risk Assessment/methods ; Neoplasm Grading ; Prostatectomy ; }, abstract = {BACKGROUND: Pretreatment stratification tools can help in clinical decision making in prostate cancer. To date, none incorporates well-established routinely reported adverse prognostic pathologic features such as intraductal carcinoma of prostate (IDC) or cribriform pattern 4 (CC).

OBJECTIVE: To assess the impact of addition of CC and/or IDC on the Cancer of Prostate Risk Assessment (CAPRA) and National Cancer Comprehensive Network (NCCN) tools for predicting biochemical recurrence free survival (BCR-FS) and event-free survival (EFS) across multiple patient cohorts.

Matched prostate biopsies and radical prostatectomies from institutions in Toronto, Wisconsin and Rotterdam. The presence/absence of CC/IDC was recorded on all biopsies.

Relationship to outcome was assessed using Cox proportional hazard models, ANOVA and Harrell's concordance index.

RESULTS AND LIMITATIONS: We included 1326 patients (Toronto- 612, Wisconsin- 542, Rotterdam- 172) with median follow up of 4.2 years (IQR 2.9-6.4 years); 306 (23.1%) had CC/IDC on biopsy with 207 (20.9%) BCR and 154 (11.6%) events (metastases/death). Addition of CC/IDC improved stratification in CAPRA scores 3 to 5 for BCR-FS (c-index increase 0.633-0.658, P < .001) and scores 6-10 for EFS (c-index increase 0.653-0.697, P < .001). For NCCN, all risk groups apart from score 1 to 2 showed improvement in BCR-FS (c-index increase 0.599-0.636, P < 0.001) and EFS prediction (c-index increase 0.648-0.697, P < .001). Sub-analysis of grade group (GG) 2 biopsies showed similar findings. The retrospective nature and inclusion of cases only reported by genitourinary pathologists are study limitations.

CONCLUSIONS: The clinical benefit of the addition of CC/IDC to both CAPRA and NCCN pretreatment tools was validated in 3 cohorts, including the subset of biopsy GG2 prostate cancer patients.

PATIENT SUMMARY: Including additional pathologic features to existing pretreatment, clinical decision making tools improves the ability to predict prostate cancer recurrence, cancer spread and death of disease.}, } @article {pmid37555360, year = {2023}, author = {Chen, H and Li, X and Li, F and Li, Y and Chen, F and Zhang, L and Ye, F and Gong, M and Bu, H}, title = {Prediction of coexisting invasive carcinoma on ductal carcinoma in situ (DCIS) lesions by mass spectrometry imaging.}, journal = {The Journal of pathology}, volume = {261}, number = {2}, pages = {125-138}, doi = {10.1002/path.6154}, pmid = {37555360}, issn = {1096-9896}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/metabolism ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Antioxidants ; Mass Spectrometry ; *Breast Neoplasms/diagnostic imaging ; }, abstract = {Due to limited biopsy samples, ~20% of DCIS lesions confirmed by biopsy are upgraded to invasive ductal carcinoma (IDC) upon surgical resection. Avoiding underestimation of IDC when diagnosing DCIS has become an urgent challenge in an era discouraging overtreatment of DCIS. In this study, the metabolic profiles of 284 fresh frozen breast samples, including tumor tissues and adjacent benign tissues (ABTs) and distant surrounding tissues (DSTs), were analyzed using desorption electrospray ionization-mass spectrometry (DESI-MS) imaging. Metabolomics analysis using DESI-MS data revealed significant differences in metabolite levels, including small-molecule antioxidants, long-chain polyunsaturated fatty acids (PUFAs) and phospholipids between pure DCIS and IDC. However, the metabolic profile in DCIS with invasive carcinoma components clearly shifts to be closer to adjacent IDC components. For instance, DCIS with invasive carcinoma components showed lower levels of antioxidants and higher levels of free fatty acids compared to pure DCIS. Furthermore, the accumulation of long-chain PUFAs and the phosphatidylinositols (PIs) containing PUFA residues may also be associated with the progression of DCIS. These distinctive metabolic characteristics may offer valuable indications for investigating the malignant potential of DCIS. By combining DESI-MS data with machine learning (ML) methods, various breast lesions were discriminated. Importantly, the pure DCIS components were successfully distinguished from the DCIS components in samples with invasion in postoperative specimens by a Lasso prediction model, achieving an AUC value of 0.851. In addition, pixel-level prediction based on DESI-MS data enabled automatic visualization of tissue properties across whole tissue sections. Summarily, DESI-MS imaging on histopathological sections can provide abundant metabolic information about breast lesions. By analyzing the spatial metabolic characteristics in tissue sections, this technology has the potential to facilitate accurate diagnosis and individualized treatment of DCIS by inferring the presence of IDC components surrounding DCIS lesions. © 2023 The Pathological Society of Great Britain and Ireland.}, } @article {pmid37552151, year = {2024}, author = {He, Y and Cazoulat, G and Wu, C and Svensson, S and Almodovar-Abreu, L and Rigaud, B and McCollum, E and Peterson, C and Wooten, Z and Rhee, DJ and Balter, P and Pollard-Larkin, J and Cardenas, C and Court, L and Liao, Z and Mohan, R and Brock, K}, title = {Quantifying the Effect of 4-Dimensional Computed Tomography-Based Deformable Dose Accumulation on Representing Radiation Damage for Patients with Locally Advanced Non-Small Cell Lung Cancer Treated with Standard-Fractionated Intensity-Modulated Radiation Therapy.}, journal = {International journal of radiation oncology, biology, physics}, volume = {118}, number = {1}, pages = {231-241}, pmid = {37552151}, issn = {1879-355X}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; T32 CA096520/CA/NCI NIH HHS/United States ; P01 CA261669/CA/NCI NIH HHS/United States ; R01 HL157273/HL/NHLBI NIH HHS/United States ; R25 CA240137/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/diagnostic imaging/radiotherapy ; *Radiotherapy, Intensity-Modulated/adverse effects/methods ; *Lung Neoplasms/diagnostic imaging/radiotherapy ; Retrospective Studies ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted/methods ; Four-Dimensional Computed Tomography/methods ; }, abstract = {PURPOSE: The aim of this study was to investigate the dosimetric and clinical effects of 4-dimensional computed tomography (4DCT)-based longitudinal dose accumulation in patients with locally advanced non-small cell lung cancer treated with standard-fractionated intensity-modulated radiation therapy (IMRT).

METHODS AND MATERIALS: Sixty-seven patients were retrospectively selected from a randomized clinical trial. Their original IMRT plan, planning and verification 4DCTs, and ∼4-month posttreatment follow-up CTs were imported into a commercial treatment planning system. Two deformable image registration algorithms were implemented for dose accumulation, and their accuracies were assessed. The planned and accumulated doses computed using average-intensity images or phase images were compared. At the organ level, mean lung dose and normal-tissue complication probability (NTCP) for grade ≥2 radiation pneumonitis were compared. At the region level, mean dose in lung subsections and the volumetric overlap between isodose intervals were compared. At the voxel level, the accuracy in estimating the delivered dose was compared by evaluating the fit of a dose versus radiographic image density change (IDC) model. The dose-IDC model fit was also compared for subcohorts based on the magnitude of NTCP difference (|ΔNTCP|) between planned and accumulated doses.

RESULTS: Deformable image registration accuracy was quantified, and the uncertainty was considered for the voxel-level analysis. Compared with planned doses, accumulated doses on average resulted in <1-Gy lung dose increase and <2% NTCP increase (up to 8.2 Gy and 18.8% for a patient, respectively). Volumetric overlap of isodose intervals between the planned and accumulated dose distributions ranged from 0.01 to 0.93. Voxel-level dose-IDC models demonstrated a fit improvement from planned dose to accumulated dose (pseudo-R[2] increased 0.0023) and a further improvement for patients with ≥2% |ΔNTCP| versus for patients with <2% |ΔNTCP|.

CONCLUSIONS: With a relatively large cohort, robust image registrations, multilevel metric comparisons, and radiographic image-based evidence, we demonstrated that dose accumulation more accurately represents the delivered dose and can be especially beneficial for patients with greater longitudinal response.}, } @article {pmid37548682, year = {2024}, author = {Mooshage, CM and Schimpfle, L and Kender, Z and Tsilingiris, D and Aziz-Safaie, T and Hohmann, A and Szendroedi, J and Nawroth, P and Sturm, V and Heiland, S and Bendszus, M and Kopf, S and Kurz, FT and Jende, JME}, title = {Association of Small Fiber Function with Microvascular Perfusion of Peripheral Nerves in Patients with Type 2 Diabetes : Study using Quantitative Sensory Testing and Magnetic Resonance Neurography.}, journal = {Clinical neuroradiology}, volume = {34}, number = {1}, pages = {55-66}, pmid = {37548682}, issn = {1869-1447}, mesh = {Humans ; *Diabetes Mellitus, Type 2/complications/pathology ; Cross-Sectional Studies ; Pain/complications ; Sciatic Nerve ; Perfusion ; Magnetic Resonance Spectroscopy ; Magnetic Resonance Imaging ; }, abstract = {INTRODUCTION/AIMS: Diabetic small fiber neuropathy (SFN) is caused by damage to thinly myelinated A‑fibers (δ) and unmyelinated C‑fibers. This study aimed to assess associations between quantitative sensory testing (QST) and parameters of peripheral nerve perfusion obtained from dynamic contrast enhanced (DCE) magnetic resonance neurography (MRN) in type 2 diabetes patients with and without SFN.

METHODS: A total of 18 patients with type 2 diabetes (T2D, 8 with SFN, 10 without SFN) and 10 healthy controls (HC) took part in this cross-sectional single-center study and underwent QST of the right leg and DCE-MRN of the right thigh with subsequent calculation of the sciatic nerve constant of capillary permeability (K[trans]), extravascular extracellular volume fraction (Ve), and plasma volume fraction (Vp).

RESULTS: The K[trans] (HC 0.031 min[-1] ± 0.009, T2D 0.043 min[-1] ± 0.015; p = 0.033) and Ve (HC 1.2% ± 1.5, T2D: 4.1% ± 5.1; p = 0.027) were lower in T2D patients compared to controls. In T2D patients, compound z‑scores of thermal and mechanical detection correlated with K[trans] (r = 0.73; p = 0.001, and r = 0.57; p = 0.018, respectively) and Ve (r = 0.67; p = 0.002, and r = 0.69; p = 0.003, respectively). Compound z‑scores of thermal pain and Vp (r = -0.57; p = 0.015) correlated negatively.

DISCUSSION: The findings suggest that parameters of peripheral nerve microcirculation are related to different symptoms in SFN: A reduced capillary permeability may result in a loss of function related to insufficient nutritional supply, whereas increased capillary permeability may be accompanied by painful symptoms related to a gain of function.}, } @article {pmid37546823, year = {2023}, author = {Imamichi, T and Chen, Q and Sowrirajan, B and Yang, J and Laverdure, S and Mele, AR and Watkins, C and Adelsberger, JW and Higgins, J and Sui, H}, title = {Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, Autophagy, and YB-1 independent manner.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37546823}, issn = {2692-8205}, support = {HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, abstract = {Interleukin (IL)-27, a member of the IL-12 family of cytokines, induces human immunodeficiency virus (HIV)-resistant monocyte-derived macrophages and T cells. This resistance is mediated via the downregulation of spectrin beta, non-erythrocytic 1 (SPTBN1), induction of autophagy, or suppression of the acetylation of Y-box binding protein-1 (YB-1); however, the role of IL-27 administration during the induction of immature monocyte-derived dendritic cells (iDC) is poorly investigated. In the current study, we investigated the function of IL-27-induced iDC (27DC) on HIV infection. 27DC inhibited HIV infection by 95 ± 3 % without significant changes in the expression of CD4, CCR5, and SPTBN1 expression, autophagy induction and acetylation of YB-1 compared to iDC. An HIV proviral DNA copy number assay displayed that 27DC suppressed reverse transcriptase (RT) reaction without influencing the virus entry. A DNA microarray analysis was performed to identify the differentially expressed genes between 27DC and iDC. Compared to iDC, 51 genes were differentially expressed in 27DC, with more than 3-fold changes in four independent donors. Cross-reference analysis with the reported 2,214 HIV regulatory host genes identified nine genes as potential interests: Ankyrin repeat domain 22, Guanylate binding protein (GBP)-1, -2, -4, -5, Stabilin 1, Serpin family G member 1 (SERPING1), Interferon alpha inducible protein 6, and Interferon-induced protein with tetratricopeptide repeats 3. A knock-down study using si-RNA failed to determine a key factor associated with the anti-HIV activity due to the induction of robust amounts of off-target effects. Overexpression of each protein in cells had no impact on HIV infection. Thus, we could not define the mechanism of the anti-HIV effect in 27DC. However, our findings indicated that IL-27 differentiates monocytes into HIV-resistant DC, and the inhibitory mechanism differs from IL-27-induced HIV-resistant macrophages and T cells.}, } @article {pmid37540475, year = {2024}, author = {Shoshani, A and Kor, A}, title = {The longitudinal impact of the COVID-19 pandemic on adolescents' internalizing symptoms, substance use, and digital media use.}, journal = {European child & adolescent psychiatry}, volume = {33}, number = {5}, pages = {1583-1595}, pmid = {37540475}, issn = {1435-165X}, mesh = {Humans ; Adolescent ; *COVID-19/epidemiology/psychology ; Male ; Female ; Longitudinal Studies ; Child ; *Substance-Related Disorders/epidemiology ; Israel/epidemiology ; Depression/epidemiology/psychology ; Adolescent Behavior/psychology ; Social Media/statistics & numerical data ; Anxiety/epidemiology/psychology ; Screen Time ; Social Support ; SARS-CoV-2 ; Video Games/psychology/statistics & numerical data ; }, abstract = {The present study examined the long-term effects of the COVID-19 pandemic on adolescent internalizing symptoms, substance use, and digital media use before and during the pandemic. A nationally representative longitudinal cohort of 3718 Israeli adolescents aged 12-16 at baseline completed measures of internalizing symptoms (anxiety, depression, and somatization), the prevalence of substance use (i.e., previous 30-day use of tobacco, alcohol, and cannabis), and average daily use of internet/television, video games, and social media. Social support and daily routines were assessed as potential protective factors for mental health. Data were collected in 10 public schools at four measurement points: before the Covid-19 outbreak (September 2019), after the first wave lockdown (May 2020), after the third wave lockdown (May 2021), and after the fifth wave of the pandemic (May 2022). Multi-level mixed models were used to analyze the longitudinal data. The results showed significant increases in internalizing symptoms, substance use (tobacco, alcohol, and cannabis), and daily screen time from the start of the study to the 33-month follow-up. Social support and daily routines moderated the increases in internalizing symptoms and digital media use. These findings highlight the need for public and educational mental health services to address the continuing impact of the pandemic on adolescents.}, } @article {pmid37536436, year = {2023}, author = {Abdollahi, E and Mozdarani, H}, title = {Epigenetic regulation of circ-HIPK3, circ-PVT1, miR-25, and miR-149 in radiosensitivity of breast cancer.}, journal = {Experimental and molecular pathology}, volume = {132-133}, number = {}, pages = {104865}, doi = {10.1016/j.yexmp.2023.104865}, pmid = {37536436}, issn = {1096-0945}, mesh = {Humans ; Female ; Adult ; Middle Aged ; *Breast Neoplasms/genetics/radiotherapy ; Epigenesis, Genetic ; Leukocytes, Mononuclear ; Radiation Tolerance/genetics ; *MicroRNAs/genetics ; Cell Proliferation ; Protein Serine-Threonine Kinases ; Intracellular Signaling Peptides and Proteins ; }, abstract = {Assessing the radiosensitivity of cells before administering radiation therapy (RT) to individuals diagnosed with breast cancer (BC) can facilitate the selection of appropriate treatment regimens and minimize the incidence of adverse side effects in patients undergoing radiation exposure. In this research, blood samples were obtained from 60 women who had been diagnosed with Invasive Ductal Carcinoma (IDC) Breast Cancer. The average age of the patients was 47 ± 9.93. Additionally, the study incorporated 20 healthy women, with an average age of 44.43 ± 6.7. A standard G2 assay was conducted to predict the cellular response to radiation. Out of the 60 samples, the G2 assay identified 20 patients with breast cancer who exhibited radiosensitivity. Hence, molecular investigations were ultimately conducted on two equivalent cohorts comprising 20 subjects each, one with and the other without cellular radiosensitivity. The expression levels of miR-149, miR-25, circ-PVT1, and circ-HIPK3 in peripheral blood mononuclear cells (PBMCs) were evaluated using quantitative polymerase chain reaction (qPCR). Receiver Operating Characteristic (ROC) curves were used to evaluate the sensitivity and specificity of the RNAs. An analysis using binary logistic regression was performed to investigate the relationship between RNAs and both BC and cellular radiosensitivity (CR) in patients with BC. The findings revealed a significant upregulation of Circ-HIPK3 and circ-PVT1 in individuals diagnosed with BC. The levels of Circ-HIPK3 and Circ-PVT1 were found to be directly associated with CR in BC patients. The analysis of the ROC curve demonstrated that circ-HIPK3 and circ-PVT1 exhibit favorable specificity and sensitivity in accurately predicting both BC and CR in patients with BC. The findings from the binary logistic regression analysis demonstrated that circ-HIPK3 and circ-PVT1 were effective predictors of both BC and CR. The ROC curve and binary logistic regression analyses provide evidence that miR-25 is a reliable predictor for BC patients exclusively. Our research has demonstrated that circ-HIPK3, circ-PVT1, and miR-25 may be involved in BC regulatory processes. The circular RNAs Circ-HIPK3 and circ-PVT1, as well as miR-25, among other significant biomarkers, could potentially serve as promising biomarkers for predicting BC. Furthermore, Circ-HIPK3 and circ-PVT1 have the potential to serve as biomarkers for predicting CR in BC patients.}, } @article {pmid37530887, year = {2023}, author = {Kishore, A and Venkataramana, L and Prasad, DVV and Mohan, A and Jha, B}, title = {Enhancing the prediction of IDC breast cancer staging from gene expression profiles using hybrid feature selection methods and deep learning architecture.}, journal = {Medical & biological engineering & computing}, volume = {61}, number = {11}, pages = {2895-2919}, pmid = {37530887}, issn = {1741-0444}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics ; Transcriptome ; Neoplasm Staging ; *Deep Learning ; Gene Expression Profiling/methods ; }, abstract = {Prediction of the stage of cancer plays an important role in planning the course of treatment and has been largely reliant on imaging tools which do not capture molecular events that cause cancer progression. Gene-expression data-based analyses are able to identify these events, allowing RNA-sequence and microarray cancer data to be used for cancer analyses. Breast cancer is the most common cancer worldwide, and is classified into four stages - stages 1, 2, 3, and 4 [2]. While machine learning models have previously been explored to perform stage classification with limited success, multi-class stage classification has not had significant progress. There is a need for improved multi-class classification models, such as by investigating deep learning models. Gene-expression-based cancer data is characterised by the small size of available datasets, class imbalance, and high dimensionality. Class balancing methods must be applied to the dataset. Since all the genes are not necessary for stage prediction, retaining only the necessary genes can improve classification accuracy. The breast cancer samples are to be classified into 4 classes of stages 1 to 4. Invasive ductal carcinoma breast cancer samples are obtained from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets and combined. Two class balancing techniques are explored, synthetic minority oversampling technique (SMOTE) and SMOTE followed by random undersampling. A hybrid feature selection pipeline is proposed, with three pipelines explored involving combinations of filter and embedded feature selection methods: Pipeline 1 - minimum-redundancy maximum-relevancy (mRMR) and correlation feature selection (CFS), Pipeline 2 - mRMR, mutual information (MI) and CFS, and Pipeline 3 - mRMR and support vector machine-recursive feature elimination (SVM-RFE). The classification is done using deep learning models, namely deep neural network, convolutional neural network, recurrent neural network, a modified deep neural network, and an AutoKeras generated model. Classification performance post class-balancing and various feature selection techniques show marked improvement over classification prior to feature selection. The best multiclass classification was found to be by a deep neural network post SMOTE and random undersampling, and feature selection using mRMR and recursive feature elimination, with a Cohen-Kappa score of 0.303 and a classification accuracy of 53.1%. For binary classification into early and late-stage cancer, the best performance is obtained by a modified deep neural network (DNN) post SMOTE and random undersampling, and feature selection using mRMR and recursive feature elimination, with an accuracy of 81.0% and a Cohen-Kappa score (CKS) of 0.280. This pipeline also showed improved multiclass classification performance on neuroblastoma cancer data, with a best area under the receiver operating characteristic (auROC) curve score of 0.872, as compared to 0.71 obtained in previous work, an improvement of 22.81%. The results and analysis reveal that feature selection techniques play a vital role in gene-expression data-based classification, and the proposed hybrid feature selection pipeline improves classification performance. Multi-class classification is possible using deep learning models, though further improvement particularly in late-stage classification is necessary and should be explored further.}, } @article {pmid37530324, year = {2023}, author = {Cakir, Y and Talu, CK and Trabulus, DC and Mermut, O}, title = {The immunohistochemical Galectin-3 expression in tumor and cancer-associated fibroblasts in invasive ductal carcinomas of breast and their relationship with clinicopathological parameters.}, journal = {Indian journal of pathology & microbiology}, volume = {66}, number = {3}, pages = {456-464}, doi = {10.4103/ijpm.ijpm_284_21}, pmid = {37530324}, issn = {0974-5130}, mesh = {Humans ; Female ; *Cancer-Associated Fibroblasts/metabolism/pathology ; Galectin 3/genetics ; *Triple Negative Breast Neoplasms/pathology ; Retrospective Studies ; *Carcinoma, Ductal ; *Breast Neoplasms ; Biomarkers, Tumor/metabolism ; }, abstract = {BACKGROUND: Galectin-3 has an important role in metastasis, therefore, Galectin-3-focused therapies have attracted attention for various cancers.

AIM: We aimed to reveal the relationship between the expression of Galectin-3 within the tumor/cancer-associated fibroblasts (CAF) and clinicopathological parameters in patients with invasive ductal carcinomas.

MATERIALS AND METHODS: Hematoxylin and eosin-stained slides of breast excision materials diagnosed between 2010 and 2016 were re-examined retrospectively. Accordingly, 118 cases (luminal group = 58, Human epidermal growth factor receptor 2 (HER2) group = 27, and triple-negative breast carcinoma group [TNBC] =33 cases) were included. Galectin-3 levels were evaluated with a calculated H-score in tumor and semiquantitatively in CAFs.

STATISTICAL ANALYSIS: Data was analyzed with t-tests and Chi-square tests. Kaplan-Meier and Log-rank tests were used for survival analysis.

RESULTS: The presence of Galectin-3 expression in CAFs but not in the tumor was associated with the greater number of axillary metastatic nodes and advanced pN stage. The loss of Galectin-3 expression in CAFs was more frequent in TNBC. There was no significant relationship between the expression level of Galectin-3 and survival status. However, in most of the cases with distant metastasis or patients who died, Galectin-3 was negative in the tumor, whereas it was positive in CAFs.

CONCLUSIONS: The expression of Galectin-3 in tumors and CAFs may have a role in metastasis to axillary lymph nodes and distant sites. In terms of molecular subtype, TNBCs show a relationship with Galectin-3 negativity in CAFs.}, } @article {pmid37526280, year = {2023}, author = {Dao, E and Gohla, G and Williams, P and Lovrics, P and Badr, F and Fang, Q and Farrell, T and Farquharson, M}, title = {Breast tissue analysis using a clinically compatible combined time-resolved fluorescence and diffuse reflectance (TRF-DR) system.}, journal = {Lasers in surgery and medicine}, volume = {55}, number = {8}, pages = {769-783}, doi = {10.1002/lsm.23710}, pmid = {37526280}, issn = {1096-9101}, mesh = {Humans ; Female ; Flavin-Adenine Dinucleotide ; NAD ; Breast/pathology ; *Neoplasms/pathology ; Spectrometry, Fluorescence ; *Breast Neoplasms/diagnostic imaging/surgery/pathology ; }, abstract = {OBJECTIVE: This work aims to develop a clinically compatible system that can perform breast tissue analysis in a more time efficient process than conventional histopathological assessment. The potential for such a system to be used in vivo in the operating room or surgical suite to improve patient outcome is investigated.

METHOD: In this work, 80 matched pairs of invasive ductal carcinoma and adjacent normal breast tissue were measured in a combined time-resolved fluorescence and diffuse reflectance (DA) system. Following measurement, the fluorescence intensity of collagen and flavin adenine dinucleotide (FAD); the fluorescence lifetime of collagen, nicotinamide adenine dinucleotide (NADH), and FAD; the DA; absorption coefficient; and reduced scattering coefficient were extracted. Samples then underwent histological processing and H&E staining to classify composition as tumor, fibroglandular, and/or adipose tissue.

RESULTS: Statistically significant differences in the collagen and FAD fluorescence intensity, collagen and FAD fluorescence lifetime, DA, and scattering coefficient were found between each tissue group. The NADH fluorescence lifetime and absorption coefficient were statistically different between the tumor and fibroglandular groups, and the tumor and adipose groups. While many breast tissue analysis studies label fibroglandular and adipose together as "normal" breast tissue, this work indicates that some differences between tumor and fibroglandular tissue are not the same as differences between tumor and adipose tissue. Observations of the reduced scatter coefficient may also indicate further classification to include fibro-adipose may be necessary. Future work would benefit from the additional tissue classification.

CONCLUSION: With observable differences in optical parameters between the three tissue types, this system shows promise as a breast analysis tool in a clinical setting. With further work involving samples of mixed composition, this combined system could potentially be used intraoperatively for rapid margin assessment.}, } @article {pmid37524533, year = {2023}, author = {Neth, BJ and Raghunathan, A and Kizilbash, SH and Uhm, JH and Breen, WG and Johnson, DR and Daniels, DJ and Sener, U and Carabenciov, ID and Campian, JL and Khatua, S and Mahajan, A and Ruff, MW}, title = {Management and Long-term Outcomes of Adults With Medulloblastoma: A Single-Center Experience.}, journal = {Neurology}, volume = {101}, number = {12}, pages = {e1256-e1271}, pmid = {37524533}, issn = {1526-632X}, mesh = {Child ; Humans ; Adult ; Male ; Adolescent ; Young Adult ; Middle Aged ; Aged ; Female ; *Medulloblastoma/therapy/diagnosis ; Retrospective Studies ; *Cerebellar Neoplasms/therapy/diagnosis ; Prognosis ; Survival Analysis ; }, abstract = {BACKGROUND AND OBJECTIVES: Medulloblastomas are embryonal tumors predominantly affecting children. Recognition of molecularly defined subgroups has advanced management. Factors influencing the management and prognosis of adult patients with medulloblastoma remains poorly understood.

METHODS: We examined the management, prognostic factors, and, when possible, molecular subgroup differences (subset) in adult patients (aged 18 years or older) with medulloblastoma from our center (specialty Neuro-Oncology clinic within a large academic practice) diagnosed between 1992 and 2020. Molecular subtyping corresponding to the 2021 WHO Classification was performed. Kaplan-Meier estimates (with log-rank test) were performed for univariate survival analysis with Cox regression used for multivariate analyses.

RESULTS: We included 76 adult patients with medulloblastoma (62% male), with a median age of 32 years at diagnosis (range: 18-66) and median follow-up of 7.7 years (range: 0.6-27). A subset of 58 patients had molecular subgroup characterization-37 SHH-activated, 12 non-WNT/non-SHH, and 9 WNT-activated. Approximately 67% underwent gross total resection, 75% received chemotherapy at diagnosis, and 97% received craniospinal irradiation with boost. The median overall survival (OS) for the whole cohort was 14.8 years. The 2-, 5-, and 10-year OS rates were 93% (95% CI 88-99), 86% (78-94), and 64% (53-78), respectively. Survival was longer for younger patients (aged 30 years or older: 9.9 years; younger than 30 years: estimated >15.4 years; log-rank p < 0.001). There was no survival difference by molecular subgroup or extent of resection. Only age at diagnosis remained significant in multivariate survival analyses.

DISCUSSION: We report one of the largest retrospective cohorts in adult patients with medulloblastoma with molecular subtyping. Survival and molecular subgroup frequencies were similar to prior reports. Survival was better for adult patients younger than 30 years at diagnosis and was not significantly different by molecular subgroup or management characteristics (extent of resection, RT characteristics, or chemotherapy timing or regimen).}, } @article {pmid37521588, year = {2023}, author = {Shah, MH and Batool, M}, title = {Surviving the Test of Time: A Young Patient's Triumph Over Early-Onset Invasive Ductal Carcinoma and Its Recurrence a Decade Later.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e42613}, pmid = {37521588}, issn = {2168-8184}, abstract = {Breast cancer is a complex, heterogeneous disease with diverse clinical presentations and variable outcomes. In this report, we provide a detailed analysis of a case involving a 22-year-old woman diagnosed with invasive ductal carcinoma, highlighting the difficulties of managing breast cancer in young patients. Through the examination of this patient's 10-year journey, from the initial diagnosis to surgery, adjuvant therapy, and recurrence, we underline the crucial role of early detection, personalised treatment, and interdisciplinary cooperation in optimising patient outcomes. Overall, the case study serves as a compelling narrative, effectively highlighting the aggressive nature of breast cancer in younger individuals and underscoring the need to provide care that addresses the multifaceted dimensions of this disease.}, } @article {pmid37520394, year = {2023}, author = {McFarland, BJ and Luo, A and Wang, X}, title = {Male breast cancer: Report of two cases with bloody nipple discharge.}, journal = {Radiology case reports}, volume = {18}, number = {9}, pages = {3323-3330}, pmid = {37520394}, issn = {1930-0433}, abstract = {We report 2 rare cases of male breast cancer with bloody nipple discharge. Patient 1, a 32-year-old male, presented with a bloody nipple discharge from the left breast. Diagnostic workup revealed papillary ductal carcinoma in situ. Patient 1 underwent bilateral mastectomy with left axillary sentinel lymph node biopsy and has been doing well ever since. Patient 2, a 70-year-old male with concomitant metastatic prostate cancer, presented with a palpable right breast mass and with initially serous, then bloody nipple discharge. Diagnostic workup revealed invasive ductal carcinoma with ductal carcinoma in situ of the right breast. Patient 2 received aromatase inhibitor therapy prior to right total mastectomy with SLN biopsy followed by adjuvant tamoxifen therapy. Patient 2 recovered without complication for 2 years until metastatic disease recurrence was detected. This case report's purpose is to increase awareness and enhance understanding of the presentation, diagnosis, treatment, and outcomes of rare malignant pathologies.}, } @article {pmid37519599, year = {2023}, author = {Grewal, IS and Rajagopal, T}, title = {Studying the Presentation of Paget Disease of the Breast.}, journal = {Cureus}, volume = {15}, number = {6}, pages = {e41057}, pmid = {37519599}, issn = {2168-8184}, abstract = {Paget disease of the breast is a rare breast cancer that accounts for 1-3% of all new presentations of breast cancer. It is characterized by an eczematous and ulcerative lesion of the nipple that may extend to the areola. Nearly 90% of cases are associated with underlying breast cancer. We report the presentation of Paget disease of the breast in a 41-year-old female, who presented due to a one-year history of an eczematous lesion of the left nipple area with no palpable mass, who was later found to have high-grade invasive ductal carcinoma treated with unilateral mastectomy and sentinel node biopsy.}, } @article {pmid37517027, year = {2023}, author = {Amato, S and Ramsey, J and Ahern, TP and Rovnak, J and Barlow, J and Weaver, D and Eyasu, L and Singh, R and Cintolo-Gonzalez, J}, title = {Exploring the presence of bovine leukemia virus among breast cancer tumors in a rural state.}, journal = {Breast cancer research and treatment}, volume = {202}, number = {2}, pages = {325-334}, pmid = {37517027}, issn = {1573-7217}, mesh = {Cattle ; Humans ; Female ; Animals ; Sheep/genetics ; *Breast Neoplasms/epidemiology/genetics ; *Leukemia Virus, Bovine/genetics ; DNA, Viral/genetics ; Breast ; *Mammary Neoplasms, Animal ; }, abstract = {PURPOSE: The bovine leukemia virus (BLV) is a deltaretrovirus that causes malignant lymphoma and lymphosarcomas in cattle globally and has high prevalence among large scale U.S. dairy herds. Associations between presence of BLV DNA in human mammary tissue and human breast cancer incidence have been reported. We sought to estimate the prevalence of BLV DNA in breast cancer tissue samples in a rural state with an active dairy industry.

METHODS: We purified genomic DNA from 56 fresh-frozen breast cancer tissue samples (51 tumor samples, 5 samples representing adjacent normal breast tissue) banked between 2016 and 2019. Using nested PCR assays, multiple BLV tax sequence primers and primers for the long terminal repeat (LTR) were used to detect BLV DNA in tissue samples and known positive control samples, including the permanently infected fetal lamb kidney cell line (FLK-BLV) and blood from BLV positive cattle.

RESULTS: The median age of patients from which samples were obtained at the time of treatment was 60 (40-93) and all were female. Ninety percent of patients had invasive ductal carcinoma. The majority were poorly differentiated (60%). On PCR assay, none of the tumor samples tested positive for BLV DNA, despite having consistent signals in positive controls.

CONCLUSION: We did not find BLV DNA in fresh-frozen breast cancer tumors from patients presenting to a hospital in Vermont. Our findings suggest a low prevalence of BLV in our patient population and a need to reevaluate the association between BLV and human breast cancer.}, } @article {pmid37513591, year = {2023}, author = {Hardt, LM and Herrmann, HJ and Reljic, D and Jaensch, P and Zerth, J and Neurath, MF and Zopf, Y}, title = {Are Guideline Recommendations on Supportive Nutrition and Exercise Therapy for Cancer Patients Implemented in Clinical Routine? A National Survey with Real-Life Data.}, journal = {Nutrients}, volume = {15}, number = {14}, pages = {}, pmid = {37513591}, issn = {2072-6643}, support = {MED1710//Hector-Stiftung/ ; N.N.//Research Foundation for Medicine at the University Hospital Erlangen/ ; }, mesh = {Humans ; Quality of Life ; Nutritional Support ; *Malnutrition/diagnosis ; *Neoplasms/complications/therapy ; Exercise Therapy ; }, abstract = {Malnutrition and cancer cachexia are highly prevalent comorbidities of cancer, limiting patients' quality of life and being relevant to prognosis. International and national clinical guidelines recommend supportive nutrition and exercise therapy for cancer patients. However, there is little current epidemiological evidence on the implementation of these guideline recommendations in clinical routine. To close this data gap, a national survey in Germany using an online questionnaire was conducted. There were 261 of a total of 5074 contacted hospitals and medical offices who participated in the survey (5.1% response rate). The data indicated that nutrition and exercise therapy for cancer patients is so far inadequately implemented, with 59% of the respondents reporting nutrition therapy as an integral part of oncological treatment, 66.7% having a nutrition specialist/team, and 65.1% routinely conducting a screening for nutritional status. Only half of the participants stated that there are defined goals in nutrition therapy. The majority of respondents (85.8%) generally recommend exercise therapy, but only a few of them provide specific offers at their own institution (19.6%) or at cooperation partners (31.7%). In order to implement the recommended combined nutrition and exercise therapy as part of regular care, there is a need for nationwide availability of multidisciplinary nutrition teams and targeted offers of individualized exercise therapy. Health policy support would be important to create the structural, financial, and staff conditions for appropriate guideline implementation in order to achieve the optimal treatment of cancer patients.}, } @article {pmid37512689, year = {2023}, author = {Harnsoongnoen, S and Buranrat, B}, title = {Microwave Sensor for the Determination of DMSO Concentration in Water-DMSO Binary Mixture.}, journal = {Micromachines}, volume = {14}, number = {7}, pages = {}, pmid = {37512689}, issn = {2072-666X}, support = {//This research project was financially supported by Thailand Science Research and Innovation (TSRI)./ ; }, abstract = {This research aims to develop a microwave sensor to accurately measure the concentration of dimethyl sulfoxide (DMSO) in water-DMSO binary mixtures. The proposed sensor will utilize microwave frequency measurements to determine the DMSO concentration, providing a non-invasive and efficient method for analyzing DMSO solutions. The research will involve the design, fabrication, and testing of the sensor, as well as the development of an appropriate calibration model. The outcomes of this study will contribute to improved monitoring and quality control in various fields, including pharmaceuticals, chemical synthesis, and biomedical research. The binary mixtures of dimethyl sulfoxide (DMSO) and water with varying concentrations were investigated in the frequency range of 1 GHz to 5 GHz at room temperature using a microwave sensor. The proposed microwave sensor design was based on an interdigital capacitor (IDC) microstrip antenna loaded with a hexagonal complementary ring resonator (HCRR). The performance of the sensor, fabricated using the print circuit board (PCB) technique, was validated through simulations and experiments. The reflection coefficient (S11) and resonance frequency (Fr) of binary mixtures of DMSO and water solutions were recorded and analyzed for DMSO concentrations ranging from 0% v/v to 75% v/v. Mathematical models were developed to analyze the data, and laboratory tests showed that the sensor can detect levels of DMSO/water binary mixtures. The sensor is capable of detecting DMSO concentrations ranging from 0% v/v to 75% v/v, with a maximum sensitivity of 0.138 dB/% for S11 and ΔS11 and 0.2 MHz/% for Fr and ΔFr at a concentration of 50% v/v. The developed microwave sensor can serve as an alternative for detecting DMSO concentrations in water using a simple and cost-effective technique. This method can effectively analyze a wide range of concentrations, including highly concentrated solutions, quickly and easily.}, } @article {pmid37511674, year = {2023}, author = {Faraz, K and Dauce, G and Bouhamama, A and Leporq, B and Sasaki, H and Bito, Y and Beuf, O and Pilleul, F}, title = {Characterization of Breast Tumors from MR Images Using Radiomics and Machine Learning Approaches.}, journal = {Journal of personalized medicine}, volume = {13}, number = {7}, pages = {}, pmid = {37511674}, issn = {2075-4426}, support = {Not able to provide at the moment//FUJIFILM Healthcare Corporation/ ; }, abstract = {Determining histological subtypes, such as invasive ductal and invasive lobular carcinomas (IDCs and ILCs) and immunohistochemical markers, such as estrogen response (ER), progesterone response (PR), and the HER2 protein status is important in planning breast cancer treatment. MRI-based radiomic analysis is emerging as a non-invasive substitute for biopsy to determine these signatures. We explore the effectiveness of radiomics-based and CNN (convolutional neural network)-based classification models to this end. T1-weighted dynamic contrast-enhanced, contrast-subtracted T1, and T2-weighted MR images of 429 breast cancer tumors from 323 patients are used. Various combinations of input data and classification schemes are applied for ER[+] vs. ER[-], PR[+] vs. PR[-], HER2[+] vs. HER2[-], and IDC vs. ILC classification tasks. The best results were obtained for the ER[+] vs. ER[-] and IDC vs. ILC classification tasks, with their respective AUCs reaching 0.78 and 0.73 on test data. The results with multi-contrast input data were generally better than the mono-contrast alone. The radiomics and CNN-based approaches generally exhibited comparable results. ER and IDC/ILC classification results were promising. PR and HER2 classifications need further investigation through a larger dataset. Better results by using multi-contrast data might indicate that multi-parametric quantitative MRI could be used to achieve more reliable classifiers.}, } @article {pmid37503233, year = {2023}, author = {Rothschild, HT and Clelland, EN and Abel, MK and Chien, AJ and Shui, AM and Esserman, L and Khan, SA and Mukhtar, RA}, title = {The impact of histologic subtype on primary site surgery in the management of metastatic lobular versus ductal breast cancer: a population based study from the National Cancer Database.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37503233}, issn = {2693-5015}, support = {K08 CA256047/CA/NCI NIH HHS/United States ; TL1 TR001871/TR/NCATS NIH HHS/United States ; }, abstract = {PURPOSE: Primary site surgery for metastatic breast cancer improves local control but does not impact overall survival. Whether histologic subtype influences patient selection for surgery is unknown. Given differences in surgical management between early-stage lobular versus ductal disease, we evaluated the impact of histology on primary site surgery in patients with metastatic breast cancer.

METHODS: The National Cancer Database (NCDB, 2010-2016) was queried for patients with stage IV HR-positive, HER2-negative invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). We compared clinicopathologic features, primary site surgery rates, and outcomes by histologic subtype. Multivariable Cox proportional hazard models with and without propensity score matching were used for overall survival (OS) analyses.

RESULTS: In 25,294 patients, primary site surgery was slightly but significantly less common in the 6,123 patients with ILC compared to the 19,171 patients with IDC (26.9% versus 28.8%, p = 0.004). Those with ILC were less likely to receive chemotherapy (41.3% versus 47.4%, p < 0.0001) or radiotherapy (29.1% versus 37.9%, p < 0.0001), and had shorter OS. While mastectomy rates were similar, those with ILC had more positive margins (10.6% versus 8.3%, p = 0.005). In both groups, the odds of undergoing surgery decreased over time, and were higher in younger patients with T2/T3 tumors and higher nodal burden.

CONCLUSION: Lobular histology is associated with less primary site surgery, higher positive margin rates, less radiotherapy and chemotherapy, and shorter OS compared to those with HR-positive HER2-negative IDC. These findings support the need for ILC-specific data and treatment approaches in the setting of metastatic disease.}, } @article {pmid37500355, year = {2023}, author = {Ding, W and Ye, D and Zhu, H and Lin, Y and Li, Z and Ruan, G}, title = {Survival Benefit of Adjuvant Chemotherapy in Node-Positive Breast Cancer With a 21-Gene Recurrence Score of 14 to 25: A Real-World Study Based on the Inverse Probability of Treatment Weighting Method.}, journal = {Clinical breast cancer}, volume = {23}, number = {7}, pages = {e441-e450}, doi = {10.1016/j.clbc.2023.07.004}, pmid = {37500355}, issn = {1938-0666}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; Retrospective Studies ; Biomarkers, Tumor ; Prognosis ; Chemotherapy, Adjuvant ; Proportional Hazards Models ; Neoplasm Recurrence, Local/pathology ; }, abstract = {INTRODUCTION: The role of recurrence score in predicting the benefits of adjuvant chemotherapy for lymph-node-positive breast cancer remains uncertain. We studied chemotherapy usage in patients with 1 to 3 positive lymph nodes and a recurrence score (RS) of 25 or lower to assess changes in clinical practice based on the RxPONDER trial.

METHODS: A retrospective study using the SEER database identified female patients diagnosed with ER-positive, HER2-negative breast cancer, 1 to 3 positive lymph nodes, and an RS of 25 or lower between 2010 and 2015. Patients were divided into nonchemotherapy and chemotherapy groups, with propensity score weighting to balance clinicopathologic factors.

RESULTS: Among 7965 patients, 5774 (72.5%) were in the nonchemotherapy group, while 2191 (27.5%) were in the chemotherapy group. Median follow-up was 39 months. Breast cancer accounted for 67 deaths, while 128 deaths were due to other causes. The weighted 5-year overall survival (OS) rates were 95.7% for the nonchemotherapy group and 97.2% for the chemotherapy group. For high-risk patients, the weighted 5-year OS rates were 95.2% and 97.0% for the nonchemotherapy and chemotherapy groups, respectively, with a significant absolute difference of 1.8% (P = .014). Multivariate analysis showed a significant difference in weighted hazard ratios for OS between the nonchemotherapy and chemotherapy groups in high-risk patients (hazard ratio: 0.64; 95% CI: 0.48-0.86). However, there were no significant differences in weighted hazard ratios for lower-risk patients, and similar results were observed for breast cancer-specific survival (BCSS).

CONCLUSION: Patients with ER-positive, HER2-negative breast cancer and 1 to 3 positive lymph nodes, assessed by a 21-gene RS of 0 to 25, exhibited heterogeneous prognosis. Adjuvant chemotherapy provided a significant survival benefit, especially for patients with RS of 14 to 25, particularly those with invasive ductal carcinoma (IDC) and 2 to 3 positive lymph nodes.}, } @article {pmid37500131, year = {2023}, author = {Namikawa, T and Yokota, K and Maeda, H and Kitagawa, H and Tamura, M and Satake, H and Sugimoto, T and Kobayashi, M and Hanazaki, K and Seo, S}, title = {Gastric and Bone Metastases Arising from Invasive Lobular Carcinoma With Ductal Carcinoma Occurring in one Breast Synchronously.}, journal = {Anticancer research}, volume = {43}, number = {8}, pages = {3701-3707}, doi = {10.21873/anticanres.16553}, pmid = {37500131}, issn = {1791-7530}, mesh = {Female ; Humans ; Aged ; *Carcinoma, Lobular/pathology ; Fluorodeoxyglucose F18 ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Bone Neoplasms ; Stomach/pathology ; }, abstract = {BACKGROUND/AIM: We report the case of a patient with gastric and bone metastases arising from an invasive lobular carcinoma of the breast coexisting with ductal carcinoma at the same time.

CASE REPORT: A 68-year-old woman with gastric and right costal tumors was referred to our hospital. Esophagogastroduodenoscopy (EGD) revealed irregular, slightly elevated lesions extending from the gastric body to the antrum, and biopsy specimens revealed a poorly differentiated adenocarcinoma. Furthermore, abdominal contrast-enhanced computed tomography (CT) revealed extensive wall thickening with homogeneous enhancement in the stomach. 18F-2-deoxy-2-fluoro-glucose positron emission tomography (FDG-PET) showed intense FDG uptake in the right mammary gland and right third rib. Moreover, fine-needle aspiration of the third right rib lump and the right breast mass lesion was performed, and subsequent pathological investigations revealed metastatic adenocarcinoma and invasive ductal carcinoma, respectively. Immunohistochemical examination revealed that estrogen receptor was strongly positive (>95%) in breast cancer and focally positive (<5%) in gastric cancer with bone metastasis. In addition, another right breast tumor was detected by breast magnetic resonance imaging (MRI), and biopsy revealed invasive lobular carcinoma that matched the histological findings of bone and gastric lesions, including immunohistochemical examination. The patient was treated with an aromatase inhibitor, a CDK4/6 inhibitor, and a receptor activator of nuclear factor-kappa B ligand (RANKL) monoclonal antibody. She showed no symptoms or disease progression at 9-month follow-up after the initiation of systemic drug treatment.

CONCLUSION: Invasive lobular carcinoma can metastasize to the gastrointestinal tract, and new treatment developments are expected as more cases will accumulate in the future.}, } @article {pmid37498719, year = {2024}, author = {Shoshani, A}, title = {Longitudinal changes in children's and adolescents' mental health and well-being and associated protective factors during the COVID-19 pandemic.}, journal = {Psychological trauma : theory, research, practice and policy}, volume = {16}, number = {7}, pages = {1158-1168}, doi = {10.1037/tra0001556}, pmid = {37498719}, issn = {1942-969X}, mesh = {Humans ; *COVID-19/psychology/prevention & control ; Child ; Adolescent ; Male ; Female ; Longitudinal Studies ; *Protective Factors ; *Social Support ; Israel ; Mental Health ; Resilience, Psychological ; Personal Satisfaction ; Depression/psychology ; }, abstract = {OBJECTIVE: The COVID-19 pandemic has heightened children's and adolescents' risk of experiencing long-term mental health problems and a decline in subjective well-being. To better understand the longitudinal impact of COVID-19, this study explored the role of demographic variables and the potential moderating effects of social support and daily routines as resilience factors.

METHOD: A nationally representative, longitudinal cohort of 5,217 Israeli children and adolescents aged 10-15 at baseline completed measures of mental health symptoms, life satisfaction, positive and negative emotions, gratitude, social support, and daily routines. Data were collected in school at four measurement points: September 2019 (before the outbreak of COVID-19; N = 5,127), May 2020 (after the first lockdown; N = 4,698), May 2021 (after the third wave lockdown; N = 4,813), and May 2022 (after the fourth and fifth waves of the pandemic; N = 4,897). The data were analyzed using multilevel mixed models.

RESULTS: Significant increases in depression, anxiety, and panic along with decreases in psychological well-being were found as a function of time. These effects were moderated by age and gender. Participants with high social support and structured daily routines reported smaller increases in mental health symptoms than students with low social support or irregular daily routines.

CONCLUSION: There is a critical need for clinical and educational interventions for young people during this period to promote the resilience factors that can moderate well-being and counter the decline in mental health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid37496230, year = {2023}, author = {Konishi, K and Araya, J and Nagabuchi, M and Sakamoto, T and Ogino, J and Hirano, S}, title = {[A Case of Breast Carcinoma That Changed Subtype to Squamous Cell Carcinoma after Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {7}, pages = {825-827}, pmid = {37496230}, issn = {0385-0684}, mesh = {Female ; Humans ; *Breast Neoplasms/drug therapy/surgery/pathology ; Docetaxel/therapeutic use ; Mastectomy ; Quality of Life ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Carcinoma, Squamous Cell/drug therapy/surgery/pathology ; Capecitabine/therapeutic use ; Cyclophosphamide/therapeutic use ; *Liver Neoplasms/drug therapy/surgery/secondary ; }, abstract = {Metaplastic carcinoma is a rare histological malignancy, often triple-negative, and has a poor prognosis. Here, we report a case of breast cancer in which the primary lesion degenerated into squamous cell carcinoma(triple negative)after drug treatment for invasive ductal carcinoma(Luminal type). The patient was a 41-year-old woman who was diagnosed with Stage Ⅳ left breast cancer T2N2bM1(HEP)(ER 90%, PR 70%, HER2 2+, FISH-)at another hospital and participated in the PATHWAY study(tamoxifen plus goserelin plus palbociclib/placebo). Since the primary lesion and liver metastasis increased in size, the study was discontinued after 8 weeks. She was treated at our hospital thereafter, with capecitabine plus cyclophosphamide, palbociclib plus fulvestrant plus leuprorelin, paclitaxel plus bevacizumab, eribulin, EC therapy, and docetaxel. However, both the primary lesion and liver metastasis increased. In particular, the increase in primary lesion size was remarkable, and the QOL significantly reduced due to bleeding and exudation. Biopsy performed during docetaxel treatment revealed metaplastic/squamous cell carcinoma(ER-, PR-, HER2 0, Ki-67 90-100%)histopathological findings. BRCA and microsatellite instability tests were negative, and PDL1 expression was less than 1%. Although Mohs ointment was used, tumor bleeding, exudate, and stink were poorly controlled, and the patient experienced painful symptoms due to the weight of the tumor. Therefore, left mastectomy plus pectoralis major muscle resection was performed. The patient died one month after the operation.}, } @article {pmid37495452, year = {2023}, author = {Bódis, K and Bombrich, M and Schön, M and Knebel, B and Zaharia, OP and Bönhof, G and Karusheva, Y and Strassburger, K and Kupriyanova, Y and Kotzka, J and Guthoff, R and Schrauwen-Hinderling, V and Al-Hasani, H and Burkart, V and Szendroedi, J and Wagner, R and Markgraf, DF and Roden, M and , }, title = {Effects of TM6SF2 rs58542926 polymorphism on hepatocellular lipids and insulin resistance in early type 2 diabetes.}, journal = {Nutrition, metabolism, and cardiovascular diseases : NMCD}, volume = {33}, number = {9}, pages = {1785-1796}, doi = {10.1016/j.numecd.2023.06.004}, pmid = {37495452}, issn = {1590-3729}, mesh = {Humans ; Male ; Case-Control Studies ; *Diabetes Mellitus, Type 2/diagnosis/genetics/complications ; *Insulin Resistance/genetics ; Liver/metabolism ; *Liver Neoplasms ; Membrane Proteins/genetics/metabolism ; *Non-alcoholic Fatty Liver Disease/diagnosis/genetics/complications ; Polymorphism, Single Nucleotide ; Triglycerides/metabolism ; }, abstract = {BACKGROUND AND AIMS: Increased hepatocellular lipid content (HCL) is linked to insulin resistance, risk of type 2 diabetes and related complications. Conversely, a single-nucleotide polymorphism (TM6SF2[EK]; rs58542926) in the transmembrane 6 superfamily member 2-gene has been associated with nonalcoholic fatty liver disease (NAFLD), but lower cardiovascular risk. This case-control study tested the role of this polymorphism for tissue-specific insulin sensitivity during early course of diabetes.

METHODS AND RESULTS: Males with recent-onset type 2 diabetes with (TM6SF2[EK]: n = 16) or without (TM6SF2[EE]: n = 16) the heterozygous TM6SF2-polymorphism of similar age and body mass index, underwent Botnia-clamps with [6,6-[2]H2]glucose to measure whole-body-, hepatic- and adipose tissue-insulin sensitivity. HCL was assessed with [1]H-magnetic-resonance-spectroscopy. A subset of both groups (n = 24) was re-evaluated after 5 years. Despite doubled HCL, TM6SF2[EK] had similar hepatic- and adipose tissue-insulin sensitivity and 27% higher whole-body-insulin sensitivity than TM6SF2[EE]. After 5 years, whole-body-insulin sensitivity, HCL were similar between groups, while adipose tissue-insulin sensitivity decreased by 87% and 55% within both groups and circulating triacylglycerol increased in TM6SF2[EE] only.

CONCLUSIONS: The TM6SF2-polymorphism rs58542926 dissociates HCL from insulin resistance in recent-onset type 2 diabetes, which is attenuated by disease duration. This suggests that diabetes-related metabolic alterations dominate over effects of the TM6SF2-polymorphism during early course of diabetes and NAFLD.}, } @article {pmid37493324, year = {2024}, author = {Lee, SE and Yoon, JH and Son, NH and Han, K and Moon, HJ}, title = {Screening in Patients With Dense Breasts: Comparison of Mammography, Artificial Intelligence, and Supplementary Ultrasound.}, journal = {AJR. American journal of roentgenology}, volume = {222}, number = {1}, pages = {e2329655}, doi = {10.2214/AJR.23.29655}, pmid = {37493324}, issn = {1546-3141}, mesh = {Humans ; Female ; Middle Aged ; *Mammography/methods ; Breast Density ; Retrospective Studies ; Artificial Intelligence ; *Breast Neoplasms ; Early Detection of Cancer/methods ; Mass Screening/methods ; }, abstract = {BACKGROUND. Screening mammography has decreased performance in patients with dense breasts. Supplementary screening ultrasound is a recommended option in such patients, although it has yielded mixed results in prior investigations. OBJECTIVE. The purpose of this article is to compare the performance characteristics of screening mammography alone, standalone artificial intelligence (AI), ultrasound alone, and mammography in combination with AI and/or ultrasound in patients with dense breasts. METHODS. This retrospective study included 1325 women (mean age, 53 years) with dense breasts who underwent both screening mammography and supplementary breast ultrasound within a 1-month interval from January 2017 to December 2017; prior mammography and prior ultrasound examinations were available for comparison in 91.2% and 91.8%, respectively. Mammography and ultrasound examinations were interpreted by one of 15 radiologists (five staff; 10 fellows); clinical reports were used for the present analysis. A commercial AI tool was used to retrospectively evaluate mammographic examinations for presence of cancer. Screening performances were compared among mammography, AI, ultrasound, and test combinations, using generalized estimating equations. Benign diagnoses required 24 months or longer of imaging stability. RESULTS. Twelve cancers (six invasive ductal carcinoma; six ductal carcinoma in situ) were diagnosed. Mammography, standalone AI, and ultrasound showed cancer detection rates (per 1000 patients) of 6.0, 6.8, and 6.0 (all p > .05); recall rates of 4.4%, 11.9%, and 9.2% (all p < .05); sensitivity of 66.7%, 75.0%, and 66.7% (all p > .05); specificity of 96.2%, 88.7%, and 91.3% (all p < .05); and accuracy of 95.9%, 88.5%, and 91.1% (all p < .05). Mammography with AI, mammography with ultrasound, and mammography with both ultrasound and AI showed cancer detection rates of 7.5, 9.1, and 9.1 (all p > .05); recall rates of 14.9, 11.7, and 21.4 (all p < .05); sensitivity of 83.3%, 100.0%, and 100.0% (all p > .05); specificity of 85.8%, 89.1%, and 79.4% (all p < .05); and accuracy of 85.7%, 89.2%, and 79.5% (all p < .05). CONCLUSION. Mammography with supplementary ultrasound showed higher accuracy, higher specificity, and lower recall rate in comparison with mammography with AI and in comparison with mammography with both ultrasound and AI. CLINICAL IMPACT. The findings fail to show benefit of AI with respect to screening mammography performed with supplementary breast ultrasound in patients with dense breasts.}, } @article {pmid37492824, year = {2023}, author = {Kalantri, P and Lomashvili, K}, title = {Deruxtecan-Induced Reversible Fanconi Syndrome.}, journal = {Cureus}, volume = {15}, number = {6}, pages = {e40890}, pmid = {37492824}, issn = {2168-8184}, abstract = {Increasingly complex and constantly emerging cancer treatment protocols are associated with kidney toxicities. Data clearly demonstrate that when patients with cancer develop acute or chronic kidney disease, severe fluid and electrolyte abnormalities, outcomes are inferior, and the promise of curative therapeutic regimens is lessened. We present a case of a 74-year-old woman with metastatic, recurrent ER+/PR-/HER2+ invasive ductal carcinoma of the right breast, status post bilateral mastectomies, chemotherapy, radiation therapy, and hormonal therapies, who were clinically stable on Trastuzumab/Pertuzumab maintenance for about a year. She then experienced disease progression. She was started on Trastuzumab+Deruxtecan (T-Dxt). However, due to worsening diarrhea of more than 12 episodes per day, decreased oral intake, weakness and weight loss, she got admitted to the hospital. Laboratory data showed hyponatremia, hypokalemia, non-anion gap metabolic acidosis, hypomagnesemia, and hypophosphatemia. These laboratory abnormalities were initially attributed to diarrhea. Renal losses were suspected when the electrolyte abnormalities did not correct despite improving diarrhea. Urine electrolytes were hence tested. There was evidence of Fanconi syndrome with glucosuria, proteinuria, and renal potassium and phosphorus wasting. Fanconi syndrome was attributed to the Deruxtecan component of the combination chemotherapy, as she was previously on Trastuzumab with no such abnormalities. The electrolyte abnormalities resolved over the course of a few months. To our knowledge, this is the first case of Fanconi syndrome due to T-Dxt.}, } @article {pmid37492470, year = {2023}, author = {Li, Y and Zhang, Y and Zhou, Z and Shang, L and Huang, Y and Lu, X and Cheng, S}, title = {Predictive value of controlling nutritional status score in postoperative recurrence and metastasis of breast cancer patients with HER2-low expression.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1116631}, pmid = {37492470}, issn = {2234-943X}, abstract = {BACKGROUND: To investigate the predictive value of controlling nutritional status (CONUT) score in Postoperative Recurrence and Metastasis of Breast Cancer Patients with HER2-Low Expression.

METHODS: The clinicopathological data of 697 female breast cancer patients who pathology confirmed invasive ductal carcinoma and surgery in Harbin Medical University Tumor Hospital from January 2014 to January 2017 were retrospectively analyzed. The relationship between CONUT score and various clinicopathological factors as well as prognosis was evaluated.

RESULTS: Based on the cut-off point of ROC curve, compared with the low CONUT score group, the high CONUT score group had worse 5-year RFS. In subgroup analysis, compared with the low CONUT group, the high CONUT group had worse prognosis at different TNM stages. Univariate and multivariate results showed that the low CONUT score group had better overall survival and recurrence-free survival than the high CONUT group.

CONCLUSION: CONUT score is an independent predictor of postoperative recurrence and metastasis in HER2-low breast cancer patients. It is may be used as an effective tool to predict the recurrence and metastasis of HER2-low breast cancer.}, } @article {pmid37490163, year = {2023}, author = {Goldhaber, NH and O'Keefe, T and Kang, J and Douglas, S and Blair, SL}, title = {Is Choosing Wisely Wise for Lobular Carcinoma in Patients Over 70 Years of Age? A National Cancer Database Analysis of Sentinel Node Practice Patterns.}, journal = {Annals of surgical oncology}, volume = {30}, number = {10}, pages = {6024-6032}, pmid = {37490163}, issn = {1534-4681}, mesh = {Humans ; Female ; Aged ; Aged, 80 and over ; *Carcinoma, Lobular/surgery/pathology ; *Carcinoma, Ductal, Breast/surgery/pathology ; Neoplasm Staging ; *Breast Neoplasms/surgery/pathology ; *Sentinel Lymph Node/surgery/pathology ; *Lymphadenopathy ; }, abstract = {BACKGROUND: Controversy continues in the treatment of breast cancer in women over 70 years of age. In 2016, the Society of Surgical Oncology recommended against routine use of sentinel lymph node biopsy (SLNBx) as part of the 'Choosing Wisely Campaign'. This study examines the oncologic safety of avoidance of routine SLNBx in patients over 70 years of age with invasive lobular carcinoma (ILC).

METHODS: The National Cancer Database was used to identify women with invasive ductal carcinoma (IDC) and ILC diagnosed between 2012 and 2020. Clinical and pathological staging, axillary staging, surgery type, and lymph node positivity between patients with IDC or ILC were compared.

RESULTS: Among women with T1 tumors, 85,949 (79.6%) patients with IDC and 12,761 (81.5%) patients with ILC underwent SLNBx (p < 0.001). Among patients who underwent SLNBx, those with IDC were more likely to have positive nodes (n = 7535, 8.8%) than those with ILC (n = 1041, 8.2%; p = 0.02). During the time interval of interest, for both IDC and ILC patients, the rate of axillary lymph node dissection decreased and rates of SLNBx or no axillary staging increased. On multivariate analysis, ILC histology was associated with use of SLNBx, but without nodal positivity.

CONCLUSION: A trend de-escalation of axillary staging was identified in this study, however the majority of patients meeting the 'Choosing Wisely' criteria are still undergoing SLNBx. No increased risk of nodal positivity was identified among patients with ILC, suggesting that surgeons can continue to choose wisely and limit the use of SLNBx in women over 70 years of age with T1 ILC tumors.}, } @article {pmid37490055, year = {2023}, author = {Choo, ZY and Xu, AZ}, title = {Predictors and outcomes of cutaneous metastatic breast carcinoma: a retrospective, single-institution review.}, journal = {Archives of dermatological research}, volume = {315}, number = {9}, pages = {2725-2728}, pmid = {37490055}, issn = {1432-069X}, mesh = {Humans ; Female ; Retrospective Studies ; *Breast Neoplasms/therapy ; Skin/pathology ; Administration, Cutaneous ; *Carcinoma, Lobular/pathology/secondary ; }, } @article {pmid37489961, year = {2023}, author = {Sanchez, D and Bloomquist, E and Wright, H and Barnavon, Y}, title = {Immediate Nipple Reconstruction With Areolar Flaps After Nipple Excision.}, journal = {Annals of plastic surgery}, volume = {91}, number = {2}, pages = {211-214}, doi = {10.1097/SAP.0000000000003570}, pmid = {37489961}, issn = {1536-3708}, mesh = {Humans ; Female ; Nipples ; *Carcinoma, Intraductal, Noninfiltrating ; *Breast Neoplasms ; Esthetics ; Genetic Predisposition to Disease ; }, abstract = {Nipple-sparing mastectomies (NSMs) have become a common surgical approach in the management of invasive breast cancers and ductal carcinoma in situ, and as a risk-reducing approach in genetically predisposed patients. The current standard of care in the management of positive nipple margin after NSM is total excision of the nipple-areola complex. In this article, we aimed to present a case series describing a novel approach to positive nipple margins with nipple-only excision and immediate nipple reconstruction using areolar flaps in patients who underwent NSM for noninvasive tumors. We conducted a retrospective review of patients who underwent NSM and were found to have positive nipple margins and underwent subsequent nipple excision with immediate areolar flap reconstruction. We identified 6 patients who underwent NSM and were found to have nipple margins-5 for ductal carcinoma in situ and 1 for invasive ductal carcinoma. These patients underwent nipple excision with immediate reconstruction using "sickle" flaps. We concluded that if nipple excision and immediate reconstruction with areolar sickle flaps can be performed, it results in good aesthetic outcomes without compromising oncologic results.}, } @article {pmid37480503, year = {2023}, author = {D'Iorio, A and Aiello, EN and Amboni, M and Vitale, C and Verde, F and Silani, V and Ticozzi, N and Ciammola, A and Poletti, B and Santangelo, G}, title = {Validity and diagnostics of the Italian version of the Montreal Cognitive Assessment (MoCA) in non-demented Parkinson's disease patients.}, journal = {Aging clinical and experimental research}, volume = {35}, number = {10}, pages = {2157-2163}, pmid = {37480503}, issn = {1720-8319}, mesh = {Humans ; *Parkinson Disease/complications/diagnosis ; Retrospective Studies ; Mental Status and Dementia Tests ; *Cognitive Dysfunction/diagnosis/etiology ; Language ; }, abstract = {BACKGROUND: This study aimed at: (1) assessing, in an Italian cohort of non-demented Parkinson's disease (PD) patients, the construct validity of the Montreal Cognitive Assessment (MoCA) against both first- and second-level cognitive measures; (2) delivering an exhaustive and updated evaluation of its diagnostic properties.

METHODS: A retrospective cohort of N = 237 non-demented PD patients having been administered the MoCA was addressed, of whom N = 169 further underwent the Mini-Mental State Examination (MMSE) and N = 68 the Parkinson's Disease Cognitive Rating Scale (PD-CRS). A subsample (N = 60) also underwent a second-level cognitive battery encompassing measures of attention/executive functioning, language, memory, praxis and visuo-spatial abilities. Construct validity was assessed against both the PD-CRS and the second-level cognitive battery. Diagnostics were tested via receiver-operating characteristics analyses against a below-cut-off MMSE score.

RESULTS: The MoCA was associated with both PD-CRS scores (p < .001) and the vast majority of second-level cognitive measures (ps < .003). Both raw and adjusted MoCA scores proved to be highly accurate to the aim of identifying patients with MMSE-confirmed cognitive dysfunctions. A MoCA score adjusted for age and education according to the most recent normative dataset and < 19.015 is herewith suggested as indexing cognitive impairment in this population (AUC = .92; sensitivity = .92; specificity = .80).

DISCUSSION: The Italian MoCA is a valid and diagnostically sound screener for global cognitive inefficiency in non-demented PD patients. Further studies are nevertheless needed that confirm its diagnostic values against a measure other than the MMSE.}, } @article {pmid37480256, year = {2023}, author = {White, D and Sadough Shahmirzadi, M and Boulmay, B}, title = {Multi-Phenotypic Breast Cancer Post-Radiotherapy for Hodgkin Lymphoma: A Case of Secondary Malignancy.}, journal = {Journal of investigative medicine high impact case reports}, volume = {11}, number = {}, pages = {23247096231188251}, pmid = {37480256}, issn = {2324-7096}, mesh = {Female ; Humans ; Middle Aged ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; *Breast Neoplasms/radiotherapy ; *Hodgkin Disease/radiotherapy ; Mastectomy ; Breast/pathology ; *Neoplasms, Second Primary/etiology ; }, abstract = {Morbidity and mortality associated with radiation-induced secondary malignancies (RISMs) have shifted treatment paradigms to minimize or eliminate radiation from treatment regimens. In this case, a 48-year-old woman was diagnosed with Hodgkin lymphoma (HL) and treated with radiotherapy in 2000. In 2018, she was diagnosed with ductal carcinoma in situ (DCIS) of the right breast and treated with a mastectomy. Soon after, she developed triple-negative invasive ductal carcinoma (IDC) in her reconstructed breast. The patient underwent a left lumpectomy, and pathology showed ER-/PR-/HER2+ IDC. This patient's multi-phenotypic DCIS and IDC presentation are suspected to be RISM due to her previous HL treatment regimen.}, } @article {pmid37479943, year = {2023}, author = {Adachi, Y and Asaga, S and Kumamaru, H and Kinugawa, N and Sagara, Y and Niikura, N and Jinno, H and Saji, S and Toi, M}, title = {Analysis of prognosis in different subtypes of invasive lobular carcinoma using the Japanese National Cancer Database-Breast Cancer Registry.}, journal = {Breast cancer research and treatment}, volume = {201}, number = {3}, pages = {397-408}, pmid = {37479943}, issn = {1573-7217}, mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/therapy ; *Carcinoma, Lobular/therapy ; East Asian People ; Prognosis ; Registries ; }, abstract = {PURPOSE: Many studies have shown that the prognosis of invasive lobular carcinoma (ILC) is better than that of invasive ductal carcinoma (IDC). However, both disorders exhibit different prognoses according to molecular subtype, and the prognosis of ILC subtypes might depend on their hormone receptor positivity rate. This study clarified the prognosis of ILC and IDC in each subtype and examined the effectiveness of adjuvant chemotherapy (CT) in luminal ILC.

METHODS: We planned the analysis using data from the Breast Cancer Registry in Japan. Because it was presumed that there are differences in characteristics between ILC and IDC, we created matched cohorts using exact matching to compare their prognoses. We compared the prognosis of ILC and IDC for each subtype. We also compared the prognosis of luminal ILC between the CT and non-CT groups.

RESULTS: For all subtypes, the disease-free survival (DFS) and overall survival (OS) of ILC were poorer than those of IDC. In the analysis by each subtype, no statistically significant difference was found in DFS and OS in luminal human epidermal growth factor 2 (HER2), HER2, and triple-negative cohorts; however, luminal ILC had significantly poorer DFS and OS than luminal IDC. The CT effects on the prognosis of luminal ILC were greater in more advanced cases.

CONCLUSION: Luminal ILC had a poorer prognosis than luminal IDC, contributing to the worse prognosis of ILC than that of IDC in the overall cohort. Different therapeutic approaches from luminal IDC are essential for a better prognosis of luminal ILC.}, } @article {pmid37479782, year = {2023}, author = {Fond, G and Falissard, B and Nuss, P and Collin, C and Duret, S and Rabbani, M and De Chefdebien, I and Tonelli, I and Llorca, PM and Boyer, L}, title = {How can we improve the care of patients with schizophrenia in the real-world? A population-based cohort study of 456,003 patients.}, journal = {Molecular psychiatry}, volume = {28}, number = {12}, pages = {5328-5336}, pmid = {37479782}, issn = {1476-5578}, mesh = {Humans ; *Schizophrenia/drug therapy/epidemiology ; Male ; Female ; Middle Aged ; Adult ; *Antipsychotic Agents/therapeutic use ; Cohort Studies ; Aged ; Comorbidity ; Antidepressive Agents/therapeutic use ; Anticonvulsants/therapeutic use ; Adolescent ; Young Adult ; }, abstract = {An important step to improve outcomes for patients with schizophrenia is to understand treatment patterns in routine practice. The aim of the current study was to describe the long-term management of patients with schizophrenia treated with antipsychotics (APs) in real-world practice. This population-based study included adults with schizophrenia and who had received ≥3 deliveries of an AP from 2012-2017, identified using a National Health Data System. Primary endpoints were real-life prescription patterns, patient characteristics, healthcare utilization, comorbidities and mortality. Of the 456,003 patients included, 96% received oral APs, 17.5% first-generation long-acting injectable APs (LAIs), and 16.1% second generation LAIs. Persistence rates at 24 months after treatment initiation were 23.9% (oral APs), 11.5% (first-generation LAIs) and 20.8% (second-generation LAIs). Median persistence of oral APs, first-generation LAIs and second-generation LAIs was 5.0, 3.3, and 6.1 months, respectively. Overall, 62.1% of patients were administered anxiolytics, 45.7% antidepressants and 28.5% anticonvulsants, these treatments being more frequently prescribed in women and patients aged ≥50 years. Dyslipidemia was the most frequent metabolic comorbidity (16.2%) but lipid monitoring was insufficient (median of one occasion). Metabolic comorbidities were more frequent in women. Standardized patient mortality remained consistently high between 2013 and 2015 (3.3-3.7 times higher than the general French population) with a loss of life expectancy of 17 years for men and 8 years for women. Cancer (20.2%) and cardiovascular diseases (17.2%) were the main causes of mortality, and suicide was responsible for 25.4% of deaths among 18-34-year-olds. These results highlight future priorities for care of schizophrenia patients. The global persistence of APs used in this population was low, whereas rates of psychiatric hospitalization remain high. More focus on specific populations is needed, such as patients aged >50 years to prevent metabolic disturbances and 18-34-year-olds to reduce suicide rates.}, } @article {pmid37479781, year = {2023}, author = {Boyer, L and Falissard, B and Nuss, P and Collin, C and Duret, S and Rabbani, M and De Chefdebien, I and Tonelli, I and Llorca, PM and Fond, G}, title = {Real-world effectiveness of long-acting injectable antipsychotic treatments in a nationwide cohort of 12,373 patients with schizophrenia-spectrum disorders.}, journal = {Molecular psychiatry}, volume = {28}, number = {9}, pages = {3709-3716}, pmid = {37479781}, issn = {1476-5578}, mesh = {Male ; Humans ; Female ; *Antipsychotic Agents/therapeutic use ; *Schizophrenia/drug therapy ; Risperidone/therapeutic use ; Paliperidone Palmitate/therapeutic use ; Aripiprazole ; Injections ; Administration, Oral ; }, abstract = {This mirror-image study aimed to evaluate the real-life effectiveness of long-acting injectable antipsychotics (LAI) in schizophrenia. Patients with schizophrenia initiating LAIs January 2015-December 2016 were enrolled from the French National Health Data System (SNDS). Standardized mean differences (SMD > 0.1 deemed clinically significant) were calculated for psychiatric healthcare resource utilization measures assessed one year before (during oral AP treatment) and one year after LAI initiation. LAI effectiveness was analyzed overall and by age group, gender and compliance to oral AP, defined as exposure to an AP for at least 80% of the year before LAI initiation. 12,373 patients were included. LAIs were more frequently initiated in men (58.1%), young (18-34 years, 42.0%) and non-compliant (63.7%) patients. LAI initiation was effective in reducing the number and duration of psychiatric hospitalizations and psychiatric emergency department (ED) admissions in non-compliant patients (SMD = -0.19, -0.26 and -0.12, respectively), but not in compliant patients. First-generation LAIs, paliperidone and aripiprazole LAIs reduced psychiatric hospitalizations (SMD = -0.20, -0.24, -0.21, respectively) and ED admissions (SMD = -0.15, -0.13, -0.15, respectively). No differences in effectiveness were found for age or gender. In compliant patients, only aripiprazole LAI reduced the number of psychiatric hospitalizations (SMD = -0.13). Risperidone and paliperidone LAIs increased hospitalization duration (SMD = 0.15 and 0.18, respectively). The prescription of LAIs (except risperidone) should be recommended in all non-compliant patients, even in women and patients aged 35 or older. The lower frequency of administration of LAIs than of oral APs may improve compliance and hence reduce the risk of relapse. Aripiprazole LAI may represent a treatment of choice for compliant patients that should be further investigated.}, } @article {pmid37479756, year = {2023}, author = {Tian, Z and Yang, Z and Jin, M and Ding, R and Wang, Y and Chai, Y and Wu, J and Yang, M and Zhao, W}, title = {Identification of cytokine-predominant immunosuppressive class and prognostic risk signatures in glioma.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {14}, pages = {13185-13200}, pmid = {37479756}, issn = {1432-1335}, support = {JJKH20181256KJ//The Scientific Research Planning Project of the Education Department of Jilin Province/ ; }, abstract = {PURPOSE: The advent of immune checkpoint blockade (ICB) therapies this year has changed the way glioblastoma (GBM) is treated. Meanwhile, some patients with strong PD-L1 expression remain immune checkpoint resistant. To better understand the molecular processes that influence the immune environment, there is an urgent need to characterize the immunosuppressive tumor microenvironment and identify biomarkers to predict patient survival outcomes.

PATIENTS AND METHODS: Our study analyzed RNA-sequencing data from 178 GBM samples. Their unique gene expression patterns in the tumor microenvironment were analyzed by an unsupervised clustering algorithm. Through these expression patterns, a panel of T-cell exhaustion signatures, immunosuppressive cells, and clinical features correlates with immunotherapy response. The presence or absence of immune status and prognostic signatures was then validated with the test dataset.

RESULTS: 38.2% of GBM patients showed increased expression of anti-inflammatory cytokines, significant enrichment of T cell exhaustion signals, higher proportion of immunosuppressive cells (macrophages and CD4 regulatory T cells) and nine inhibitory checkpoints (CTLA4, PDCD1, LAG3, BTLA, TIGIT, HAVCR2, IDO1, SIGLEC7, and VISTA). The immunodepleted class (IDC) was used to classify these immunocompromised individuals. Despite the high density of tumor-infiltrating lymphocytes shown by IDC, such patients have a poor prognosis. Although PD-L1 was highly expressed in IDC, it suggested that there might be ICB resistance. There are many IDC predictive signatures to discover.

CONCLUSION: PD-1 is strongly expressed in a novel immunosuppressive class of GBM, but this cluster may be resistant to ICB therapy. A comprehensive description of this drug-resistant tumor microenvironment could provide new insights into drug resistance mechanisms and improved immunotherapy techniques.}, } @article {pmid37478120, year = {2023}, author = {Shi, K and Liu, XL and Guo, Q and Zhang, YQ and Fan, ST and Dai, L and Jiang, N and Li, D}, title = {TMEM41A overexpression correlates with poor prognosis and immune alterations in patients with endometrial carcinoma.}, journal = {PloS one}, volume = {18}, number = {7}, pages = {e0285817}, pmid = {37478120}, issn = {1932-6203}, mesh = {Female ; Humans ; Biomarkers, Tumor/genetics/metabolism ; *Endometrial Neoplasms/pathology ; Nomograms ; Prognosis ; RNA ; Tumor Microenvironment/genetics ; Membrane Proteins ; Oncogene Proteins ; }, abstract = {BACKGROUND: Expression levels of transmembrane protein 41A (TMEM41A) are related to the progression of malignant tumors. However, the association between TMEM41A expression and endometrial carcinoma (EC) remains unclear. This study aims to identify the roles of TMEM41A expression in the prognosis of patients with EC and its correlation with EC progression.

METHODS: The TMEM41A expression and its correlation with the survival of patients with EC were assessed. Cox regression analysis was used to identify the prognostic factors, while nomograms were used to examine the association between the prognostic factors and the survival of patients with EC. Finally, the link between TMEM41A level and immune microenvironment and RNA modifications was investigated in EC.

RESULTS: TMEM41A was overexpressed in EC. TMEM41A overexpression could diagnose the EC and evaluate the poor prognosis of patients. Overexpression of TMEM41A was associated with clinical stage, age, weight, histological subtype, tumor grade, and survival status of patients with EC. Clinical stage, age, tumor grade, radiotherapy, and TMEM41A overexpression were factors of poor prognosis in patients with EC. The nomograms revealed the correlation between the TMEM41A level and survival time of patients with EC at 1, 3, and 5 years. Furthermore, TMEM41A overexpression was significantly correlated with the level of the stromal score, immune score, estimate score, NK CD56 bright cells, iDC, NK cells, eosinophils, pDC, T cells, TReg, cytotoxic cells, mast cells, Th17 cells, neutrophils, aDC, NK CD56 dim cells, TFH, Th2 cells, CD8 T cells, macrophages, immune cell markers, and RNA modifications.

CONCLUSIONS: TMEM41A is overexpressed in EC tissues and is associated with the prognosis, immune microenvironment, and RNA modification. Our preliminary studies indicate that overexpression of TMEM41A can potentially serve as a biomarker for EC treatment.}, } @article {pmid37478042, year = {2024}, author = {Zhang, W and Yang, L and Geng, S and Hong, S}, title = {Self-Supervised Time Series Representation Learning via Cross Reconstruction Transformer.}, journal = {IEEE transactions on neural networks and learning systems}, volume = {35}, number = {11}, pages = {16129-16138}, doi = {10.1109/TNNLS.2023.3292066}, pmid = {37478042}, issn = {2162-2388}, abstract = {Since labeled samples are typically scarce in real-world scenarios, self-supervised representation learning in time series is critical. Existing approaches mainly employ the contrastive learning framework, which automatically learns to understand similar and dissimilar data pairs. However, they are constrained by the request for cumbersome sampling policies and prior knowledge of constructing pairs. Also, few works have focused on effectively modeling temporal-spectral correlations to improve the capacity of representations. In this article, we propose the cross reconstruction transformer (CRT) to solve the aforementioned issues. CRT achieves time series representation learning through a cross-domain dropping-reconstruction task. Specifically, we obtain the frequency domain of the time series via the fast Fourier transform (FFT) and randomly drop certain patches in both time and frequency domains. Dropping is employed to maximally preserve the global context while masking leads to the distribution shift. Then a Transformer architecture is utilized to adequately discover the cross-domain correlations between temporal and spectral information through reconstructing data in both domains, which is called Dropped Temporal-Spectral Modeling. To discriminate the representations in global latent space, we propose instance discrimination constraint (IDC) to reduce the mutual information between different time series samples and sharpen the decision boundaries. Additionally, a specified curriculum learning (CL) strategy is employed to improve the robustness during the pretraining phase, which progressively increases the dropping ratio in the training process. We conduct extensive experiments to evaluate the effectiveness of the proposed method on multiple real-world datasets. Results show that CRT consistently achieves the best performance over existing methods by 2%-9%. The code is publicly available at https://github.com/BobZwr/Cross-Reconstruction-Transformer.}, } @article {pmid37474400, year = {2024}, author = {Chappidi, MR and Sjöström, M and Greenland, NY and Cowan, JE and Baskin, AS and Shee, K and Simko, JP and Chan, E and Stohr, BA and Washington, SL and Nguyen, HG and Quigley, DA and Davicioni, E and Feng, FY and Carroll, PR and Cooperberg, MR}, title = {Transcriptomic Heterogeneity of Expansile Cribriform and Other Gleason Pattern 4 Prostate Cancer Subtypes.}, journal = {European urology oncology}, volume = {7}, number = {2}, pages = {222-230}, doi = {10.1016/j.euo.2023.06.007}, pmid = {37474400}, issn = {2588-9311}, mesh = {Male ; Humans ; *Prostate-Specific Antigen ; Retrospective Studies ; Transcriptome ; *Prostatic Neoplasms/genetics/surgery/pathology ; Gene Expression Profiling ; }, abstract = {BACKGROUND: Prostate cancers featuring an expansile cribriform (EC) pattern are associated with worse clinical outcomes following radical prostatectomy (RP). However, studies of the genomic characteristics of Gleason pattern 4 subtypes are limited.

OBJECTIVE: To explore transcriptomic characteristics and heterogeneity within Gleason pattern 4 subtypes (fused/poorly formed, glomeruloid, small cribriform, EC/intraductal carcinoma [IDC]) and the association with biochemical recurrence (BCR)-free survival.

This was a retrospective cohort study including 165 men with grade group 2-4 prostate cancer who underwent RP at a single academic institution (2016-2020) and Decipher testing of the RP specimen. Patients with Gleason pattern 5 were excluded. IDC and EC patterns were grouped. Median follow-up was 2.5 yr after RP for patients without BCR.

Prompted by heterogeneity within pattern 4 subtypes identified via exploratory analyses, we investigated transcriptomic consensus clusters using partitioning around medoids and hallmark gene set scores. The primary clinical outcome was BCR, defined as two consecutive prostate-specific antigen measurements >0.2 ng/ml at least 8 wk after RP, or any additional treatment. Multivariable Cox proportional-hazards models were used to determine factors associated with BCR-free survival.

RESULTS AND LIMITATIONS: In this cohort, 99/165 patients (60%) had EC and 67 experienced BCR. Exploratory analyses and clustering demonstrated transcriptomic heterogeneity within each Gleason pattern 4 subtype. In the multivariable model controlled for pattern 4 subtype, margin status, Cancer of the Prostate Risk Assessment Post-Surgical score, and Decipher score, a newly identified steroid hormone-driven cluster (hazard ratio 2.35 95% confidence interval 1.01-5.47) was associated with worse BCR-free survival. The study is limited by intermediate follow-up, no validation cohort, and lack of accounting for intratumoral and intraprostatic heterogeneity.

CONCLUSIONS: Transcriptomic heterogeneity was present within and across each Gleason pattern 4 subtype, demonstrating there is additional biologic diversity not captured by histologic subtypes. This heterogeneity can be used to develop novel signatures and to classify transcriptomic subtypes, which may help in refining risk stratification following RP to further guide decision-making on adjuvant and salvage treatments.

PATIENT SUMMARY: We studied prostatectomy specimens and found that tumors with similar microscopic appearance can have genetic differences that may help to predict outcomes after prostatectomy for prostate cancer. Our results demonstrate that further gene expression analysis of prostate cancer subtypes may improve risk stratification after prostatectomy. Future studies are needed to develop novel gene expression signatures and validate these findings in independent sets of patients.}, } @article {pmid37470893, year = {2023}, author = {Chen, BF and Tsai, YF and Lien, PJ and Lin, YS and Feng, CJ and Chen, YJ and Cheng, HF and Tseng, LM and Huang, CC}, title = {Clinical characteristics and treatment outcomes of invasive ductal and lobular carcinoma: analyses of 54,832 taiwan cancer registry index cases.}, journal = {Breast cancer research and treatment}, volume = {201}, number = {3}, pages = {547-560}, pmid = {37470893}, issn = {1573-7217}, support = {V110E-005-3//Taipei Veterans General Hospital/ ; V111E-006-3//Taipei Veterans General Hospital/ ; V112E-004-3//Taipei Veterans General Hospital/ ; }, mesh = {Humans ; Female ; *Carcinoma, Lobular/pathology ; *Breast Neoplasms/epidemiology/genetics/therapy ; *Carcinoma, Ductal, Breast/therapy/drug therapy ; Taiwan/epidemiology ; Mastectomy ; Neoplasm Recurrence, Local/pathology ; Treatment Outcome ; Registries ; Retrospective Studies ; }, abstract = {PURPOSE: Invasive lobular cancer (ILC) is the second most common histology type of breast cancer followed by invasive ductal carcinoma (IDC). This study aimed to investigate the characteristic, treatment strategies, and clinical outcomes of ILC based on a national population-based cancer registry.

METHODS: This study recruited 2671 ILC and 52,215 IDC patients diagnosed between 2011 and 2017 using the Taiwan Cancer Registry (TCR). Correlations between ILC and IDC subgroups were assessed using 1:4 propensity score matching and compared using the χ2 test. Disease free survival(DFS) and overall survival(OS) were estimated using the Kaplan-Meier method with the log-rank test. The risk of disease relapse and mortality were assessed using Cox proportional hazards model.

RESULTS: ILC patients had larger tumor sizes, more positive axillary lymph node involvement, lower tumor grade, and higher cancer stage than IDC patients. After matching, ILC patients had a significantly higher rate of receiving mastectomy (58.93% and 53.85%) and positive surgical margin regardless of surgery type. ILC exhibited a significantly higher rate of distant metastasis than IDC(3.67% and 2.93%), but no difference in local recurrence rate, DFS or OS between the two groups. Higher cancer stage, higher grade, and mastectomy were risk factors for disease relapse and cancer-specific mortality. The hormone receptor-positive and HER2 over-expression subtypes were found to be associated with a reduced risk of disease relapse, while only PR positivity was associated with a decreased risk of mortality. (all P-values < 0.05).

CONCLUSION: ILC patients had a higher mastectomy rate, higher surgical margin rate and distant metastasis rate than IDC patients. There is no significant difference in DFS or OS between ILC and IDC patients. Mastectomy was associated with poor outcomes regardless of ILC or IDC.}, } @article {pmid37458802, year = {2023}, author = {de Araújo, RA and da Luz, FAC and da Costa Marinho, E and Nascimento, CP and Mendes, TR and Mosca, ERT and de Andrade Marques, L and Delfino, PFR and Antonioli, RM and da Silva, ACAL and Dos Reis Monteiro, MLG and Neto, MB and Silva, MJB}, title = {The elusive Luminal B breast cancer and the mysterious chemokines.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {14}, pages = {12807-12819}, pmid = {37458802}, issn = {1432-1335}, abstract = {PURPOSE: Invasive ductal breast cancer (IDC) is heterogeneous. Staging and immunohistochemistry (IH) allow for effective therapy but are not yet ideal. Women with Luminal B tumors show an erratic response to treatment. This prospective study with 81 women with breast cancer aims to improve the prognostic stratification of Luminal B patients.

METHODS: This is a prospective translational study with 81 women with infiltrating ductal carcinoma, grouped by TNM staging and immunohistochemistry, for survival analysis, and their correlations with the chemokines. Serum measurements of 13 chemokines were performed, including 7 CC chemokines [CCL2(MCP1), CCL3(MIP1α), CCL4(MIP1β), CCL5(Rantes), CCL11(Eotaxin), CCL17(TARC), CCL20(MIP3α)], 6 CXC chemokines [CXCL1(GroAlpha), CXCL5(ENA78), CCXCL8(IL-8), CXCL9(MIG), CXCL10(IP10), CXCL11(ITAC)].

RESULTS: Overall survival was significantly dependent on tumor staging and subtypes by immunohistochemistry, with a median follow-up time the 32.87 months (3.67-65.63 months). There were age correlations with IP10/CXCL10 chemokines (r =  0.4360; p = 0.0079) and TARC/CCL17 (Spearman + 0.2648; p = 0.0360). An inverse correlation was found between body weight and the chemokines Rantes/CCL5 (r = - 0.3098; p = 0.0169) and Eotaxin/CCL11 (r = - 0.2575; p = 0.0470). Smokers had a higher concentration of MIP3α/CCL20 (Spearman + 0.3344; p = 0.0267). Luminal B subtype patients who expressed lower concentrations of ENA78/CXCL5 (≤ 254.83 pg/ml) (Log-Rank p = 0.016) and higher expression of MIP1β/CCL4 (> 34.84 pg/ml) (Log-Rank p = 0.014) had a higher risk of metastases.

CONCLUSION: Patients with Luminal B breast tumors can be better stratified by serum chemokine expression, suggesting that prognosis is dependent on biomarkers other than TNM and IH.}, } @article {pmid37444563, year = {2023}, author = {Modena, D and Moras, ML and Sandrone, G and Stevenazzi, A and Vergani, B and Dasgupta, P and Kliever, A and Gulde, S and Marangelo, A and Schillmaier, M and Luque, RM and Bäuerle, S and Pellegata, NS and Schulz, S and Steinkühler, C}, title = {Identification of a Novel SSTR3 Full Agonist for the Treatment of Nonfunctioning Pituitary Adenomas.}, journal = {Cancers}, volume = {15}, number = {13}, pages = {}, pmid = {37444563}, issn = {2072-6694}, abstract = {Somatostatin receptor (SSTR) agonists have been extensively used for treating neuroendocrine tumors. Synthetic therapeutic agonists showing selectivity for SSTR2 (Octreotide) or for SSTR2 and SSTR5 (Pasireotide) have been approved for the treatment of patients with acromegaly and Cushing's syndrome, as their pituitary tumors highly express SSTR2 or SSTR2/SSTR5, respectively. Nonfunctioning pituitary adenomas (NFPAs), which express high levels of SSTR3 and show only modest response to currently available SSTR agonists, are often invasive and cannot be completely resected, and therefore easily recur. The aim of the present study was the evaluation of ITF2984, a somatostatin analog and full SSTR3 agonist, as a new potential treatment for NFPAs. ITF2984 shows a 10-fold improved affinity for SSTR3 compared to Octreotide or Pasireotide. Molecular modeling and NMR studies indicated that the higher affinity for SSTR3 correlates with a higher stability of a distorted β-I turn in the cyclic peptide backbone. ITF2984 induces receptor internalization and phosphorylation, and triggers G-protein signaling at pharmacologically relevant concentrations. Furthermore, ITF2984 displays antitumor activity that is dependent on SSTR3 expression levels in the MENX (homozygous mutant) NFPA rat model, which closely recapitulates human disease. Therefore, ITF2984 may represent a novel therapeutic option for patients affected by NFPA.}, } @article {pmid37444482, year = {2023}, author = {Kang, MK and Jiang, F and Kim, YJ and Ryu, K and Masamune, A and Hamada, S and Park, YY and Koh, SS}, title = {CTHRC1 Induces Pancreatic Stellate Cells (PSCs) into Myofibroblast-like Cancer-Associated Fibroblasts (myCAFs).}, journal = {Cancers}, volume = {15}, number = {13}, pages = {}, pmid = {37444482}, issn = {2072-6694}, support = {No. 2018R1D1A3B05050725//Ministry of Education/ ; }, abstract = {[BACKGROUND] Collagen triple helix repeat containing-1 (CTHRC1) is a secreted protein that contributes to the progression of various cancers, including pancreatic cancer. The higher expression of CTHRC1 in tumor tissues is associated with poorer survival outcomes. However, its specific roles in tumor extracellular matrix (ECM) remodeling remain unclear. Our study aims to investigate the influences of CTHRC1 on pancreatic stellate cells (PSCs), a main source of ECM production in pancreatic cancer. [METHODS AND RESULTS] The analyses of the publicly available pancreatic cancer patient data revealed that CTHRC1 is mainly expressed in cancer stroma and highly correlated with ECM-related genes. An in vitro study showed that more than 40% of these genes can be upregulated by CTHRC1. CTHRC1 specifically activated PSC into myofibroblast-like cancer-associated fibroblasts (myCAFs), which are characterized by a significantly upregulated POSTN gene expression. Periostin (coded by the POSTN gene) has a central role in the CTHRC1-PSCs-cancer metastasis axis. Furthermore, CTHRC1 promoted pancreatic cancer cell proliferation through PSC activation to a greater extent than via direct stimulation. Proof-of-concept experiments showed that the long-term (4-week) inhibition of CTHRC1 led to significant tumor suppression and ECM reduction, and also resulted in an unexpected shift in the CAF subtype from myCAFs to inflammatory CAFs (iCAFs). [CONCLUSION] PSC activation was demonstrated to be the key molecular mechanism responsible for the tumor-promoting effects of CTHRC1, and CTHRC1 has a critical role in CAF subtype differentiation and tumor microenvironment (TME) remodeling. The inhibition of CTHRC1 as a therapeutic strategy for the treatment of pancreatic cancer warrants further investigation.}, } @article {pmid37443686, year = {2023}, author = {Su, IL and Chen, YK}, title = {Utility of FDG PET/CT in Patient with Synchronous Breast and Colon Cancer.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {13}, pages = {}, pmid = {37443686}, issn = {2075-4418}, abstract = {The most common malignancy in women is breast cancer, and the second one is colon cancer. Synchronous breast and colon cancers are rare. Here, we reported a 60-year-old woman with a left breast mass for six months. Biopsy revealed an invasive ductal carcinoma. She underwent 2-[Fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) scan for evaluation of the extent of the disease. FDG PET/CT revealed an advanced left breast cancer with multiple metastases in both regional and distant lymph nodes (in left axilla level I/II, lower paratracheal region, and right lung hilum), bilateral lungs, and axial and proximal appendicular skeletons. An early staged synchronous colon cancer was detected incidentally on FDG PET/CT images. After endoscopic mucosal resection of colon cancer, she received palliative chemotherapy for breast cancer with a marked therapeutic response. The disease status of post-treated breast cancer remained relatively stationary for more than one year. Brain metastasis was noted afterward. Nevertheless, there was no evidence of colon cancer recurrence throughout her breast cancer disease course.}, } @article {pmid37442866, year = {2023}, author = {Yang, J and Hussein Kadir, D}, title = {Data mining techniques in breast cancer diagnosis at the cellular-molecular level.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {14}, pages = {12605-12620}, pmid = {37442866}, issn = {1432-1335}, abstract = {INTRODUCTION: Studies in the field of better diagnosis of breast cancer using machine learning and data mining techniques have always been promising. A new diagnostic method can detect the characteristics of breast cancer in the early stages and help in better treatment. The aim of this study is to provide a method for early detection of breast cancer by reducing human errors based on data mining techniques in medicine using accurate and rapid screening.

METHODOLOGY: The proposed method includes data pre-processing and image quality improvement in the first step. The second step consists of separating cancer cells from healthy breast tissue and removing outliers using image segmentation. Finally, a classification model is configured by combining deep neural networks in the third phase. The proposed ensemble classification model uses several effective features extracted from images and is based on majority vote. This model can be used as a screening system to diagnose the grade of invasive ductal carcinoma of the breast.

RESULTS: Evaluations have been done using two histopathological microscopic datasets including patients with invasive ductal carcinoma of the breast. With extracting high-level features with average accuracies of 92.65% and 93.34% in these two datasets, the proposed method has succeeded in quickly diagnosing and classifying breast cancer with high performance.

CONCLUSION: By combining deep neural networks and extracting features affecting breast cancer, the ability to diagnose with the highest accuracy is provided, and this is a step toward helping specialists and increasing the chances of patients' survival.}, } @article {pmid37441009, year = {2023}, author = {Sasamoto, M and Yamada, A and Oshi, M and Ota, I and Yoshida, K and Yakeishi, M and Tsuura, Y and Masui, H and Endo, I}, title = {Breast carcinoma with spontaneous regression after needle biopsy: a case report and literature review.}, journal = {Gland surgery}, volume = {12}, number = {6}, pages = {853-859}, pmid = {37441009}, issn = {2227-684X}, abstract = {BACKGROUND: Spontaneous regression (SR) of cancer is a rare condition in which the cancer partially or completely disappears without treatment. We report a case of breast cancer with tumor regression and spontaneously induced T-cell-mediated immunological responses in a surgical specimen obtained after core needle biopsy (CNB).

CASE DESCRIPTION: A 52-year-old woman presented with a mass in the right breast. Mammography showed a high-density mass with fine serrated margins in the right lower outer quadrant. Breast ultrasonography showed an irregular hypoechoic mass with a maximum diameter of 22 mm. CNB was performed and revealed an invasive ductal carcinoma with negative estrogen receptors, positive progesterone receptors, and negative HER2 (1+). The Ki67 index was 70% to 80%. Luminal B cT2N1M0 stage IIB right breast cancer was diagnosed. Although preoperative chemotherapy was considered, surgery was selected because of her history of schizophrenia. She underwent right mastectomy and axillary lymph node dissection. A postoperative pathological analysis revealed a 20 mm × 10 mm × 10 mm mass. However, most areas of the mass regressed and appeared as necrotic tissue with no obvious invasive areas. Only intraductal extension was observed in one glandular duct. Axillary lymph node metastases were not observed. These results suggest that the tumor may have spontaneously regressed, possibly because of the CNB procedure. Follow-up without treatment was performed, and no recurrence occurred during 2 years after surgery.

CONCLUSIONS: Invasive ductal carcinoma may spontaneously regress after preoperative CNB.}, } @article {pmid37439959, year = {2023}, author = {Tsunokake, S and Iwabuchi, E and Miki, Y and Kanai, A and Onodera, Y and Sasano, H and Ishida, T and Suzuki, T}, title = {SGLT1 as an adverse prognostic factor in invasive ductal carcinoma of the breast.}, journal = {Breast cancer research and treatment}, volume = {201}, number = {3}, pages = {499-513}, pmid = {37439959}, issn = {1573-7217}, mesh = {Humans ; Female ; *Sodium-Glucose Transporter 2 Inhibitors/pharmacology/therapeutic use ; Sodium-Glucose Transporter 2/metabolism ; Prognosis ; Vascular Endothelial Growth Factor A/metabolism ; *Breast Neoplasms/drug therapy/genetics ; Glucose/metabolism ; *Carcinoma, Ductal ; }, abstract = {PURPOSE: Sodium/glucose cotransporter (SGLT) 1 and 2 expression in carcinoma cells was recently examined, but their association with the clinicopathological factors of the patients and their biological effects on breast carcinoma cells have remained remain virtually unknown. Therefore, in this study, we explored the expression status of SGLT1 and SGLT2 in breast cancer patients and examined the effects of SGLT1 inhibitors on breast carcinoma cells in vitro.

METHODS: SGLT1 and SGLT2 were immunolocalized and we first correlated the findings with clinicopathological factors of the patients. We then administered mizagliflozin and KGA-2727, SGLT1 specific inhibitors to MCF-7 and MDA-MB-468 breast carcinoma cell lines, and their growth-inhibitory effects were examined. Protein arrays were then used to further explore their effects on the growth factors.

RESULTS: The SGLT1 high group had significantly worse clinical outcome including both overall survival and disease-free survival than low group. SGLT2 status was not significantly correlated with clinical outcome of the patients. Both mizagliflozin and KGA-2727 inhibited the growth of breast cancer cell lines. Of particular interest, mizagliflozin inhibited the proliferation of MCF-7 cells, even under very low glucose conditions. Mizagliflozin downregulated vascular endothelial growth factor receptor 2 phosphorylation.

CONCLUSION: High SGLT1 expression turned out as an adverse clinical prognostic factor in breast cancer patient. This is the first study demonstrating that SGLT1 inhibitors suppressed breast carcinoma cell proliferation. These results indicated that SGLT1 inhibitors could be used as therapeutic agents for breast cancer patients with aggressive biological behaviors.}, } @article {pmid37436978, year = {2023}, author = {Conway, JRW and Dinç, DD and Follain, G and Paavolainen, O and Kaivola, J and Boström, P and Hartiala, P and Peuhu, E and Ivaska, J}, title = {IGFBP2 secretion by mammary adipocytes limits breast cancer invasion.}, journal = {Science advances}, volume = {9}, number = {28}, pages = {eadg1840}, pmid = {37436978}, issn = {2375-2548}, mesh = {Female ; Humans ; Adipocytes ; Antibodies, Neutralizing ; Breast ; *Breast Neoplasms ; Insulin-Like Growth Factor II ; Insulin-Like Growth Factor Binding Protein 2 ; }, abstract = {The progression of noninvasive ductal carcinoma in situ to invasive ductal carcinoma for patients with breast cancer results in a significantly poorer prognosis and is the precursor to metastatic disease. In this work, we have identified insulin-like growth factor-binding protein 2 (IGFBP2) as a potent adipocrine factor secreted by healthy breast adipocytes that acts as a barrier against invasive progression. In line with this role, adipocytes differentiated from patient-derived stromal cells were found to secrete IGFBP2, which significantly inhibited breast cancer invasion. This occurred through binding and sequestration of cancer-derived IGF-II. Moreover, depletion of IGF-II in invading cancer cells using small interfering RNAs or an IGF-II-neutralizing antibody ablated breast cancer invasion, highlighting the importance of IGF-II autocrine signaling for breast cancer invasive progression. Given the abundance of adipocytes in the healthy breast, this work exposes the important role they play in suppressing cancer progression and may help expound upon the link between increased mammary density and poorer prognosis.}, } @article {pmid37435234, year = {2023}, author = {Li, S and Tong, J and Li, H and Mao, C and Shen, W and Lei, Y and Hu, P}, title = {L. pneumophila Infection Diagnosed by tNGS in a Lady with Lymphadenopathy.}, journal = {Infection and drug resistance}, volume = {16}, number = {}, pages = {4435-4442}, pmid = {37435234}, issn = {1178-6973}, abstract = {We report a case of a 34-year-old lady with multiple joint pain. Autoimmune diseases were considered first with a positive result of anti-Ro antibody and her right knee joint cavity effusion. Later, bilateral interstitial changes in her lungs and mediastinal lymphadenopathy were found after chest CT scanning. Empirical quinolone therapy was given although pathological examinations of blood, sputum and bronchoalveolar lavage fluid (BALF) did not find anything. Finally, Legionella pneumophila was identified by target next-generation sequencing (tNGS) detection. This case highlighted the timely use of tNGS, a new tool with fast speed, high accuracy and effective cost, could help to identify atypical infection and start an early therapy.}, } @article {pmid37428725, year = {2023}, author = {Cosar, R and Sut, N and Topaloglu, S and Tastekin, E and Nurlu, D and Ozler, T and Şenödeyici, E and Dedeli, M and Chousein, M and Cicin, I}, title = {Classifying invasive lobular carcinoma as special type breast cancer may be reducing its treatment success: A comparison of survival among invasive lobular carcinoma, invasive ductal carcinoma, and no-lobular special type breast cancer.}, journal = {PloS one}, volume = {18}, number = {7}, pages = {e0283445}, pmid = {37428725}, issn = {1932-6203}, mesh = {Humans ; Female ; Male ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/therapy/pathology ; Mastectomy ; Treatment Outcome ; Prognosis ; *Breast Neoplasms, Male/surgery ; *Carcinoma, Ductal ; *Carcinoma, Ductal, Breast/pathology ; Retrospective Studies ; }, abstract = {PURPOSE: The literature contains different information about the prognosis of invasive lobular carcinoma of breast cancer (BC). We aimed to address the inconsistency by comparatively examining the clinical features and prognosis of invasive lobular carcinoma patients in our university and to report our experience by dividing our patients into various subgroups.

PATIENTS AND METHODS: Records of patients with BC admitted to Trakya University School of Medicine Department of Oncology between July 1999 and December 2021 were reviewed. The patients were divided into three groups (No-Special Type BC, Invasive Lobular Special Type BC, No-Lobular Special Type BC). Patient characteristics, treatment methods and oncological results are presented. Survival curves were generated using the Kaplan-Meier method. Statistical significance of survival among the selected variables was compared by using the log-rank test.

RESULTS: The patients in our study consisted of 2142 female and 15 male BC patients. There were 1814 patients with No-Special Type BC, 193 patients with Invasive Lobular Special Type BC, and 150 patients with No-Lobular Special Type BC. The duration of disease-free survival (DFS) was 226.5 months for the No-Special Type BC group, 216.7 months for the No-Lobular Special Type BC group, and 197.2 months for the Invasive Lobular Special Type BC group, whereas the duration of overall survival (OS) was 233.2 months for the No-Special Type BC group, 227.9 for the No-Lobular Special Type BC group, and 209.8 for the Invasive Lobular Special Type BC group. The duration of both DFS and OS was the lowest in the Invasive Lobular Special Type BC group. Multivariate factors that were significant risk factors for OS were Invasive Lobular Special Type BC histopathology (p = .045), T stage, N stage, stage, skin infiltration, positive surgical margins, high histological grade, and mitotic index. Modified radical mastectomy, chemotherapy, radiotherapy and use of tamoxifen and aromatase inhibitors for more than 5 years were significant protective factors for overall survival.

CONCLUSION: The histopathological subgroup with the worst prognosis in our study was Invasive Lobular Special Type BC. Duration of DFS and OS were significantly shorter in Invasive Lobular Special Type BC than No-Lobular Special Type BC group. The classification of Invasive Lobular BC under the title of Special Type BC should be reconsidered and a more accurate treatment and follow-up process may be required.}, } @article {pmid37421735, year = {2023}, author = {Krishna Swaroop, A and Krishnan Namboori, PK and Esakkimuthukumar, M and Praveen, TK and Nagarjuna, P and Patnaik, SK and Selvaraj, J}, title = {Leveraging decagonal in-silico strategies for uncovering IL-6 inhibitors with precision.}, journal = {Computers in biology and medicine}, volume = {163}, number = {}, pages = {107231}, doi = {10.1016/j.compbiomed.2023.107231}, pmid = {37421735}, issn = {1879-0534}, mesh = {Humans ; Molecular Docking Simulation ; *Interleukin-6 Inhibitors ; *Methotrexate ; Interleukin-6 ; Molecular Dynamics Simulation ; Inflammation ; Indans ; }, abstract = {Interleukin-6 upregulation leads to various acute phase reactions such as local inflammation and systemic inflammation in many diseases like cancer, multiple sclerosis, rheumatoid arthritis, anemia, and Alzheimer's disease stimulating JAK/STAT3, Ras/MAPK, PI3K-PKB/Akt pathogenic pathways. Since no small molecules are available in the market against IL-6 till now, we have designed a class of small bioactive 1,3 - indanedione (IDC) molecules for inhibiting IL-6 using a decagonal approach computational studies. The IL-6 mutations were mapped in the IL-6 protein (PDB ID: 1ALU) from thorough pharmacogenomic and proteomics studies. The protein-drug interaction networking analysis for 2637 FFDA-approved drugs with IL-6 protein using Cytoscape software showed that 14 drugs have prominent interactions with IL-6. Molecular docking studies showed that the designed compound IDC-24 (-11.8 kcal/mol) and methotrexate (-5.20) bound most strongly to the 1ALU south asian population mutated protein. MMGBSA results indicated that IDC-24 (-41.78 kcal/mol) and methotrexate (-36.81 kcal/mol) had the highest binding energy when compared to the standard molecules LMT-28 (-35.87 kcal/mol) and MDL-A (-26.18 kcal/mol). These results we substantiated by the molecular dynamic studies in which the compound IDC-24 and the methotrexate had the highest stability. Further, the MMPBSA computations produced energies of -28 kcal/mol and -14.69 kcal/mol for IDC-24 and LMT-28. KDeep absolute binding affinity computations revealed energies of -5.81 kcal/mol and -4.74 kcal/mol for IDC-24 and LMT-28 respectively. Finally, our decagonal approach established the compound IDC-24 from the designed 1,3-indanedione library and methotrexate from protein drug interaction networking as suitable HITs against IL-6.}, } @article {pmid37420729, year = {2023}, author = {Sharma, RK and Issac, B and Xin, Q and Gadekallu, TR and Nath, K}, title = {Plant and Salamander Inspired Network Attack Detection and Data Recovery Model.}, journal = {Sensors (Basel, Switzerland)}, volume = {23}, number = {12}, pages = {}, pmid = {37420729}, issn = {1424-8220}, mesh = {*Biological Evolution ; *Internet ; Machine Learning ; }, abstract = {The number of users of the Internet has been continuously rising, with an estimated 5.1 billion users in 2023, which comprises around 64.7% of the total world population. This indicates the rise of more connected devices to the network. On average, 30,000 websites are hacked daily, and nearly 64% of companies worldwide experience at least one type of cyberattack. As per IDC's 2022 Ransomware study, two-thirds of global organizations were hit by a ransomware attack that year. This creates the desire for a more robust and evolutionary attack detection and recovery model. One aspect of the study is the bio-inspiration models. This is because of the natural ability of living organisms to withstand various odd circumstances and overcome them with an optimization strategy. In contrast to the limitations of machine learning models with the need for quality datasets and computational availability, bio-inspired models can perform in low computational environments, and their performances are designed to evolve naturally with time. This study concentrates on exploring the evolutionary defence mechanism in plants and understanding how plants react to any known external attacks and how the response mechanism changes to unknown attacks. This study also explores how regenerative models, such as salamander limb regeneration, could build a network recovery system where services could be automatically activated after a network attack, and data could be recovered automatically by the network after a ransomware-like attack. The performance of the proposed model is compared to open-source IDS Snort and data recovery systems such as Burp and Casandra.}, } @article {pmid37409201, year = {2023}, author = {Khalid, S and Atiq, A and Khalid, F and Khan, FW and Bashir, A}, title = {Invasive Micropapillary Carcinoma of the Breast With Solid Papillary Carcinoma: A Case Report.}, journal = {Cureus}, volume = {15}, number = {6}, pages = {e39928}, pmid = {37409201}, issn = {2168-8184}, abstract = {Invasive micropapillary carcinoma and Solid papillary carcinomas are rare histologic subtypes of breast cancer. Co-existence of tumors of the breast like invasive ductal and lobular carcinomas, or invasive ductal carcinoma and mucinous carcinomas have been reported before. But the existence of invasive micropapillary carcinoma with solid papillary carcinoma is a rare occurrence. Here, we are reporting a rare case of a 60-year-old female with a mass in her left breast. The histopathology report showed a tumor containing these two histologic subtypes. Recognition of all tumor subtypes is necessary, as this can impact the treatment strategy.}, } @article {pmid37408681, year = {2023}, author = {Martinez, C and Meterissian, S and Saidi, A and Tremblay, F and Meguerditchian, AN and Fleiszer, D and Lambert, C and David, M and Panet-Raymond, V and Abdulkarim, B and Hijal, T}, title = {Targeted Intraoperative Radiation Therapy during Breast-Conserving Surgery for Patients with Early Stage Breast Cancer: A Phase II Single Center Prospective Trial.}, journal = {Advances in radiation oncology}, volume = {8}, number = {5}, pages = {101236}, pmid = {37408681}, issn = {2452-1094}, abstract = {PURPOSE: Patients with early stage breast cancer (ESBC) are conventionally treated with breast-conserving surgery (BCS) followed by whole-breast external beam radiation therapy (EBRT). The emergence of targeted intraoperative radiation therapy (TARGIT) with Intrabeam has been used as a therapeutic alternative for patients with risk-adapted ESBC. Here we present our radiation therapy toxicities (RTT), postoperative complications (PC), and short-term outcomes of the prospective phase II trial at the McGill University Health Center.

METHODS AND MATERIALS: Patients aged ≥50 years with biopsy-proven hormone receptor-positive, grade 1 or 2, invasive ductal carcinoma of the breast, cT1N0, were eligible for the study. Enrolled patients underwent BCS followed by immediate TARGIT of 20 Gy in 1 fraction. Upon final pathology, patients with low-risk breast cancer (LRBC) received no further EBRT, and those with high-risk breast cancer (HRBC) received further 15 to 16 fractions of whole breast EBRT. HRBC criteria included pathologic tumor size >2 cm, grade 3, positive lympho-vascular invasion, multifocal disease, close margins (<2 mm), or positive nodal disease.

RESULTS: A total of 61 patients with ESBC were enrolled in the study; upon final pathology, 40 (65.6%) had LRBC, and 21 (34.4%) had HRBC. The median follow-up was 3.9 years. The most common HRBC criteria were close margins in 66.6% (n = 14) and lymphovascular invasion in 28.6% (n = 6). No grade 4 RTT were observed in either group. The most common PC were seroma and cellulitis for both groups. The rate of locoregional recurrence was 0% in both groups. The overall survival in LRBC was 97.5% and in HRBC 95.2% with no significant differences. Deaths were nonbreast cancer related.

CONCLUSIONS: In patients with ESBC undergoing BCS, the use of TARGIT shows low rates of RTT and PC complications. Moreover, our short-term outcomes show no significant difference at 3.9 years median follow-up for locoregional recurrence or overall survival between groups of patients receiving TARGIT alone or TARGIT followed by EBRT. Of all patients, 34.4% required further EBRT, most commonly due to close margins.}, } @article {pmid37408309, year = {2023}, author = {Ji, H and Englmaier, F and Morigny, P and Giroud, M and Gräsle, P and Brings, S and Szendrödi, J and Berriel Diaz, M and Plettenburg, O and Herzig, S and Rohm, M}, title = {Development of a peptide drug restoring AMPK and adipose tissue functionality in cancer cachexia.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {31}, number = {8}, pages = {2408-2421}, pmid = {37408309}, issn = {1525-0024}, support = {R01 GM129325/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Adipose Tissue/metabolism ; *AMP-Activated Protein Kinases/metabolism ; Cachexia/drug therapy/etiology/metabolism ; *Neoplasms/complications/metabolism ; Peptides/pharmacology ; Pharmaceutical Preparations/metabolism ; Quality of Life ; }, abstract = {Cancer cachexia is a severe systemic wasting disease that negatively affects quality of life and survival in patients with cancer. To date, treating cancer cachexia is still a major unmet clinical need. We recently discovered the destabilization of the AMP-activated protein kinase (AMPK) complex in adipose tissue as a key event in cachexia-related adipose tissue dysfunction and developed an adeno-associated virus (AAV)-based approach to prevent AMPK degradation and prolong cachexia-free survival. Here, we show the development and optimization of a prototypic peptide, Pen-X-ACIP, where the AMPK-stabilizing peptide ACIP is fused to the cell-penetrating peptide moiety penetratin via a propargylic glycine linker to enable late-stage functionalization using click chemistry. Pen-X-ACIP was efficiently taken up by adipocytes, inhibited lipolysis, and restored AMPK signaling. Tissue uptake assays showed a favorable uptake profile into adipose tissue upon intraperitoneal injection. Systemic delivery of Pen-X-ACIP into tumor-bearing animals prevented the progression of cancer cachexia without affecting tumor growth and preserved body weight and adipose tissue mass with no discernable side effects in other peripheral organs, thereby achieving proof of concept. As Pen-X-ACIP also exerted its anti-lipolytic activity in human adipocytes, it now provides a promising platform for further (pre)clinical development toward a novel, first-in-class approach against cancer cachexia.}, } @article {pmid37405478, year = {2023}, author = {Rong, XC and Kang, YH and Shi, GF and Ren, JL and Liu, YH and Li, ZG and Yang, G}, title = {The use of mammography-based radiomics nomograms for the preoperative prediction of the histological grade of invasive ductal carcinoma.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {13}, pages = {11635-11645}, pmid = {37405478}, issn = {1432-1335}, mesh = {Humans ; *Nomograms ; Retrospective Studies ; Logistic Models ; Mammography ; *Carcinoma, Ductal ; }, abstract = {BACKGROUND: Accurate prediction of the grade of invasive ductal carcinoma (IDC) before treatment is vital for individualized therapy and improving patient outcomes. This study aimed to develop and validate a mammography-based radiomics nomogram that would incorporate the radiomics signature and clinical risk factors in the preoperative prediction of the histological grade of IDC.

METHODS: The data of 534 patients from our hospital with pathologically confirmed IDC (374 in the training cohort and 160 in the validation cohort) were retrospectively analyzed. A total of 792 radiomics features were extracted from the patients' craniocaudal and mediolateral oblique view images. A radiomics signature was generated using the least absolute shrinkage and selection operator method. Multivariate logistic regression was adopted to establish a radiomics nomogram, the utility of which was evaluated using a receiver-operating characteristic curve, calibration curve, and decision curve analysis (DCA).

RESULTS: The radiomics signature was found to have a significant correlation with histological grade (P < 0.01), but the efficacy of the model is limited. The radiomics nomogram, which incorporated the radiomics signature and spicule sign into mammography, showed good consistency and discrimination in both the training cohort [area under the curve (AUC) = 0.75] and the validation cohort (AUC = 0.75). The calibration curves and DCA demonstrated the clinical usefulness of the proposed radiomics nomogram model.

CONCLUSIONS: A radiomics nomogram based on the radiomics signature and spicule sign can be used to predict the histological grade of IDC and assist in clinical decision-making for patients with IDC.}, } @article {pmid37404109, year = {2023}, author = {Yang, L and Li, XM and Zhang, MN and Yao, J and Song, B}, title = {Nomogram Models for Distinguishing Intraductal Carcinoma of the Prostate From Prostatic Acinar Adenocarcinoma Based on Multiparametric Magnetic Resonance Imaging.}, journal = {Korean journal of radiology}, volume = {24}, number = {7}, pages = {668-680}, pmid = {37404109}, issn = {2005-8330}, mesh = {Male ; Humans ; Prostate/diagnostic imaging/pathology ; *Multiparametric Magnetic Resonance Imaging ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Nomograms ; Prostatectomy ; Retrospective Studies ; *Prostatic Neoplasms/pathology ; *Carcinoma, Acinar Cell/diagnostic imaging ; Magnetic Resonance Imaging/methods ; }, abstract = {OBJECTIVE: To compare multiparametric magnetic resonance imaging (MRI) features of intraductal carcinoma of the prostate (IDC-P) with those of prostatic acinar adenocarcinoma (PAC) and develop prediction models to distinguish IDC-P from PAC and IDC-P with a high proportion (IDC ≥ 10%, hpIDC-P) from IDC-P with a low proportion (IDC < 10%, lpIDC-P) and PAC.

MATERIALS AND METHODS: One hundred and six patients with hpIDC-P, 105 with lpIDC-P and 168 with PAC, who underwent pretreatment multiparametric MRI between January 2015 and December 2020 were included in this study. Imaging parameters, including invasiveness and metastasis, were evaluated and compared between the PAC and IDC-P groups as well as between the hpIDC-P and lpIDC-P subgroups. Nomograms for distinguishing IDC-P from PAC, and hpIDC-P from lpIDC-P and PAC, were made using multivariable logistic regression analysis. The discrimination performance of the models was assessed using the receiver operating characteristic area under the curve (ROC-AUC) in the sample, where the models were derived from without an independent validation sample.

RESULTS: The tumor diameter was larger and invasive and metastatic features were more common in the IDC-P than in the PAC group (P < 0.001). The distribution of extraprostatic extension (EPE) and pelvic lymphadenopathy was even greater, and the apparent diffusion coefficient (ADC) ratio was lower in the hpIDC-P than in the lpIDC-P group (P < 0.05). The ROC-AUCs of the stepwise models based solely on imaging features for distinguishing IDC-P from PAC and hpIDC-P from lpIDC-P and PAC were 0.797 (95% confidence interval, 0.750-0.843) and 0.777 (0.727-0.827), respectively.

CONCLUSION: IDC-P was more likely to be larger, more invasive, and more metastatic, with obviously restricted diffusion. EPE, pelvic lymphadenopathy, and a lower ADC ratio were more likely to occur in hpIDC-P, and were also the most useful variables in both nomograms for predicting IDC-P and hpIDC-P.}, } @article {pmid37402637, year = {2023}, author = {Shulder, S and Tamma, PD and Fiawoo, S and Dzintars, K and Escobar, D and Livorsi, DJ and Malani, AN and Palacio, D and Spivak, ES and Zimmerman, M and Bork, JT}, title = {Infectious Diseases Consultation Associated With Reduced Mortality in Gram-Negative Bacteremia.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {9}, pages = {1234-1237}, doi = {10.1093/cid/ciad383}, pmid = {37402637}, issn = {1537-6591}, mesh = {Humans ; *Communicable Diseases ; Cohort Studies ; *Bacteremia ; Referral and Consultation ; Retrospective Studies ; *Gram-Negative Bacterial Infections ; }, abstract = {Gram-negative bacteremia (GN-BSI) can cause significant morbidity and mortality, but the benefit of infectious diseases consultation (IDC) is not well defined. A 24-site observational cohort study of unique hospitalized patients with 4861 GN-BSI episodes demonstrated a 40% decreased risk of 30-day mortality in patients with IDC compared to those without IDC.}, } @article {pmid37397657, year = {2023}, author = {Godbole, M and Wani, K and Zia, S and Dabak, V}, title = {Carcinoma En Cuirasse: A Rare but Striking Cutaneous Manifestation of Metastatic Breast Cancer.}, journal = {Cureus}, volume = {15}, number = {6}, pages = {e39838}, pmid = {37397657}, issn = {2168-8184}, abstract = {Carcinoma en cuirasse is a rare cutaneous metastatic presentation of breast cancer with a poor prognosis. We report a female in her 70s with a prior history of left breast ductal carcinoma in situ status post-radiation and lumpectomy who presented with skin thickening of the left breast and a few solid masses in bilateral breasts. Biopsy showed invasive ductal carcinoma of the left breast (estrogen receptor [ER]/progesterone receptor positive [PR], human epidermal growth factor receptor-2 [HER2] negative) and ductal carcinoma in situ of the right breast (ER/PR positive). She underwent a right breast lumpectomy; however, the left breast mastectomy was aborted due to the worsening of her skin findings on preoperative examination. A skin biopsy revealed poorly differentiated invasive ductal carcinoma. She was diagnosed with stage 4 breast cancer, specifically carcinoma en cuirasse. Systemic treatment was initiated, followed by a left breast mastectomy. A surgical biopsy was HER2-positive, and therefore anti-HER2 therapy was given. She remains on maintenance therapy with an excellent response at present.Any unexplained skin findings in breast cancer patients should prompt consideration of carcinoma en cuirasse. With ongoing treatment advances, many newer therapy options are available for metastatic breast cancer. Based on our case, we think that patients with this disease can have better outcomes.}, } @article {pmid37387350, year = {2023}, author = {Jin, M and Wang, Y and Zhou, T and Li, W and Wen, Q}, title = {Norepinephrine/β2-Adrenergic Receptor Pathway Promotes the Cell Proliferation and Nerve Growth Factor Production in Triple-Negative Breast Cancer.}, journal = {Journal of breast cancer}, volume = {26}, number = {3}, pages = {268-285}, pmid = {37387350}, issn = {1738-6756}, support = {81273923//National Natural Science Foundation of China/China ; }, abstract = {PURPOSE: Invasive ductal carcinoma (IDC) accounts for 90% of triple-negative breast cancer (TNBC). IDC is mainly derived from the breast ductal epithelium which is innervated by the 4th to 6th thoracic sympathetic nerves. However, little is known about the contribution of the interactions between sympathetic nerves and breast cancer cells to the malignant progression of TNBC.

METHODS: The expression levels of the β2-adrenergic receptor (β2-AR, encoded by ADRB2 gene), nerve growth factor (NGF), and tropomyosin receptor kinase A (TrkA) were determined using immunohistochemistry (IHC). NGF expression levels in the serum were compared by enzyme-linked immunosorbent assay (ELISA). Cell proliferation was assessed using the Cell Counting Kit-8 assay. The β2-AR, NGF, p-ERK, and p-CERB expression levels were determined using western blotting. TNBC cells and neuronal cells of the dorsal root ganglion (DRG) in 2-day-old Sprague Dawley rats were co-cultured. Using norepinephrine (NE), NGF, and β2-AR, NGF/TrkA blocker pretreatments, the axon growth of each group of DRG neuron cells was detected by immunofluorescence analysis.

RESULTS: The sympathetic adrenergic neurotransmitter NE activated the ERK signaling pathway in TNBC cells. NE/β2-AR signaling promotes NGF secretion. NGF further facilitates the malignant progression of TNBC by increasing sympathetic neurogenesis. In the co-culture assay, the sympathetic adrenergic NE/β2-AR signal pathway also enhanced NGF secretion. NGF binds TrkA in DRG neurons and promotes axonal growth.

CONCLUSION: These results suggest that NE/β2-AR pathway promotes cell proliferation and NGF production in triple-negative breast cancer.}, } @article {pmid37386078, year = {2023}, author = {Szekeres, H and Halperin, E and Kende, A and Saguy, T}, title = {The aversive bystander effect whereby egalitarian bystanders overestimate the confrontation of prejudice.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {10538}, pmid = {37386078}, issn = {2045-2322}, mesh = {Humans ; Black or African American ; *Prejudice/ethnology/prevention & control ; United States ; Hungary ; *Human Rights ; Motivation ; Self-Assessment ; Social Behavior ; Romani People ; Hispanic or Latino ; Islam ; }, abstract = {Everyday expression of prejudice continues to pose a social challenge across societies. We tend to assume that to the extent people are egalitarian, they are more likely to confront prejudice-but this might not necessarily be the case. We tested this assumption in two countries (US and Hungary) among majority members of society, using a behavioral paradigm for measuring confronting. Prejudice was directed at various outgroup minority individuals (African Americans, Muslims and Latinos in the US, and Roma in Hungary). Across four experiments (N = 1116), we predicted and found that egalitarian (anti-prejudiced) values were only associated with hypothetical confronting intentions, but not with actual confronting, and stronger egalitarians were more likely to overestimate their confronting than weaker egalitarians-to the point that while intentions differed, the actual confronting rate of stronger and weaker egalitarians were similar. We also predicted and found that such overestimation was associated with internal (and not external) motivation to respond without prejudice. We also identified behavioral uncertainty (being uncertain how to intervene) as a potential explanation for egalitarians' overestimation. The implications of these findings for egalitarians' self-reflection, intergroup interventions, and research are discussed.}, } @article {pmid37385107, year = {2023}, author = {Chen, J and Gao, P and Xiao, W and Cheng, G and Krishna, S and Wang, J and Wong, YK and Wang, C and Gu, L and Yang, DH and Wang, J}, title = {Multi-omics dissection of stage-specific artemisinin tolerance mechanisms in Kelch13-mutant Plasmodium falciparum.}, journal = {Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy}, volume = {70}, number = {}, pages = {100978}, doi = {10.1016/j.drup.2023.100978}, pmid = {37385107}, issn = {1532-2084}, mesh = {Humans ; Plasmodium falciparum/genetics ; Multiomics ; Drug Resistance/genetics ; Protozoan Proteins/genetics/pharmacology/therapeutic use ; *Artemisinins/pharmacology/therapeutic use ; *Antimalarials/pharmacology/therapeutic use ; *Malaria, Falciparum/drug therapy/parasitology ; Mutation ; }, abstract = {AIMS: We investigated the stage-specific mechanisms of partial resistance to artemisinin (ART, an antimalarial drug) in Plasmodium falciparum (P. falciparum) carrying the Kelch13 C580Y mutation.

METHODS: Using fluorescence labeling and activity-based protein profiling, we systematically profile the ART activation levels in P. falciparum during the entire intra-erythrocytic developmental cycle (IDC), and determined the ART-targets profile of the ART-sensitive and -resistant strains at different stages. We retrieved and integrated datasets of single-cell transcriptomics and label-free proteomics across three IDC stages of wild-type P. falciparum. We also employed lipidomics to validate lipid metabolic reprogramming in the resistant strain.

RESULTS: The activation and expression patterns of genes and proteins of ART-targets in both ART-sensitive and resistant strains varied at different stages and periods of P. falciparum development, with the late trophozoite stage harboring the largest number of ART targets. We identified and validated 36 overlapping targets, such as GAPDH, EGF-1a, and SpdSyn, during the IDC stages in both strains. We revealed the ART-insensitivity of fatty acid-associated activities in the partially resistant strain at both the early ring and early trophozoite stages.

CONCLUSIONS: Our multi-omics strategies provide novel insights into the mechanisms of ART partial resistance in Kelch13 mutant P. falciparum, demonstrating the stage-specific interaction between ART and malaria parasites.}, } @article {pmid37383682, year = {2023}, author = {Ricks-Santi, LJ and Fredenburg, K and Rajaei, M and Esnakula, A and Naab, T and McDonald, JT and Kanaan, Y}, title = {Characterization of GATA3 and Mammaglobin in breast tumors from African American Women.}, journal = {Archives of microbiology & immunology}, volume = {7}, number = {1}, pages = {18-28}, pmid = {37383682}, issn = {2572-9365}, support = {R15 CA239100/CA/NCI NIH HHS/United States ; }, abstract = {GATA3 and Mammaglobin are often used in the clinic to identify metastases of mammary origin due to their robust and diffuse expression in mammary tissue. However, the expression of these markers has not been well characterized in tumors from African American women. The goal of this study was to characterize and evaluate the expression of GATA3 and mammaglobin in breast tumors from African American women and determine their association with clinicopathological outcomes including breast cancer subtypes. Tissue microarrays (TMAs) were constructed from well preserved, morphologically representative tumors in archived formalin-fixed, paraffin-embedded (FFPE) surgical blocks from 202 patients with primary invasive ductal carcinoma. Mammaglobin and GATA3 expression was assessed using immunohistochemistry (IHC). Univariate analysis was carried out to determine the association between expression of GATA3, mammaglobin and clinicopathological characteristics. Kaplan-Meier estimates of overall survival and disease-free survival were also plotted and a log-rank test performed to compare estimates among groups. GATA3 expression showed statistically significant association with lower grade (p<0.001), ER-positivity (p<0.001), PR-positivity (p<0.001), and the luminal subtype (p<0.001). Mammaglobin expression was also significantly associated with lower grade (p=0.031), ER-positivity (p=0.007), and PR-positivity (p=0.022). There was no association with recurrence-free or overall survival. Our results confirm that GATA3 and mammaglobin demonstrate expression predominantly in luminal breast cancers from African American women. Additional markers with improved specificity and sensitivity are warranted for triple negative breast tumors given the high prevalence in women of African descent.}, } @article {pmid37383152, year = {2023}, author = {Shirian, F and Kheradmand, P and Ranjbari, N and Shahbazian, H and Latifi, SM}, title = {Immunoexpression of the GCDFP-15 Marker in Different Grades of Breast Carcinoma.}, journal = {Iranian journal of pathology}, volume = {18}, number = {1}, pages = {75-81}, pmid = {37383152}, issn = {1735-5303}, abstract = {BACKGROUND & OBJECTIVE: During the last decade, biological markers of breast cancer have been considered to predict the degree of histology, behavior, and extent of tumor invasion and the possibility of lymph node involvement. The aim of this study was to evaluate the expression of GCDFP-15 in different grades of invasive ductal carcinoma, as the most common type of breast cancer.

METHODS: In this retrospective study, paraffin blocks of tumors of 60 breast cancer patients registered in the histopathology laboratory of Imam Khomeini Hospital in Ahvaz between 2019 and 2020 were reviewed. Information on grade, invasion, stage and lymph node involvement was extracted from the pathology reports and immunohistochemical staining for GCDFP-15 was performed. Data were analyzed by SPSS 22.

RESULTS: GCDFP-15 marker expression was observed in 20 out of 60 breast cancer patients (33.3%). GCDFP-15 staining intensity was weak in 7 cases (35%), moderate in 8 cases (40%), and strong in 5 cases (25%). The patient's age and sex showed no significant relationship with the expression of GCDFP-15 and intensity of staining. Expression of the GCDFP-15 marker was correlated significantly with tumor grade, stage, and vascular invasion (P<0.05)) and its expression was higher in tumors with a lower grade, less depth of invasion, and no vascular invasion but unrelated to perineural invasion, lymph node involvement, and tumor size. The intensity of staining for GCDFP-15 showed significant relationship with the tumor grade (P<0.0001) but unrelated to the other factors.

CONCLUSION: GCDFP-15 marker may be significantly associated with tumor grade, depth of invasion, and vascular invasion, thus can be used as a prognostic marker.}, } @article {pmid37382756, year = {2024}, author = {Abouegylah, M and Elemary, O and Ahmed, AA and ElFeky, AM and Fayed, H and Gawish, M and Mahmoud, AA and Gawish, A}, title = {Impact of breath hold on regional nodal irradiation and heart volume in field in left breast cancer adjuvant irradiation.}, journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {26}, number = {1}, pages = {288-296}, pmid = {37382756}, issn = {1699-3055}, mesh = {Humans ; Middle Aged ; Female ; *Breast Neoplasms/radiotherapy/surgery ; Breath Holding ; Cardiac Volume ; *Radiotherapy, Intensity-Modulated/methods ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted/methods ; Organs at Risk/radiation effects ; Mastectomy ; Heart/radiation effects ; }, abstract = {PURPOSE: Compared to the free-breathing technique, adjuvant left breast irradiation after breast-conserving surgery or mastectomy using the breath-hold method significantly reduces the heart mean dose, Left anterior descending artery, and ipsilateral lung doses. Movement with deep inspiration may also reduce heart volume in the field and regional node doses.

MATERIALS AND METHODS: Pre-radiotherapy planning CT was performed in the free-breathing, and breath-hold techniques using RPM, demographic information, clinicopathological data, heart volume in the field, heart mean dose, LAD mean dose, and regional nodal doses were calculated in both free breathing and DIBH. Fifty patients with left breast cancer receiving left breast adjuvant radiation were enrolled.

RESULTS: There was no significant difference in axillary LN coverage between the two techniques, except for SCL maximum dose, Axilla I node maximum dose, and Axilla II minimum dose in favor of the breath hold technique. The mean age was 47.54 years, 78% had GII IDC, 66% had positive LVSI results, and 74% of patients had T2. The breath hold strategy resulted in considerably decreased mean heart dose (p = 0.000), LAD dose (p = 0.000), ipsilateral lung mean dose (p = 0.012), and heart volume if the field (p = 0.013). The mean cardiac dosage and the dose of the LAD were significantly correlated (p = 0.000, R = 0.673). Heart volume in the field and heart mean dosage was not significantly correlated (p = 0.285, r = - 0.108).

CONCLUSION: When compared to free breathing scans, DIBH procedures result in considerably reduced dosage to the OAR and no appreciable changes in dose exposure to regional lymph node stations in patients with left-sided breast cancer.}, } @article {pmid37377907, year = {2023}, author = {Ding, R and Wang, Y and Fan, J and Tian, Z and Wang, S and Qin, X and Su, W and Wang, Y}, title = {Identification of immunosuppressive signature subtypes and prognostic risk signatures in triple-negative breast cancer.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1108472}, pmid = {37377907}, issn = {2234-943X}, abstract = {PURPOSE: Immune checkpoint blockade (ICB) therapy has transformed the treatment of triple-negative breast cancer (TNBC) in recent years. However, some TNBC patients with high programmed death-ligand 1 (PD-L1) expression levels develop immune checkpoint resistance. Hence, there is an urgent need to characterize the immunosuppressive tumor microenvironment and identify biomarkers to construct prognostic models of patient survival outcomes in order to understand biological mechanisms operating within the tumor microenvironment.

PATIENTS AND METHODS: RNA sequence (RNA-seq) data from 303 TNBC samples were analyzed using an unsupervised cluster analysis approach to reveal distinctive cellular gene expression patterns within the TNBC tumor microenvironment (TME). A panel of T cell exhaustion signatures, immunosuppressive cell subtypes and clinical features were correlated with the immunotherapeutic response, as assessed according to gene expression patterns. The test dataset was then used to confirm the occurrence of immune depletion status and prognostic features and to formulate clinical treatment recommendations. Concurrently, a reliable risk prediction model and clinical treatment strategy were proposed based on TME immunosuppressive signature differences between TNBC patients with good versus poor survival status and other clinical prognostic factors.

RESULTS: Significantly enriched TNBC microenvironment T cell depletion signatures were detected in the analyzed RNA-seq data. A high proportion of certain immunosuppressive cell subtypes, 9 inhibitory checkpoints and enhanced anti-inflammatory cytokine expression profiles were noted in 21.4% of TNBC patients that led to the designation of this group of immunosuppressed patients as the immune depletion class (IDC). Although IDC group TNBC samples contained tumor-infiltrating lymphocytes present at high densities, IDC patient prognosis was poor. Notably, PD-L1 expression was relatively elevated in IDC patients that indicated their cancers were resistant to ICB treatment. Based on these findings, a set of gene expression signatures predicting IDC group PD-L1 resistance was identified then used to develop risk models for use in predicting clinical therapeutic outcomes.

CONCLUSION: A novel TNBC immunosuppressive tumor microenvironment subtype associated with strong PD-L1 expression and possible resistance to ICB treatment was identified. This comprehensive gene expression pattern may provide fresh insights into drug resistance mechanisms for use in optimizing immunotherapeutic approaches for TNBC patients.}, } @article {pmid37371442, year = {2023}, author = {Maggi, G and Vitale, C and Delle Curti, A and Amboni, M and Santangelo, G}, title = {Unawareness of Apathy in Parkinson's Disease: The Role of Executive Dysfunction on Symptom Recognition.}, journal = {Brain sciences}, volume = {13}, number = {6}, pages = {}, pmid = {37371442}, issn = {2076-3425}, abstract = {Altered self-awareness or anosognosia may impact patients' everyday life by interfering with their safe and independent functioning. Symptom awareness has been linked to executive dysfunctions caused by damage to frontal regions. Apathy is a frequent neuropsychiatric manifestation of Parkinson's disease (PD) and is considered a consequence of altered functioning of cortico-subcortical circuitries connecting the prefrontal cortex (PFC) with the basal ganglia. Thus, apathetic PD patients may be not be fully aware of their condition due to shared neuropathophysiological mechanisms. The present study aimed to explore the awareness of apathy in PD patients by comparing the self-reported evaluations with their caregivers' ratings. Moreover, we explored the clinical predictors of possible discrepancies and their consequences on patients' self-reported evaluation of quality of life (QoL). We found a fair agreement between patients' self-reports and caregivers' ratings on apathy scores, with patients reporting less severe apathetic symptoms, especially those related to executive and auto-activation processing, compared to their caregivers' reports. Executive functioning was found to mediate the relationship between disease stage and awareness of the apathetic state. Awareness of executive apathy impacted patients' self-reported QoL. Therefore, PD patients might be unaware of their apathetic symptoms, especially those with worse executive functioning, which plays a key role in metacognitive processes such as self-monitoring and error detection. Anosognosia for apathy in PD patients may affect their QoL perception and leads to misleading self-report evaluations that delay diagnosis and treatment.}, } @article {pmid37370954, year = {2023}, author = {Abubakar, S and More, S and Tag, N and Olabinjo, A and Isah, A and Lawal, I}, title = {Differences in Tumour Aggressiveness Based on Molecular Subtype and Race Measured by [[18]F]FDG PET Metabolic Metrics in Patients with Invasive Carcinoma of the Breast.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {12}, pages = {}, pmid = {37370954}, issn = {2075-4418}, abstract = {Breast cancer in women of African descent tends to be more aggressive with poorer prognosis. This is irrespective of the molecular subtype. [[18]F]FDG PET/CT metrics correlate with breast cancer aggressiveness based on molecular subtype. This study investigated the differences in [[18]F]FDG PET/CT metrics of locally advanced invasive ductal carcinoma (IDC) among different racial groups and molecular subtypes. Qualitative and semiquantitative readings of [[18]F]FDG PET/CT acquired in women with locally advanced IDC were performed. Biodata including self-identified racial grouping and histopathological data of the primary breast cancer were retrieved. Statistical analysis for differences in SUVmax, MTV and TLG of the primary tumour and the presence of regional and distant metastases was conducted based on molecular subtype and race. The primary tumour SUVmax, MTV, TLG and the prevalence of distant metastases were significantly higher in Black patients compared with other races (p < 0.05). The primary tumour SUVmax and presence of distant metastases in the luminal subtype and the primary tumour SUVmax and TLG in the basal subtype were significantly higher in Black patients compared with other races (p < 0.05). The significantly higher PET parameters in Black patients with IDC in general and in those with luminal and basal carcinoma subtypes suggest a more aggressive disease phenotype in this race.}, } @article {pmid37369698, year = {2023}, author = {Meng, X and Morita, M and Kuba, S and Hayashi, H and Otsubo, R and Matsumoto, M and Yamanouchi, K and Kobayashi, K and Soyama, A and Hidaka, M and Kanetaka, K and Nagayasu, T and Eguchi, S}, title = {Association of quantitative analysis of intratumoral reduced E-cadherin expression with lymph node metastasis and prognosis in patients with breast cancer.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {10434}, pmid = {37369698}, issn = {2045-2322}, mesh = {Female ; Humans ; Biomarkers, Tumor/analysis ; *Breast Neoplasms/pathology ; Cadherins/metabolism ; Immunohistochemistry ; Lymphatic Metastasis ; Prognosis ; Antigens, CD ; }, abstract = {Loss of E-cadherin expression is a poor prognostic factor in patients with breast cancer. Breast cancer cells co-cultured with adipocytes reportedly promote E-cadherin attenuation and tumor progression. The current study aimed to investigate the association of reduced E-cadherin expression with adipose tissue invasion (ATI) and prognosis in breast cancer. Surgical specimens were collected from 188 women with invasive ductal carcinoma of the breast who had undergone surgery without neoadjuvant treatment. We compared E-cadherin expression in ATI and invasive front (IF) using immunohistochemistry with ImageJ. Reduced E-cadherin expression was detected not only in the ATI area but also in the IF, and the degree of reduced E-cadherin expression was positively correlated with both areas. In patients with lymph node metastasis compared to those without, E-cadherin expression was reduced and this reduction was associated with poor recurrence-free survival. We concluded that E-cadherin expression is reduced not only at the ATI area but also at the IF of the tumor. Reduced E-cadherin expression is a clear prognostic factor for breast cancer. Hence, future research is warranted for establishing an objective and quantitative E-cadherin staining assay that will allow clinical use of E-cadherin as a prognostic factor.}, } @article {pmid37364826, year = {2023}, author = {Wang, Y and Teramoto, Y and Miyamoto, H}, title = {Comedonecrosis within conventional prostatic adenocarcinoma vs. intraductal carcinoma of the prostate: their clinical significance is not comparable.}, journal = {Human pathology}, volume = {138}, number = {}, pages = {112-120}, doi = {10.1016/j.humpath.2023.06.011}, pmid = {37364826}, issn = {1532-8392}, mesh = {Male ; Humans ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Prostate/pathology ; Clinical Relevance ; *Prostatic Neoplasms/pathology ; Prognosis ; Neoplasm Grading ; Prostatectomy ; Necrosis/pathology ; }, abstract = {It remains controversial if Gleason grade should be assigned to intraductal carcinoma of the prostate (IDC-P) and if the prognostic value of comedonecrosis associated with IDC-P is equivalent to that in conventional/invasive prostatic adenocarcinoma (CPA) as a Gleason grade 5 pattern. We herein assessed radical prostatectomy findings and postoperative outcomes in 287 patients with CPA exhibiting any Gleason pattern 5. Our cases were divided into 4 cohorts according to the absence or presence of necrosis within CPA and/or IDC-P: Cohort-1) no necrosis in CPA/IDC-P (n = 179; 62.4%); Cohort-2) necrosis only in CPA (n = 25; 8.7%); Cohort-3) necrosis only in IDC-P (n = 62; 21.6%); and Cohort-4) necrosis in both CPA and IDC-P (n = 21; 7.3%). Univariate analysis revealed patients with necrosis only in IDC-P (P < .001) or both CPA and IDC-P (P = .001) had a higher risk of progression than those with necrosis only in CPA, while the prognosis was comparable between the no necrosis group vs. the CPA only necrosis group (P = .680) or the IDC-P only necrosis group vs. the CPA/IDC-P necrosis group (P = .715). In a subgroup of patients exhibiting IDC-P (n = 198), the presence of IDC-P necrosis was still associated with a significantly higher progression risk, compared with CPA necrosis only. In multivariable analysis, necrosis only in IDC-P (vs. necrosis only in CPA) showed significantly worse progression-free survival (HR = 3.193, P = .003). IDC-P necrosis, as an independent predictor, was thus found to be associated with significantly worse oncologic outcomes, compared with necrosis only in CPA, and might therefore be better not to be simply considered as a grade 5 pattern.}, } @article {pmid37363526, year = {2023}, author = {Kara Tahhan, N and Abou Azan, A and Jomaa Al Ali, I and Abdul Aziz, J and Sara, S}, title = {Cutaneous metastases as a primary manifestation of invasive ductal carcinoma of the breast: a case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {6}, pages = {3062-3065}, pmid = {37363526}, issn = {2049-0801}, abstract = {UNLABELLED: Cutaneous metastases as the first sign of invasive ductal carcinoma are not common. The ambiguous presentation of asymptomatic lesions may result in various diagnoses including dermatologic causes. Early diagnosis is essential in such cases.

CASE PRESENTATION: A 43-year-old woman with no risk factors for developing breast cancer at a young age was diagnosed with invasive ductal carcinoma of the left breast after dermatologic complaints of diffuse lesions on the left-back and right subclavian region. The patient remained asymptomatic except for the recent cutaneous presentation, which did not arouse much suspicion.

CONCLUSION: Cutaneous metastases of breast cancer remain uncommon, but at the same time represent a poor prognosis for the patient, and when they do occur, treatment options are limited. The delay in taking the proper diagnostic measures in such cases imposes a need to adopt a wider perspective when dealing with the possible occurrence of advanced disease. This also adds up to the importance of breast self-examination by women at a young age and full examination by physicians, especially when they encounter a misguiding presentation.}, } @article {pmid37363420, year = {2023}, author = {Singh, S and Singh, AL and Pal, KK and Reddy, KK and Gangadhara, K and Dey, R and Mahatma, MK and Verma, A and Kumar, N and Patel, CB and Thawait, LK and Ahmed, S and Navapara, R and Rani, K and Kona, P}, title = {Accumulation of resveratrol, ferulic acid and iron in seeds confer iron deficiency chlorosis tolerance to a novel genetic stock of peanut (Arachis hypogaea L.) grown in calcareous soils.}, journal = {Physiology and molecular biology of plants : an international journal of functional plant biology}, volume = {29}, number = {5}, pages = {725-737}, pmid = {37363420}, issn = {0971-5894}, abstract = {UNLABELLED: Peanut is mostly grown in calcareous soils with high pH which are deficient in available iron (Fe[2+]) for plant uptake causing iron deficiency chlorosis (IDC). The most pertinent solution is to identify efficient genotypes showing tolerance to limited Fe availability in the soil. A field screening of 40 advanced breeding lines of peanut using NRCG 7472 and ICGV 86031 as IDC susceptible and tolerant checks, respectively, was envisaged for four years. PBS 22040 and 29,192 exhibited maximum tolerance while PBS 12215 and 12,185 were most susceptible. PBS 22040 accumulated maximum seed resveratrol (5.8 ± 0.08 ppm), ferulic acid (378.6 ± 0.31 ppm) and Fe (45.59 ± 0.41 ppm) content. Enhanced chlorophyll retention (8.72-9.50 µg ml[-1]), carotenoid accumulation (1.96-2.08 µg ml[-1]), and antioxidant enzyme activity (APX: 35.9-103.9%; POX: 51- 145%) reduced the MDA accumulation (5.61-9.11 µM cm[-1]) in tolerant lines. The overexpression of Fe transporters IRT1, ZIP5, YSL3 was recorded to the tune of 2.3-9.54; 1.45-3.7; 2.20-2.32- folds respectively in PBS 22040 and 29,192, over NRCG 7472. PBS 22040 recorded the maximum pod yield (282 ± 4.6 g/row), hundred kernel weight (55 ± 0.7 g) and number of pods per three plants (54 ± 1.7). The study thus reports new insights into the roles of resveratrol, ferulic acid and differential antioxidant enzyme activities in imparting IDC tolerance. PBS 22040, being the best performing line, can be the potent source of IDC tolerance for introgression in high yielding but susceptible genotypes under similar edaphic conditions.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-023-01321-9.}, } @article {pmid37363122, year = {2023}, author = {Wani, K and Patel, K and Dabak, V}, title = {Hepatotoxicity After CDK 4/6 Inhibitor Initiation in the Treatment of Hormone-Positive Metastatic Breast Cancer.}, journal = {Cureus}, volume = {15}, number = {6}, pages = {e40871}, pmid = {37363122}, issn = {2168-8184}, abstract = {Cancer cells proliferate using various mechanisms. One mechanism of preventing tumor cell growth is blockade of the cyclin-dependent kinase (CDK) 4/6 axis. Multiple CDK 4/6 inhibitors - ribociclib, palbociclib, and abemaciclib - have significantly improved progression-free survival rates. However, they can cause hepatotoxicity. We present a case of a 67-year-old female who was diagnosed with stage 1C invasive ductal carcinoma. She was treated with letrozole and ribociclib due to recurrence as metastatic disease, but within 10 days, she developed transaminitis. She then started palbociclib but experienced elevated transaminases within two weeks, needing discontinuation of palbociclib. Subsequent positron-emission tomography/computed tomography imaging showed disease progression, and she was started on fulvestrant. We considered adding abemaciclib, but the patient declined and has had stable disease for more than a year on fulvestrant. CDK 4/6 inhibitors are used to treat metastatic breast cancer and are generally well tolerated. The most common side effect is neutropenia; however, our patient developed transaminitis. The novelty of our case is the development of hepatotoxicity even after the introduction of another CDK 4/6 inhibitor, indicating at least some degree of class effect. In summary, CDK 4/6 inhibitors have significantly improved outcomes in hormone-positive metastatic breast cancers. However, a small percentage suffer from hepatic injury enough to warrant discontinuation of the drug, and we must continue to assess the risk versus benefit profile when offering them to our patients.}, } @article {pmid37355360, year = {2023}, author = {Fatehi, P and Mahboubi-Fooladi, Z and Dastmardi, M and Jafarzadeh Esfehani, R and Khameneh Bagheri, A}, title = {The correlation between imaging findings and breast cancer cell receptors status.}, journal = {Journal of medical imaging and radiation sciences}, volume = {54}, number = {3}, pages = {446-450}, doi = {10.1016/j.jmir.2023.05.044}, pmid = {37355360}, issn = {1876-7982}, mesh = {Humans ; Female ; Adult ; Middle Aged ; *Breast Neoplasms/diagnosis ; Cross-Sectional Studies ; Mammography ; Receptors, Estrogen/metabolism ; Ultrasonography, Mammary ; }, abstract = {INTRODUCTION: Breast cancer is the most common malignancy among women, and subtypes are mainly defined based on hormone receptors such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). The relationship between breast cancer subtypes and imaging features in mammography and sonography has been studied but the results are controversial. The purpose of this study was to determine the relationship between the hormonal receptor status of breast tumors and the radiologic feature of the tumors on mammography and sonography.

METHODS: Eighty patients with breast cancer enrolled in this cross-sectional study. ER, PR, and HER2 determined by immunohistochemistry. Every patient underwent mammography and sonography before the biopsy. We evaluated the relationship between the hormonal receptor status and radiographic features of tumors on breast sonography and mammography.

RESULTS: The majority of the patients (n=75 (93.8%)) were diagnosed with invasive ductal carcinoma (IDC). The mean and standard deviation of the age was 49 ± 9 years. There was no significant relationship between the hormonal receptor status and the sonographic margin and shape (P>0.05). However, PR (P=0.002) and ER (P=0.001) status were significantly correlated with posterior features on sonography. ER-positive patients were more likely to have indistinct or speculated masses on mammography (P=0.017). Irregular or oval masses on mammography were higher in patients with ER (p=0.032).

CONCLUSION: There was a significant correlation between PR and ER status and posterior features on sonography. Positive ER was associated with indistinct or speculated masses on mammography, as well as irregular or oval masses.}, } @article {pmid37354822, year = {2023}, author = {Farho, MA and Sawas, MN and Alnajjar, M and Al-Kurdi, MA and Nawlo, A and Alloush, H}, title = {Subtrochanteric fracture in previously treated breast cancer patient handled by proximal femoral nail: A case report.}, journal = {International journal of surgery case reports}, volume = {108}, number = {}, pages = {108411}, pmid = {37354822}, issn = {2210-2612}, abstract = {INTRODUCTION: Breast cancer (BC) is the most common and high mortality rate cancer in females. The main complication of BC is metastases, where bone metastases (BM) are present in 90 % of women with distant metastases and commonly recurrence after BC therapy. However, treatment options are numerous, and improving patients' quality of life (QoL) is a priority.

PRESENTATION OF CASE: A 58-year-old female patient presented to the emergency department with pain and movement restriction in the right lower extremity after minor trauma. Clinical history included a surgically resected BC eight years ago, besides chemotherapy and radiotherapy. After clinical and radiographic examination, we encountered a subtrochanteric femoral fracture although the patient is in the end stage, the multidisciplinary team discussed the surgery option with the patient and eventually internally fixed the fracture.

DISCUSSION: Subtrochanteric femur fractures represent a challenging orthopedic issue, ranging from 10 % to 34 % of all hip fractures. Hence, after a detailed discussion, the proximal femoral nail (PFN) was the procedure of choice acording to the patient's preferences and tumor prognosis. Proximal femoral metastasis treatment aims to improve the quality of life (QoL), alleviate bone pain, and rehabilitate skeletal function.

CONCLUSION: In this case report, we highlight the surgical decision consequences for a patient with end-stage cancer, as it may put their life at risk or improve their QoL, likewise the patient in this report.}, } @article {pmid37354223, year = {2023}, author = {Liu, Y and Yu, T}, title = {Clinicopathological characteristics and prognosis of triple-negative breast cancer invasive ductal carcinoma with ductal carcinoma in situ.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {13}, pages = {11181-11191}, pmid = {37354223}, issn = {1432-1335}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; *Triple Negative Breast Neoplasms/therapy ; Retrospective Studies ; *Breast Neoplasms ; *Carcinoma, Ductal, Breast/therapy/pathology ; Prognosis ; }, abstract = {PURPOSE: The purpose of this study is to compare and analyze the clinicopathological characteristics and prognosis of patients with invasive ductal carcinoma coexisting with ductal carcinoma in situ (IDC-DCIS) and invasive ductal carcinoma (IDC) in triple-negative breast cancer (TNBC), and to explore the factors affecting the prognosis, so as to provide new ideas for clinical diagnosis and treatment of these patients.

METHODS: The patients with TNBC underwent surgery in the Department of Breast Surgery of Harbin Medical University Cancer Hospital from October 2012 to December 2018 were retrospectively analyzed and divided into IDC-DCIS group and IDC group. The clinicopathological characteristics and prognosis of the two groups were compared. P < 0.05 was considered statistically significant.

RESULTS: A total of 358 patients were enrolled. There were significant differences in age (P = 0.002), family history (P = 0.016), menopausal status (P = 0.003), KI-67% (P < 0.001), lymphovascular invasion (P = 0.010), histologic grade of IDC (P < 0.001) and multifocal (P < 0.001) between the two groups. The disease-free survival (DFS) of the IDC-DCIS group was better than that of the IDC group (the 5-year DFS was 87.9% vs. 82.6%, P = 0.045), but the overall survival (OS) of the two groups was not statistically significant (the 5-year OS was 96.2% vs. 96.0%, P = 0.573). In addition, the coexistence of DCIS (P = 0.030), lymph node pathologic stage (P = 0.001), tumor location (P = 0.011), and adjuvant chemotherapy (P < 0.001) were independent prognostic factors for DFS.

CONCLUSION: In TNBC, the IDC-DCIS group had less invasive biological characteristics. The DFS of the IDC-DCIS group was better than that of the IDC group, but there was no statistical difference in OS between the two groups. In addition, the coexistence of DCIS, lymph node stage, tumor location and adjuvant chemotherapy may be independent prognostic factors for DFS.}, } @article {pmid37353557, year = {2023}, author = {Thomas, A and Reis-Filho, JS and Geyer, CE and Wen, HY}, title = {Rare subtypes of triple negative breast cancer: Current understanding and future directions.}, journal = {NPJ breast cancer}, volume = {9}, number = {1}, pages = {55}, pmid = {37353557}, issn = {2374-4677}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P50 CA247749/CA/NCI NIH HHS/United States ; }, abstract = {Rare subtypes of triple-negative breast cancers (TNBC) are a heterogenous group of tumors, comprising 5-10% of all TNBCs. Despite accounting for an absolute number of cases in aggregate approaching that of other less common, but well studied solid tumors, rare subtypes of triple-negative disease remain understudied. Low prevalence, diagnostic challenges and overlapping diagnoses have hindered consistent categorization of these breast cancers. Here we review epidemiology, histology and clinical and molecular characteristics of metaplastic, triple-negative lobular, apocrine, adenoid cystic, secretory and high-grade neuroendocrine TNBCs. Medullary pattern invasive ductal carcinoma no special type, which until recently was a considered a distinct subtype, is also discussed. With this background, we review how applying biological principals often applied to study TNBC no special type could improve our understanding of rare TNBCs. These could include the utilization of targeted molecular approaches or disease agnostic tools such as tumor mutational burden or germline mutation-directed treatments. Burgeoning data also suggest that pathologic response to neoadjuvant therapy and circulating tumor DNA have value in understanding rare subtypes of TNBC. Finally, we discuss a framework for advancing disease-specific knowledge in this space. While the conduct of randomized trials in rare TNBC subtypes has been challenging, re-envisioning trial design and technologic tools may offer new opportunities. These include embedding rare TNBC subtypes in umbrella studies of rare tumors, retrospective review of contemporary trials, prospective identification of patients with rare TNBC subtypes entering on clinical trials and querying big data for outcomes of patients with rare breast tumors.}, } @article {pmid37351769, year = {2023}, author = {Byrd, BK and Wells, WA and Strawbridge, RR and Barth, CW and Samkoe, KS and Gibbs, SL and Davis, SC}, title = {Evaluating Receptor-Specific Fresh Specimen Staining for Tumor Margin Detection in Clinical Breast Specimens.}, journal = {Molecular imaging and biology}, volume = {25}, number = {5}, pages = {911-922}, pmid = {37351769}, issn = {1860-2002}, support = {R01 CA188491/CA/NCI NIH HHS/United States ; T32 EB021966/EB/NIBIB NIH HHS/United States ; }, mesh = {Humans ; Female ; *Mastectomy ; *Breast Neoplasms/diagnostic imaging/surgery ; Mastectomy, Segmental ; Coloring Agents ; Staining and Labeling ; }, abstract = {PURPOSE: Reliable and rapid identification of tumor in the margins of breast specimens during breast-conserving surgery to reduce repeat surgery rates is an active area of investigation. Dual-stain difference imaging (DDSI) is one of many approaches under evaluation for this application. This technique aims to topically apply fluorescent stain pairs (one targeted to a receptor-of-interest and the other a spectrally distinct isotype), image both stains, and compute a normalized difference image between the two channels. Prior evaluation and optimization in a variety of preclinical models produced encouraging diagnostic performance. Herein, we report on a pilot clinical study which evaluated HER2-targeted DDSI on 11 human breast specimens.

PROCEDURES: Gross sections from 11 freshly excised mastectomy specimens were processed using a HER2-receptor-targeted DDSI protocol shortly after resection. After staining with the dual-probe protocol, specimens were imaged on a fluorescence scanner, followed by tissue fixation for hematoxylin and eosin and anti-HER2 immunohistochemical staining. Receiver operator characteristic curves and area under the curve (AUC) analysis were used to assess diagnostic performance of the resulting images. Performance values were also compared to expression level determined from IHC staining.

RESULTS: Eight of the 11 specimens presented with distinguishable invasive ductal carcinoma and/or were not affected by an imaging artifact. In these specimens, the DDSI technique provided an AUC = 0.90 ± 0.07 for tumor-to-adipose tissue and 0.81 ± 0.15 for tumor-to-glandular tissue, which was significantly higher than AUC values recovered from images of the targeted probe alone. DDSI values and diagnostic performance did not correlate with HER2 expression level, and tumors with low HER2 expression often produced high AUC, suggesting that even the low expression levels were enough to help distinguish tumor.

CONCLUSIONS: The results from this preliminary study of rapid receptor-specific staining in human specimens were consistent with prior preclinical results and demonstrated promising diagnostic potential.}, } @article {pmid37350603, year = {2023}, author = {Ruiz Ramos, J and Calderón Hernanz, B and Castellanos Clemente, Y and Bonete Sánchez, M and Vallve Alcon, E and Santolaya Perrin, MªR and García Martín, MªÁ and de Lorenzo Pinto, A and Real Campaña, JM and Ramos Rodríguez, J and Calzón Blanco, C and García Peláez, M and Alonso Ramos, H and Altimiras Ruiz, J and Sempere Serrano, P and Martín Cerezuela, M and Periañez Parraga, L and Juanes Borrego, AM and Somoza Fernández, B and Rodríguez Camacho, JM and Puig Campmany, M and Miguens Blanco, I and Tomás Vecina, S and Nadal Galmes, C and Povar Marco, J}, title = {Pharmacist care in hospital emergency departments: a consensus paper from the Spanish hospital pharmacy and emergency medicine associations.}, journal = {Emergencias : revista de la Sociedad Espanola de Medicina de Emergencias}, volume = {35}, number = {3}, pages = {205-217}, doi = {10.55633/s3me/E063.2023}, pmid = {37350603}, issn = {2386-5857}, mesh = {Humans ; Pharmacists ; *Pharmacy Service, Hospital ; Emergency Service, Hospital ; *Emergency Medicine ; Hospitals ; }, abstract = {OBJECTIVES: To draft a list of actions and quality indicators for pharmacist care in hospital emergency departments, based on consensus among a panel of experts regarding which actions to prioritize in this setting.

MATERIAL AND METHODS: A panel of experts from the Spanish Society of Hospital Pharmacy (SEFH) and the Spanish Society of Emergency Medicine (SEMES) evaluated a preliminary list of potential actions and quality of care indicators. The experts used a questionnaire to assess the proposals on the basis of available evidence. In the first round, each expert individually assessed the importance of each proposed action based on 4 dimensions: evidence base, impact on clinical response and patient safety, ease of implementation, and priority. In the second round the experts attended a virtual meeting to reach consensus on a revised list of proposals; suggestions and comments that had been made anonymously in the first round were included. The group then prioritized each action as basic, intermediate, or advanced.

RESULTS: The experts evaluated a total of 26 potential actions and associated quality indicators. No items were eliminated in the analysis of scores and comments from the first round. After the second round, 25 actions survived. Nine were considered basic, 10 intermediate, and 6 advanced.

CONCLUSION: The expert panel's list of pharmacist actions and care quality indicators provides a basis for developing a pharmacist care program in Spanish emergency departments on 3 levels of priority. The list can serve as a guide to pharmacists, managers, physicians, and nurses involved in the effort to improve drug therapy in this hospital setting.}, } @article {pmid37344429, year = {2024}, author = {Kishimoto, K and Shibagaki, K and Araki, A and Murakami, K and Takahashi, Y and Kotani, S and Oka, A and Yazaki, T and Fukuba, N and Mishima, Y and Oshima, N and Kawashima, K and Ishimura, N and Kadota, K and Ishihara, S}, title = {Gastric Metastasis from Salivary Duct Carcinoma Mimicking Scirrhous Gastric Cancer.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {63}, number = {3}, pages = {373-378}, pmid = {37344429}, issn = {1349-7235}, mesh = {Male ; Humans ; Middle Aged ; *Stomach Neoplasms/diagnosis/pathology ; Salivary Ducts/metabolism/pathology ; Biomarkers, Tumor ; *Salivary Gland Neoplasms/diagnosis/metabolism/pathology ; *Carcinoma, Ductal/pathology ; }, abstract = {A 59-year-old man underwent submandibular gland excision for salivary duct carcinoma (SDC). One year later, esophagogastroduodenoscopy indicated gastric diffuse mucosal thickening with luminal contraction, mimicking scirrhous gastric carcinoma. Biopsy specimens showed dense proliferation of neoplastic cells expressing androgen receptor and human epidermal growth factor 2, indicating SDC. Gastric diffuse infiltrative metastasis is generally characteristic of gastric metastasis from invasive ductal carcinoma, which shows histologic features similar to SDC. This is the first known report of gastric diffusely infiltrating metastasis in an SDC patient. Rapidly progressing, diffuse gastric wall thickening should also be considered indicative of salivary tumor-associated gastric metastasis.}, } @article {pmid37341223, year = {2023}, author = {Saeed, U and Uppal, MR and Uppal, MS and Uppal, R and Khan, AA and Hassan, A and Piracha, ZZ}, title = {Hepatitis C virus associated ALT, AST, GGT, Bili T, HB, HBA1C, CREAT, PT, aPPT, AFP, CEA, CA 125, CA 19-9, iPTH biomarkers, computed tomography and HCV burden of disease during pre COVID-19 era (2018-2019) and post COVID-19 era (2020-2022) in Pakistan.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {84}, number = {}, pages = {e271451}, doi = {10.1590/1519-6984.271451}, pmid = {37341223}, issn = {1678-4375}, mesh = {Humans ; Hepacivirus ; Glycated Hemoglobin ; alpha-Fetoproteins ; Pakistan/epidemiology ; *COVID-19 ; *Hepatitis C/epidemiology ; Biomarkers ; Tomography, X-Ray Computed ; Cost of Illness ; }, abstract = {The national burden of HCV has significantly mounted over the period of last few decades placing Pakistan at the worst placement of second largest burden of HCV globally. Herein for the first time from Pakistan, we examined clinical correlation of potential biomarkers with HCV. Nation-wide study was conducted on 13,348 suspected HCV patients during 2018-2022. During pre-COVID-19 era of 2018-2019, prevalence of HCV remained 30%. During 2018, among HCV positive patients, 91% of ALT, 63% of AST, 67% of GGT, 28% of Bili T, 62% of HB, 15% of HBA1C, 25% of CREAT, 15% of PT, 15% of aPTT and 64% of AFP were abnormal. During 2019, among HCV infected 74.47% of ALT, 63.54% of AST, 70.24% of GGT, 24.71% of Bili T, 8.77% of HB and 75% of AFP were raised. CT/CAT scan revealed 4.65% liver complications (mild 13.04%, moderate 30.43% and severe 56.52%). During 2020, HCV prevalence remained 25%. 65.17% of ALT, 64.20% of AST, 68.75% of GGT, 31.25% of Bili T, 20.97% of HB, 4.65% of CREAT and 73.68% of AFP levels were raised. CAT analysis revealed liver complications among 4.41% (14.81% mild, 40.74% moderate, and 44.44% sever). 85.71% of participants diabetes was out of control. During 2021, HCV prevalence remained 27.1%. ALT (73.86%), AST (50.6%), GGT (67.95%), Bili T (28.21%), HB (20%), CREAT (5.8%) and AFP (82.14%) levels were abnormal. During 2022, the levels of ALT (56.06%), AST (56.36%), GGT (56.6%), Bili T (19.23%), HB (43.48%), HBA1C (14.81), CREAT (18.92%), AFP (93.75%) were abnormal. CAT analysis revealed 7.46% liver complications (25% mild, 30.36% moderate, and 42.86% sever). During 2021-2022, 83.33% of subject's diabetes was not controlled.}, } @article {pmid37340705, year = {2023}, author = {Nassar, L and Nakad, S and Abou Zeid, F and Farah, Z and Saheb, G and Mroueh, N and Debs, P and Berjawi, G}, title = {Additional occult cancers identified on staging breast MRI: imaging appearances and pathologic characteristics.}, journal = {Journal of medical radiation sciences}, volume = {70}, number = {4}, pages = {360-368}, pmid = {37340705}, issn = {2051-3909}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; *Carcinoma, Ductal, Breast/diagnosis/pathology ; Retrospective Studies ; *Breast Neoplasms/pathology ; Magnetic Resonance Imaging/methods ; }, abstract = {INTRODUCTION: Breast magnetic resonance imaging (MRI) is increasingly being used for staging of patients with breast cancer due to its high sensitivity in detecting additional cancers (ACs). However, the clinical impact of diagnosing and treating these cancers remains unclear.

METHODS: A retrospective study was undertaken of patients with newly diagnosed breast cancer who underwent staging MRI at The American University of Beirut Medical Centre (AUBMC) between 2012 and 2020. Pathology reports and breast MRI examinations were reviewed. Eighteen breast cancer patients with 19 pathology-proven index cancers (ICs) and 19 pathology-proven MRI-detected ACs were included. Chi-square and Fisher's exact tests for categorical variables and Wilcoxon signed rank test for numerical variables were used to compare ICs to ACs.

RESULTS: The ICs consisted of four ductal carcinoma in situ (DCIS), 13 invasive ductal carcinomas (IDC), of which five with associated DCIS, and two invasive lobular carcinomas, (ILC) of which one with associated DCIS. ACs comprised 12 DCIS, five IDC, two with associated DCIS and two ILC, one with associated DCIS. Interval cancers were more frequently invasive whereas ACs were more frequently in situ (P = 0.021). ACs were more frequently nuclear grade 2 (P = 0.009). There was no statistically significant difference between ICs and ACs in lesion type (P = 0.062), shape (P = 0.073), initial enhancement (P = 1), delayed enhancement (P = 0.732), hormonal receptor profile (P = 0.68) and Ki67 (P = 0.388). Among ACs, ten (53%) were larger than 10 mm of which five (26%) were invasive cancers, and five (26%) were larger than the ICs.

CONCLUSIONS: ACs detected by breast MRI were more likely to be in situ and to show a nuclear grade 2. Although not reaching statistical significance, some ACs tend to be clinically significant by their type, size or nuclear grade. The impact on clinical management remains to be determined.}, } @article {pmid37337121, year = {2023}, author = {Lemmer, IL and Bartelt, A}, title = {Brown fat has a sweet tooth.}, journal = {Nature metabolism}, volume = {5}, number = {7}, pages = {1080-1081}, pmid = {37337121}, issn = {2522-5812}, mesh = {*Adipose Tissue, Brown ; *Taste ; Dietary Fats ; }, } @article {pmid37329252, year = {2023}, author = {Rousseau, S and Feldman, T and Shlomi Polachek, I and Frenkel, TI}, title = {Persistent symptoms of maternal post-traumatic stress following childbirth across the first months postpartum: Associations with perturbations in maternal behavior and infant avoidance of social gaze toward mother.}, journal = {Infancy : the official journal of the International Society on Infant Studies}, volume = {28}, number = {5}, pages = {882-909}, doi = {10.1111/infa.12553}, pmid = {37329252}, issn = {1532-7078}, mesh = {Pregnancy ; Female ; Humans ; Infant ; Male ; *Mothers ; *Stress Disorders, Post-Traumatic ; Mother-Child Relations ; Postpartum Period ; Maternal Behavior ; }, abstract = {Recent literature identifies childbirth as a potentially traumatic event, following which mothers may develop symptoms of Post-Traumatic-Stress-Following-Childbirth (PTS-FC). The current study examines whether stable symptoms of PTS-FC during the early postpartum period may impose risk for perturbations in maternal behavior and infant social-engagement with mother, controlling for comorbid postpartum internalizing symptoms. Mother-infant dyads (N = 192) were recruited from the general population, during the third trimester of pregnancy. 49.5% of the mothers were primipara, and 48.4% of the infants were girls. Maternal PTS-FC was assessed at 3-day, 1-month and 4-month postpartum, via self-report and clinician-administered interview. Latent Profile Analysis generated two profiles of symptomology: "Stable-High-PTS-FC" (17.0%), and "Stable-Low-PTS-FC" (83%). Membership in the "Stable-High-PTS-FC" profile associated with perturbed maternal sensitivity, which was in turn significantly associated with infant avoidance of social gaze toward mother (Indirect effect β = -0.15). Results suggest the need for early screening and inform the planning of early preventive interventions.}, } @article {pmid37328333, year = {2023}, author = {Han, LK and Hussain, A and Dodelzon, K and Ginter, PS and Towne, WS and Marti, JL}, title = {Active Surveillance of Atypical Ductal Hyperplasia of the Breast.}, journal = {Clinical breast cancer}, volume = {23}, number = {6}, pages = {649-657}, doi = {10.1016/j.clbc.2023.05.008}, pmid = {37328333}, issn = {1938-0666}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/surgery/pathology ; Retrospective Studies ; Prospective Studies ; Watchful Waiting ; *Breast Neoplasms/diagnostic imaging/surgery/pathology ; Breast/diagnostic imaging/surgery/pathology ; Biopsy, Large-Core Needle ; Hyperplasia/diagnostic imaging/surgery/pathology ; }, abstract = {BACKGROUND: When needle core biopsy (NCB) of the breast yields atypical ductal hyperplasia (ADH), excision is typically recommended. The natural history of ADH undergoing active surveillance (AS) is not well described. We investigate the rates of upgrade to malignancy of excised ADH and the rates of radiographic progression under AS.

MATERIALS AND METHODS: We retrospectively reviewed records of 220 cases of ADH on NCB. Of patients who had surgery within 6 months of NCB, we examined the malignancy upgrade rate. In the AS cohort, we examined rates of radiographic progression on interval imaging.

RESULTS: The malignancy upgrade rate among patients who underwent immediate excision (n = 185) was 15.7%: 14.1% (n = 26) ductal carcinoma in situ (DCIS) and 1.6% (n = 3) invasive ductal carcinoma (IDC). Upgrade to malignancy was less common in lesions <4 mm in size (0%) or with focal ADH (5%), and more common among lesions presenting with a radiographic mass (26%). Among the 35 patients who underwent AS, median follow-up was 20 months. Two lesions progressed on imaging (incidence 3.8% at 2 years). One patient without radiographic progression was found to have IDC at delayed surgery. The remaining lesions remained stable (46%), decreased in size (11%), or resolved (37%).

CONCLUSIONS: Our findings suggest that AS is a safe approach to managing ADH on NCB for most patients. This could spare many patients with ADH from unnecessary surgery. Given that AS is being investigated for low-risk DCIS in multiple international prospective trials, these results suggest that AS should also be investigated for ADH.}, } @article {pmid37327766, year = {2023}, author = {Adiputra, PAT and Sudarsa, IW and Irawan, H and Saputra, H}, title = {Malignant adnexal tumor of the skin on breast: A case report of apocrine carcinoma.}, journal = {International journal of surgery case reports}, volume = {108}, number = {}, pages = {108383}, pmid = {37327766}, issn = {2210-2612}, abstract = {INTRODUCTION: Malignant adnexal tumors of the skin (MATS) are a group of rare and varied tumors that lack standardized guidelines for their management. Apocrine carcinoma (AC) is a highly uncommon form of breast malignancy, contributing to less than 1 % of all female invasive breast carcinomas. AC has a similar microscopic growth pattern to invasive ductal carcinoma, which can result in early misdiagnosis.

PRESENTATION OF CASE: This report presents a case of a 67-year-old female with a lump in the superior lateral quadrant of her left breast for six years. Surgical therapy was performed with wide excision due to clinical operability, no significant involvement of the axillary lymph nodes, and without metatasis. During the operation, Wide excision of 1-2 cm free margin according to standard and local reconstruction flaps were performed, with berry packing for the identified lymph nodes.

DISCUSSION: The tumor was ER and PR negative, so hormonal treatment would be ineffective, assuming that this is an apocrine carcinoma of the breast. A metastatic work up was already done, and no metastasis was found. A mastectomy would appear to be a viable option.

CONCLUSION: It is important to perform a clinical reevaluation to provide optimal treatment for breast malignancy. Misdiagnosis can occur early. In this case, a surgical procedure involving wide excision was performed, and as of now, the patient has not reported any recurrence.}, } @article {pmid37325006, year = {2023}, author = {Kim, HJ and Lee, JH and Park, YM and Lim, K}, title = {Clustered Microcysts Detected on Breast US in Asymptomatic Women.}, journal = {Journal of the Korean Society of Radiology}, volume = {84}, number = {3}, pages = {676-685}, pmid = {37325006}, issn = {2951-0805}, abstract = {PURPOSE: To investigate the incidence, outcomes, and imaging characteristics of clustered microcysts detected on breast US in asymptomatic women, and suggest appropriate management guidelines.

MATERIALS AND METHODS: We identified and reviewed the lesions recorded as "clustered microcysts" on breast US performed in asymptomatic women between August 2014 and December 2019. The final diagnosis was based on pathology and imaging follow-up results for at least 12 months.

RESULTS: The incidence was 1.5% and 100 patients with 117 lesions were included. Among 117 lesions, 3 (2.6%), 2 (1.7%), and 112 (95.7%) were malignant, high-risk benign, and benign lesions, respectively. The malignant lesions included two cases of ductal carcinoma in situ and one invasive ductal carcinoma. Two of them were assessed as category 4, showing mammographic suspicious microcalcifications and internal vascularity on Doppler US. The remainder was a false negative case and showed echo pattern change on the 12-month follow-up US.

CONCLUSION: The incidence of clustered microcysts on breast US in asymptomatic women was 1.5% and malignancy rate was 2.6% (3 of 117). Knowledge of outcomes and imaging features of benign and malignant clustered microcysts may be helpful for radiologists, thereby aiding categorization and management recommendations.}, } @article {pmid37324999, year = {2023}, author = {Han, YJ and Kim, YM}, title = {Squamous Cell Carcinoma Arising from Epidermal Inclusion Cyst of Breast: Imaging Findings and Literature Review.}, journal = {Journal of the Korean Society of Radiology}, volume = {84}, number = {3}, pages = {776-781}, pmid = {37324999}, issn = {2951-0805}, abstract = {Commonly, epidermal inclusion cysts (EICs) are benign cutaneous lesions that are lined with stratified squamous epithelium and may occur in all body parts, including the breasts. EICs in the breast (EICB) are commonly encountered clinically; it may be under-reported because of their mild and non-specific clinical presentation. Malignant transformation of EICs is extremely rare, occurring 0.011%-0.045%. Presently, we report a rare case of squamous cell carcinoma arising from an EICB of a woman with invasive ductal carcinoma.}, } @article {pmid37324312, year = {2023}, author = {Jain, AK}, title = {Locally Advanced Breast Cancer: Response Evaluation to Neoadjuvant Chemotherapy by Clinico-Histopathological Parameters and Molecular Imaging.}, journal = {Indian journal of surgical oncology}, volume = {14}, number = {2}, pages = {279-287}, pmid = {37324312}, issn = {0975-7651}, abstract = {In India, breast cancer (BC) is not only the commonest cancer but also the commonest cause of cancer mortality among females. Advanced BC constitutes >70% of BC cases at initial presentation in India, among which locally advanced breast cancer (LABC) requires a multi-disciplinary approach with a combination of systemic and locoregional therapies. This descriptive hospital-based study was conducted over 1½ years after seeking approval from the institutional ethics committee. Fifty-five patients satisfying all the criteria of the study were enrolled. The data, thus, collected was pooled into Excel spreadsheet and analyzed using appropriate statistical tools. Most of the patients were postmenopausal, multiparous with breast lump being the commonest symptom. Mean baseline characteristics were age - 48 years, SUV max - 9.2, and Ki-67 - 17.8%. cT4 and cN2 were the commonest pre-NACT tumor and lymph node stage. Invasive ductal carcinoma was the commonest tumor type with the most common tumor grade being grade 3. Hormone receptor positivity and HER2 overexpression were seen in 33 and 17 patients respectively. Post-NACT 32 patients underwent breast-conserving surgery. Pathological complete response (pCR), i.e., ypT0N0, was seen in 13 patients (23.6%). There was slight alteration in hormone receptor status, HER2 expression and Ki-67 in the post-NACT resected tumor. pCR, which is a surrogate marker for improved clinical outcome (DFS and OS) in LABC patients, occurred more commonly in patients with pre-NACT grade 3 tumors, high Ki-67, hormone receptor-negative, and HER2 overexpressing BC (overall, in triple negative BC) but was statistically significant only with Ki-67. Post-NACT, SUV max with a cut off ≤1.5, and ΔSUV max of >80% correlated closely with pCR.}, } @article {pmid37322939, year = {2023}, author = {Chaudhury, S and Sau, K and Khan, MA and Shabaz, M}, title = {Deep transfer learning for IDC breast cancer detection using fast AI technique and Sqeezenet architecture.}, journal = {Mathematical biosciences and engineering : MBE}, volume = {20}, number = {6}, pages = {10404-10427}, doi = {10.3934/mbe.2023457}, pmid = {37322939}, issn = {1551-0018}, mesh = {Humans ; Female ; *Deep Learning ; *Breast Neoplasms/diagnostic imaging/pathology ; Neural Networks, Computer ; }, abstract = {One of the most effective approaches for identifying breast cancer is histology, which is the meticulous inspection of tissues under a microscope. The kind of cancer cells, or whether they are cancerous (malignant) or non-cancerous, is typically determined by the type of tissue that is analyzed by the test performed by the technician (benign). The goal of this study was to automate IDC classification within breast cancer histology samples using a transfer learning technique. To improve our outcomes, we combined a Gradient Color Activation Mapping (Grad CAM) and image coloring mechanism with a discriminative fine-tuning methodology employing a one-cycle strategy using FastAI techniques. There have been lots of research studies related to deep transfer learning which use the same mechanism, but this report uses a transfer learning mechanism based on lightweight Squeeze Net architecture, a variant of CNN (Convolution neural network). This strategy demonstrates that fine-tuning on Squeeze Net makes it possible to achieve satisfactory results when transitioning generic features from natural images to medical images.}, } @article {pmid37318317, year = {2023}, author = {Gómez, AM and Bartelt, A}, title = {Endocrine communication of endoplasmic reticulum stress.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {45}, number = {8}, pages = {e2300093}, doi = {10.1002/bies.202300093}, pmid = {37318317}, issn = {1521-1878}, mesh = {*Endoplasmic Reticulum Stress ; *Endoplasmic Reticulum ; Apoptosis ; }, } @article {pmid37307248, year = {2023}, author = {Saito, M and Kato, S and Maeda, T and Komaya, K and Takagi, T and Sekimura, A and Kobayashi, S and Hori, A}, title = {Surgical Management of Breast Cancer Developing Along the Pathway of a Ventriculoperitoneal Shunt: A Case Report.}, journal = {The American journal of case reports}, volume = {24}, number = {}, pages = {e939639}, pmid = {37307248}, issn = {1941-5923}, mesh = {Female ; Humans ; Aged, 80 and over ; *Breast Neoplasms ; Ventriculoperitoneal Shunt ; Mastectomy ; Neoplasm Recurrence, Local ; *Hydrocephalus ; *Carcinoma, Ductal ; }, abstract = {BACKGROUND Ventriculoperitoneal shunts are commonly used in neurosurgery for the treatment of hydrocephalus. This case report details an unusual instance where breast cancer developed along the pathway of an existing ventriculoperitoneal shunt. CASE REPORT An 86-year-old woman, who previously underwent ventriculoperitoneal shunt placement for normal-pressure hydrocephalus, visited our hospital upon detecting a mass in her left breast. The physical examination discovered an irregular mass located at the 9 o'clock position of the left breast. Subsequent breast ultrasonography identified a 36 mm mass with indistinct borders, rough margins, and signs of skin infiltration. Invasive ductal carcinoma of a triple-negative subtype was diagnosed through a core-needle biopsy. Contrast-enhanced computed tomography indicated the ventriculoperitoneal shunt's pathway, running from the left ventricle, passing through the center of the breast mass, and leading into the abdominal cavity. Fears of shunt occlusion and potential infection due to the untreated breast cancer prompted surgical intervention after consultation with the neurosurgeon. The surgery involved rerouting the ventriculoperitoneal shunt from the left thoracoabdomen to the right, performing a left mastectomy, and removing the fistula in the abdominal wall to minimize the risk of cancer recurrence along the shunt pathway. Postoperative histopathological examination confirmed the initial diagnosis of invasive ductal carcinoma of a triple-negative subtype, with no malignancy detected in the removed abdominal wall fistula. CONCLUSIONS Taking into account prior cases of cancer metastasizing distantly due to ventriculoperitoneal shunts, our case emphasizes the necessity to consider additional preventative measures against cancer seeding. This approach is particularly significant when treating breast cancer that arises along the pathway of a ventriculoperitoneal shunt, apart from performing conventional breast cancer surgery.}, } @article {pmid37305344, year = {2023}, author = {Safari, A and Hamza, S and Paton, D}, title = {A rare case: synchronous ipsilateral breast implant-associated anaplastic large cell lymphoma and invasive ductal carcinoma.}, journal = {Journal of surgical case reports}, volume = {2023}, number = {6}, pages = {rjad338}, pmid = {37305344}, issn = {2042-8812}, abstract = {A 78-year-old female with a history of cosmetic breast implants presented with unilateral breast enlargement and was subsequently diagnosed with stage IA breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) as well as stage IB ipsilateral synchronous invasive ductal carcinoma (IDC). Her assessment included bilateral breast ultrasounds,mammograms and MRIs with right-sided fine needle aspiration of peri-implant fluid, core biopsy of right breast mass and a whole-body positron emission tomography scan. She was surgically treated with bilateral capsulectomy, implant removal and mastectomy. No adjuvant treatment was required for the BIA-ALCL. The IDC required adjuvant chemotherapy, radiotherapy and endocrine therapy. This rare case highlights the paramount importance of thorough evaluation of suspected BIA-ALCL patients for synchronous breast pathologies. We conclude with a concise summary of the salient points on evaluation and management of BIA-ALCL for surgeons.}, } @article {pmid37302209, year = {2023}, author = {Birnbaum, GE}, title = {The enticement of feeling understood, validated, and cared for: How does perceiving a partner as responsive affect the sexual arena?.}, journal = {Current opinion in psychology}, volume = {52}, number = {}, pages = {101594}, doi = {10.1016/j.copsyc.2023.101594}, pmid = {37302209}, issn = {2352-2518}, mesh = {Humans ; *Interpersonal Relations ; *Sexual Behavior ; Sexual Partners ; Emotions ; }, abstract = {Partners' behaviors outside the bedroom may spill over into the bedroom. One such behavior is responsiveness, as it creates a relationship ambiance conducive to the development of intimacy. In this article, I review research demonstrating how perceiving partners as responsive outside the bedroom affects the quality of sexual interactions, highlighting changes in the contextual meaning of partner responsiveness across individuals and relationship stages. I then provide an overview of the costs and benefits of responsiveness within the bedroom. I conclude by suggesting directions for future research on the potential of partner responsiveness for fostering a relationship environment that inoculates against alternative partners as well as for designing social robots and virtual mates for those in need of a surrogate partner.}, } @article {pmid37301537, year = {2023}, author = {Wu, K and Li, W and Liu, H and Niu, C and Shi, Q and Zhang, J and Gao, G and Sun, H and Liu, F and Fu, L}, title = {Metabolome Sequencing Reveals that Protein Arginine-N-Methyltransferase 1 Promotes the Progression of Invasive Micropapillary Carcinoma of the Breast and Predicts a Poor Prognosis.}, journal = {The American journal of pathology}, volume = {193}, number = {9}, pages = {1267-1283}, doi = {10.1016/j.ajpath.2023.05.010}, pmid = {37301537}, issn = {1525-2191}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/metabolism ; Disease-Free Survival ; *Carcinoma, Papillary/pathology ; *Breast Neoplasms/metabolism ; Metabolome ; Methyltransferases/metabolism ; Prognosis ; Protein-Arginine N-Methyltransferases/genetics/metabolism ; Repressor Proteins/metabolism ; }, abstract = {Invasive micropapillary carcinoma (IMPC) of the breast is a special histopathologic type of cancer with a high recurrence rate and the biological features of invasion and metastasis. Previous spatial transcriptome studies indicated extensive metabolic reprogramming in IMPC, which contributes to tumor cell heterogeneity. However, the impact of metabolome alterations on IMPC biological behavior is unclear. Herein, endogenous metabolite-targeted metabolomic analysis was done on frozen tumor tissue samples from 25 patients with breast IMPC and 34 patients with invasive ductal carcinoma not otherwise specified (IDC-NOS) by liquid chromatography-mass spectrometry. An IMPC-like state, which is an intermediate transitional morphologic phenotype between IMPC and IDC-NOS, was observed. The metabolic type of IMPC and IDC-NOS was related to breast cancer molecular type. Arginine methylation modification and 4-hydroxy-phenylpyruvate metabolic changes play a major role in the metabolic reprogramming of IMPC. High protein arginine-N-methyltransferase (PRMT) 1 expression was an independent factor related to the poor prognosis of patients with IMPC in terms of disease-free survival. PRMT1 promoted H4R3me2a, which induced tumor cell proliferation via cell cycle regulation and facilitated tumor cell metastasis via the tumor necrosis factor signaling pathway. This study identified the metabolic type-related features and intermediate transition morphology of IMPC. The identification of potential targets of PRMT1 has the potential to provide a basis for the precise diagnosis and treatment of breast IMPC.}, } @article {pmid37300453, year = {2023}, author = {Cicek, SK and Simsek, B and Gundogdu, C}, title = {Right Common Femoral Vein Invasion: A Unique Case of Inguinal Ectopic Breast Cancer.}, journal = {Vascular and endovascular surgery}, volume = {57}, number = {8}, pages = {914-918}, doi = {10.1177/15385744231183489}, pmid = {37300453}, issn = {1938-9116}, mesh = {Animals ; Cattle ; Humans ; Female ; *Breast Neoplasms/diagnostic imaging/therapy ; Breast/pathology ; Groin ; Femoral Vein/diagnostic imaging/surgery/pathology ; Treatment Outcome ; *Choristoma/diagnosis/pathology ; }, abstract = {OBJECTIVES: Ectopic breast cancer may present anywhere in the milk line, from the axilla to the groin which is extremely rare in the inguinal region. Despite morphologic differences, ectopic breast tissue presents characteristics related to orthotopic breast tissue in terms of function and pathologic degeneration. The case report describes the treatment of a unique ectopic breast carcinoma which was located in the inguinal region with a common femoral vein invasion.

METHODS: We present a unique case of an ectopic breast carcinoma presenting in an unusual anatomic location along the milk line. The study was approved by the local Ethics Committee (protocol no: 12.01.2023-2023/02) Informed consent was obtained from the patient.

RESULTS: The patient is surgically treated and supplemented with neoadjuvant chemotherapy,radiotherapy and endocrine therapy. Histopathological examination revealed the diagnosis of invasive ductal carcinoma. The right common femoral vein was reconstructed with bovine pericardial patch after totally removal of the mass.

CONCLUSIONS: This report alerts the reader to be cognizant of the unusual location of an ectopic breast cancer which was detected in the inguinal region with a common femoral vein invasion and discusses the treatment, suggesting novel therapeutic advice that could bring considerable clinical advantages. A multidisciplinary approach should be warranted in such cases to confirm a complete remission.}, } @article {pmid37296828, year = {2023}, author = {Kumaraswamy, E and Kumar, S and Sharma, M}, title = {An Invasive Ductal Carcinomas Breast Cancer Grade Classification Using an Ensemble of Convolutional Neural Networks.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {11}, pages = {}, pmid = {37296828}, issn = {2075-4418}, abstract = {Invasive Ductal Carcinoma Breast Cancer (IDC-BC) is the most common type of cancer and its asymptomatic nature has led to an increased mortality rate globally. Advancements in artificial intelligence and machine learning have revolutionized the medical field with the development of AI-enabled computer-aided diagnosis (CAD) systems, which help in determining diseases at an early stage. CAD systems assist pathologists in their decision-making process to produce more reliable outcomes in order to treat patients well. In this work, the potential of pre-trained convolutional neural networks (CNNs) (i.e., EfficientNetV2L, ResNet152V2, DenseNet201), singly or as an ensemble, was thoroughly explored. The performances of these models were evaluated for IDC-BC grade classification using the DataBiox dataset. Data augmentation was used to avoid the issues of data scarcity and data imbalances. The performance of the best model was compared to three different balanced datasets of Databiox (i.e., 1200, 1400, and 1600 images) to determine the implications of this data augmentation. Furthermore, the effects of the number of epochs were analysed to ensure the coherency of the most optimal model. The experimental results analysis revealed that the proposed ensemble model outperformed the existing state-of-the-art techniques in relation to classifying the IDC-BC grades of the Databiox dataset. The proposed ensemble model of the CNNs achieved a 94% classification accuracy and attained a significant area under the ROC curves for grades 1, 2, and 3, i.e., 96%, 94%, and 96%, respectively.}, } @article {pmid37293082, year = {2023}, author = {Subudhi, AK and Green, JL and Satyam, R and Lenz, T and Salunke, RP and Shuaib, M and Isaioglou, I and Abel, S and Gupta, M and Esau, L and Mourier, T and Nugmanova, R and Mfarrej, S and Sivapurkar, R and Stead, Z and Rached, FB and Otswal, Y and Sougrat, R and Dada, A and Kadamany, AF and Fischle, W and Merzaban, J and Knuepfer, E and Ferguson, DJP and Gupta, I and Le Roch, KG and Holder, AA and Pain, A}, title = {PfAP2-MRP DNA-binding protein is a master regulator of parasite pathogenesis during malaria parasite blood stages.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37293082}, issn = {2692-8205}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 AI136511/AI/NIAID NIH HHS/United States ; R21 AI142506/AI/NIAID NIH HHS/United States ; }, abstract = {Malaria pathogenicity results from the parasite's ability to invade, multiply within and then egress from the host red blood cell (RBC). Infected RBCs are remodeled, expressing antigenic variant proteins (such as PfEMP1, coded by the var gene family) for immune evasion and survival. These processes require the concerted actions of many proteins, but the molecular regulation is poorly understood. We have characterized an essential Plasmodium specific Apicomplexan AP2 (ApiAP2) transcription factor in Plasmodium falciparum (PfAP2-MRP; Master Regulator of Pathogenesis) during the intraerythrocytic developmental cycle (IDC). An inducible gene knockout approach showed that PfAP2-MRP is essential for development during the trophozoite stage, and critical for var gene regulation, merozoite development and parasite egress. ChIP-seq experiments performed at 16 hour post invasion (h.p.i.) and 40 h.p.i. matching the two peaks of PfAP2-MRP expression, demonstrate binding of PfAP2-MRP to the promoters of genes controlling trophozoite development and host cell remodeling at 16 h.p.i. and antigenic variation and pathogenicity at 40 h.p.i. Using single-cell RNA-seq and fluorescence-activated cell sorting, we show de-repression of most var genes in Δpfap2-mrp parasites that express multiple PfEMP1 proteins on the surface of infected RBCs. In addition, the Δpfap2-mrp parasites overexpress several early gametocyte marker genes at both 16 and 40 h.p.i., indicating a regulatory role in the sexual stage conversion. Using the Chromosomes Conformation Capture experiment (Hi-C), we demonstrate that deletion of PfAP2-MRP results in significant reduction of both intra-chromosomal and inter-chromosomal interactions in heterochromatin clusters. We conclude that PfAP2-MRP is a vital upstream transcriptional regulator controlling essential processes in two distinct developmental stages during the IDC that include parasite growth, chromatin structure and var gene expression.}, } @article {pmid37292245, year = {2023}, author = {Thu Huong, N and Hue, TT and Duy Hung, N and Minh Duc, N}, title = {Ductal carcinoma in situ arises from microglandular adenosis and atypical microglandular adenosis in a young woman.}, journal = {Journal of clinical imaging science}, volume = {13}, number = {}, pages = {15}, pmid = {37292245}, issn = {2156-7514}, abstract = {Microglandular adenosis (MGA) and atypical microglandular adenosis (AMGA) are intensely rare and distinctive forms of adenosis of the breast, usually occurring in middle-aged women. Carcinoma arising in MGA is an extremely rare subtype of breast carcinoma, and most reported cases are of invasive carcinoma. Ultrasound and magnetic resonance imaging are accurate imaging modalities for diagnosing these abnormalities. Our goal in this article was to report a rare instance of ductal carcinoma in situ (DCIS) arising from MGA and AMGA in a very young Vietnamese woman who presented with a palpable mass in her right breast for 1 month. During clinical examination and imaging, suspected lesions were found and categorized as BI-RADS 4a. The final histopathological findings confirmed DCIS arising from MGA/AMGA. In this patient, the disease was detected and managed early when the lesion was localized in the duct and there were no signs of invasive ductal carcinoma.}, } @article {pmid37290673, year = {2023}, author = {Nieborak, A and Lukauskas, S and Capellades, J and Heyn, P and Santos, GS and Motzler, K and Zeigerer, A and Bester, R and Protzer, U and Schelter, F and Wagner, M and Carell, T and Hruscha, A and Schmid, B and Yanes, O and Schneider, R}, title = {Depletion of pyruvate kinase (PK) activity causes glycolytic intermediate imbalances and reveals a PK-TXNIP regulatory axis.}, journal = {Molecular metabolism}, volume = {74}, number = {}, pages = {101748}, pmid = {37290673}, issn = {2212-8778}, mesh = {Animals ; *Pyruvate Kinase/genetics ; Reactive Oxygen Species ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism ; *Neoplasms/genetics/metabolism ; Thioredoxins/chemistry/metabolism ; }, abstract = {OBJECTIVE: Cancer cells convert more glucose into lactate than healthy cells, what contributes to their growth advantage. Pyruvate kinase (PK) is a key rate limiting enzyme in this process, what makes it a promising potential therapeutic target. However, currently it is still unclear what consequences the inhibition of PK has on cellular processes. Here, we systematically investigate the consequences of PK depletion for gene expression, histone modifications and metabolism.

METHODS: Epigenetic, transcriptional and metabolic targets were analysed in different cellular and animal models with stable knockdown or knockout of PK.

RESULTS: Depleting PK activity reduces the glycolytic flux and causes accumulation of glucose-6-phosphate (G6P). Such metabolic perturbation results in stimulation of the activity of a heterodimeric pair of transcription factors MondoA and MLX but not in a major reprogramming of the global H3K9ac and H3K4me3 histone modification landscape. The MondoA:MLX heterodimer upregulates expression of thioredoxin-interacting protein (TXNIP) - a tumour suppressor with multifaceted anticancer activity. This effect of TXNIP upregulation extends beyond immortalised cancer cell lines and is applicable to multiple cellular and animal models.

CONCLUSIONS: Our work shows that actions of often pro-tumorigenic PK and anti-tumorigenic TXNIP are tightly linked via a glycolytic intermediate. We suggest that PK depletion stimulates the activity of MondoA:MLX transcription factor heterodimers and subsequently, increases cellular TXNIP levels. TXNIP-mediated inhibition of thioredoxin (TXN) can reduce the ability of cells to scavenge reactive oxygen species (ROS) leading to the oxidative damage of cellular structures including DNA. These findings highlight an important regulatory axis affecting tumour suppression mechanisms and provide an attractive opportunity for combination cancer therapies targeting glycolytic activity and ROS-generating pathways.}, } @article {pmid37284541, year = {2023}, author = {De Matos, CC and Guignard, B and Castro, FS and Guimard, A}, title = {Effects of paddles and fins on front crawl kinematics, arm stroke efficiency, coordination, and estimated energy cost.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1174090}, pmid = {37284541}, issn = {1664-042X}, abstract = {Paddles and fins are used in swimmers training with different objectives (e.g., increase propulsive areas of hands and feet, improve the feeling of water flow). These artificial modifications of the stroke might be viewed as external constraints of the stroke task, both will either disturb or facilitate swimming modalities, so the coaches should manipulate its use to extract benefits for performance. This study seeks to investigate the precise effects of wearing either paddles (PAD) or fins (FINS) vs. a no-equipment (NE) trial in three all-out front crawl exercises on swimmer kinematics, arm stroke efficiency (ηp), upper-limbs coordination patterns (Index of Coordination, IdC), and estimated energy cost (C). Eleven regional to national-level male swimmers participated in the study (age: 25.8 ± 5.5 years, body mass: 75.2 ± 5.5 kg, height: 177 ± 6.5 cm) and were recorded from both sides of the swimming pool to collect all variables. Repeated measures ANOVA and Bonferroni post hoc were used to compare the variables. Effects sizes were calculated. Time to cover the distance and velocity were higher in FINS swimming, with larger values of stroke length (SL) and lower kick amplitude in comparison to the other trials (PAD and NE). The use of FINS also modified the stroke phases durations by presenting significant lower propulsion time during the stroke in comparison to PAD or NE. Values of IdC were lower (IdC < -1%, so catch-up pattern of coordination) for FINS in comparison to NE. In terms of ηp, using PAD or FINS demonstrate higher arm stroke efficiency than swimming without equipment. Finally, C was significantly higher in FINS swimming in comparison to NE and PAD. From the present results, it should be noted that the use of equipment such as fins deeply modify the structure of the swimming stroke (from the performance-related parameters through the kinematics of both upper and lower limbs to the stroke efficiency and coordination pattern). So, using equipment should be appropriately scaled by the coaches to the objectives of the training session in swimming, and in emergent sports such as "SwimRun", paddles and fins must be viewed as tools to achieve higher velocities to cover a given distance.}, } @article {pmid37283256, year = {2023}, author = {Bukamal, Z and AlRayes, A}, title = {Prevalence of BRCA1 and BRCA2 Mutations Among High-risk Bahraini Patients with Breast Cancer.}, journal = {The Gulf journal of oncology}, volume = {1}, number = {42}, pages = {22-25}, pmid = {37283256}, issn = {2078-2101}, mesh = {Humans ; Female ; Male ; *Breast Neoplasms/epidemiology/genetics/diagnosis ; Bahrain/epidemiology ; Retrospective Studies ; Prevalence ; Mutation ; *Carcinoma, Ductal ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; }, abstract = {OBJECTIVE: The purpose is to study the prevalence of BRCA1 and BRCA2 mutations in high-risk Bahraini patients diagnosed with breast cancer, its relation to family history, and to determine the clinicopathologic features of breast cancer associated with these genetic mutations, over a period of 7 years.

BACKGROUND: Breast cancer is the most common type of cancer occurring in women and the second most common type generally. Approximately 12% of women worldwide will develop carcinoma of the breast sometime during their life. Additionally, 72% of women with an inherited BRCA1 mutation and 69% of those with a mutated BRCA2 will develop breast cancer by 80 years of age. The incidence of breast cancer in Bahraini women have increased over the last decade. Still, the data on BRCA1 & BRCA2 mutations in relation to breast cancer patients is limited in the Arab region, not omitting Bahrain as a country with deficient BRCA prevalence data.

METHODS: This retrospective study was carried out in Salmaniya Medical Complex, Bahrain, to determine the prevalence of BRCA1 and BRCA2 mutations and to observe the breast cancer's histopathologic features that are associated with these mutations.

RESULTS: 271 patients underwent the BRCA gene testing between 2013 and 2019. Out of 271 patients, 35 were excluded. Out of the 236 breast cancer patients, 219 (93%) did not have the mutation. The BRCA gene was carried by a total of 17 (7%) patients; 13 (5%) BRCA1 and 4 (2%) BRCA2. Thirteen BRCA carrier patients had invasive ductal carcinoma (IDC) (76%), 2 had ductal carcinoma in situ (DCIS) (12%), while 2 patients' histopathology was not available. Molecular subtypes showed 4 triple negative basal sub-type (TNBC), 10 positive ER and PR hormonal status, 1 positive HER-2, while 2 patients' hormonal receptor status was not available. Two BRCA1 carriers had both breast and ovarian cancers. A total of 5 (2%) breast cancer male patients were among the tested population, out of which, 1 (0.4% of the total and 20% of the male patients) was a BRCA2 carrier. Out of the 236 patients, 76 (32%) were younger than 40 years of age at the time of diagnosis. Then again, out of the 17 BRCA carrier patients, 7 (41%) were younger than 40 years.

CONCLUSION: The prevalence of BRCA mutation in high risk Bahraini breast cancer patients is 7%. Among those patients, BRCA1 mutation is the most prevalent (5%) and invasive ductal carcinoma (IDC) is the most common histopathological subtype. However, there was not enough data to conclude the most prevalent molecular subtype of breast cancer in BRCA carriers due to deficiency of overseas pathology reports for patients operated outside Bahrain. When developing treatment plans for younger patients with breast cancer, inherited syndromes and precisely BRCA mutations need to be considered. Bahrain is implementing genetic testing for breast cancer patients ≤ 50 years of age since 2018, according to NCCN guidelines. We will continue to build our database to better characterize breast cancer subtypes and determine their hereditary pattern for identification of high risk families in Bahrain and for future development of more specific therapeutic approaches.

KEY WORDS: Breast cancer, BRCA1, BRCA2, BRCA mutation, Bahrain, Arab region.}, } @article {pmid37276118, year = {2023}, author = {Chen, CB and Wang, Y and Fu, X and Yang, H}, title = {Recurrence Network Analysis of Histopathological Images for the Detection of Invasive Ductal Carcinoma in Breast Cancer.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {20}, number = {5}, pages = {3234-3244}, doi = {10.1109/TCBB.2023.3282798}, pmid = {37276118}, issn = {1557-9964}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; *Breast Neoplasms/diagnostic imaging ; }, abstract = {The histopathological image analysis is one of the most crucial diagnostic procedures to identify Invasive ductal carcinoma (IDC) in breast cancers. However, this diagnosis process is currently time-consuming and heavily dependent on human expertise. Prior research has shown that different degrees of tumors present various microstructures in the histopathological images. However, very little has been done to utilize spatial recurrence features of microstructures for identifying IDC. This paper presents a novel recurrence analysis methodology for automatic image-guided IDC detection. We first utilize wavelet decomposition to delineate the subtle information in the images. Then, we model the patches with a weighted recurrence network approach to characterize the recurrence patterns of the histopathological images. Finally, we develop automated IDC detection models leveraging machine learning methods with spatial recurrence features extracted. The developed recurrence analysis models successfully characterize the complex microstructures of histopathological images and achieve the IDC detection performances of at least AUC = 0.96. This research developed a spatial recurrence analysis methodology to effectively identify IDC regions in histopathological images for BC. It shows a high potential to assist physicians in the decision-making process. The proposed methodology can further be applicable to image processing for other medical or biological applications.}, } @article {pmid37274780, year = {2023}, author = {Xiang, J and Gong, W and Liu, J and Zhang, H and Li, M and Wang, R and Lv, Y and Sun, P}, title = {Identification of DLL3-related genes affecting the prognosis of patients with colon adenocarcinoma.}, journal = {Frontiers in genetics}, volume = {14}, number = {}, pages = {1098190}, pmid = {37274780}, issn = {1664-8021}, abstract = {Background: Delta-like ligand 3 (DLL3) is one of the NOTCH family of ligands, which plays a pro- or anti-carcinogenic role in some cancers. But the role of DLL3 in colon adenocarcinoma (COAD) has not been studied in depth. Materials and methods: First, we used Kaplan-Meier (K-M) curve to evaluate the effect of DLL3 on the prognosis of COAD in The Cancer Genome Atlas (TCGA), which was further validated in clinical samples for immunohistochemistry. Then we screened for differentially expressed genes (DEGs) of DLL3 by analyzing datasets of COAD samples from Gene Expression Omnibus (GEO) and TCGA. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and Gene Set Enrichment Analysis (GSEA) were conducted to explore the underlying mechanisms of DLL3-related in the development and prognosis of COAD. On the basis of DLL3-related signature genes, a prognostic model and a nomogram were constructed. Finally, CIBERSORT was applied to assess the proportion of immune cell types in COAD sample. Results: Survival analysis showed a significant difference in overall survival between high- and low-expression group (p = 0.0092), with COAD patients in the high-group having poorer 5-year survival rate. Gene functional enrichment analysis revealed that DLL3-related DEGs were mainly enriched in tumor- and immunity-related signaling pathways, containing AMPK pathway and mitophagy-animal. The comparison of COAD tumor and normal, DLL3 high- and low-expression groups by GSEA found that AMPK signaling pathway and mitophagy-animal were inhibited. Nomogram constructed from DLL3-related signature genes had a good predictive effect on the prognosis of COAD. We found the highest correlation between DLL3 and interstitial dendritic cell (iDC), natural killer (NK) cell and Interstitial dendritic cell (Tem). DLL3 was also revealed to be diagnostic for COAD. In clinical sample, we identified higher DLL3 expression in colon cancer tissue than in adjacent control (p < 0.0001) and in metastasis than in primary lesion (p = 0.0056). DLL3 expression was associated with stage and high DLL3 expression was observed to predict poorer overall survival (p = 0.004). Conclusion: It suggested that DLL3 may offer prognostic value and therapeutic potential for individualized treatment of COAD, and that it may has a diagnostic role in COAD.}, } @article {pmid37270436, year = {2023}, author = {Jiao, Y and Guo, X and Wu, H and Lv, Q}, title = {Surgery on Metastatic Foci is a Better Strategy for Stage IV Breast Cancer Patients with only Nonregional Lymph Node Metastasis.}, journal = {Advances in therapy}, volume = {40}, number = {7}, pages = {3247-3262}, pmid = {37270436}, issn = {1865-8652}, support = {ZYJC18018//West China Hospital, Sichuan University/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy ; Lymphatic Metastasis/pathology ; Lymph Nodes/surgery/pathology ; Prognosis ; Lymph Node Excision ; }, abstract = {INTRODUCTION: Our study aims to explore whether breast cancer patients with non-regional lymph node (NRLN) metastasis benefit from surgery on distant nodes, and to determine the influencing factors affecting the prognosis of this type of patient.

METHODS: Information of invasive ductal carcinoma (IDC) patients from 2004 to 2016 was extracted from the Surveillance, Epidemiology, and End Results (SEER) database and analyzed by statistical methods, including multivariate Cox regression model, chi-squared test, propensity score matching (PSM), Kaplan-Meier plot, and log-rank test.

RESULTS: A total of 4236 M1 patients met the designated criteria. Among 847 patients with only NRLN metastasis who have detailed information, only 114 patients received surgery on metastatic distant lymph nodes. The Kaplan-Meier plot for overall survival (OS) showed that the prognosis of NRLN metastatic patients was superior to visceral metastasis (P < 0.0001) but similar to supraclavicular metastasis (P = 0.33). In addition, NRLN metastatic patients who underwent surgery on the NRLNs were found to have superior prognoses in terms of both OS (P = 0.041) and cancer-specific survival (P = 0.034) compared with those who did not undergo NRLN surgery. We have also demonstrated that NRLN metastatic patients who have received radiotherapy plus chemotherapy for primary tumors gain superior survival compared with those who only received chemotherapy apart from NRLN surgery.

CONCLUSION: Surgery on NRLN and radiotherapy for the primary tumor improved the prognosis of NRLN metastatic patients. Thus, the classification of NRLN, especially contralateral axillary lymph node metastasis (CAM), into the M1 breast cancer stage should be reconsidered. Different locoregional treatment strategies for metastatic foci should be recommended for patients with only NRLN and patients with visceral metastasis.}, } @article {pmid37268513, year = {2023}, author = {Bernardino, R and Sayyid, RK and Al-Daqqaq, Z and Tiwari, R and Cockburn, J and Vijayakanthan, S and Qaoud, Y and Berjaoui, MB and Metser, U and Berlin, A and van der Kwast, T and Fleshner, NE}, title = {Lymphotropic Pattern of Prostate-specific Membrane Antigen-detected Metastases Among Biochemically Recurrent Radical Prostatectomy Patients with Cribriform Disease.}, journal = {European urology focus}, volume = {9}, number = {6}, pages = {1016-1023}, doi = {10.1016/j.euf.2023.05.005}, pmid = {37268513}, issn = {2405-4569}, mesh = {Male ; Humans ; *Positron Emission Tomography Computed Tomography/methods ; Prostate/pathology ; Cross-Sectional Studies ; *Prostatic Neoplasms/pathology ; Prostatectomy/methods ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Cribriform morphology portends worse oncologic outcomes, and has unique cellular intrinsic pathway alterations and tumor microenvironments that may impact metastatic spread patterns.

OBJECTIVE: To determine whether the presence of cribriform morphology in prostatectomy specimens of patients with biochemical recurrence after radical prostatectomy (RP) is associated with the presence of metastasis on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and a distinct pattern of spread.

A cross-sectional analysis was conducted of all prostate cancer patients with biochemical recurrence after RP undergoing [18]F-DCFPyL-PET/CT between December 2018 and February 2021 at the Princess Margaret Cancer Centre.

Outcomes were presence of any metastasis in the overall cohort and lymphatic versus bone/visceral metastases among patients with metastatic disease. The associations between the presence of intraductal (IDC) and/or invasive cribriform (ICC) carcinoma on the RP specimen and study outcomes were evaluated using logistic regression analyses.

RESULTS AND LIMITATIONS: The cohort included 176 patients. IDC and ICC were observed in 77 (43.8%) and 80 (45.5%) RP specimens, respectively. The median time from RP to PSMA-PET/CT was 5.0 yr. The median serum prostate-specific antigen level at PSMA-PET/CT was 1.12 ng/ml. Overall, metastasis was observed in 77 patients, of whom 58 were had lymphatic-only metastasis. On a multivariable analysis, presence of IDC on RP was associated with increased odds of overall metastasis (odds ratio [OR]: 2.17; 95% confidence interval [CI]: 1.07-4.45; p = 0.033). Presence of ICC on RP was associated with significantly increased odds of lymphatic versus bone/visceral metastases (OR: 3.13; 95% CI: 1.09-21.7; p = 0.004).

CONCLUSIONS: Presence of cribriform morphology on RP specimens of patients with biochemical failure after RP is associated with increased odds of PSMA-PET/CT-detected metastases with a lymphatic predominant pattern of spread. These findings have implications for the design and evaluation of post-RP salvage therapies.

PATIENT SUMMARY: We found that microscopic cribriform appearance correlates with disease spread on imaging in prostate cancer patients with recurrence and has a predilection for spread to lymph nodes, as opposed to bone or visceral organs.}, } @article {pmid37266479, year = {2023}, author = {Al-Zadjali, Y and Al-Rashdi, A and Al-Husaini, S and Al-Badi, S and Al-Badi, H and Arafa, M}, title = {Clinicopathological Study of Breast Carcinoma Patients with Equivocal HER2 Immunohistochemical Status: Five-Year Experience from a Tertiary Care Center.}, journal = {Maedica}, volume = {18}, number = {1}, pages = {27-34}, pmid = {37266479}, issn = {1841-9038}, abstract = {Background and objectives: Assessment of HER2 gene status has central role in the management of breast cancer patients. For determining HER2 status, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are the most commonly used tests. Immunohistochemistry scores of 3+ and 1+ were considered as HER2 positive and negative, respectively. On the other hand, HER2 equivocal cases need further confirmation by FISH test assessment. This study aimed to identify the clinicopathological characteristics of patients with HER2 equivocal tumors served by Sultan Qaboos University Hospital (SQUH) in Muscat, Oman, with emphasis on treatment plans and disease outcome. Methods: This was a retrospective cross-sectional study, which involved all breast cancer female patients who were referred to SQUH from 2016 to 2020. It included a total of 108 patients who were diagnosed with HER2 (2+) breast cancer. Patients' data were analyzed in relation to the subsequent FISH status. Results: During the study period, data from 108 females with HER2 2+ were collected; among them, 22 (20%) were FISH positive, 64 (59%) FISH negative, 17 (16%) FISH borderline and five (5%) with no results. Regarding patients' characteristics, 91.2% of all subjects had invasive ductal carcinoma, 93.2% expressed estrogen receptors and 77.6% progesterone receptor. Age, postmenopausal histopathology, tumor grade, TNM staging, ER, PR, Ki67, LVSI, NLR, treatment and follow-up did not show significant association with different FISH results. Conclusions: The majority of HER2 equivocal breast cancer cases were FISH negative. In trastuzumab chemotherapy, an association between different FISH results was expected.}, } @article {pmid37266061, year = {2023}, author = {Jogie, JA and Maharaj, A and Mahase, T and Bhagwandeen, S and Ramcharan, L and Mohammed, R and Ramdass, J and Deyalsingh, V}, title = {A Preliminary Analysis of Ki-67 Expression in Breast Cancer in the Caribbean.}, journal = {Cureus}, volume = {15}, number = {4}, pages = {e38351}, pmid = {37266061}, issn = {2168-8184}, abstract = {OBJECTIVE: There has been a void of data regarding Ki-67 expression in breast cancer in the Caribbean. Ki-67 is a widely used marker to determine the grade and prognosis of breast cancer. Ki-67 has been shown to be a valuable tool in predicting the response to chemotherapy and hormonal therapy in breast cancer patients. The objective of this preliminary study aims to describe the Ki-67 (Ki) status in this population and its correlations with other parameters in breast cancer histology. This study also aims to lay the groundwork for Ki-67 analysis in this population so that future studies may better describe it.

METHOD: The methodology involved gathering data from histology reports for all breast cancer-related biopsies from the 1st of January 2018 to the 12th of July 2021. This data was retrospectively analyzed.

RESULTS: Twenty-three Ki-67 cases were obtained, 19 of which had Ki expression >10%. This >10% group was mostly staged from T1c up (one T1, three T1c cases, two T2 cases, four T3 cases while nine were not T staged). Two were N2/M1 while 9 were N0 and two were M0, the rest were not staged. The mean age was 65.6 years with a range of 54 and a standard deviation of 12.5. Lymphovascular invasion was confirmed in four cases and suspected in three. Axillary lymph node dissection (ALND) yielded >10 nodes involved in two cases while <5 nodes in the remaining. The most common receptor status was hormone positive/ human epidermal growth factor receptor-2 (HER) negative (eight). Invasive Ductal Carcinoma (IDC) occurred in 10 cases while intermediate grade was in 14 cases. The Ki 6-10 % group consisted of two cases, one staged at T1aN0Mx while the other T2NxMx. Lymphovascular invasion was suspected in one. The average age was 67.5 years. ALND yielded less than five nodes in one case and 5-10 nodes in the other. Grades were high and intermediate. Histology was invasive ductal carcinoma/ductal carcinoma in situ (IDC/DCIS), and ductal carcinoma in situ (DCIS) respectively. The Ki <6% group comprised two cases, staged at T1NxMx and T3N2M1. Lymphovascular invasion was absent in both. The mean age was 58.5 years. ALND yielded >10 nodes in one case and <5 in the other. Grades were high and intermediate. Histology was IDC/DCIS in both. There were no sentinel nodes involved in all but two cases belonging to the Ki >10% group.

CONCLUSION: This preliminary study was the first to describe the Ki-67 marker in the Caribbean population. The vast majority of this population has a Ki-67 level of>10%. Higher Ki-67 expression is associated with larger tumors, lymphovascular invasion, metastases, and higher tumor grades. There is a need for consistent Ki-67 reporting in histology samples before follow-up studies are conducted.}, } @article {pmid37260825, year = {2023}, author = {Boșoteanu, LA and Așchie, M and Orǎșanu, CI and Boșoteanu, M}, title = {HER2 Negative Mammary Paget's Disease or In Situ Melanoma? A Case Report and Review of the Literature.}, journal = {Case reports in pathology}, volume = {2023}, number = {}, pages = {1101130}, pmid = {37260825}, issn = {2090-6781}, abstract = {Mammary Paget's disease (MPD) is a rare histological condition, accounting for 1-4% of female breast cancers, which may appear either independently (1.4-13% of the cases), or in association with an in situ or invasive ductal carcinoma (approximately 90% of the cases). The purpose of this article is to highlight the histopathological challenges related to the microscopical polymorphism of this disease and the utmost importance of immunohistochemistry in the thorough process of Paget's disease differential diagnosis. Moreover, the primary objective of this review of literature was to corroborate the existing data concerning the potential peculiar immunohistochemical profile that mammary Paget's disease might express. We report the case of a 44-year-old female patient, histopathologically diagnosed with HER2-negative MPD accompanying an invasive mammary carcinoma. The histopathological and immunohistochemical approach is derived from the exigency of excluding the possibility of synchronous tumors-a mammary invasive carcinoma, accompanied by another component with MPD phenotypic mimicry. The unexpected negative HER2 reaction is conducted to a primary focus on excluding a malignant melanoma in situ. The absence of MelanA and S100 immunoexpression and lack of pigmentation and clinical aspects infirmed it. Bowen's disease was invalidated by its rare presentation in the breast cutaneous tissue and the absence of individual risk factors suggestive of an existing immunosuppressive status. In the case of similar morphoimmunohistochemical aspects, significant expression of Ki-67 signals MPD, an immunoreactivity that helped distinguish the cellular population from Toker cells. The great similarity of MPD with other benign and malignant cutaneous tumors might determine delay or misdiagnosis. Thus, the utmost importance of immunohistochemistry is reflected in its prognostic significance and geared towards extending the therapeutic arsenal.}, } @article {pmid37256575, year = {2024}, author = {Lobato, P and Moriano, JA and Laguía, A and Molero, F and Mikulincer, M}, title = {Security providing leadership and work stress in Spanish Air Force.}, journal = {Military psychology : the official journal of the Division of Military Psychology, American Psychological Association}, volume = {36}, number = {5}, pages = {504-515}, pmid = {37256575}, issn = {1532-7876}, mesh = {Humans ; *Leadership ; Male ; Female ; *Occupational Stress/prevention & control/psychology/epidemiology ; Adult ; Spain ; *Military Personnel/psychology ; *Organizational Culture ; Surveys and Questionnaires ; Middle Aged ; Young Adult ; }, abstract = {Leadership plays a key role in the well-being of military personnel, either contributing to health improvement or, conversely, becoming a source of stress. In the present study we propose that security providing leadership can reduce work stress in the military context. Furthermore, we suggest that security-providing leaders exert their positive influence on work stress by creating a psychological safety climate and preventing organizational dehumanization. A sample of 204 members (72.5% men) of the Spanish Air Force volunteered to participate in this empirical study and completed an online questionnaire and both the direct and indirect structural equation models were analyzed. Results show a negative relationship between security providing leadership and work stress. Additionally, organizational dehumanization and psychological safety climate act as mediators in this relationship. These results support this novel approach to leadership in the military context. They also offer new ways to create better organizational environments. By treating their subordinates in a personalized manner and supporting them, security-providing leaders can improve employees' perceptions of psychological safety climate and combat feelings of organizational dehumanization, which, in turn, can reduce work stress.}, } @article {pmid37253791, year = {2023}, author = {Sorin, V and Klang, E and Sklair-Levy, M and Cohen, I and Zippel, DB and Balint Lahat, N and Konen, E and Barash, Y}, title = {Large language model (ChatGPT) as a support tool for breast tumor board.}, journal = {NPJ breast cancer}, volume = {9}, number = {1}, pages = {44}, pmid = {37253791}, issn = {2374-4677}, abstract = {Large language models (LLM) such as ChatGPT have gained public and scientific attention. The aim of this study is to evaluate ChatGPT as a support tool for breast tumor board decisions making. We inserted into ChatGPT-3.5 clinical information of ten consecutive patients presented in a breast tumor board in our institution. We asked the chatbot to recommend management. The results generated by ChatGPT were compared to the final recommendations of the tumor board. They were also graded independently by two senior radiologists. Grading scores were between 1-5 (1 = completely disagree, 5 = completely agree), and in three different categories: summarization, recommendation, and explanation. The mean age was 49.4, 8/10 (80%) of patients had invasive ductal carcinoma, one patient (1/10, 10%) had a ductal carcinoma in-situ and one patient (1/10, 10%) had a phyllodes tumor with atypia. In seven out of ten cases (70%), ChatGPT's recommendations were similar to the tumor board's decisions. Mean scores while grading the chatbot's summarization, recommendation and explanation by the first reviewer were 3.7, 4.3, and 4.6 respectively. Mean values for the second reviewer were 4.3, 4.0, and 4.3, respectively. In this proof-of-concept study, we present initial results on the use of an LLM as a decision support tool in a breast tumor board. Given the significant advancements, it is warranted for clinicians to be familiar with the potential benefits and harms of the technology.}, } @article {pmid37251671, year = {2023}, author = {Kender, Z and von Rauchhaupt, E and Schwarz, D and Tsilingiris, D and Schimpfle, L and Bartl, H and Longo, VD and Bendszus, M and Kopf, S and Herzig, S and Heiland, S and Szendroedi, J and Sulaj, A}, title = {Six-month periodic fasting does not affect somatosensory nerve function in type 2 diabetes patients.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1143799}, pmid = {37251671}, issn = {1664-2392}, mesh = {Humans ; Action Potentials ; *Diabetes Mellitus, Type 2/complications/pathology ; *Diabetic Neuropathies/diagnosis ; Fasting ; Pain ; }, abstract = {BACKGROUND AND AIM: Current strategies for preventing diabetic sensorimotor polyneuropathy (DSPN) are limited mainly to glucose control but rapid decrease of glycemia can lead to acute onset or worsening of DSPN. The aim of this study was to examine the effects of periodic fasting on somatosensory nerve function in patients with type 2 diabetes (T2D).

STUDY DESIGN AND METHODS: Somatosensory nerve function was assessed in thirty-one patients with T2D (HbA1c 7.8 ± 1.3% [61.4 ± 14.3 mmol/mol]) before and after a six-month fasting-mimicking diet (FMD; n=14) or a control Mediterranean diet (M-diet; n=17). Neuropathy disability score (NDS), neuropathy symptoms score (NSS), nerve conduction velocity and quantitative sensory testing (QST) were analyzed. 6 participants of the M-Diet group and 7 of the FMD group underwent diffusion-weighted high-resolution magnetic resonance neurography (MRN) of the right leg before and after the diet intervention.

RESULTS: Clinical neuropathy scores did not differ between study groups at baseline (64% in the M-Diet group and 47% in the FMD group had DSPN) and no change was found after intervention. The differences in sensory NCV and sensory nerve action potential (SNAP) of sural nerve were comparable between study groups. Motor NCV of tibial nerve decreased by 12% in the M-Diet group (P=0.04), but did not change in the FMD group (P=0.39). Compound motor action potential (CMAP) of tibial nerve did not change in M-Diet group (P=0.8) and increased in the FMD group by 18% (P=0.02). Motor NCV and CMAP of peroneal nerve remained unchanged in both groups. In QST M-diet-group showed a decrease by 45% in heat pain threshold (P=0.02), FMD group showed no change (P=0.50). Changes in thermal detection, mechanical detection and mechanical pain did not differ between groups. MRN analysis showed stable fascicular nerve lesions irrespective of the degree of structural pathology. Fractional anisotropy and T2-time did not change in both study groups, while a correlation with the clinical degree of DSPN could be confirmed for both.

CONCLUSIONS: Our study shows that six-month periodic fasting was safe in preserving nerve function and had no detrimental effects on somatosensory nerve function in T2D patients.

CLINICAL TRIAL REGISTRATION: https://drks.de/search/en/trial/DRKS00014287, identifier DRKS00014287.}, } @article {pmid37248945, year = {2023}, author = {Ma, J}, title = {Application value of digital tungsten-molybdenum dual target three-dimensional positioning indwelling guide wire excision biopsy in diagnosis of breast microcalcification.}, journal = {Journal of X-ray science and technology}, volume = {31}, number = {4}, pages = {853-864}, doi = {10.3233/XST-230039}, pmid = {37248945}, issn = {1095-9114}, mesh = {Humans ; Female ; Molybdenum ; Tungsten ; Retrospective Studies ; Hyperplasia/pathology ; *Breast Diseases/diagnostic imaging/surgery/pathology ; *Breast Neoplasms/diagnostic imaging/surgery ; Breast/diagnostic imaging/surgery/pathology ; Biopsy/methods ; Mammography/methods ; *Calcinosis/diagnostic imaging/surgery/pathology ; }, abstract = {OBJECTIVE: To explore the application value of digital tungsten-molybdenum double target three-dimensional positioning indwelling guide wire and guided surgical resection biopsy in the diagnosis of breast microcalcification.

METHODS: A retrospective analysis of 168 patients with negative clinical palpation and molybdenum target X-ray examination found breast abnormalities were equally divided into two groups according to different surgical positioning methods. The control and observation group underwent gross positioning biopsy and digital tungsten-molybdenum dual-target three-dimensional positioning indwelling guide wire to guide surgical resection biopsy, respectively. The results of molybdenum target X-ray examination and the success rate of one-time complete resection of the lesions were compared between the two groups, and the corresponding relationship between the pathological diagnosis results of the lesions after surgical resection and the performance of mammography in the observation group was compared.

RESULTS: There was no significant difference in age and molybdenum target X-ray examination results between the two groups (P > 0.05). General information is comparable; the success rate of one-time complete resection of lesions in the observation group was significantly higher than that in the control group (95.2% vs 78.6%, P = 0.024). There were 34 cases of malignant lesions in the observation group, accounting for 40.5% (34/84), including 11 cases of invasive ductal carcinoma (64.7%), 50 cases of benign lesions, accounting for 59.5% (50/84), including 16 cases of breast lobular hyperplasia (32%), 18 cases of breast cystic hyperplasia (36%).

CONCLUSION: In diagnosis of breast microcalcifications, surgical resection biopsy guided using digital tungsten-molybdenum double target three-dimensional positioning indwelling guide wire achieves high success rate and has advantages of high safety and accurate diagnosis. Thus, it has potential to play a greater role in early diagnosis of breast cancer and is worthy of clinical application.}, } @article {pmid37246414, year = {2023}, author = {Lee, J and Park, S and Jung, HA and Lee, SH and Seo, S and Kim, SB and Kim, JW and Lee, KW and Kang, EJ and Kim, JW and Choi, YJ and Shim, BY and An, HJ and Park, LC and Shin, SH and Kim, JJ and Oh, SY and Kim, MK and Ahn, MJ}, title = {A phase 2 multicenter study of docetaxel-PM and trastuzumab-pkrb combination therapy in recurrent or metastatic salivary gland carcinomas.}, journal = {Cancer}, volume = {129}, number = {19}, pages = {2966-2974}, doi = {10.1002/cncr.34892}, pmid = {37246414}, issn = {1097-0142}, mesh = {Humans ; Female ; Docetaxel/therapeutic use ; Micelles ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Trastuzumab/therapeutic use ; Erb-b2 Receptor Tyrosine Kinases/genetics/metabolism ; *Carcinoma, Ductal ; Salivary Glands/metabolism ; *Breast Neoplasms/drug therapy ; }, abstract = {BACKGROUND: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2-targeted agents. Docetaxel-PM (polymeric micelle) is a low-molecular-weight, nontoxic, biodegradable, and docetaxel-loaded micellar formulation. Trastuzumab-pkrb is a biosimilar to trastuzumab.

METHODS: This was a multicenter, single-arm, open-label phase 2 study. Patients with HER2-positive (immunohistochemistry [IHC] score of ≥2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of ≥2.0) advanced SDCs were enrolled. Patients received docetaxel-PM (75 mg/m[2]) and trastuzumab-pkrb (8 mg/kg in the first cycle and 6 mg/kg in subsequent cycles) every 3 weeks. Primary end point was objective response rate (ORR).

RESULTS: A total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9-82.8) and a disease control rate of 93.0% (80.9-98.5). Median progression-free survival, duration of response, and overall survival were 7.9 (6.3-9.5), 6.7 (5.1-8.4), and 23.3 (19.9-26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio ≥2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty-eight (88.4%) patients experienced treatment-related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively.

CONCLUSIONS: The combination of docetaxel-PM and trastuzumab-pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2-positive advanced SDC.

PLAIN LANGUAGE SUMMARY: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC. In this study, patients with HER2-positive SDC were enrolled and treated with combination of docetaxel-polymeric micelle and trastuzumab-pkrb. Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression-free survival of 7.9 months, median duration of response of 6.7 months, and median overall survival of 23.3 months.}, } @article {pmid37235845, year = {2023}, author = {Dayes, IS and Metser, U and Hodgson, N and Parpia, S and Eisen, AF and George, R and Blanchette, P and Cil, TD and Arnaout, A and Chan, A and Levine, MN}, title = {Impact of [18]F-Labeled Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Versus Conventional Staging in Patients With Locally Advanced Breast Cancer.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {41}, number = {23}, pages = {3909-3916}, doi = {10.1200/JCO.23.00249}, pmid = {37235845}, issn = {1527-7755}, mesh = {Humans ; Female ; *Positron Emission Tomography Computed Tomography/methods ; *Breast Neoplasms/diagnostic imaging/therapy/pathology ; Radiopharmaceuticals ; Neoplasm Staging ; Fluorodeoxyglucose F18 ; Positron-Emission Tomography/methods ; }, abstract = {PURPOSE: Patients with locally advanced breast cancer (LABC) typically undergo staging tests at presentation. If staging does not detect metastases, treatment consists of curative intent combined modality therapy (neoadjuvant chemotherapy, surgery, and regional radiation). Positron emission tomography-computed tomography (PET-CT) may detect more asymptomatic distant metastases, but the evidence is based on uncontrolled studies.

METHODS: For inclusion, patients had histological evidence of invasive ductal carcinoma of the breast and TNM stage III or IIb (T3N0, but not T2N1). Consenting patients from six regional cancer centers in Ontario were randomly assigned to [18]F-labeled fluorodeoxyglucose PET-CT or conventional staging (bone scan, CT of the chest/abdomen and pelvis). The primary end point was upstaging to stage IV. A key secondary outcome was receiving curative intent combined modality therapy (ClinicalTrials.gov identifier: NCT02751710).

RESULTS: Between December 2016 and April 2022, 184 patients were randomly assigned to whole-body PET-CT and 185 patients to conventional staging. Forty-three (23%) PET-CT patients were upstaged to stage IV compared with 21 (11%) conventional staged patients (absolute difference, 12.3% [95% CI, 3.9 to 19.9]; P = .002). Consequently, treatment was changed in 35 (81.3%) of 43 upstaged PET-CT patients and 20 (95.2%) of the 21 upstaged conventional patients. Subsequently, 149 (81%) patients in the PET-CT group received combined modality treatment versus 165 (89.2%) patients in the conventional staging group (absolute difference, 8.2% [95% CI, 0.1 to 15.4]; P = .03).

CONCLUSION: In patients with LABC, PET-CT detected more distant metastases than conventional staging, and fewer PET-CT patients received combined modality therapy. Our randomized trial demonstrates the utility of the PET-CT staging strategy.}, } @article {pmid37233606, year = {2023}, author = {Belachew, EB and Desta, AF and Deneke, DB and Fenta, BD and Alem, AT and Abafogi, AK and Lukas, FY and Bezabih, M and Sewasew, DT and Kantelhardt, EJ and Tessema, TS and Howe, R}, title = {Clinicopathological Features of Invasive Breast Cancer: A Five-Year Retrospective Study in Southern and South-Western Ethiopia.}, journal = {Medicines (Basel, Switzerland)}, volume = {10}, number = {5}, pages = {}, pmid = {37233606}, issn = {2305-6320}, abstract = {Background: Breast cancer (BC) is the most common type of cancer in Ethiopia. The incidence of BC is also rising, but the exact figure is still poorly known. Therefore, this study was conducted to address the gap in epidemiological data on BC in southern and southwestern Ethiopia. Materials and Methods: This is a five-year (2015-2019) retrospective study. The demographic and clinicopathological data were collected from biopsy reports of different kinds of breast carcinomas in the pathology department of Jimma University Specialized Hospital and Hawassa University Specialized Referral Hospital. Histopathological grades and stages were conducted using Nottingham grading and TNM staging system, respectively. Collected data were entered and analyzed using SPSS Version-20 software. Results: The mean age of patients at diagnosis was 42.27 (SD = 13.57) years. The pathological stage of most BC patients was stage III, and most of them had tumor sizes greater than 5 cm. Most patients had moderately differentiated tumor grade, and mastectomy was the most common type of surgery at the time of diagnosis. Invasive ductal carcinoma was the most common histological type of BC, followed by invasive lobular carcinoma. Lymph node involvement was seen in 60.5% of cases. Lymph node involvement was associated with tumor size (χ[2] = 8.55, p = 0.033) and type of surgery (χ[2] = 39.69, p < 0.001). Conclusions: This study showed that BC patients in southern and southwestern Ethiopia displayed advanced pathological stages, relatively young age at diagnosis, and predominant invasive ductal carcinoma histological patterns.}, } @article {pmid37233002, year = {2023}, author = {Trivedi, J and Chourasia, A}, title = {Sodium Salt of Partially Carboxymethylated Sodium Alginate-g-Poly(acrylonitrile): I. Photo-Induced Synthesis, Characterization, and Alkaline Hydrolysis.}, journal = {Gels (Basel, Switzerland)}, volume = {9}, number = {5}, pages = {}, pmid = {37233002}, issn = {2310-2861}, support = {F-No.40-93/2011//University Grants Commission/ ; }, abstract = {An efficient redox initiating system, ceric ammonium nitrate/nitric acid, has been employed for the first time to carry out photo-induced graft copolymerization of acrylonitrile (AN) onto sodium salt of partially carboxymethylated sodium alginate, having an average degree of substitution value to be 1.10. The photo-grafting reaction conditions for maximum grafting have been systematically optimized by varying the reaction variables such as reaction time, temperature, the concentration of acrylonitrile monomer, ceric ammonium nitrate, and nitric acid, as well as the amount of the backbone. The optimum reaction conditions are obtained with a reaction time of 4 h, reaction temperature of 30 °C, acrylonitrile monomer concentration of 0.152 mol/L, initiator concentration of 5 × 10[-3] mol/L, nitric acid concentration of 0.20 mol/L, amount of backbone of 0.20 (dry basis) and the total volume of the reaction system of 150 mL. The highest percentage of grafting (%G) and grafting efficiency (%GE) achieved are 316.53% and 99.31%, respectively. The optimally prepared graft copolymer, sodium salt of partially carboxymethylated sodium alginate-g-polyacrylonitrile (%G = 316.53), has been hydrolyzed in an alkaline medium (0.7N NaOH, 90-95 °C for ~2.5 h) to obtain the superabsorbent hydrogel, H-Na-PCMSA-g-PAN. The chemical structure, thermal characteristics, and morphology of the products have also been studied.}, } @article {pmid37232999, year = {2023}, author = {Trivedi, J and Chourasia, A}, title = {Sodium Salt of Partially Carboxymethylated Sodium Alginate-Graft-Poly(Acrylonitrile): II Superabsorbency, Salt Sensitivity and Swelling Kinetics of Hydrogel, H-Na-PCMSA-g-PAN.}, journal = {Gels (Basel, Switzerland)}, volume = {9}, number = {5}, pages = {}, pmid = {37232999}, issn = {2310-2861}, support = {F.No. 40-93/2011//University Grants Commission/ ; }, abstract = {The water absorption measurements of a novel superabsorbent anionic hydrogel, H-Na-PCMSA-g-PAN, has been reported first time in water with a poor conductivity, 0.15 M saline (NaCl, CaCl2, and AlCl3) solutions, and simulated urine (SU) solutions at various times. The hydrogel has been prepared by the saponification of the graft copolymer, Na-PCMSA-g-PAN (%G = 316.53, %GE = 99.31). Results indicated that as compared to the swelling capacity values evaluated in water with a poor conductivity, the ability of the hydrogel to swell in various saline solutions with the same concentration is significantly reduced at all different durations. The swelling tends to be Na[+] > Ca[2+] > Al[3+] at the same saline concentration in the solution. Studies of the absorbency in various aqueous saline (NaCl) solutions also revealed that the swelling capacity decreased as the ionic strength of the swelling medium rose, which is consistent with the experimental results and Flory's equation. Furthermore, the experimental results strongly suggested that second-order kinetics governs the swelling process of the hydrogel in various swelling media. The swelling characteristics and equilibrium water contents for the hydrogel in various swelling media have also been researched. The hydrogel samples have been successfully characterized by FTIR to show the change in chemical environment to COO[-] and CONH2 groups after swelling in different swelling media. The samples have also been characterized by SEM technique.}, } @article {pmid37228888, year = {2023}, author = {Ayandipo, OO and Ogun, GO and Adepoju, OJ and Afuwape, OO and Fatunla, EO and Orunmuyi, AT}, title = {Immunohistochemical Profiling of HER-2/neu, Steroid Hormone Receptors and KI-67 Biomarkers in A Cohort of Nigerian Women with Breast Cancer.}, journal = {Journal of the West African College of Surgeons}, volume = {13}, number = {2}, pages = {7-15}, pmid = {37228888}, issn = {2276-6944}, abstract = {BACKGROUND: Progressive improvement in the accuracy of profiling of hormone receptors in breast cancer provides the basis for targeted endocrine therapy, a major pillar of multimodal breast cancer treatment. However, the disparity in findings from comparatively smaller sample-sized studies in West Africa has led to somewhat conflicting conclusions and recommendations.

OBJECTIVES: This study investigates the immunohistochemical (IHC) profile of breast cancer specimens for estrogen receptor (ER), progesterone receptor (PR), human epidermal receptor-2 (HER2)/neu, and Ki-67 in a tertiary hospital in Ibadan, Nigeria over 12 years.

MATERIALS AND METHODS: We reviewed 998 IHC reports, documented clinicopathologic parameters, computed patterns of biomarkers, and stratified them based on the American Society of Clinical Oncology/College of American Pathologists recommendations. Descriptive analysis including frequency, mean, and median were generated from the data extracted.

RESULTS: Out of the 998 cases, 975 (97.7%) were females and 23 (2.3%) were males. The mean age was 48.84 ± 11.99 years. Open biopsies were the most common types of specimens (320, 41.6%): lumpectomy and incisional biopsy of ulcerated, fungating or unresectable tumours. In those cases, 246 (32.0%) were samples of breast-conserving or ablative surgical extirpation (mastectomy/wide local excision/quadrantectomy), and 203 (26.4%) were obtained by core needle biopsies. Invasive ductal carcinoma was the most common histopathological type (673, 94.5%). The majority of graded tumours were intermediate grade (444, 53.5%). Four hundred and sixty-nine (48.4%) were ER positive, 414 (42.8%) were PR positive, and 180 (19.4%) were HER2/neu positive. Three hundred and thirty-four (34.0%) were triple-negative. Eighty-nine cases had Ki-67 staining done, and of these 61 (68.5%) had positive nuclear staining.

CONCLUSION: Steroid hormone receptors and HER-2/neu proportions in our cohort are likely to be more representative than the widely varied figures hitherto reported in the sub-region. We advocate routine IHC analysis of breast cancer samples as a guide to personalized endocrine therapy.}, } @article {pmid37226494, year = {2024}, author = {Yoshida, H and Hiranuma, K and Nakahara, M and Kobayashi-Kato, M and Tanase, Y and Uno, M and Shiraishi, K and Ishikawa, M and Kato, T}, title = {Ovarian Mucinous Tumor Presenting Atypical Lobular Endocervical Glandular Hyperplasia-Like Appearance in a Patient With Germline STK11 p.F354L Variant: A Case Report.}, journal = {International journal of surgical pathology}, volume = {32}, number = {2}, pages = {394-400}, doi = {10.1177/10668969231177256}, pmid = {37226494}, issn = {1940-2465}, mesh = {Humans ; Female ; Middle Aged ; Young Adult ; Adult ; Hyperplasia ; *Ovarian Neoplasms/diagnosis ; *Adenocarcinoma ; Biopsy, Needle ; Germ Cells ; AMP-Activated Protein Kinase Kinases ; }, abstract = {Peutz-Jeghers syndrome (PJS) is associated with female genital lesions, such as cervical gastric-type adenocarcinoma and lobular endocervical glandular hyperplasia (LEGH). However, ovarian mucinous borderline tumors (OMBT) with atypical LEGH-like histology have not been described. The patient was a 60-year-old female with PJS clinically diagnosed at 23 years old with gastrointestinal polyposis. Abdominal distension was noted, and computed tomography scan revealed bilateral breast masses, multiple lung nodules, and a multicystic ovarian tumor. A needle biopsy revealed invasive ductal carcinoma of the breast. For the ovarian tumor, simple hysterectomy and bilateral salpingo-oophorectomy were performed. The left ovarian tumor was 25 × 20 × 12 cm in size and a multicystic tumor containing yellowish mucus without a solid part. Histologically, the cyst wall was covered with mucus cells with focal mild-to-moderate cellular atypia, forming LEGH-like architectures. The glandular cells were immunohistochemically positive for MUC5AC, MUC6 (focal), HIK1083 (focal), and HNF4α. Stromal invasion was not observed. Cervical lesions were not observed. The final pathological diagnosis was OMBT showing atypical LEGH morphology. Targeted sequencing of nontumor tissues revealed the germline STK11 p.F354L variant. Six months later, peritoneal dissemination of adenocarcinoma showing features similar to those of the ovarian tumor was observed, and the patient died of the disease. In summary, we report a case of OMBT with an atypical LEGH-like appearance in a patient with germline STK11 p.F354L variant. This case provides us with unresolved questions regarding the pathogenicity of this STK11 variant and the malignant potential of OMBT with this unusual morphology.}, } @article {pmid37222952, year = {2023}, author = {Abdollahi, E and Mozdarani, H and Alizadeh, BZ}, title = {Role of circ-FOXO3 and miR-23a in radiosensitivity of breast cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {30}, number = {5}, pages = {714-726}, pmid = {37222952}, issn = {1880-4233}, support = {Grant Number: IG-39711//Tarbiat Modares University/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/radiotherapy ; Leukocytes, Mononuclear ; Apoptosis/genetics ; *Carcinoma ; *Drug-Related Side Effects and Adverse Reactions ; *MicroRNAs/genetics ; Cell Proliferation ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Forkhead Box Protein O3/genetics ; }, abstract = {Identifying the radiosensitivity of cells before radiotherapy (RT) in breast cancer (BC) patients allows appropriate switching between routinely used treatment regimens and reduces adverse side effects in exposed patients. In this study, blood was collected from 60 women diagnosed with Invasive Ductal Carcinoma (IDC) BC and 20 healthy women. To predict cellular radiosensitivity, a standard G2-chromosomal assay was performed. From these 60 samples, 20 BC patients were found to be radiosensitive based on the G2 assay. Therefore, molecular studies were finally performed on two equal groups (20 samples each) of patients with and without cellular radiosensitivity. QPCR was performed to examine the expression levels of circ-FOXO3 and miR-23a in peripheral blood mononuclear cells (PBMCs) and RNA sensitivity and specificity were determined by plotting Receiver Operating Characteristic (ROC) curves. Binary logistic regression was performed to identify RNA involvement in BC and cellular radiosensitivity (CR) in BC patients. Meanwhile, qPCR was used to compare differential RNA expression in the radiosensitive MCF-7 and radioresistant MDA-MB-231 cell lines. An annexin -V FITC/PI binding assay was used to measure cell apoptosis 24 and 48 h after 2 Gy, 4 Gy, and 8 Gy gamma-irradiation. Results indicated that circ-FOXO3 was downregulated and miR-23a was upregulated in BC patients. RNA expression levels were directly associated with CR. Cell line results showed that circ-FOXO3 overexpression induced apoptosis in the MCF-7 cell line and miR-23a overexpression inhibited apoptosis in the MDA-MB-231 cell line. Evaluation of the ROC curves revealed that both RNAs had acceptable specificity and sensitivity in predicting CR in BC patients. Binary logistic regression showed that both RNAs were also successful in predicting breast cancer. Although only circ-FOXO3 has been shown to predict CR in BC patients, circ-FOXO3 may function as a tumor suppressor and miR-23a may function as oncomiR in BC. Circ-FOXO3 and miR-23a may be promising potential biomarkers for BC prediction. Furthermore, Circ-FOXO3 could be a potential biomarker for predicting CR in BC patients.}, } @article {pmid37217416, year = {2023}, author = {Rummel, KA and Gao, RW and Francis, LN and Petersen, IA and Mutter, RW and Corbin, KS}, title = {Secondary breast angiosarcoma following accelerated partial breast irradiation with intracavitary multicatheter applicator brachytherapy.}, journal = {Brachytherapy}, volume = {22}, number = {4}, pages = {487-490}, doi = {10.1016/j.brachy.2023.04.007}, pmid = {37217416}, issn = {1873-1449}, mesh = {Female ; Humans ; Aged ; *Hemangiosarcoma/etiology ; *Brachytherapy/methods ; *Breast Neoplasms/surgery ; Breast/pathology ; Mastectomy, Segmental ; }, abstract = {PURPOSE: Secondary angiosarcoma of the breast is a rare complication of breast radiotherapy and is associated with a poor prognosis. There are many reported cases of secondary angiosarcoma following whole breast irradiation (WBI), however development of secondary angiosarcoma following brachytherapy-based accelerated partial breast irradiation (APBI) is not as well characterized.

METHODS AND MATERIALS: We reviewed and reported a case of a patient who developed secondary angiosarcoma of the breast following intracavitary multicatheter applicator brachytherapy APBI.

RESULTS: A 69-year-old female was originally diagnosed with T1N0M0 invasive ductal carcinoma of the left breast and treated with lumpectomy followed by adjuvant intracavitary multicatheter applicator brachytherapy APBI. Seven years following her treatment, she developed secondary angiosarcoma. However, the diagnosis of secondary angiosarcoma was delayed due to nonspecific imaging findings and a negative biopsy.

CONCLUSIONS: Our case highlights the need for secondary angiosarcoma to be considered in the differential diagnosis when patients present with symptoms such as breast ecchymosis and skin thickening following WBI or APBI. Prompt diagnosis and referral to a high-volume sarcoma treatment center for multidisciplinary evaluation is vital.}, } @article {pmid37211759, year = {2023}, author = {Moradpour, M and Azizinik, F and Zeidabadi, H and Ghomi, Z and Shakki Katouli, F and Tavakol, E and Torabi Parizi, S}, title = {The imaging findings and diagnostic value of radiology modalities to assess breast malignancy among women aged younger than 30 years.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {64}, number = {8}, pages = {2363-2370}, doi = {10.1177/02841851231176271}, pmid = {37211759}, issn = {1600-0455}, mesh = {Female ; Humans ; Ultrasonography, Mammary/methods ; Sensitivity and Specificity ; *Breast Neoplasms/pathology ; Mammography/methods ; Magnetic Resonance Imaging/methods ; *Radiology ; }, abstract = {BACKGROUND: Breast cancer mainly affects women aged >50 years; however, younger women may also have advanced breast cancer, so early detection is important.

PURPOSE: To collect and review the imaging findings of women aged <30 years with breast cancer to find better diagnostic approaches for the early diagnosis of breast cancer in young women.

MATERIAL AND METHODS: In this study, 45 patients aged <30 years with a diagnosis of breast cancer were evaluated. Imaging assessments were performed based on ultrasound, mammography, and magnetic resonance imaging (MRI) findings. Finally, the findings were compared with the pathological results.

RESULTS: Predominant findings in ultrasound included irregular spiculated mass in 59.4%. In mammography, irregular high-density mass (46.5%) and suspicious micro calcification (42.8%) were the most common findings. In MRI, the predominant feature was a heterogeneous enhancing mass with an irregular shape and irregular margin (81%) with a 45% plateau and 36% washout kinetic pattern. In the pathology assessment, invasive ductal carcinoma was the most common finding (84.4%). All three modalities-MRI, ultrasonography, and mammography-are valuable, with sensitivities of 100%, 93.3%, and 90%, respectively.

CONCLUSION: Ultrasound, mammography, and MRI are highly sensitive and accurate tools for detecting breast cancer lesions in young women. Regular clinical breast examination with breast self-examination, and in suspected cases, ultrasound as the first imaging modality followed by mammography and/or MRI are the preferred diagnostic approach.}, } @article {pmid37210429, year = {2023}, author = {Joshi, U and Budhathoki, P and Gaire, S and Yadav, SK and Shah, A and Adhikari, A and Choong, G and Couzi, R and Giridhar, KV and Leon-Ferre, RA and Boughey, JC and Hieken, TJ and Mutter, R and Ruddy, KJ and Haddad, TC and Goetz, MP and Couch, FJ and Yadav, S}, title = {Clinical outcomes and prognostic factors in triple-negative invasive lobular carcinoma of the breast.}, journal = {Breast cancer research and treatment}, volume = {200}, number = {2}, pages = {217-224}, pmid = {37210429}, issn = {1573-7217}, support = {K12 CA090628/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; }, mesh = {Female ; Humans ; Aged ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/pathology ; Prognosis ; *Carcinoma, Ductal, Breast/pathology ; Mastectomy ; }, abstract = {PURPOSE: Triple-negative invasive lobular carcinoma (TN-ILC) of breast cancer is a rare disease and the clinical outcomes and prognostic factors are not well-defined.

METHODS: Women with stage I-III TN-ILC or triple-negative invasive ductal carcinoma (TN-IDC) of the breast undergoing mastectomy or breast-conserving surgery between 2010 and 2018 in the National Cancer Database were included. Kaplan-Meier curves and multivariate Cox proportional hazard regression were used to compare overall survival (OS) and evaluate prognostic factors. Multivariate logistic regression was performed to analyze the factors associated with pathological response to neoadjuvant chemotherapy.

RESULTS: The median age at diagnosis for women with TN-ILC was 67 years compared to 58 years in TN-IDC (p < 0.001). There was no significant difference in the OS between TN-ILC and TN-IDC in multivariate analysis (HR 0.96, p = 0.44). Black race and higher TNM stage were associated with worse OS, whereas receipt of chemotherapy or radiation was associated with better OS in TN-ILC. Among women with TN-ILC receiving neoadjuvant chemotherapy, the 5-year OS was 77.3% in women with a complete pathological response (pCR) compared to 39.8% in women without any response. The odds of achieving pCR following neoadjuvant chemotherapy were significantly lower in women with TN-ILC compared to TN-IDC (OR 0.53, p < 0.001).

CONCLUSION: Women with TN-ILC are older at diagnosis but have similar OS compared to TN-IDC after adjusting for tumor and demographic characteristics. Administration of chemotherapy was associated with improved OS in TN-ILC, but women with TN-ILC were less likely to achieve complete response to neoadjuvant therapy compared to TN-IDC.}, } @article {pmid37204630, year = {2023}, author = {Ito, Y and Fujii, K and Saito, M and Banno, H and Ido, M and Goto, M and Ando, T and Mouri, Y and Kousaka, J and Imai, T and Nakano, S}, title = {Invasive lobular carcinoma of the breast detected with real-time virtual sonography: a case report.}, journal = {Surgical case reports}, volume = {9}, number = {1}, pages = {85}, pmid = {37204630}, issn = {2198-7793}, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) sometimes presents with unique clinical, pathologic, and radiographic features. In this case report, we describe a patient with ILC, whose initial presentation consisted with symptoms secondary to bone-marrow dissemination. In addition, the breast primary was revealed only by magnetic resonance imaging (MRI) followed by real-time virtual sonography (RVS).

CASE PRESENTATION: A 51-year-old woman presented to our outpatient clinic with dyspnea on exertion. She had severe anemia (hemoglobin, 5.3 g/dL) and thrombocytopenia (platelet count, 31 × 10[3]/mL). Bone-marrow biopsy was performed to evaluate hematopoietic function. The pathologic diagnosis was bone-marrow carcinomatosis due to metastatic breast cancer. Initial mammography followed by ultrasonography (US) failed to detect the primary tumor. On MRI, a non-mass-enhancement lesion was observed. While second-look US also did not detect the lesion, it was clearly visualized with RVS. We were finally able to biopsy the breast lesion. The pathologic diagnosis was ILC positive for both estrogen receptor and progesterone receptor, with 1 + immunohistochemical staining for human epidermal growth factor receptor 2. This case of ILC was characterized by bone-marrow metastasis. Due to decreased cell adhesion, the risk of bone-marrow metastasis is higher in ILC than in invasive ductal carcinoma, the most prevalent type of breast cancer. Biopsy of the primary lesion, which was initially only detected with MRI, was successfully performed with clear visualization during RVS, which is based on the fusion of MRI and US images.

CONCLUSION: In this case report and literature review, we describe the unique clinical characteristics of ILC and a strategy for identifying primary lesions that are initially only visualized with MRI.}, } @article {pmid37202608, year = {2023}, author = {Shawky, A and Sabit, H and Nazih, M and Baraka, K and El-Zawahry, M}, title = {CYP2C19 Polymorphism in Ischemic Heart Disease Patients Taking Clopidogrel After Percutaneous Coronary Intervention in Egypt.}, journal = {Journal of epidemiology and global health}, volume = {13}, number = {2}, pages = {374-383}, pmid = {37202608}, issn = {2210-6014}, mesh = {Humans ; *Cardiovascular Diseases ; Clopidogrel/adverse effects/metabolism/therapeutic use ; Cytochrome P-450 CYP2C19/genetics/metabolism ; Egypt/epidemiology ; *Myocardial Ischemia/genetics/therapy/chemically induced ; *Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/adverse effects/metabolism/therapeutic use ; Treatment Outcome ; }, abstract = {BACKGROUND: Cardiovascular diseases (CVDs) are considered a leading cause of death worldwide. Allelic variation in the CYP2C19 gene leads to a dysfunctional enzyme, and patients with this loss-of-function allele will have an impaired clopidogrel metabolism, which eventually results in major adverse cardiovascular events (MACE). Ischemic heart disease patients (n = 102) who underwent percutaneous cardiac intervention (PCI) followed by clopidogrel were enrolled in the present study.

METHODS: The genetic variations in the CYP2C19 gene were identified using the TaqMan chemistry-based qPCR technique. Patients were followed up for 1 year to monitor MACE, and the correlations between the allelic variations in CYP2C19 and MACE were recorded.

RESULTS: During the follow-up, we reported 64 patients without MACE (29 with unstable angina (UA), 8 with myocadiac infarction (MI), 1 patient with non-STEMI, and 1 patient with ischemic dilated cardiomyopathy (IDC)). Genotyping of CYP2C19 in the patients who underwent PCI and were treated with clopidogrel revealed that 50 patients (49%) were normal metabolizers for clopidogrel with genotype CYP2C19*1/*1 and 52 patients (51%) were abnormal metabolizers, with genotypes CYP2C19*1/*2 (n = 15), CYP2C19*1/*3 (n = 1), CYP2C19*1/*17 (n = 35), and CYP2C19*2/*17 (n = 1). Demographic data indicated that age and residency were significantly associated with abnormal clopidogrel metabolism. Moreover, diabetes, hypertension, and cigarette smoking were significantly associated with the abnormal metabolism of clopidogrel. These data shed light on the inter-ethnic variation in metabolizing clopidogrel based on the CYP2C19 allelic distribution.

CONCLUSION: This study, along with other studies that address genotype variation of clopidogrel-metabolizing enzymes, might pave the way for further understanding of the pharmacogenetic background of CVD-related drugs.}, } @article {pmid37201361, year = {2023}, author = {Mekni, K and Mejri, O and Ayadi, A and ElFekif, C}, title = {Unexpected association between breast cancer and molar pregnancy in a 52-year-old woman: A case report.}, journal = {International journal of surgery case reports}, volume = {107}, number = {}, pages = {108253}, pmid = {37201361}, issn = {2210-2612}, abstract = {INTRODUCTION: There was no prior discussion about the association between breast cancer and molar pregnancy, particularly at an advanced age. Through our case and a systematic review, we will discuss the relevance of ovarian castration in hormone-receptor-positive breast cancer.

CASE PRESENTATION: We reported the case of a 52-year-old woman, not yet menopausal, who was diagnosed with a right breast tumor classified as BI-RADS category 4. The anatomopathological analysis of mammary biopsy revealed an invasive ductal carcinoma of no special type (grade 2). Hormone receptors were positive. It was a HER2-negative Breast cancer. It was then decided to treat the patient with radical surgery followed by chemotherapy, radiotherapy, and hormonotherapy. The patient had a "Patey operation". The postoperative course was without significant complications. No medical or surgical castration was indicated in the expectation that chemotherapy would cause ovarian failure. Unlikely, during chemotherapy course our patient developed a molar pregnancy.

CLINICAL DISCUSSION: Our case illustrates the possibility of pregnancy in non-menopausal women with estrogen-receptor-positive breast cancer. The combination of tamoxifen or aromatase inhibitors with ovarian suppression as standard adjuvant therapy may be recommended in such cases.

CONCLUSIONS: Ovarian function suppression in non-menopausal women with hormone receptor-positive breast cancer seems to be necessary. So that, we can avoid unexpected manifestations like molar pregnancy.}, } @article {pmid37201100, year = {2023}, author = {Koçberber, Z and Willemsen, N and Bartelt, A}, title = {The role of proteasome activators PA28αβ and PA200 in brown adipocyte differentiation and function.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1176733}, pmid = {37201100}, issn = {1664-2392}, mesh = {Animals ; Mice ; *Adipocytes, Brown/metabolism ; *Proteasome Endopeptidase Complex/metabolism ; Adipose Tissue, Brown/metabolism ; Adipogenesis/genetics ; Temperature ; Nuclear Proteins/metabolism ; }, abstract = {INTRODUCTION: Brown adipocytes produce heat through non shivering thermogenesis (NST). To adapt to temperature cues, they possess a remarkably dynamic metabolism and undergo substantial cellular remodeling. The proteasome plays a central role in proteostasis and adaptive proteasome activity is required for sustained NST. Proteasome activators (PAs) are a class of proteasome regulators but the role of PAs in brown adipocytes is unknown. Here, we studied the roles of PA28α (encoded by Psme1) and PA200 (encoded by Psme4) in brown adipocyte differentiation and function.

METHODS: We measured gene expression in mouse brown adipose tissue. In cultured brown adipocytes, we silenced Psme1 and/or Psme4 expression through siRNA transfection. We then assessed impact on the ubiquitin proteasome system, brown adipocyte differentiation and function.

RESULTS: We found that Psme1 and Psme4 are expressed in brown adipocytes in vivo and in vitro. Through silencing of Psme1 and/or Psme4 expression in cultured brown adipocytes, we found that loss of PAs did not impair proteasome assembly or activity, and that PAs were not required for proteostasis in this model. Loss of Psme1 and/or Psme4 did not impair brown adipocyte development or activation, suggesting that PAs are neither required for brown adipogenesis nor NST.

DISCUSSION: In summary, we found no role for Psme1 and Psme4 in brown adipocyte proteostasis, differentiation, or function. These findings contribute to our basic understanding of proteasome biology and the roles of proteasome activators in brown adipocytes.}, } @article {pmid37200388, year = {2023}, author = {Amer, NN and Khairat, R and Hammad, AM and Kamel, MM}, title = {DDX43 mRNA expression and protein levels in relation to clinicopathological profile of breast cancer.}, journal = {PloS one}, volume = {18}, number = {5}, pages = {e0284455}, pmid = {37200388}, issn = {1932-6203}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology ; Neoplasm Proteins/genetics ; RNA, Messenger/genetics ; Prognosis ; Disease Progression ; Biomarkers, Tumor/genetics/analysis ; DEAD-box RNA Helicases/genetics/metabolism ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most often diagnosed cancer in women globally. Cancer cells appear to rely heavily on RNA helicases. DDX43 is one of DEAD- box RNA helicase family members. But, the relationship between clinicopathological, prognostic significance in different BC subtypes and DDX43 expression remains unclear. Therefore, the purpose of this study was to assess the clinicopathological significance of DDX43 protein and mRNA expression in different BC subtypes.

MATERIALS AND METHODS: A total of 80 females newly diagnosed with BC and 20 control females that were age-matched were recruited for this study. DDX43 protein levels were measured by ELISA technique. We used a real-time polymerase chain reaction quantification (real-time PCR) to measure the levels of DDX43 mRNA expression. Levels of DDX43 protein and mRNA expression within BC patients had been compared to those of control subjects and correlated with clinicopathological data.

RESULTS: The mean normalized serum levels of DDX43 protein were slightly higher in control than in both benign and malignant groups, but this result was non-significant. The mean normalized level of DDX43 mRNA expression was higher in the control than in both benign and malignant cases, although the results were not statistically significant and marginally significant, respectively. Moreover, the mean normalized level of DDX43 mRNA expression was significantly higher in benign than in malignant cases. In malignant cases, low DDX43 protein expression was linked to higher nuclear grade and invasive duct carcinoma (IDC), whereas high mRNA expression was linked to the aggressive types of breast cancer such as TNBC, higher tumor and nuclear grades.

CONCLUSION: This study explored the potential of using blood DDX43 mRNA expression or protein levels, or both in clinical settings as a marker of disease progression in human breast cancer. DDX43 mRNA expression proposes a less invasive method for discriminating benign from malignant BC.}, } @article {pmid37198611, year = {2023}, author = {Abdulraheem, AM and Naji, D and Al Heyasat, AN and Alhasan, M and Almasri, NM and Odeh, R}, title = {Breast cancer with scalp metastases: a case report.}, journal = {Journal of medical case reports}, volume = {17}, number = {1}, pages = {203}, pmid = {37198611}, issn = {1752-1947}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/pathology ; Scalp/pathology ; Mastectomy ; *Skin Neoplasms/pathology ; *Carcinoma, Ductal, Breast/therapy ; Cutaneous Malignant Melanoma ; }, abstract = {BACKGROUND: While breast cancer is the most common cancer in women, cutaneous metastases are rare in breast cancer. Additionally, scalp involvement in breast cancer metastasis is extremely rare. That being said, scalp lesions should always be thoroughly investigated to distinguish metastatic lesions from other neoplasms.

CASE PRESENTATION: A 47-year-old female Middle-Eastern patient presented with metastatic breast cancer in the lungs, bone, liver, and brain with no signs of multiple organ failure, in addition to cutaneous metastases, including the scalp. Between 2017 and 2022, she was managed through modified radical mastectomy, radiotherapy, and several lines of chemotherapy. She presented in September of 2022 with enlarging scalp nodules, which started developing 2 months prior to her presentation. Physical examination revealed firm, non-tender, and immobile skin lesions. Magnetic resonance imaging scan of the head showed soft tissue nodules in different sequences. A punch biopsy was taken from the largest scalp lesion and showed metastatic invasive ductal carcinoma. A panel of immunohistochemistry stains was applied, because a single specific marker for differentiating primary cutaneous adnexal tumors or other malignant neoplasms from breast cancer has not yet been identified. The panel showed positive estrogen receptor 95%, progesterone receptor 5%, negative human epidermal growth factor receptor 2, positive GATA binding protein 3, positive cytokeratin-7, negative P63, and negative KIT (CD117).

CONCLUSION: Breast cancer metastases to the scalp are extremely uncommon. When a scalp metastasis is present, it might be the only symptomatic sign of disease progression or widespread metastatic lesions. However, such lesions warrant a comprehensive radiologic and pathologic workup to rule out other possibilities of skin pathologies, such as sebaceous skin adenocarcinoma as it effects the management plan.}, } @article {pmid37195240, year = {2023}, author = {Murata, S and Yamashita, H and Kido, S and Harada, D and Ohtsuru, S and Sato, N}, title = {DYNAMIC METABOLIC CHANGES OBSERVED IN AN LPS-INDUCED SYSTEMIC INFLAMMATION RAT MODEL USING CONTINUOUS LONG-TERM INDIRECT CALORIMETRY EXPERIMENTS.}, journal = {Shock (Augusta, Ga.)}, volume = {60}, number = {1}, pages = {130-136}, pmid = {37195240}, issn = {1540-0514}, mesh = {Humans ; *Lipopolysaccharides/toxicity ; Calorimetry, Indirect/methods ; *Critical Illness ; Energy Metabolism/physiology ; Critical Care ; }, abstract = {Background : Nutritional management is crucial for severely ill patients. Measuring metabolism is believed to be necessary for the acute sepsis phase to accurately estimate nutrition. Indirect calorimetry (IDC) is assumed to be useful for acute intensive care; however, there are few studies on long-term IDC measurement in patients with systemic inflammation. Methods : Rats were categorized into the LPS received or control groups; LPS rats were categorized into underfeeding (UF), adjusted feeding (AF), and overfeeding (OF) groups. Indirect calorimetry measurement was performed until 72 or 144 h. Body composition was measured at -24 and 72 or 144 h, and tissue weight was measured at 72 or 144 h. Results : Low energy consumption and loss of diurnal variation of resting energy expenditure were observed in the LPS group compared with the control group until 72 h, after which the LPS group recovered. The resting energy expenditure in the OF group was higher than that in the UF and AF groups. In the first phase, low energy consumption was observed in all groups. In the second and third phases, higher energy consumption occurred in the OF group than in the UF and AF groups. In the third phase, diurnal variation recovered in all groups. Muscle atrophy caused body weight loss, but fat tissue loss did not occur. Conclusions : We observed metabolic changes with IDC during the acute systemic inflammation phase owing to differences in calorie intake. This is the first report of long-term IDC measurement using the LPS-induced systemic inflammation rat model.}, } @article {pmid37190710, year = {2023}, author = {Shahid, A and Mushtaq, S and Maqbool, H and Hassan, U and Hussain, M and Syed, M}, title = {Grading Intraductal Carcinoma of the Prostate; ISUP versus GUPS Recommendations.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {33}, number = {4}, pages = {396-399}, doi = {10.29271/jcpsp.2023.04.396}, pmid = {37190710}, issn = {1681-7168}, mesh = {Male ; Humans ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Prostate/pathology ; *Prostatic Neoplasms/pathology ; *Adenocarcinoma/pathology ; Biopsy ; Neoplasm Grading ; Prostatectomy ; }, abstract = {OBJECTIVE: To evaluate the frequency of intraductal component (IDC-P) in prostatic adenocarcinoma and its effect on the final grade using the ISUP and GUPS grading system.

STUDY DESIGN:  Descriptive study. Place and Duration of the Study: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, between June 2021 and June 2022.

METHODOLOGY: The study included 250 cases of prostatic adenocarcinoma. The presence of the intraductal carcinoma prostate (IDC-P) was confirmed by patchy or complete staining of the basal cell layer by p63 immunohistochemical stain. Cases with IDC-P were then graded using two different methods, first using the grading criteria based on the ISUP recommendations and then by the grading criteria based on the GUPS recommendations.

RESULTS: Two hundred and fifty cases showed invasive prostatic carcinoma ranging from Gleason grade group 2-5. IDC-P was identified in 5 of the 250 biopsies (2%). The final Gleason grade remained unchanged in these cases, when they were graded using the ISUP and GUPS recommendations.

CONCLUSION:  Although the present results are based on a relatively small sample size, IDC-P was not frequently present in biopsies of patients with adenocarcinoma in the studied population. Grading IDC-P in invasive prostate cancer led to only a minor change in grade group assignment of prostate cancer biopsies.

KEY WORDS:  Prostatic adenocarcinoma, Intraductal carcinoma, IDC-P, ISUP, GUPS, Gleason Grade group.}, } @article {pmid37190690, year = {2023}, author = {Zehra, T and Shams, M and Ahmad, Z and Chundriger, Q and Ahmed, A and Jaffar, N}, title = {Ki-67 Quantification in Breast Cancer by Digital Imaging AI Software and its Concordance with Manual Method.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {33}, number = {5}, pages = {544-547}, doi = {10.29271/jcpsp.2023.05.544}, pmid = {37190690}, issn = {1681-7168}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology ; Ki-67 Antigen ; Retrospective Studies ; Artificial Intelligence ; Reproducibility of Results ; Software ; }, abstract = {OBJECTIVE: To validate the concordance of automated detection of Ki67 in digital images of breast cancer with the manual eyeball / hotspot method.

STUDY DESIGN: Descriptive study. Place and Duration of the Study: Jinnah Sindh Medical University, Karachi, from 1st January to 15th February 2022.

METHODOLOGY: Glass slides of cases diagnosed as invasive ductal carcinoma (IDC) were obtained from the Agha Khan Medical University Hospital, selected retrospectively and randomly from 60 patients. They were stained with the Ki67 antibody. An expert pathologist evaluated the Ki67 index in the hotspot fields using eyeball method. Digital images were taken from the hotspots using a camera attached to the microscope. The images were uploaded in the Mindpeak software to detect the exact percentage of Ki67-positive cells. The results obtained through automated detection were compared with the results reported by expert pathologists to see the differential outcome.

RESULTS: The manual and automated scoring methods showed strong positive concordance (p <0.001).

CONCLUSION: Automated scoring of Ki-67 staining has tremendous potential as the issues of lack of consistency, reproducibility, and accuracy can be eliminated. In the era of personalised medicine, pathologists can efficiently give a precise clinical diagnosis with the support of AI.

KEY WORDS: Artificial intelligence, Algorithms, Breast cancer, Deep learning, Image detection, Ki-67.}, } @article {pmid37190184, year = {2023}, author = {Bernhardt, SM and Mitchell, E and Stamnes, S and Hoffmann, RJ and Calhoun, A and Klug, A and Russell, TD and Pennock, ND and Walker, JM and Schedin, P}, title = {Isogenic Mammary Models of Intraductal Carcinoma Reveal Progression to Invasiveness in the Absence of a Non-Obligatory In Situ Stage.}, journal = {Cancers}, volume = {15}, number = {8}, pages = {}, pmid = {37190184}, issn = {2072-6694}, support = {P30 CA069533/CA/NCI NIH HHS/United States ; R01 CA169175/CA/NCI NIH HHS/United States ; PDF17480342/KOMEN/Susan G. Komen/United States ; R01CA169175/CA/NCI NIH HHS/United States ; }, abstract = {In breast cancer, progression to invasive ductal carcinoma (IDC) involves interactions between immune, myoepithelial, and tumor cells. Development of IDC can proceed through ductal carcinoma in situ (DCIS), a non-obligate, non-invasive stage, or IDC can develop without evidence of DCIS and these cases associate with poorer prognosis. Tractable, immune-competent mouse models are needed to help delineate distinct mechanisms of local tumor cell invasion and prognostic implications. To address these gaps, we delivered murine mammary carcinoma cell lines directly into the main mammary lactiferous duct of immune-competent mice. Using two strains of immune-competent mice (BALB/c, C57BL/6), one immune-compromised (severe combined immunodeficiency; SCID) C57BL/6 strain, and six different murine mammary cancer cell lines (D2.OR, D2A1, 4T1, EMT6, EO771, Py230), we found early loss of ductal myoepithelial cell differentiation markers p63, α-smooth muscle actin, and calponin, and rapid formation of IDC in the absence of DCIS. Rapid IDC formation also occurred in the absence of adaptive immunity. Combined, these studies demonstrate that loss of myoepithelial barrier function does not require an intact immune system, and suggest that these isogenic murine models may prove a useful tool to study IDC in the absence of a non-obligatory DCIS stage-an under-investigated subset of poor prognostic human breast cancer.}, } @article {pmid37190147, year = {2023}, author = {Diop, MK and Molina, OE and Birlea, M and LaRue, H and Hovington, H and Têtu, B and Lacombe, L and Bergeron, A and Fradet, Y and Trudel, D}, title = {Leukocytic Infiltration of Intraductal Carcinoma of the Prostate: An Exploratory Study.}, journal = {Cancers}, volume = {15}, number = {8}, pages = {}, pmid = {37190147}, issn = {2072-6694}, support = {CRP-154487/CAPMC/CIHR/Canada ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is an aggressive histological subtype of prostate cancer (PCa) detected in approximately 20% of radical prostatectomy (RP) specimens. As IDC-P has been associated with PCa-related death and poor responses to standard treatment, the purpose of this study was to explore the immune infiltrate of IDC-P. Hematoxylin- and eosin-stained slides from 96 patients with locally advanced PCa who underwent RP were reviewed to identify IDC-P. Immunohistochemical staining of CD3, CD8, CD45RO, FoxP3, CD68, CD163, CD209 and CD83 was performed. For each slide, the number of positive cells per mm[2] in the benign tissues, tumor margins, cancer and IDC-P was calculated. Consequently, IDC-P was found in a total of 33 patients (34%). Overall, the immune infiltrate was similar in the IDC-P-positive and the IDC-P-negative patients. However, FoxP3[+] regulatory T cells (p < 0.001), CD68[+] and CD163[+] macrophages (p < 0.001 for both) and CD209[+] and CD83[+] dendritic cells (p = 0.002 and p = 0.013, respectively) were less abundant in the IDC-P tissues compared to the adjacent PCa. Moreover, the patients were classified as having immunologically "cold" or "hot" IDC-P, according to the immune-cell densities averaged in the total IDC-P or in the immune hotspots. The CD68/CD163/CD209-immune hotspots predicted metastatic dissemination (p = 0.014) and PCa-related death (p = 0.009) in a Kaplan-Meier survival analysis. Further studies on larger cohorts are necessary to evaluate the clinical utility of assessing the immune infiltrate of IDC-P with regards to patient prognosis and the use of immunotherapy for lethal PCa.}, } @article {pmid37189694, year = {2023}, author = {Minic, Z and Li, Y and Hüttmann, N and Uppal, GK and D'Mello, R and Berezovski, MV}, title = {Lysine Acetylome of Breast Cancer-Derived Small Extracellular Vesicles Reveals Specific Acetylation Patterns for Metabolic Enzymes.}, journal = {Biomedicines}, volume = {11}, number = {4}, pages = {}, pmid = {37189694}, issn = {2227-9059}, support = {RGPIN-2020-05775//Natural Sciences and Engineering Research Council/ ; }, abstract = {Cancer-derived small extracellular vesicles have been proposed as promising potential biomarkers for diagnosis and prognosis of breast cancer (BC). We performed a proteomic study of lysine acetylation of breast cancer-derived small extracellular vesicles (sEVs) to understand the potential role of the aberrant acetylated proteins in the biology of invasive ductal carcinoma and triple-negative BC. Three cell lines were used as models for this study: MCF10A (non-metastatic), MCF7 (estrogen and progesterone receptor-positive, metastatic) and MDA-MB-231 (triple-negative, highly metastatic). For a comprehensive protein acetylation analysis of the sEVs derived from each cell line, acetylated peptides were enriched using the anti-acetyl-lysine antibody, followed by LC-MS/MS analysis. In total, there were 118 lysine-acetylated peptides, of which 22, 58 and 82 have been identified in MCF10A, MCF7 and MDA-MB-231 cell lines, respectively. These acetylated peptides were mapped to 60 distinct proteins and mainly identified proteins involved in metabolic pathways. Among the acetylated proteins identified in cancer-derived sEVs from MCF7 and MDA-MB-231 cell lines are proteins associated with the glycolysis pathway, annexins and histones. Five acetylated enzymes from the glycolytic pathway, present only in cancer-derived sEVs, were validated. These include aldolase (ALDOA), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase (PGK1), enolase (ENO) and pyruvate kinase M1/2 (PKM). For three of these enzymes (ALDOA, PGK1 and ENO) the specific enzymatic activity was significantly higher in MDA-MB-231 when compared with MCF10A-derived sEVs. This study reveals that sEVs contain acetylated glycolytic metabolic enzymes that could be interesting potential candidates for early BC diagnostics.}, } @article {pmid37186041, year = {2023}, author = {Wei, S and Bao, M and Zhu, Y and Zhang, W and Jiang, L}, title = {Identifying potential targets for lung cancer intervention by analyzing the crosstalk of cancer-associated fibroblasts and immune and metabolism microenvironment.}, journal = {Environmental toxicology}, volume = {38}, number = {8}, pages = {1951-1967}, doi = {10.1002/tox.23821}, pmid = {37186041}, issn = {1522-7278}, support = {82103309//Youth Found of National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Cancer-Associated Fibroblasts/metabolism/pathology ; *Lung Neoplasms/pathology ; Lung/pathology ; Signal Transduction ; Glycerophospholipids/metabolism ; Tumor Microenvironment/genetics ; }, abstract = {BACKGROUND: Cancer-associated fibroblasts (CAFs) have been reported to play a crucial role in the tumor microenvironment and progression.

METHODS: The data used in this study were obtained from the Cancer Genome Atlas and Gene Expression Omnibus databases, and all analyses were performed using R software.

RESULTS: We first quantified the CAFs infiltration through single sample gene set enrichment analysis in the TCGA and combined GEO cohort (GSE30219, GSE37745, and GSE50081). Our result showed that patients with high levels of CAF infiltration were associated with worse clinical features and poor prognosis. Immune microenvironment analysis indicated that high CAF infiltration might result in increased infiltration of immune cells, including aDC, B cells, CD8+ T cells, cytotoxic cells, DC, eosinophils, iDC, macrophages, mast cells, neutrophils, NK CD56dim cells, NK cells, pDC, and T cells. Correlation analysis showed a significant positive correlation between CAFs and M2 macrophages, while a negative correlation was found between CAFs and glycerophospholipid metabolism. Kaplan-Meier survival curves indicated that glycerophospholipid metabolism was a protective factor against lung cancer. Biological enrichment analysis showed that pathways such as allograft rejection, epithelial-mesenchymal transition, KRAS signaling, TNF-α signaling, myogenesis, IL6/JAK/STAT3 signaling, IL2/STAT5 signaling were upregulated in the patients with high CAF infiltration. Moreover, patients with high CAF infiltration had a lower proportion of immunotherapy responders. Genome analysis showed that low CAFs infiltration was associated with high genome instability. We identified FGF5 and CELF3 as key genes involved in the interaction between CAFs, M2 macrophages, and glycerophospholipid metabolism, and further analyzed FGF5. In vitro experiments showed that FGF5 promoted the proliferation, invasion and migration of lung cancer cells and was primarily localized in the nucleoli fibrillar center.

CONCLUSIONS: Our study provides novel insights into the roles of CAFs in lung cancer progression and the underlying crosstalk of tumor metabolism and immune microenvironment.}, } @article {pmid37182091, year = {2023}, author = {Alvarez Moreno, JC and He, J}, title = {Invasive Breast Carcinoma With Sebaceous Morphologic Pattern Showing Lymph Node Macrometastasis: A Case Report.}, journal = {Cureus}, volume = {15}, number = {4}, pages = {e37365}, pmid = {37182091}, issn = {2168-8184}, abstract = {Invasive ductal carcinoma of no special type can present with various patterns. It is not possible to diagnose them through imaging alone. Microscopic examination is necessary to accurately identify and characterize them. The sebaceous pattern was historically considered a distinct subtype of breast carcinoma. However, the number of cases is relatively small and the prognosis has not been fully established. In this paper, we present a case of invasive ductal carcinoma with focal sebaceous features, which had a macrometastasis to the axillary lymph nodes showing the sebaceous morphology.}, } @article {pmid37178723, year = {2023}, author = {Ogawa, M and Kan, H and Urano, M and Kawai, T and Nakajima, H and Murai, K and Miyaji, H and Toyama, T and Hiwatashi, A}, title = {Three-compartment spectral diffusion analysis for breast cancer magnetic resonance imaging.}, journal = {Magnetic resonance imaging}, volume = {103}, number = {}, pages = {179-184}, doi = {10.1016/j.mri.2023.04.006}, pmid = {37178723}, issn = {1873-5894}, mesh = {Humans ; Female ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; *Breast Neoplasms/diagnostic imaging/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; Retrospective Studies ; Magnetic Resonance Imaging ; Diffusion Magnetic Resonance Imaging/methods ; Motion ; }, abstract = {RATIONALE AND OBJECTIVES: To examine the diagnostic performance of a three-compartment diffusion model with the fixed cut-off diffusion coefficient (D) using magnetic resonance spectral diffusion analysis for differentiating between invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) and compare the conventional apparent D (ADC), and mean kurtosis (MK), with the tissue D (DIVIM), perfusion D (D*IVIM), and perfusion fraction (fIVIM) calculated by conventional intravoxel incoherent motion.

PATIENTS AND METHODS: This retrospective study included women who underwent breast MRI with eight b-value diffusion-weighted imaging between February 2019 and March 2022. Spectral diffusion analysis was performed; very-slow, cellular, and perfusion compartments were defined using cut-off Ds of 0.1 × 10[-3] and 3.0 × 10[-3] mm[2]/s (static water D). The mean D (Ds, Dc, Dp, respectively) and fraction F (Fs, Fc, Fp, respectively) for each compartment were calculated. ADC and MK values were also calculated; receiver operating characteristic analyses were performed.

RESULTS: Histologically confirmed 132 ICD and 62 DCIS (age range 31-87 [53 ± 11] years) were evaluated. The areas under the curve (AUCs) for ADC, MK, DIVIM, D*IVIM, fIVIM, Ds, Dc, Dp, Fs, Fc, and Fp were 0.77, 0.72, 0.77, 0.51, 0.67, 0.54, 0.78, 0.51, 0.57, 0.54, and 0.57, respectively. The AUCs for the model combining very-slow and cellular compartments and the model combining the three compartments were 0.81 each, slightly and significantly higher than for ADC, DIVIM, and Dc (P = 0.09-0.14); and MK (P < 0.05), respectively.

CONCLUSION: Three-compartment model analysis using the diffusion spectrum accurately differentiated IDC from DCIS; however, it was not superior to ADC and DIVIM. The diagnostic performance of MK was lower than that of the three-compartment model.}, } @article {pmid37171457, year = {2023}, author = {Traberg, WC and Uribe, J and Druet, V and Hama, A and Moysidou, CM and Huerta, M and McCoy, R and Hayward, D and Savva, A and Genovese, AMR and Pavagada, S and Lu, Z and Koklu, A and Pappa, AM and Fitzgerald, R and Inal, S and Daniel, S and Owens, RM}, title = {Organic Electronic Platform for Real-Time Phenotypic Screening of Extracellular-Vesicle-Driven Breast Cancer Metastasis.}, journal = {Advanced healthcare materials}, volume = {12}, number = {27}, pages = {e2301194}, pmid = {37171457}, issn = {2192-2659}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/pathology ; Cell Line, Tumor ; Early Detection of Cancer ; *Triple Negative Breast Neoplasms/drug therapy/pathology ; *Extracellular Vesicles ; Epithelial-Mesenchymal Transition/genetics ; Cell Movement ; Cutaneous Malignant Melanoma ; }, abstract = {Tumor-derived extracellular vesicles (TEVs) induce the epithelial-to-mesenchymal transition (EMT) in nonmalignant cells to promote invasion and cancer metastasis, representing a novel therapeutic target in a field severely lacking in efficacious antimetastasis treatments. However, scalable technologies that allow continuous, multiparametric monitoring for identifying metastasis inhibitors are absent. Here, the development of a functional phenotypic screening platform based on organic electrochemical transistors (OECTs) for real-time, noninvasive monitoring of TEV-induced EMT and screening of antimetastatic drugs is reported. TEVs derived from the triple-negative breast cancer cell line MDA-MB-231 induce EMT in nonmalignant breast epithelial cells (MCF10A) over a nine-day period, recapitulating a model of invasive ductal carcinoma metastasis. Immunoblot analysis and immunofluorescence imaging confirm the EMT status of TEV-treated cells, while dual optical and electrical readouts of cell phenotype are obtained using OECTs. Further, heparin, a competitive inhibitor of cell surface receptors, is identified as an effective blocker of TEV-induced EMT. Together, these results demonstrate the utility of the platform for TEV-targeted drug discovery, allowing for facile modeling of the transient drug response using electrical measurements, and provide proof of concept that inhibitors of TEV function have potential as antimetastatic drug candidates.}, } @article {pmid37170638, year = {2024}, author = {Antón Rodriguez, Á and Odriozola Herrán, A and Echavarría Rodríguez, VJ and Alonso Fernández, S}, title = {Secondary sclerosing cholangitis induced by systemic chemotherapy.}, journal = {Revista espanola de enfermedades digestivas}, volume = {116}, number = {3}, pages = {173-174}, doi = {10.17235/reed.2023.9653/2023}, pmid = {37170638}, issn = {1130-0108}, mesh = {Female ; Humans ; Middle Aged ; *Cholangitis, Sclerosing/chemically induced/complications ; Cholangiopancreatography, Endoscopic Retrograde ; Liver ; Paclitaxel/adverse effects ; Immunoglobulin G ; }, abstract = {There are multiple causes of secondary sclerosing cholangitis (SSC), including mechanical obstruction, ischemia, congenital abnormalities, cholangiopathy of the critically ill patient and rarely, chemotherapy (1,2). We present the case of a 52-year-old female with a history of left breast invasive ductal carcinoma treated with neoadjuvant chemotherapy (adriamycin, cyclophosphamide and paclitaxel), surgery and radiotherapy in March 2021. She was admitted in July 2022 due to painless jaundice and pruritus with marked serum cholestasis. Magnetic resonance cholangiopancreatography showed multiple strictures and dilatations involving the intra and extrahepatic bile ducts (Figure 1.A), without any extrinsic stenotic cause. Findings were confirmed by endoscopic retrograde cholangiopancreatography (ERCP) with cholangioscopy (Figure 1.B). Biopsies were negative for malignancy and IgG4 disease. In addition, autoantibodies were negative and serum IgG4 levels were normal. Due to these findings and the history of recent chemotherapy, the patient was diagnosed with paclitaxel-induced sclerosing cholangitis, initiating treatment with ursodeoxycholic acid. Over the following two months, she suffered two episodes of Klebsiella Pneumoniae bacteraemia due to acute cholangitis. Dilatation and placement of plastic stents in both biliary trees were performed and prophylactic antibiotherapy was started. The patient had a poor evolution and was not candidate for liver transplantation on account of a recent neoplasia. She died six months later due to sepsis secondary to multiple hepatic abscesses.}, } @article {pmid37163201, year = {2023}, author = {Kuroda, H and Yoshizako, T and Yamamoto, N and Kataoka, Y and Hyakudomi, M and Itakura, M and Kaji, Y}, title = {A case of breast cancer: Suppression of lactation-related FDG uptake 2 days after cabergoline administration.}, journal = {Acta radiologica open}, volume = {12}, number = {5}, pages = {20584601231174611}, pmid = {37163201}, issn = {2058-4601}, abstract = {We present a case of a 35-year-old woman with breast cancer in lactation 3 months after childbirth, in which a lactation inhibitor was useful for 18F-FDG PET/CT examination. Via ultrasonography and biopsy with histopathology, we diagnosed the lesion in the upper region of the left breast as invasive ductal carcinoma. She stopped breastfeeding and was administered cabergoline to suppress lactation. Two days after the administration, 18F-FDG PET/CT revealed segmental uptake (10 cm in diameter) and no lactation-related uptakes. Dynamic MRI also revealed a segmental enhancement of the same size as 18F-FDG PET/CT. The lactation inhibitor was useful to delineate the extent of the lesion during the 18F-FDG PET/CT examination.}, } @article {pmid37160814, year = {2023}, author = {Hu, J and Lang, R and Zhao, W and Jia, Y and Tong, Z and Shi, Y}, title = {The mixed subtype has a worse prognosis than other histological subtypes: a retrospective analysis of 217 patients with metaplastic breast cancer.}, journal = {Breast cancer research and treatment}, volume = {200}, number = {1}, pages = {23-36}, pmid = {37160814}, issn = {1573-7217}, support = {18ZXXYSY00070//Natural Science Foundation of Tianjin-Science and Technology Correspondent Project/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Retrospective Studies ; *Triple Negative Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; Prognosis ; *Carcinoma, Squamous Cell ; }, abstract = {OBJECTIVE: Metaplastic breast cancer (MpBC) is an aggressive subtype of all breast cancer. We aimed to investigate the clinicopathological features, treatments and prognoses of MpBC patients.

METHODS: We collected the data from MpBC patients diagnosed at Tianjin Medical University Cancer Hospital from 2010 to 2017. Kaplan Meier curves and Cox regression model were used to evaluating clinical outcomes and prognostic factors. After removing baseline differences by propensity score matching (PSM), we analyzed the prognosis between MpBC patients and invasive ductal carcinomas of no special type (IDC-NST) patients.

RESULTS: A total of 217 MpBC patients were subsumed. Of all histological subtypes, 45.1% were mixed subtypes, followed by with mesenchymal differentiation (27.2%), pure squamous (15.2%) and pure spindle (12.4%) subtypes. 69.6% of MpBC were triple-negative, 25.3% and 6.5% were HR-positive and HER2-positive. MpBC patients had worse survival compared to IDC-NST patients, with 5-year RFS of 73.8 and 83.6% (HR = 1.177 95%CI (1.171-2.676) P = 0.0068), and 5-year BCSS of 79.0% and 89.7% (HR = 2.187 95%CI (1.357-3.523) P = 0.0013). In the multivariate COX model, AJCC stage, mixed subtype and chemotherapy were independent prognostic factors. Mixed MpBC is more aggressive than pure and with heterologous mesenchymal differentiation subtypes. And whether squamous or spindle MpBC, mixed forms have shorter outcomes than pure forms.

CONCLUSIONS: MpBCs are associated with poorer prognoses than IDC-NSTs. They are heterogeneous with different clinicopathological features and clinical outcomes between histological subtypes. Pure and with heterologous mesenchymal differentiation subtypes have more survival benefits than the mixed subtype.}, } @article {pmid37159793, year = {2023}, author = {Jaramillo, C and Nazario-Toole, A and Xia, H and Adams, T and Josey, M}, title = {Luminal-Type Invasive Carcinoma in Association With Microglandular Adenosis/Atypical Microglandular Adenosis: A Case Report and Molecular Comparison.}, journal = {Cureus}, volume = {15}, number = {4}, pages = {e37198}, pmid = {37159793}, issn = {2168-8184}, abstract = {Microglandular adenosis (MGA) is a proliferative breast lesion composed of small, uniform glands lacking a myoepithelial cell layer while still invested by the basement membrane. The glands percolate haphazardly through the breast parenchyma rather than maintaining a lobular architecture, typical of other forms of adenosis.MGA is a benign lesion though atypical forms have been well described, often in close association with carcinoma. MGA, atypical MGA (AMGA), and the vast majority of MGA-associated carcinomas (MGACA) are negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) by immunohistochemistry. In light of these findings and early molecular studies, MGA is hypothesized to represent a clonal process and nonobligate precursor of basal-type breast carcinomas. We present the case of a 58-year-old woman and the first published molecular comparison of a luminal-type invasive ductal carcinoma with its associated MGA/AMGA. Analysis of small nucleotide variants (SNVs) revealed that 63% of the SNVs identified in the MGA were present in the AMGA while only 10% of them were present in the MGACA, suggesting a direct relationship between MGA and AMGA but not MGA and MGACA.}, } @article {pmid37159559, year = {2023}, author = {Mnikhovich, MV and Romanov, AV and Nguyen, TM and Bezuglova, TV and Pastukhova, DA}, title = {Histological and electron microscopic features of the extracellular matrix of invasive breast ductal carcinoma of no special type. Report of 5 cases and literature review.}, journal = {Ultrastructural pathology}, volume = {47}, number = {4}, pages = {261-270}, doi = {10.1080/01913123.2023.2209162}, pmid = {37159559}, issn = {1521-0758}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/blood supply/metabolism/pathology ; Microcirculation ; Electrons ; *Breast Neoplasms/pathology ; Extracellular Matrix/metabolism ; Tumor Microenvironment ; }, abstract = {Invasive ductal carcinoma of no special type is the most common type of breast cancer. In light of the above, many authors have reported the histological and electron microscopic characteristics of these tumors. On the other hand, a limited number of works exist where the authors have concentrated on investigating the extracellular matrix. This article presents data received as the results of light and electron microscopic examination of the extracellular matrix, angiogenesis, and cellular microenvironment of invasive breast ductal carcinoma of no special type. The authors have shown that the processes of stroma formation in the IDC NOS type are associated with the presence of fibroblasts, macrophages, dendritic cells, lymphocytes, and other cells. It was also shown the detailed interaction of the above cells with each other, as well as with vessels and fibrillar proteins such as collagen and elastin. The microcirculatory component is characterized by histophysiological heterogeneity, which manifests as the activation of angiogenesis, relative vascular differentiation, and regression of individual microcirculation components.}, } @article {pmid37156698, year = {2023}, author = {Khosravi, S and Khayyamfar, A and Karimi, J and Tutuni, M and Negahi, A and Akbari, ME and Nafissi, N}, title = {Machine Learning Approach for the Determination of the Best Cut-Off Points for Ki67 Proliferation Index in Adjuvant and Neo-Adjuvant Therapy Breast Cancer Patients.}, journal = {Clinical breast cancer}, volume = {23}, number = {5}, pages = {519-526}, doi = {10.1016/j.clbc.2023.03.015}, pmid = {37156698}, issn = {1938-0666}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Ki-67 Antigen ; Neoadjuvant Therapy ; Receptors, Progesterone ; Cell Proliferation ; Prognosis ; Erb-b2 Receptor Tyrosine Kinases ; }, abstract = {BACKGROUND: This study aims to evaluate Ki67 cut-off points for differentiating low and high-risk patients based on survival and recurrence and find the best Ki67 cut-off points in breast cancer patients undergoing adjuvant and neoadjuvant therapy using machine learning methods.

PATIENTS AND METHODS: Patients with breast cancer treated at 2 referral hospitals between December 2000 and March 2021 who had invasive breast cancer entered this study. There were 257 patients in the neoadjuvant group and 2139 in the adjuvant group. A decision tree method was used to predict the likelihood of survival and recurrence. The 2-ensemble technique of RUSboost and bagged tree were imposed on the decision tree method to increase the accuracy of the determination. 80 percent of the data was used to train and validate the model, and 20% was used as a test.

RESULTS: In adjuvant therapy breast cancer patients with Invasive ductal carcinoma (IDC) and Invasive lobular carcinoma (ILC) the cutoff points for survival were 20 and 10, respectively. For luminal A, luminal B, Her2 neu, and triple-negative adjuvant therapy patients' the cutoff points for survival were 25, 15, 20, and 20, respectively. For neoadjuvant therapy luminal A and luminal B group, survival cutoff points were 25 and 20, respectively.

CONCLUSION: Despite variability in measurement and cut-off points, the Ki-67 proliferation index is still helpful in the clinic. Further investigation is needed to determine the best cut-off points for different patients. The sensitivity and specificity of Ki-67 cutoff point prediction models in this study could further prove its significance as a prognostic factor.}, } @article {pmid37146126, year = {2023}, author = {Ma, Q and Zhang, J and Qi, W and Li, Z and Jiang, Y and Zhang, M and He, H and Su, K and Shi, H}, title = {Store-Operated Ca[2+] Channels Contribute to the Generation of Ca[2+] Waves in Interdental Cells in the Cochleae.}, journal = {ACS chemical neuroscience}, volume = {14}, number = {10}, pages = {1896-1904}, doi = {10.1021/acschemneuro.3c00161}, pmid = {37146126}, issn = {1948-7193}, mesh = {*Cochlea/cytology/growth & development ; *Calcium Signaling ; *Intracellular Calcium-Sensing Proteins/physiology ; *Single-Cell Analysis/methods ; Microscopy, Fluorescence, Multiphoton ; Animals ; Mice ; Mice, Inbred C57BL ; }, abstract = {Cochlear calcium (Ca[2+]) waves are vital regulators of the cochlear development and establishment of hearing function. Inner supporting cells are believed to be the main region generating Ca[2+] waves that work as internal stimuli to coordinate the development of hair cells and the mapping of neurons in the cochlea. However, Ca[2+] waves in interdental cells (IDCs) that connect to inner supporting cells and spiral ganglion neurons are rarely observed and poorly understood. Herein, we reported the mechanism of IDC Ca[2+] wave formation and propagation by developing a single-cell Ca[2+] excitation technology, which can easily be accomplished using a two-photon microscope for simultaneous microscopy and femtosecond laser Ca[2+] excitation in any target individual cell in fresh cochlear tissues. We demonstrated that the store-operated Ca[2+] channels in IDCs are responsible for Ca[2+] wave formation in these cells. The specific architecture of the IDCs determines the propagation of Ca[2+] waves. Our results provide the mechanism of Ca[2+] formation in IDCs and a controllable, precise, and noninvasive technology to excite local Ca[2+] waves in the cochlea, with good potential for research on cochlear Ca[2+] and hearing functions.}, } @article {pmid37143728, year = {2023}, author = {Cipolletti, M and Leone, S and Bartoloni, S and Acconcia, F}, title = {A functional genetic screen for metabolic proteins unveils GART and the de novo purine biosynthetic pathway as novel targets for the treatment of luminal A ERα expressing primary and metastatic invasive ductal carcinoma.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1129162}, pmid = {37143728}, issn = {1664-2392}, mesh = {Female ; Humans ; Estrogen Receptor alpha/genetics/metabolism ; Biosynthetic Pathways ; Neoplasm Recurrence, Local ; *Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast ; Purines ; *Carbon-Nitrogen Ligases/metabolism ; Phosphoribosylglycinamide Formyltransferase/metabolism ; }, abstract = {Targeting tumor cell metabolism is a new frontier in cancer management. Thus, metabolic pathway inhibitors could be used as anti-estrogen receptor α (ERα) breast cancer (BC) drugs. Here, the interplay among metabolic enzyme(s), the ERα levels and cell proliferation was studied. siRNA-based screen directed against different metabolic proteins in MCF10a, MCF-7 and MCF-7 cells genetically resistant to endocrine therapy (ET) drugs and metabolomic analyses in numerous BC cell lines unveil that the inhibition of GART, a key enzyme in the purine de novo biosynthetic pathway, induces ERα degradation and prevent BC cell proliferation. We report here that a reduced GART expression correlates with a longer relapse-free-survival (RFS) in women with ERα-positive BCs. ERα-expressing luminal A invasive ductal carcinomas (IDCs) are sensitive to GART inhibition and GART expression is increased in receptor-positive IDCs of high grade and stage and plays a role in the development of ET resistance. Accordingly, GART inhibition reduces ERα stability and cell proliferation in IDC luminal A cells where it deregulates 17β-estradiol (E2):ERα signaling to cell proliferation. Moreover, the GART inhibitor lometrexol (LMX) and drugs approved for clinical treatment of primary and metastatic BC (4OH-tamoxifen and the CDK4/CDK6 inhibitors) exert synergic antiproliferative effects in BC cells. In conclusion, GART inhibition by LMX or other inhibitors of the de novo purine biosynthetic pathway could be a novel effective strategy for the treatment of primary and metastatic BCs.}, } @article {pmid37140551, year = {2023}, author = {van der Slot, MA and Remmers, S and Kweldam, CF and den Bakker, MA and Nieboer, D and Busstra, MB and Gan, M and Klaver, S and Rietbergen, JBW and van Leenders, GJLH and , }, title = {Biopsy prostate cancer perineural invasion and tumour load are associated with positive posterolateral margins at radical prostatectomy: implications for planning of nerve-sparing surgery.}, journal = {Histopathology}, volume = {83}, number = {3}, pages = {348-356}, doi = {10.1111/his.14934}, pmid = {37140551}, issn = {1365-2559}, support = {//BeterKeten Foundation/ ; }, mesh = {Male ; Humans ; *Prostate/surgery/pathology ; Margins of Excision ; Tumor Burden ; Neoplasm Invasiveness/pathology ; *Prostatic Neoplasms/surgery/pathology ; Biopsy ; Prostatectomy/adverse effects/methods ; }, abstract = {AIMS: Radical prostatectomy (RP) for prostate cancer is frequently complicated by erectile dysfunction and urinary incontinence. However, sparing of the nerve bundles adjacent to the posterolateral sides of the prostate reduces the number of complications at the risk of positive surgical margins. Preoperative selection of men eligible for safe, nerve-sparing surgery is therefore needed. Our aim was to identify pathological factors associated with positive posterolateral surgical margins in men undergoing bilateral nerve-sparing RP.

METHODS AND RESULTS: Prostate cancer patients undergoing RP with standardised intra-operative surgical margin assessment according to the NeuroSAFE technique were included. Preoperative biopsies were reviewed for grade group (GG), cribriform and/or intraductal carcinoma (CR/IDC), perineural invasion (PNI), cumulative tumour length and extraprostatic extension (EPE). Of 624 included patients, 573 (91.8%) received NeuroSAFE bilaterally and 51 (8.2%) unilaterally, resulting in a total of 1197 intraoperative posterolateral surgical margin assessments. Side-specific biopsy findings were correlated to ipsilateral NeuroSAFE outcome. Higher biopsy GG, CR/IDC, PNI, EPE, number of positive biopsies and cumulative tumour length were all associated with positive posterolateral margins. In multivariable bivariate logistic regression, ipsilateral PNI [odds ratio (OR) = 2.98, 95% confidence interval (CI) = 1.62-5.48; P < 0.001] and percentage of positive cores (OR = 1.18, 95% CI = 1.08-1.29; P < 0.001) were significant predictors for a positive posterolateral margin, while GG and CR/IDC were not.

CONCLUSIONS: Ipsilateral PNI and percentage of positive cores were significant predictors for a positive posterolateral surgical margin at RP. Biopsy PNI and tumour volume can therefore support clinical decision-making on the level of nerve-sparing surgery in prostate cancer patients.}, } @article {pmid37140069, year = {2023}, author = {Nonnemacher, CJ and Dale, P and Scott, A and Bonner, M}, title = {Pathologic Tumor Size versus Mammography, Sonography, and MRI in Breast Cancer Based on Pathologic Subtypes.}, journal = {The American surgeon}, volume = {89}, number = {8}, pages = {3652-3654}, doi = {10.1177/00031348231174019}, pmid = {37140069}, issn = {1555-9823}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/surgery/pathology ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging ; Retrospective Studies ; *Carcinoma, Ductal, Breast/diagnostic imaging/surgery/pathology ; *Carcinoma, Lobular/diagnostic imaging/surgery/pathology ; Mammography ; Magnetic Resonance Imaging/methods ; }, abstract = {INTRODUCTION: The standard of care for imaging of breast pathology has historically been mammography and sonography. MRI is a modern adjunct in the surgeon's toolkit. We looked to examine the differences in imaging modalities and their ability to predict the size in relation to the pathologic size after excision with focus on pathologic subtypes.

METHODS: We analyzed patient records across a 4-year period from 2017 to 2021 who were treated surgically for breast cancer at our facility. We used a retrospective chart review to collect measurements that were recorded of the tumors by the radiologist for available mammography, ultrasound, and MRI which were compared to pathology report measurements of the final specimens. We subdivided the results by pathologic subtypes including invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and ductal carcinoma in situ (DCIS).

RESULTS: 658 total patients met criteria for analysis. Mammography overestimated specimens with DCIS by 1.93 mm (P = .15), US underestimated by .56 (.55), and MRI overestimated by 5.77 mm (P < .01). There was no statistically significant difference in any modalities with IDC. With specimens of ILC, all 3 imaging modalities underestimated tumor size, with only US being significant.

DISCUSSION: Mammography and MRI consistently overestimated tumor size with the exception of ILC while US underestimated tumor size on all pathologic subtypes. MRI significantly overestimated tumor size in DCIS by 5.77 mm. Mammography was the most accurate imaging modality for all pathologic subtypes and never had a statistically significant difference from actual tumor size.}, } @article {pmid37139855, year = {2023}, author = {Tsilingiris, D and Schimpfle, L and von Rauchhaupt, E and Sulaj, A and Seebauer, L and Bartl, H and Herzig, S and Szendroedi, J and Kopf, S and Kender, Z}, title = {Dysmetabolism-related Early Sensory Deficits and Their Relationship With Peripheral Neuropathy Development.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {108}, number = {10}, pages = {e979-e988}, pmid = {37139855}, issn = {1945-7197}, mesh = {Humans ; Male ; *Diabetes Mellitus, Type 2/complications ; *Metabolic Syndrome/complications/epidemiology ; *Peripheral Nervous System Diseases/epidemiology/etiology ; *Insulin Resistance ; Glycation End Products, Advanced ; }, abstract = {AIM: To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to a dysmetabolic status in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development.

METHODS: A total of 225 individuals (117 and 108 without and with T2DM, respectively) without PN based on clinical and electrophysiological criteria were analyzed. Comparative analysis was conducted between those identified as "healthy" and those with EPSD based on a standardized QST protocol. A total of 196 were followed-up over a mean of 2.64 years for PN occurrence.

RESULTS: Among those without T2DM, apart from male sex, height, and higher fat and lower lean mass, only higher insulin resistance (IR; homeostatic model assessment for IR: odds ratio [OR], 1.70; P = .009; McAuley index OR, 0.62, P = .008), was independently associated with EPSD. In T2DM, metabolic syndrome (OR, 18.32; P < .001) and skin advanced glycation end-products (AGEs; OR, 5.66; P = .003) were independent predictors of EPSD. In longitudinal analysis, T2DM (hazard ratio [HR], 3.32 vs no diabetes mellitus; P < .001), EPSD (adjusted HR, 1.88 vs healthy; P = .049 adjusted for diabetes mellitus and sex), higher IR and AGEs predicted PN development. Among the 3 EPSD-associated sensory phenotypes, "sensory loss" was most strongly associated with PN development (adjusted HR, 4.35; P = .011).

CONCLUSION: We demonstrate for the first time the utility of a standardized QST-based approach in identifying early sensory deficits in individuals with and without T2DM. These are associated with a dysmetabolic status signified by IR markers, metabolic syndrome, and higher AGEs, which in turn are shown to influence PN development.}, } @article {pmid37129492, year = {2023}, author = {Berg, WA and López Aldrete, AL and Jairaj, A and Ledesma Parea, JC and García, CY and McClennan, RC and Cen, SY and Larsen, LH and de Lara, MTS and Love, S}, title = {Toward AI-supported US Triage of Women with Palpable Breast Lumps in a Low-Resource Setting.}, journal = {Radiology}, volume = {307}, number = {4}, pages = {e223351}, pmid = {37129492}, issn = {1527-1315}, support = {UH3 CA189966/CA/NCI NIH HHS/United States ; }, mesh = {Female ; Humans ; Artificial Intelligence ; Triage ; Prospective Studies ; Ultrasonography, Mammary/methods ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal ; }, abstract = {Background Most low- and middle-income countries lack access to organized breast cancer screening, and women with lumps may wait months for diagnostic assessment. Purpose To demonstrate that artificial intelligence (AI) software applied to breast US images obtained with low-cost portable equipment and by minimally trained observers could accurately classify palpable breast masses for triage in a low-resource setting. Materials and Methods This prospective multicenter study evaluated participants with at least one palpable mass who were enrolled in a hospital in Jalisco, Mexico, from December 2017 through May 2021. Orthogonal US images were obtained first with portable US with and without calipers of any findings at the site of lump and adjacent tissue. Then women were imaged with standard-of-care (SOC) US with Breast Imaging Reporting and Data System assessments by a radiologist. After exclusions, 758 masses in 300 women were analyzable by AI, with outputs of benign, probably benign, suspicious, and malignant. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined. Results The mean patient age ± SD was 50.0 years ± 12.5 (range, 18-92 years) and mean largest lesion diameter was 13 mm ± 8 (range, 2-54 mm). Of 758 masses, 360 (47.5%) were palpable and 56 (7.4%) malignant, including six ductal carcinoma in situ. AI correctly identified 47 or 48 of 49 women (96%-98%) with cancer with either portable US or SOC US images, with AUCs of 0.91 and 0.95, respectively. One circumscribed invasive ductal carcinoma was classified as probably benign with SOC US, ipsilateral to a spiculated invasive ductal carcinoma. Of 251 women with benign masses, 168 (67%) imaged with SOC US were classified as benign or probably benign by AI, as were 96 of 251 masses (38%, P < .001) with portable US. AI performance with images obtained by a radiologist was significantly better than with images obtained by a minimally trained observer. Conclusion AI applied to portable US images of breast masses can accurately identify malignancies. Moderate specificity, which could triage 38%-67% of women with benign masses without tertiary referral, should further improve with AI and observer training with portable US. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Slanetz in this issue.}, } @article {pmid37124528, year = {2023}, author = {Zhang, N and Xiang, Y and Shao, Q and Wu, J and Liu, Y and Long, H and Tao, D and Zeng, X}, title = {Different risk and prognostic factors for liver metastasis of breast cancer patients with de novo and relapsed distant metastasis in a Chinese population.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1102853}, pmid = {37124528}, issn = {2234-943X}, abstract = {PURPOSE: The present study aimed to identify clinicopathological characteristics of breast cancer liver metastasis (BCLM) as well as to characterize the risk and prognostic factors for the liver metastasis (LM) of breast cancer patients with de novo and relapsed distant metastasis in a Chinese population.

MATERIALS AND METHODS: Patients with metastatic breast cancer (MBC) who were hospitalized in the Breast Cancer Center at Chongqing University between January 2011 and December 2019 were included in the present study. Logistic regression analyses were conducted to identify risk factors for the presence of BCLM. Cox proportional hazard regression models were performed to determine the prognostic factors for the survival of BCLM patients. The correlation between LM and overall survival was assessed by the Kaplan-Meier method.

RESULTS: In total, 1,228 eligible MBC patients, including 325 cases (26.5%) with de novo metastasis (cohort A) and 903 cases (73.5%) with relapsed metastasis (cohort B), were enrolled in the present study. In cohort A and cohort B, 81 (24.9%) and 226 (25.0%) patients had BCLM, respectively. Patients in these two cohorts had different clinicopathological features. Logistic regression analysis identified that the human epidermal growth factor receptor 2 (HER2) status in cohort A as well as the HER2 status and invasive ductal carcinoma histology in cohort B were risk factors for BCLM. The median OS of patients with LM was inferior to that of non-LM patients (17.1 vs. 37.7 months, P = 0.0004 and 47.6 vs. 84.0 months, P < 0.0001, respectively). Cox analysis identified that the primary T stage, Ki67 level, and breast surgery history were independent prognostic factors for cohorts A and B, respectively.

CONCLUSIONS: De novo and relapsed MBC patients have different risk and prognostic factors for LM. Patients with BCLM have an unfavorable prognosis.}, } @article {pmid37121885, year = {2023}, author = {Ikegami, M}, title = {Prognostic benefit of comprehensive genomic profiling in clinical practice remains uncertain.}, journal = {Cancer science}, volume = {114}, number = {7}, pages = {3053-3055}, pmid = {37121885}, issn = {1349-7006}, support = {#22K15571//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Pancreatic Neoplasms/pathology ; Prognosis ; *Adenocarcinoma/genetics ; Retrospective Studies ; Genomics ; *Carcinoma, Pancreatic Ductal/genetics/therapy ; }, abstract = {The overall survival of patients who received genomically matched therapy was not significantly longer than that of patients receiving treatment only other than genomically matched therapy in the breast invasive ductal carcinoma (A), colorectal adenocarcinoma (B), and pancreatic adenocarcinoma (C) cohorts.}, } @article {pmid37113357, year = {2023}, author = {Takayasu, H and Kata, Y and Otsu, Y and Inoue, S and Kaneko, T}, title = {ALK-Rearranged NSCLC With Concomitant HER2-Mutant Breast Cancer Patient Treated With Alectinib, Trastuzumab, and Pertuzumab: A Case Report.}, journal = {Cureus}, volume = {15}, number = {3}, pages = {e36711}, pmid = {37113357}, issn = {2168-8184}, abstract = {Multiple cancers are a common occurrence, and the choice of treatment can be a challenging decision. The current case report describes a 71-year-old woman with overlapping anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinoma and HER2-mutant breast cancer, who achieved improvement with concurrent use of the molecularly targeted agents Alectinib, Trastuzumab, and Pertuzumab. A 71-year-old woman was diagnosed with lung adenocarcinoma and brain metastases, and invasive ductal carcinoma of the right breast, HER2-mutant type. In March 2021, a biopsy confirmed the presence of the ALK fusion gene in lung cancer. In April 2021, he started Alectinib and showed shrinkage of lung cancer; in December 2021, a metastatic liver tumor was found, and a liver biopsy diagnosed liver metastasis of breast cancer. Therefore, Alectinib was discontinued in February 2022, and Trastuzumab, Pertuzumab, and Docetaxel were started as chemotherapy for breast cancer. She continued treatment with Trastuzumab and Pertuzumab, but in July 2022, she developed an increase in lung cancer. Her metastatic liver tumor continued shrinking, and she was started on Trastuzumab, Pertuzumab, and Alectinib. After six months of treatment, the patient showed a sustained reduction in both lung cancer, breast cancer, and brain metastases with no adverse events. ALK rearrangement lung cancer often develops in young women, and similarly, breast cancer often develops in women. Therefore, those cancers may occur simultaneously. In such cases, the choice of treatment can be difficult, as both cancers require different approaches. Alectinib has been shown to have a high response rate and prolonged progression-free survival in ALK-rearranged non-small cell lung cancer (NSCLC). Trastuzumab and Pertuzumab are commonly used for the treatment of HER2-mutant breast cancer and have been shown to significantly improve progression-free survival and overall survival. This case report provides evidence that the concurrent use of Alectinib, Trastuzumab, and Pertuzumab can be an effective treatment for patients with overlapping ALK-rearranged NSCLC and HER2-mutant breast cancer. It is important to consider concurrent treatment in patients with multiple cancers to optimize treatment outcomes and improve quality of life. However, further studies are needed to establish the safety and efficacy of this combination of drugs for the treatment of overlapping cancers.}, } @article {pmid37111277, year = {2023}, author = {Ballal, S and Yadav, MP and Roesch, F and Wakade, N and Raju, S and Sheokand, P and Mishra, P and Moon, ES and Tripathi, M and Martin, M and Bal, C}, title = {Head-to-Head Comparison between [[68]Ga]Ga-DOTA.SA.FAPi and [[18]F]F-FDG PET/CT Imaging in Patients with Breast Cancer.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {16}, number = {4}, pages = {}, pmid = {37111277}, issn = {1424-8247}, abstract = {This study aimed to compare the diagnostic performance of [[68]Ga]Ga-DOTA.SA.FAPi with that of [[18]F]F-FDG PET/CT in detecting primary and metastatic lesions of breast cancer. [[18]F]F-FDG and [[68]Ga]Ga-DOTA.SA.FAPi PET/CT scans of histologically proven breast cancer patients were compared according to patient-based and lesion-based analysis. Forty-seven patients with a mean age of 44.8 ± 9.9 years (range: 31-66 years) were evaluated. A total of 85% of patients had invasive ductal carcinoma, and 15% had invasive lobular carcinoma. The tracer uptake [SULpeak, SULavg, and the median tumor-to-background ratio (TBR)] was significantly higher in [[68]Ga]Ga-DOTA.SA.FAPi than with [[18]F]F-FDG PET/CT for lymph nodes, pleural metastases, and liver lesions (p < 0.05). However, for brain metastasis, only the median TBR was significantly higher (p < 0.05) compared to [[18]F]F-FDG. In patient-based analysis the sensitivity of [[68]Ga]Ga-DOTA.SA.FAPi PET/CT was higher, but not significant than that of [[18]F]F-FDG PET/CT in the detection of both primary tumors and metastatic lesions. According to lesion-based analysis, on diagnostic CT, 47 patients had 44 primary tumors, 248 lymph nodes, 15 pleural, 88 liver, and 42 brain metastases. [[68]Ga]Ga-DOTA.SA.FAPi scan identified more abnormal lesions than [[18]F]F-FDG in all the primary and metastatic sites with a maximum marked difference in the primary site [88.6% vs. 81.8%; p-0.001], lymph nodes [89.1% vs. 83.8%; p-0.0001], pleural metastases [93.3% vs. 73%; p-0.096] and brain metastasis [100% vs. 59.5%; p-0.0001]. [[68]Ga]Ga-DOTA.SA.FAPi PET/CT was superior to [[18]F]F-FDG PET/CT in the imaging of breast cancers.}, } @article {pmid37104801, year = {2023}, author = {Bar-Kalifa, E and Goren, O and Gilboa-Schechtman, E and Wolff, M and Rafael, D and Heimann, S and Yehezkel, I and Scheniuk, A and Ruth, F and Atzil-Slonim, D}, title = {Clients' emotional experience as a dynamic context for client-therapist physiological synchrony.}, journal = {Journal of consulting and clinical psychology}, volume = {91}, number = {6}, pages = {367-380}, doi = {10.1037/ccp0000811}, pmid = {37104801}, issn = {1939-2117}, support = {//Israel Science Foundation/ ; }, mesh = {Humans ; *Psychotherapy ; Professional-Patient Relations ; Emotions/physiology ; *Emotional Regulation ; Databases, Factual ; }, abstract = {OBJECTIVE: Client-therapist physiological synchrony has recently attracted significant empirical attention. Recent theoretical accounts propose that physiological linkages should not be considered a stable dyadic virtue but rather a dynamic process that depends on the situational context in which they transpire. The present study adopted a "momentary" (vs. "global") approach that focuses on therapist-client physiological synchrony over relatively short periods of time. These temporal data served to examine the interplay between patterns of synchrony (in-phase vs. antiphase) and clients' momentary emotional experiences (inhibited/unproductive, productive, and positive). Synchrony was assessed by measuring respiratory sinus arrhythmia (RSA), an autonomic index that is known to be associated with interpersonal emotion regulation.

METHOD: Data were drawn from 28 clients undergoing a 16-session supportive-expressive dynamic therapy for depression. Clients' and therapists' electrocardiography were recorded in five sessions; clients' emotional experiences were coded at the speech-turn level. After each session, the clients also completed the session evaluation scale.

RESULTS: Client-therapist dyads had greater momentary RSA synchrony than would be predicted by chance. Compared to moments of unproductive emotional experience, greater antiphase synchrony was observed during moments of productive emotional experiences. In addition, compared to moments of unproductive emotional experience, greater in-phase and antiphase synchrony were observed during moments of positive emotional experiences. These patterns of synchrony were associated with clients' favorable evaluations of the session.

CONCLUSION: By considering the dynamic nature of synchrony, these findings provide a fine-grained picture of physiological synchrony and its potential effects on therapy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid37103742, year = {2023}, author = {Jiao, Y and Guo, X and Lv, Q}, title = {Options of locoregional therapy for primary foci of breast cancer influence the rate of nonregional lymph node metastasis in N2-N3 status patients: a SEER database analysis.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {30}, number = {4}, pages = {647-656}, pmid = {37103742}, issn = {1880-4233}, support = {ZYJC18018//1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University/ ; }, mesh = {Humans ; Aged, 80 and over ; Female ; *Breast Neoplasms/surgery/pathology ; Lymphatic Metastasis/pathology ; Prognosis ; Mastectomy ; Lymph Nodes/surgery/pathology ; Neoplasm Staging ; Retrospective Studies ; }, abstract = {OBJECTIVE: We aim to use the SEER database to discuss the effect of various surgical methods of primary foci and other influencing factors on the nonregional lymph node (NRLN) metastasis in invasive ductal carcinoma (IDC) patients.

METHODS: Clinical information of IDC patients used in this study was obtained from the SEER database. The statistical analyses used included a multivariate logistic regression model, the chi-squared test, log-rank test and propensity score matching (PSM).

RESULTS: 243,533 patients were included in the analysis. 94.3% of NRLN patients had a high N positivity (N3) but an equal distribution in T status. The proportion of operation type, especially BCM and MRM, differed significantly between the N0-N1 and N2-N3 groups in the NRLN metastasis group and nonmetastasis group. Age > 80 years, positive PR, modified radical mastectomy (MRM)/radical mastectomy (RM) and radiotherapy for primary tumor were shown to be protective factors for NRLN metastasis, and higher N positivity was the most significant risk factors. N2-N3 patients receiving MRM had a lower metastasis to NRLN than those receiving BCM (1.4% vs 3.7%, P < 0.001), while this relevance was not discovered in N0-N1 patients. In N2-N3 patients, a better OS was observed in MRM group than BCM group (P < 0.001).

CONCLUSION: MRM exerted a protective effect on NRLN metastasis compared to BCM in N2-N3 patients but not N0-N1 patients. This implies the need for more consideration when choosing the operation methods of primary foci in patients with high N positivity.}, } @article {pmid37101747, year = {2023}, author = {Xiang, S and Wei, M and Zhao, L and Lin, A and Xiong, Z}, title = {Integrated Analyses of the Expression and Prognostic Value of EPHB6 in Cervical Cancer and Its Correlation with Immune Infiltrates.}, journal = {Journal of oncology}, volume = {2023}, number = {}, pages = {2258906}, pmid = {37101747}, issn = {1687-8450}, abstract = {Among women, cervical cancer (CC) ranks as the third most frequent form of carcinoma and the fourth greatest cancer-related cause of deaths. There is increasing evidence that points to the dysregulation of EPH receptor B6 (EPHB6) in various cancers. On the other hand, neither the expression nor the function of EPHB6 in CC has been researched. In the first part of this investigation, we analyzed the data from the TCGA and discovered that the level of EPHB6 was much lower in CC tissues than in normal cervical tissues. ROC assays revealed that high EPHB6 expression had an AUC value of 0.835 for CC. The survival study revealed that both the overall and disease-specific survivals in this condition were considerably lower among patients who had a low EPHB6 level compared to those who had a high EPHB6 level. It is important to note that the multivariate COX regression analysis indicated that the expression of EPHB6 was an independent predictive factor. In addition to this, the C-indexes and calibration plots of a nomogram derived from multivariate assays revealed an accurate prediction performance among patients with CC. Immune infiltration analysis indicated that the expression of EPHB6 was positively associated with the levels of Tcm, TReg, B cells, T cells, iDC, T helper cells, cytotoxic cells, and DC, while negatively associated with NK CD56bright cells and neutrophils. In summary, the downregulation of EPHB6 was strongly linked to a more aggressive clinical development of CC, suggesting its potential utility as a diagnostic and therapeutic target in CC.}, } @article {pmid37095978, year = {2023}, author = {Norooznezhad, AH and Yarani, R and Payandeh, M and Hoseinkhani, Z and Mahmoudi, H and Kiani, S and Mansouri, K}, title = {Treatment of persistent chemotherapy-induced hair loss (Alopecia) with human mesenchymal stromal cells exosome enriched extracellular vesicles: A case report.}, journal = {Heliyon}, volume = {9}, number = {4}, pages = {e15165}, pmid = {37095978}, issn = {2405-8440}, abstract = {INTRODUCTION: Cancer is among the leading causes of death worldwide and affects a considerable number of individuals. Chemotherapy is one the most common treatment for this condition and hair loss is among one of the most prevalent side effects. In this study, we report successful treatment of a patient suffering from persistent chemotherapy-induced alopecia (PCIA) with extracellular enriched vesicles (EVs) derived from human placental mesenchymal stromal cells (MSCs).

CASE PRESENTATION: The patient was a 36-year-old woman with a history of invasive ductal carcinoma, underwent six courses of chemotherapy with paclitaxel and adriamycin. Following this treatment and for almost 18 months, she, unfortunately, had no regrowth of hair except some light vellus hairs on the scalp. She then received MSC-derived EVs with scalp injection (subcutaneous) every 4 weeks for 3 continuous months at which point she presented complete regrowth of terminal hair on her scalp.

CONCLUSION: This report demonstrates that MSC-derived EVs could be a possible treatment for permanent chemotherapy-induced alopecia; however, further studies and trials are necessary.}, } @article {pmid37095044, year = {2023}, author = {Nelson, TJ and Kumar, A and Nalawade, V and Nonato, T and Shabaik, A and Roma, A and Rose, BS and McKay, RR}, title = {Associations Between Intraductal Prostate Cancer and Metastases Following Radical Prostatectomy in Men With Prostate Cancer in the Veterans Affairs Database.}, journal = {Clinical genitourinary cancer}, volume = {21}, number = {4}, pages = {452-458}, doi = {10.1016/j.clgc.2023.03.010}, pmid = {37095044}, issn = {1938-0682}, mesh = {Male ; Humans ; *Prostatic Neoplasms/surgery/pathology ; Prostate/pathology ; Androgen Antagonists ; *Veterans ; Prostatectomy ; Prostate-Specific Antigen ; Neoplasm Grading ; Neoplasm Recurrence, Local/pathology ; Retrospective Studies ; }, abstract = {PURPOSE: Intraductal carcinoma of the prostate (IDC-P) is a relatively unstudied feature present in some prostate cancer (PC) diagnoses with several studies suggesting associations with higher Gleason scores (GS) and earlier time to biochemical recurrence (BCR) after definitive treatment. We looked to identify cases of IDC-P in the Veterans Health Administration (VHA) database and measure associations between IDC-P and pathological stage, BCR, and metastases.

METHODS: Patients in the VHA database diagnosed with PC from 2000 to 2017, treated with radical prostatectomy (RP) at the VHA were included in the cohort. BCR was defined as post-RP PSA >0.2 or administration of androgen deprivation therapy (ADT). Time to event was defined as time from RP to event or censor. Differences in cumulative incidences were assessed through Gray's test. Associations with IDC-P and pathologic features at RP, BCR and metastases were assessed through multivariable logistic and Cox regression models.

RESULTS: Of 13,913 patients meeting inclusion criteria, 45 patients had IDC-P. Median follow up was 8.8 years from RP. Multivariable logistic regressions showed patients with IDC-P were more likely to have GS ≥8 (Odds Ratio (OR) 1.14, P = .009) and higher T stages (T3 or 4 vs. T1 or 2 OR 1.14, P < .001). In total, 4,318 patients experienced a BCR, and 1,252 patients developed metastases of whom 26 and 12, respectively, had IDC-P. On multivariable regression IDC-P was associated with higher risk of BCR (IDC-P Hazard Ratio (HR) 1.71, P = .006) and metastases (HR 2.84, P < .001). Cumulative incidence of metastases at 4 years for IDC-P and non-IDC-P were 15.9% and 5.5% (P < .001) respectively.

CONCLUSIONS: In this analysis, IDC-P was associated with higher Gleason score at RP, shorter time to BCR, and higher rates of metastases. Further studies are warranted to investigate the molecular underpinnings of IDC-P to better guide treatment strategies for this aggressive disease entity.}, } @article {pmid37094629, year = {2023}, author = {Chovsepian, A and Prokopchuk, O and Petrova, G and Gjini, T and Kuzi, H and Heisz, S and Janssen, KP and Martignoni, ME and Friess, H and Hauner, H and Rohm, M}, title = {Diabetes increases mortality in patients with pancreatic and colorectal cancer by promoting cachexia and its associated inflammatory status.}, journal = {Molecular metabolism}, volume = {73}, number = {}, pages = {101729}, pmid = {37094629}, issn = {2212-8778}, mesh = {Humans ; Cachexia/metabolism ; Retrospective Studies ; C-Reactive Protein ; *Diabetes Mellitus, Type 2/complications ; *Pancreatic Neoplasms/complications/metabolism ; Body Weight ; Obesity/complications ; Biomarkers ; *Colorectal Neoplasms/complications ; }, abstract = {OBJECTIVES: Cancer is considered an emerging diabetes complication, with higher incidence and worse prognosis in patients with diabetes. Cancer is frequently associated with cachexia, a systemic metabolic disease causing wasting. It is currently unclear how diabetes affects the development and progression of cachexia.

METHODS: We investigated the interplay between diabetes and cancer cachexia retrospectively in a cohort of 345 patients with colorectal and pancreatic cancer. We recorded body weight, fat mass, muscle mass, clinical serum values, and survival of these patients. Patients were grouped either into diabetic/non-diabetic groups based on previous diagnosis, or into obese/non-obese groups based on body mass index (BMI ≥30 kg/m[2] was considered obese).

RESULTS: The pre-existence of type 2 diabetes, but not obesity, in patients with cancer led to increased cachexia incidence (80%, compared to 61% without diabetes, p ≤ 0.05), higher weight loss (8.9% vs. 6.0%, p ≤ 0.001), and reduced survival probability (median survival days: 689 vs. 538, Chi square = 4.96, p ≤ 0.05) irrespective of the initial body weight or tumor progression. Patients with diabetes and cancer showed higher serum levels of C-reactive protein (0.919 μg/mL vs. 0.551 μg/mL, p ≤ 0.01) and interleukin 6 (5.98 pg/mL vs. 3.75 pg/mL, p ≤ 0.05) as well as lower serum albumin levels (3.98 g/dL vs. 4.18 g/dL, p ≤ 0.05) than patients with cancer without diabetes. In a sub-analysis of patients with pancreatic cancer, pre-existing diabetes worsened weight loss (9.95% vs. 6.93%, p ≤ 0.01), and increased the duration of hospitalization (24.41 days vs. 15.85 days, p ≤ 0.001). Further, diabetes aggravated clinical manifestations of cachexia, as changes in the aforementioned biomarkers were more pronounced in patients with diabetes and cachexia co-existence, compared to cachectic patients without diabetes (C-reactive protein: 2.300 μg/mL vs. 0.571 μg/mL, p ≤ 0.0001; hemoglobin: 11.24 g/dL vs. 12.52 g/dL, p ≤ 0.05).

CONCLUSIONS: We show for the first time that pre-existing diabetes aggravates cachexia development in patients with colorectal and pancreatic cancer. This is important when considering cachexia biomarkers and weight management in patients with co-existing diabetes and cancer.}, } @article {pmid37092454, year = {2023}, author = {Neagu, AN and Whitham, D and Seymour, L and Haaker, N and Pelkey, I and Darie, CC}, title = {Proteomics-Based Identification of Dysregulated Proteins and Biomarker Discovery in Invasive Ductal Carcinoma, the Most Common Breast Cancer Subtype.}, journal = {Proteomes}, volume = {11}, number = {2}, pages = {}, pmid = {37092454}, issn = {2227-7382}, support = {R15 CA260126/CA/NCI NIH HHS/United States ; }, abstract = {Invasive ductal carcinoma (IDC) is the most common histological subtype of malignant breast cancer (BC), and accounts for 70-80% of all invasive BCs. IDC demonstrates great heterogeneity in clinical and histopathological characteristics, prognoses, treatment strategies, gene expressions, and proteomic profiles. Significant proteomic determinants of the progression from intraductal pre-invasive malignant lesions of the breast, which characterize a ductal carcinoma in situ (DCIS), to IDC, are still poorly identified, validated, and clinically applied. In the era of "6P" medicine, it remains a great challenge to determine which patients should be over-treated versus which need to be actively monitored without aggressive treatment. The major difficulties for designating DCIS to IDC progression may be solved by understanding the integrated genomic, transcriptomic, and proteomic bases of invasion. In this review, we showed that multiple proteomics-based techniques, such as LC-MS/MS, MALDI-ToF MS, SELDI-ToF-MS, MALDI-ToF/ToF MS, MALDI-MSI or MasSpec Pen, applied to in-tissue, off-tissue, BC cell lines and liquid biopsies, improve the diagnosis of IDC, as well as its prognosis and treatment monitoring. Classic proteomics strategies that allow the identification of dysregulated protein expressions, biological processes, and interrelated pathway analyses based on aberrant protein-protein interaction (PPI) networks have been improved to perform non-invasive/minimally invasive biomarker detection of early-stage IDC. Thus, in modern surgical oncology, highly sensitive, rapid, and accurate MS-based detection has been coupled with "proteome point sampling" methods that allow for proteomic profiling by in vivo "proteome point characterization", or by minimal tissue removal, for ex vivo accurate differentiation and delimitation of IDC. For the detection of low-molecular-weight proteins and protein fragments in bodily fluids, LC-MS/MS and MALDI-MS techniques may be coupled to enrich and capture methods which allow for the identification of early-stage IDC protein biomarkers that were previously invisible for MS-based techniques. Moreover, the detection and characterization of protein isoforms, including posttranslational modifications of proteins (PTMs), is also essential to emphasize specific molecular mechanisms, and to assure the early-stage detection of IDC of the breast.}, } @article {pmid37092099, year = {2022}, author = {Al Nemer, A}, title = {Breast biomarkers profile of invasive lobular carcinoma in a cohort of arab women shows no significant differences from carcinoma of no special type.}, journal = {African health sciences}, volume = {22}, number = {4}, pages = {10-15}, pmid = {37092099}, issn = {1729-0503}, mesh = {Female ; Humans ; Middle Aged ; *Carcinoma, Lobular/epidemiology/diagnosis/pathology ; *Carcinoma, Ductal, Breast ; Ki-67 Antigen ; Retrospective Studies ; Arabs ; Receptors, Progesterone ; Receptors, Estrogen/metabolism ; *Breast Neoplasms/pathology ; Prognosis ; }, abstract = {OBJECTIVES: Invasive lobular carcinoma (ILC) of the breast is known for its common presentation at an older age, and the frequent expression of favourable profile of estrogen and progesterone receptors (ER & PR) positivity, and human epidermal growth factor receptor 2 (HER2) negativity combined with low proliferation rate as measured by Ki67. This study aimed to test these clinicopathological features of ILC in an Arabic cohort.

METHODS: All breast biopsies diagnosed as IDC or ILC were retrospectively reviewed over 2 years period (2017-2018) in an academic centre. Variables were compared using Fisher's exact test for statistical significance.

RESULTS: A total of 134 cases were recruited, 12.7% were ILC. The median age was 52 years for both types. Clustering of ILC cases was noticed in luminal A subtype (47.1%), but there was no statistically significant difference in subtyping between the 2 histologic groups. Ki67 was significantly lower in ILC than IDC category.

CONCLUSIONS: Our study showed that ILC in our cohort lacks the advantage of older age and the common high expression of ER positivity in comparison to IDC. There is, however, significant difference of the value of Ki67 proliferation marker. The prognosis of lobular morphology is questionable in our cohort.}, } @article {pmid37091166, year = {2023}, author = {Fang, WB and Medrano, M and Cote, P and Portsche, M and Rao, V and Hong, Y and Behbod, F and Knapp, JR and Bloomer, C and Noel-Macdonnell, J and Cheng, N}, title = {Transcriptome analysis reveals differences in cell cycle, growth and migration related genes that distinguish fibroblasts derived from pre-invasive and invasive breast cancer.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1130911}, pmid = {37091166}, issn = {2234-943X}, support = {P30 GM122731/GM/NIGMS NIH HHS/United States ; R01 CA172764/CA/NCI NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; R00 CA127462/CA/NCI NIH HHS/United States ; U54 HD090216/HD/NICHD NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND/INTRODUCTION: As the most common form of pre-invasive breast cancer, ductal carcinoma in situ (DCIS) affects over 50,000 women in the US annually. Despite standardized treatment involving lumpectomy and radiation therapy, up to 25% of patients with DCIS experience disease recurrence often with invasive ductal carcinoma (IDC), indicating that a subset of patients may be under-treated. As most DCIS cases will not progress to invasion, many patients may experience over-treatment. By understanding the underlying processes associated with DCIS to IDC progression, we can identify new biomarkers to determine which DCIS cases may become invasive and improve treatment for patients. Accumulation of fibroblasts in IDC is associated with disease progression and reduced survival. While fibroblasts have been detected in DCIS, little is understood about their role in DCIS progression.

GOALS: We sought to determine 1) whether DCIS fibroblasts were similar or distinct from normal and IDC fibroblasts at the transcriptome level, and 2) the contributions of DCIS fibroblasts to breast cancer progression.

METHODS: Fibroblasts underwent transcriptome profiling and pathway analysis. Significant DCIS fibroblast-associated genes were further analyzed in existing breast cancer mRNA databases and through tissue array immunostaining. Using the sub-renal capsule graft model, fibroblasts from normal breast, DCIS and IDC tissues were co-transplanted with DCIS.com breast cancer cells.

RESULTS: Through transcriptome profiling, we found that DCIS fibroblasts were characterized by unique alterations in cell cycle and motility related genes such as PKMYT1, TGF-α, SFRP1 and SFRP2, which predicted increased cell growth and invasion by Ingenuity Pathway Analysis. Immunostaining analysis revealed corresponding increases in expression of stromal derived PKMYT1, TGF-α and corresponding decreases in expression of SFRP1 and SFRP2 in DCIS and IDC tissues. Grafting studies in mice revealed that DCIS fibroblasts enhanced breast cancer growth and invasion associated with arginase-1+ cell recruitment.

CONCLUSION: DCIS fibroblasts are phenotypically distinct from normal breast and IDC fibroblasts, and play an important role in breast cancer growth, invasion, and recruitment of myeloid cells. These studies provide novel insight into the role of DCIS fibroblasts in breast cancer progression and identify some key biomarkers associated with DCIS progression to IDC, with important clinical implications.}, } @article {pmid37090301, year = {2023}, author = {Fakhry, J and Hanna, M}, title = {Low Radiologic Sensitivity in Detecting Radiation-Associated Breast Angiosarcoma (RAS).}, journal = {Cureus}, volume = {15}, number = {3}, pages = {e36508}, pmid = {37090301}, issn = {2168-8184}, abstract = {Due to its rarity, literature pertaining to radiation-associated breast angiosarcoma (RAS) remains sparse, with most studies focusing on retrospective review. Of more significant concern is the ambiguity of screening recommendations and modalities used to detect RAS, with current guidelines focusing on yearly mammographic imaging for women who underwent lumpectomy with radiation. Unfortunately, routine post-cancer screening has demonstrated low sensitivity in detecting RAS, often mistaking it for benign changes in roughly half of cases. We present an 83-year-old woman initially diagnosed with stage 1 invasive ductal carcinoma of the left breast who underwent a lumpectomy followed by radiation with 6040 cGy. Five years after her initial diagnosis, the patient noticed a suspicious lesion which then led her to undergo multiple modalities of imaging that described benign features. After continued concern, a biopsy was taken that demonstrated RAS of the left breast within the irradiated site. The patient underwent further radiation and declined surgical intervention. Routine screening with mammography and ultrasonography following breast radiation treatment are not sensitive modalities in detecting RAS. High-risk patient groups treated with greater than 0.5 Gy of radiation with concerning physical features 2-10 years after treatment should undergo MRI with biopsy at the initial concern to rule out angiosarcoma. Benign findings on imaging with patients in these groups should also consider biopsy.}, } @article {pmid37085500, year = {2023}, author = {Zhou, D and Li, M and Yasin, MH and Lu, Q and Fu, J and Jiang, K and Hong, R and Wang, S and Xu, F}, title = {The prognostic value and immune microenvironment association of AR in HER2+ nonmetastatic breast cancer.}, journal = {NPJ breast cancer}, volume = {9}, number = {1}, pages = {30}, pmid = {37085500}, issn = {2374-4677}, support = {320.6750.2021-10-97//Ministry of Health of China | Wu Jieping Medical Foundation/ ; 2019A1515011945//Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)/ ; }, abstract = {This study aimed to investigate the prognostic value of AR in HER2+ nonmetastatic breast invasive ductal carcinoma (IDC) and its relationship with the immune microenvironment. HER2+ nonmetastatic breast IDC patients diagnosed by pathology who underwent surgery at Sun Yat-sen University Cancer Center from 2016 to 2017 were included. AR+ and AR- breast IDC samples were matched 1:1 in age, T stage, and N stage for immune infiltration analysis. A total of 554 patients with HER2+ nonmetastatic breast cancer were included in this retrospective study, regardless of HR status. The cut-off value for AR was set at 10%. ER+ (p < 0.001) and PR+ (p < 0.001) were associated with positive AR expression. Kaplan-Meier survival curve analysis suggested that AR was closely correlated with overall survival (OS) (p = 0.001) but not disease-free survival (DFS) (p = 0.051). After eliminating the potential impact caused by HR, AR also predicted longer OS (p = 0.014) and was an independent predictive factor for OS of HER2+HR- nonmetastatic breast IDC patients, as revealed by multivariate analysis (p = 0.036). For AR+ and AR- matched HER2+HR- patients, TILs (p = 0.043) and PD-L1 (p = 0.027) levels were significantly lower in AR+ patients. The strongest negative correlation was observed between AR and PD-L1 (Pearson's r = -0.299, p = 0.001). AR+ status was markedly related to better OS in HER2+HR- nonmetastatic breast cancer patients, while a negative correlation was observed between AR and PD-L1/TILs. We provide new insights into the prognostic value of AR and its association with the immune microenvironment to optimize treatment strategies in HER2+ nonmetastatic breast IDCs.}, } @article {pmid37085014, year = {2023}, author = {van Balkom, IDC and Burdeus-Olavarrieta, M and Cooke, J and de Cuba, AG and Turner, A and , and Vogels, A and Maruani, A}, title = {Consensus recommendations on mental health issues in Phelan-McDermid syndrome.}, journal = {European journal of medical genetics}, volume = {66}, number = {6}, pages = {104770}, doi = {10.1016/j.ejmg.2023.104770}, pmid = {37085014}, issn = {1878-0849}, mesh = {Humans ; *Mental Health ; Quality of Life ; *Chromosome Disorders/genetics/psychology ; Chromosome Deletion ; Chromosomes, Human, Pair 22/genetics ; }, abstract = {Phelan-McDermid syndrome is a rare genetic condition caused by a deletion encompassing the 22q13.3 region or a pathogenic variant of the gene SHANK3. The clinical presentation is variable, but main characteristics include global developmental delay/intellectual disability (ID), marked speech impairment or delay, along with other features like hypotonia and somatic or psychiatric comorbidities. This publication delineates mental health, developmental and behavioural themes across the lifetime of individuals with PMS as informed by parents/caregivers, experts, and other key professionals involved in PMS care. We put forward several recommendations based on the available literature concerning mental health and behaviour in PMS. Additionally, this article aims to improve our awareness of the importance of considering developmental level of the individual with PMS when assessing mental health and behavioural issues. Understanding how the discrepancy between developmental level and chronological age may impact concerning behaviours offers insight into the meaning of those behaviours and informs care for individuals with PMS, enabling clinicians to address unmet (mental health) care needs and improve quality of life.}, } @article {pmid37083566, year = {2023}, author = {Bilici, A and Olmez, OF and Kaplan, MA and Oksuzoglu, B and Sezer, A and Karadurmus, N and Cubukcu, E and Sendur, MAN and Aksoy, S and Erdem, D and Basaran, G and Cakar, B and Shbair, ATM and Arslan, C and Sumbul, AT and Sezgin Goksu, S and Karadag, I and Cicin, I and Gumus, M and Selcukbiricik, F and Harputluoglu, H and Demirci, U}, title = {Impact of adding pertuzumab to trastuzumab plus chemotherapy in neoadjuvant treatment of HER2 positive breast cancer patients: a multicenter real-life HER2PATH study.}, journal = {Acta oncologica (Stockholm, Sweden)}, volume = {62}, number = {4}, pages = {381-390}, doi = {10.1080/0284186X.2023.2202330}, pmid = {37083566}, issn = {1651-226X}, mesh = {Humans ; Female ; Trastuzumab/therapeutic use ; *Breast Neoplasms/pathology ; Neoadjuvant Therapy/methods ; Docetaxel ; Retrospective Studies ; Erb-b2 Receptor Tyrosine Kinases ; Neoplasm Recurrence, Local/drug therapy/genetics ; Paclitaxel ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antibodies, Monoclonal, Humanized ; }, abstract = {AIM: To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting.

METHODS: A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR.

RESULTS: Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p < 0.001) and lower relapse (4.5 vs. 12.2%, p < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p < 0.001) and NCT-HP (41.5 vs. 32.1%, p < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p = 0.008) significantly predicted the pCR.

CONCLUSIONS: This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time.}, } @article {pmid37082801, year = {2023}, author = {Hacking, SM and Yakirevich, E and Wang, Y}, title = {Defining triple-negative breast cancer with neuroendocrine differentiation (TNBC-NED).}, journal = {The journal of pathology. Clinical research}, volume = {9}, number = {4}, pages = {313-321}, pmid = {37082801}, issn = {2056-4538}, mesh = {Humans ; *Triple Negative Breast Neoplasms/genetics/pathology ; Biomarkers, Tumor/analysis ; Tumor Suppressor Protein p53/genetics ; Retinoblastoma Protein/genetics/metabolism ; Retrospective Studies ; *Neuroendocrine Tumors/pathology ; *Carcinoma, Neuroendocrine/pathology ; *Carcinoma, Ductal, Breast ; Cell Differentiation ; RNA, Messenger ; Repressor Proteins ; }, abstract = {Primary breast neuroendocrine (NE) neoplasms are uncommon, and definitions harbor controversy. We retrospectively collected 73 triple-negative breast cancers (TNBC) and evaluated NE biomarker expression along with p53 aberrant staining (which correlates with TP53 gene mutation) and Rb protein loss by immunohistochemistry. In the study cohort, we found 11 (15%) cases of TNBC with neuroendocrine differentiation (TNBC-NED) showing positivity for one or more NE markers (synaptophysin/chromogranin/insulinoma-associated protein 1 [INSM1]). We also identified one separate small cell neuroendocrine carcinoma. Histologic types for these 11 TNBC-NED cases were as follows: 8 invasive ductal carcinoma (IDC) not otherwise specified (NOS), 2 IDC with apocrine features, 1 IDC with solid papillary features. INSM1 had the highest positivity and was seen in all 11 carcinomas. Seven (64%) cases showed p53 aberrant staining, 6 (55%) had Rb protein loss, while 6 (55%) had p53/Rb co-aberrant staining/protein loss. TNBC-NED was associated with Rb protein loss (p < 0.001), as well as p53/Rb co-aberrant staining/protein loss (p < 0.001). In 61 cases negative for NE markers, 37 (61%) showed p53 aberrant staining, while 5 (8%) had Rb protein loss. We also analyzed genomic and transcriptomic data from The Cancer Genome Atlas (TCGA) PanCancer Atlas of 171 basal/TNBC patients. Transcriptomic analysis revealed mRNA expression of RB1 to be correlated negatively with SYN1 mRNA expression (p = 0.0400) and INSM1 mRNA expression (p = 0.0106) in this cohort. We would like to highlight the importance of these findings. TNBC-NED is currently diagnosed as TNBC, and although it overlaps morphologically with TNBC without NED, the unique p53/Rb signature highlights a genetic overlap with NE carcinomas of the breast.}, } @article {pmid37082278, year = {2023}, author = {Pandiar, D and Ramani, P and Krishnan, M and Krishnan, RP}, title = {Intraductal carcinoma of right parapharyngeal space presenting as a fluctuant swelling of retromolar region: Case emphasizing on the histological differential diagnosis.}, journal = {Journal of oral and maxillofacial pathology : JOMFP}, volume = {27}, number = {Suppl 1}, pages = {S28-S32}, pmid = {37082278}, issn = {0973-029X}, abstract = {Intraductal carcinoma (IDC) of salivary gland is an extremely rare malignancy affecting mainly the parotid glands. Intraoral occurrence is seen mainly on the palate where the tumour arises from the minor salivary glands. No previous case has been described in parapharyngeal space. We report a case of low-grade IDC of the anterior compartment of the right parapharyngeal space that clinically resembled a lesion of vascular origin. Due to the extreme rarity of intraductal carcinoma, it may not be considered by dentists and dental specialists in clinical differential diagnoses, leading to delay in treatment. Intraductal carcinoma must be differentiated from its close histological but high-grade mimickers to avoid unnecessary overtreatment and better patient outcome.}, } @article {pmid37064116, year = {2023}, author = {Yang, G and Zuo, C and Lin, Y and Zhou, X and Wen, P and Zhang, C and Xiao, H and Jiang, M and Fujita, M and Gao, XD and Fu, F}, title = {Comprehensive proteome, phosphoproteome and kinome characterization of luminal A breast cancer.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1127446}, pmid = {37064116}, issn = {2234-943X}, abstract = {BACKGROUND: Breast cancer is one of the most frequently occurring malignant cancers worldwide. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two most common histological subtypes of breast cancer. In this study, we aimed to deeply explore molecular characteristics and the relationship between IDC and ILC subtypes in luminal A subgroup of breast cancer using comprehensive proteomics and phosphoproteomics analysis.

METHODS: Cancer tissues and noncancerous adjacent tissues (NATs) with the luminal A subtype (ER- and PR-positive, HER2-negative) were obtained from paired IDC and ILC patients respectively. Label-free quantitative proteomics and phosphoproteomics methods were used to detect differential proteins and the phosphorylation status between 10 paired breast cancer and NATs. Then, the difference in protein expression and its phosphorylation between IDC and ILC subtypes were explored. Meanwhile, the activation of kinases and their substrates was also revealed by Kinase-Substrate Enrichment Analysis (KSEA).

RESULTS: In the luminal A breast cancer, a total of 5,044 high-confidence proteins and 3,808 phosphoproteins were identified from 10 paired tissues. The protein phosphorylation level in ILC tissues was higher than that in IDC tissues. Histone H1.10 was significantly increased in IDC but decreased in ILC, Conversely, complement C4-B and Crk-like protein were significantly decreased in IDC but increased in ILC. Moreover, the increased protein expression of Septin-2, Septin-9, Heterogeneous nuclear ribonucleoprotein A1 and Kinectin but reduce of their phosphorylation could clearly distinguish IDC from ILC. In addition, IDC was primarily related to energy metabolism and MAPK pathway, while ILC was more closely involved in the AMPK and p53/p21 pathways. Furthermore, the kinomes in IDC were primarily significantly activated in the CMGC groups.

CONCLUSIONS: Our research provides insights into the molecular characterization of IDC and ILC and contributes to discovering novel targets for further drug development and targeted treatment.}, } @article {pmid37063453, year = {2023}, author = {Zhang, L and Hao, J and Guo, J and Zhao, X and Yin, X}, title = {Predicting of Ki-67 Expression Level Using Diffusion-Weighted and Synthetic Magnetic Resonance Imaging in Invasive Ductal Breast Cancer.}, journal = {The breast journal}, volume = {2023}, number = {}, pages = {6746326}, pmid = {37063453}, issn = {1524-4741}, mesh = {Humans ; Female ; Ki-67 Antigen/metabolism ; Retrospective Studies ; *Breast Neoplasms/diagnostic imaging ; Magnetic Resonance Imaging ; Diffusion Magnetic Resonance Imaging/methods ; ROC Curve ; }, abstract = {OBJECTIVES: To investigate the association between quantitative parameters generated using synthetic magnetic resonance imaging (SyMRI) and diffusion-weighted imaging (DWI) and Ki-67 expression level in patients with invasive ductal breast cancer (IDC).

METHOD: We retrospectively reviewed the records of patients with IDC who underwent SyMRI and DWI before treatment. Precontrast and postcontrast relaxation times (T1, longitudinal; T2, transverse), proton density (PD) parameters, and apparent diffusion coefficient (ADC) values were measured in breast lesions. Univariate and multivariate regression analyses were performed to screen for statistically significant variables to differentiate the high (≥30%) and low (<30%) Ki-67 expression groups. Their performance was evaluated by receiver operating characteristic (ROC) curve analysis.

RESULTS: We analyzed 97 patients. Multivariate regression analysis revealed that the high Ki-67 expression group (n = 57) had significantly higher parameters generated using SyMRI (pre-T1, p=0.001) and lower ADC values (p=0.036) compared with the low Ki-67 expression group (n = 40). Pre-T1 showed the best diagnostic performance for predicting the Ki-67 expression level in patients with invasive ductal breast cancer (areas under the ROC curve (AUC), 0.711; 95% confidence interval (CI), 0.609-0.813).

CONCLUSIONS: Pre-T1 could be used to predict the pretreatment Ki-67 expression level in invasive ductal breast cancer.}, } @article {pmid37061239, year = {2023}, author = {López-Janeiro, Á and Rodriguez, AM and Mendiola, M and Sabbagh, RN and Feliu, J and Villadóniga, A and Mendez, MDC}, title = {Pancreatic intraductal papillary mucinous neoplasm with sarcomatous transformation. A case report.}, journal = {Revista espanola de patologia : publicacion oficial de la Sociedad Espanola de Anatomia Patologica y de la Sociedad Espanola de Citologia}, volume = {56}, number = {2}, pages = {124-128}, doi = {10.1016/j.patol.2021.05.004}, pmid = {37061239}, issn = {1988-561X}, mesh = {Female ; Humans ; Aged ; *Pancreatic Intraductal Neoplasms ; *Carcinoma, Pancreatic Ductal/pathology ; *Adenocarcinoma, Mucinous/genetics/pathology ; Neoplasm Recurrence, Local ; *Pancreatic Neoplasms/pathology ; }, abstract = {Mixed pancreatic epithelial and mesenchymal tumors are rare, usually invasive, entities. Intraductal papillary mucinous neoplasm (IPMN) is a precursor of invasive ductal carcinoma and shares mutations with its invasive counterparts. We report the case of a 72-year-old female with a previously undescribed sarcomatous transformation of a residual IPMN with no evidence of an invasive component. The mesenchymal component showed no heterologous differentiation. Both the epithelial and the mesenchymal populations showed aberrant expression of p53 protein and the same point mutation in KRAS gene. After a 6 month follow up, there were no signs of local or distant relapse. The present case suggests that sarcomatous transformation is possible in non-invasive, intraductal pancreatic lesions.}, } @article {pmid37060681, year = {2023}, author = {Chamadoira, J and Au, F and Ghai, S and Kulkarni, S and Grant, A and Fleming, R and Alvarenga, P and Freitas, V}, title = {Effects of delayed callback from screening mammography due to the COVID-19 pandemic.}, journal = {Clinical imaging}, volume = {99}, number = {}, pages = {41-46}, pmid = {37060681}, issn = {1873-4499}, mesh = {Female ; Humans ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Mammography/methods ; *Breast Neoplasms/diagnostic imaging/epidemiology ; Pandemics ; Retrospective Studies ; Early Detection of Cancer ; *COVID-19/epidemiology ; Mass Screening ; }, abstract = {OBJECTIVE: To determine the frequency and distinguishing imaging characteristics of breast cancers detected on screening mammography which was initially evaluated as a probably benign lesion and the workup was delayed due to the COVID-19 pandemic.

MATERIALS AND METHODS: REB-approved multicenter retrospective screening mammography studies and patient's chart review carried out between February 2020 and March 2020. According to an institutional decision, the frequency and imaging findings deemed probably benign on screening mammography after review by a breast fellowship-trained radiologist with workup deferred until after the first pandemic wave plateau in late July 2020 were recorded. Results were correlated with histopathology if tissue sample performed or an uneventful 2 years follow-up. Descriptive statistical analysis was used to describe the retrieved data set.

RESULTS: Out of 1816 mammography screening between February 2020 and March 2020, 99 women, median age 58 years (range 35-84), 99 mammography had possibly benign findings with workup delayed, and two patients, age 49 and 56, had cancers (2.02%), misinterpreted as benign findings. Both malignant cases were focal asymmetries, with pathology of invasive ductal carcinoma, 12 mm and 9 mm in size. No in-situ carcinoma was detected.

CONCLUSION: The low rate of cancer detected suggests that a delay callback may be a reasonable option for some likely benign findings when immediate callback is not an option, such as during a pandemic. Larger studies would be helpful to support our findings and may allow us to translate the adoption of such a model during potential future pandemic.

CLINICAL RELEVANCE: The results of this study may be helpful for a future situation when delaying a call back from screening mammography is again required.}, } @article {pmid37056337, year = {2023}, author = {Pu, S and Xie, P and Chen, H and Li, Y and He, J and Zhang, H}, title = {Evaluation of outcome of chemotherapy for breast cancer patients older than 70 years: A SEER-based study.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {992573}, pmid = {37056337}, issn = {2234-943X}, abstract = {BACKGROUND: With the aging of the population, the number of elderly breast cancer cases has increased. However, there is a lack of effective randomized clinical trial data to support whether elderly patients should receive chemotherapy. Our goal was to observe the relationship between chemotherapy and breast cancer-specific survival (BCSS) in elderly breast cancer patients and to identify those who could benefit from chemotherapy.

METHODS: We collected the data of patients who were diagnosed with invasive ductal carcinoma and older than 70 years in the SEER database from 1995 to 2016. The independent predictors of BCSS were identified by Cox regression analysis. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to eliminate confounding factors.

RESULTS: A total of 142,537 patients were collected, including 21,782 patients in the chemotherapy group and 120,755 patients in the non-chemotherapy group. We identified the same potential predictors of BCSS after PSM and IPTW, such as age, race, grade, stage, therapy, subtype. A nomogram for predicting 3-year, 5-year and 10-year BCSS was constructed. The 3-year, 5-year and 10-year AUCs of the nomogram were 0.842, 0.819, and 0.788. According to the risk stratification of model predictive scores, patients in the high-risk group achieved the greatest improvement in BCSS after receiving chemotherapy.

CONCLUSIONS: Our study suggests that women older than 70 years with larger tumors, higher grade, positive nodes, negative hormone receptor and inactive local therapy gain prognostic benefits from chemotherapy, but for those with low- and median-risk, conventional chemotherapy should be administered cautiously.}, } @article {pmid37055018, year = {2023}, author = {De Angelis Rigotti, F and Wiedmann, L and Hubert, MO and Vacca, M and Hasan, SS and Moll, I and Carvajal, S and Jiménez, W and Starostecka, M and Billeter, AT and Müller-Stich, B and Wolff, G and Ekim-Üstünel, B and Herzig, S and Fandos-Ramo, C and Krätzner, R and Reich, M and Keitel-Anselmino, V and Heikenwälder, M and Mogler, C and Fischer, A and Rodriguez-Vita, J}, title = {Semaphorin 3C exacerbates liver fibrosis.}, journal = {Hepatology (Baltimore, Md.)}, volume = {78}, number = {4}, pages = {1092-1105}, doi = {10.1097/HEP.0000000000000407}, pmid = {37055018}, issn = {1527-3350}, mesh = {Animals ; Humans ; Mice ; *Hepatic Stellate Cells/metabolism ; Liver/pathology ; Liver Cirrhosis/pathology ; Phosphorylation ; *Semaphorins/genetics/metabolism ; Transforming Growth Factor beta/metabolism ; }, abstract = {BACKGROUND AND AIMS: Chronic liver disease is a growing epidemic, leading to fibrosis and cirrhosis. TGF-β is the pivotal profibrogenic cytokine that activates HSC, yet other molecules can modulate TGF-β signaling during liver fibrosis. Expression of the axon guidance molecules semaphorins (SEMAs), which signal through plexins and neuropilins (NRPs), have been associated with liver fibrosis in HBV-induced chronic hepatitis. This study aims at determining their function in the regulation of HSCs.

APPROACH AND RESULTS: We analyzed publicly available patient databases and liver biopsies. We used transgenic mice, in which genes are deleted only in activated HSCs to perform ex vivo analysis and animal models. SEMA3C is the most enriched member of the semaphorin family in liver samples from patients with cirrhosis. Higher expression of SEMA3C in patients with NASH, alcoholic hepatitis, or HBV-induced hepatitis discriminates those with a more profibrotic transcriptomic profile. SEMA3C expression is also elevated in different mouse models of liver fibrosis and in isolated HSCs on activation. In keeping with this, deletion of SEMA3C in activated HSCs reduces myofibroblast marker expression. Conversely, SEMA3C overexpression exacerbates TGF-β-mediated myofibroblast activation, as shown by increased SMAD2 phosphorylation and target gene expression. Among SEMA3C receptors, only NRP2 expression is maintained on activation of isolated HSCs. Interestingly, lack of NRP2 in those cells reduces myofibroblast marker expression. Finally, deletion of either SEMA3C or NRP2, specifically in activated HSCs, reduces liver fibrosis in mice.

CONCLUSION: SEMA3C is a novel marker for activated HSCs that plays a fundamental role in the acquisition of the myofibroblastic phenotype and liver fibrosis.}, } @article {pmid37042686, year = {2023}, author = {Gallucci, L and Abele, T and Fronza, R and Stolp, B and Laketa, V and Sid Ahmed, S and Flemming, A and Müller, B and Göpfrich, K and Fackler, OT}, title = {Tissue-like environments shape functional interactions of HIV-1 with immature dendritic cells.}, journal = {EMBO reports}, volume = {24}, number = {6}, pages = {e56818}, pmid = {37042686}, issn = {1469-3178}, mesh = {Humans ; *HIV-1 ; Cytokines/metabolism ; Collagen/metabolism ; Antiviral Agents ; Dendritic Cells ; *HIV Infections ; }, abstract = {Immature dendritic cells (iDCs) migrate in microenvironments with distinct cell and extracellular matrix densities in vivo and contribute to HIV-1 dissemination and mounting of antiviral immune responses. Here, we find that, compared to standard 2D suspension cultures, 3D collagen as tissue-like environment alters iDC properties and their response to HIV-1 infection. iDCs adopt an elongated morphology with increased deformability in 3D collagen at unaltered activation, differentiation, cytokine secretion, or responsiveness to LPS. While 3D collagen reduces HIV-1 particle uptake by iDCs, fusion efficiency is increased to elevate productive infection rates due to elevated cell surface exposure of the HIV-1-binding receptor DC-SIGN. In contrast, 3D collagen reduces HIV transfer to CD4 T cells from iDCs. iDC adaptations to 3D collagen include increased pro-inflammatory cytokine production and reduced antiviral gene expression in response to HIV-1 infection. Adhesion to a 2D collagen matrix is sufficient to increase iDC deformability, DC-SIGN exposure, and permissivity to HIV-1 infection. Thus, mechano-physical cues of 2D and 3D tissue-like collagen environments regulate iDC function and shape divergent roles during HIV-1 infection.}, } @article {pmid37038064, year = {2023}, author = {Cerullo, G and Videira-Silva, A and Carrancha, M and Rego, F and Nunes, R}, title = {Complexity of patient care needs in palliative care: a scoping review.}, journal = {Annals of palliative medicine}, volume = {12}, number = {4}, pages = {791-802}, doi = {10.21037/apm-22-894}, pmid = {37038064}, issn = {2224-5839}, mesh = {Humans ; *Quality of Life ; Palliative Care ; *Hospice and Palliative Care Nursing ; Patient Care ; Referral and Consultation ; }, abstract = {BACKGROUND: Recognizing the need for palliative care (PC) and referral to PC teams improves patients' quality of life. However, in patients with moderate/severe clinical complexity, early recognition of the need for PC may not correspond to referral to specialized PC services. The definition for clinical complexity is still underexplored, as well as the instruments available to assess complexity. This scoping review aims to gather relevant information on the definition of clinical complexity in PC, as well as on the instruments used to objectively assess complexity.

METHODS: According to the methodology of a Scoping Review, the keywords: "palliative care", "hospitalization criteria", "complexity criteria", "complexity assessment" and "clinical complexity", were searched in PubMed, Scopus, Cochrane, and b-on databases, during April 2022, for relevant information on the definition and/or approach and/or protocols related to clinical complexity in patients followed in PC, or on the instruments used to assess it, regardless of study design, the language, or year of publication.

RESULTS: From the 626 references found, 15 studies were included in the review. According to these studies, complexity may be organized/defined into 3, 4, or 6 domains, generally including the patient, the family, the health system, and the socio-cultural context. Of the 13 instruments mentioned for the objective assessment of complexity, the HexCom, IDC-Pal, and the recent ID-PALL seem to offer the broadest determinations of complexity.

CONCLUSIONS: Complexity is a dynamic process, which reflects the reality of patients and families, and patients, families, and health professionals' perceptions, and so it must be systematically adjusted to the stage of the disease. The definition of complexity and the development and use of suitable instruments can help to identify, assess, and improve patients' quality of life, while supporting their family across the grieving process. Yet, this may not always be summarized in a quantitative value by easy-to-use instruments, highlighting the role of PC interdisciplinary teams.}, } @article {pmid37035759, year = {2023}, author = {Fan, Z and Wu, S and Sang, H and Li, Q and Cheng, S and Zhu, H}, title = {Identification of GPD1L as a Potential Prognosis Biomarker and Associated with Immune Infiltrates in Lung Adenocarcinoma.}, journal = {Mediators of inflammation}, volume = {2023}, number = {}, pages = {9162249}, pmid = {37035759}, issn = {1466-1861}, mesh = {Humans ; *Adenocarcinoma of Lung ; *Lung Neoplasms ; Clinical Relevance ; Disease-Free Survival ; Biomarkers ; Prognosis ; }, abstract = {Lung adenocarcinoma (LUAD) is one of the most prevalent pathological kinds of lung cancer, which is a common form of cancer that has a high death rate. Over the past several years, growing studies have indicated that GPD1L was involved in the advancement of a number of different cancers. However, its clinical significance in LUAD has not been investigated. In this study, following an examination of the TGCA datasets, we found that GPD1L displayed a dysregulated state in a wide variety of cancers; this led us to believe that GPD1L is an essential regulator in the progression of malignancies. In addition, we found that the expression of GPD1L was much lower in LUAD tissues when compared with nontumor specimens. According to the findings of ROC tests, GPD1L was able to effectively identify LUAD specimens from nontumor samples with an AUC value of 0.828 (95% confidence interval: 0.793 to 0.863). On the basis of the clinical study, a low expression of GPD1L was clearly related with both the N stage and the clinical stage. Moreover, based on the findings of a Kaplan-Meier survival study, elevated GPD1L expression was a strong indicator of considerably improved overall survival (OS) and disease-specific survival (DSS). GPD1L expression and clinical stages were found to be independent prognostic indicators for overall survival and disease-free survival in LUAD patients, according to multivariate analyses. Based on multivariate analysis, the C-indexes and calibration plots of the nomogram demonstrated an effective prediction performance for LUAD patients. Besides, the expression of GPD1L was positively related to mast cells, eosinophils, Tcm, TFH, iDC, DC, and macrophages, while negatively associated with Th2 cells, NK CD56dim cells, Tgd, Treg, and neutrophils. Finally, qRT-PCR was able to demonstrate that GPD1L had a significant amount of expression in LUAD. Additionally, according to the results of functional tests, overexpression of GPD1L had a significant inhibiting effect on the proliferation of LUAD cells. In general, the results of our study suggested that GPD1L had the potential to serve as a diagnostic and prognostic marker for LUAD.}, } @article {pmid37032571, year = {2023}, author = {Zemah-Shamir, S and Zemah-Shamir, Z and Peled, Y and Sørensen, OJR and Schwartz Belkin, I and Portman, ME}, title = {Comparing spatial management tools to protect highly migratory shark species in the Eastern Mediterranean Sea hot spots.}, journal = {Journal of environmental management}, volume = {337}, number = {}, pages = {117691}, doi = {10.1016/j.jenvman.2023.117691}, pmid = {37032571}, issn = {1095-8630}, mesh = {Animals ; Humans ; Ecosystem ; *Sharks ; Mediterranean Sea ; Animals, Wild ; *Turtles ; Fisheries ; Conservation of Natural Resources/methods ; Mammals ; }, abstract = {Bycatch of non-target species is a pressing problem for ocean management. It is one of the most concerning issues related to human-wildlife interactions and it affects numerous species including sharks, seabirds, sea turtles, and many critically endangered marine mammals. This paper compares different policy tools for ocean closure management around a unique shark aggregation site in Israel's nearshore coastal waters. We provide a set of recommendations based on an optimal management approach that allows humans to enjoy marine recreational activities such as fishing, while maintaining safe conditions for these apex predators which are vital to the local marine ecosystem. To learn more about recreational fishers' derived benefits, we use a benefit transfer method. Our main conclusion is that dynamic time-area closures offer sustainable and effective management strategies. Since these closures are based on near real-time data, they might successfully preserve specific species in limited areas (i.e., small areas).}, } @article {pmid37029001, year = {2023}, author = {Ramli Hamid, MT and Ab Mumin, N and Wong, YV and Chan, WY and Rozalli, FI and Rahmat, K}, title = {The effectiveness of an ultrafast breast MRI protocol in the differentiation of benign and malignant breast lesions.}, journal = {Clinical radiology}, volume = {78}, number = {6}, pages = {444-450}, doi = {10.1016/j.crad.2023.03.006}, pmid = {37029001}, issn = {1365-229X}, mesh = {Humans ; Adult ; Middle Aged ; Aged ; Female ; *Carcinoma, Intraductal, Noninfiltrating ; Contrast Media ; Diagnosis, Differential ; Retrospective Studies ; Magnetic Resonance Imaging/methods ; *Breast Carcinoma In Situ ; *Breast Neoplasms ; }, abstract = {AIM: To evaluate the effectiveness of an ultrafast breast magnetic resonance imaging (MRI) protocol in differentiating benign and malignant breast lesions.

MATERIALS AND METHODS: Fifty-four patients with Breast Imaging Reporting and Data System (BI-RADS) 4 or 5 lesions were recruited between July 2020 to May 2021. A standard breast MRI was performed with the inclusion of the ultrafast protocol between the unenhanced sequence and the first contrast-enhanced sequence. Three radiologists performed image interpretation in consensus. Ultrafast kinetic parameters analysed included the maximum slope (MS), time to enhancement (TTE), and arteriovenous index (AVI). These parameters were compared using receiver operating characteristics with p-values of <0.05 considered to indicate statistical significance.

RESULTS: Eighty-three histopathological proven lesions from 54 patients (mean age 53.87 years, SD 12.34, range 26-78 years) were analysed. Forty-one per cent (n=34) were benign and 59% (n=49) were malignant. All malignant and 38.2% (n=13) benign lesions were visualised on the ultrafast protocol. Of the malignant lesions, 77.6% (n=53) were invasive ductal carcinoma (IDC) and 18.4% (n=9) were ductal carcinoma in situ (DCIS). The MS for malignant lesions (13.27%/s) were significantly larger than for benign (5.45%/s; p<0.0001). No significant differences were seen for TTE and AVI. The area under the ROC curve (AUC) for the MS, TTE, and AVI were 0.836, 0.647, and 0.684, respectively. Different types of invasive carcinoma had similar MS and TTE. The MS of high-grade DCIS was also similar to that of IDC. Lower MS values were observed for low-grade (5.3%/s) compared to high-grade DCIS (14.8%/s) but the results were not significant statistically.

CONCLUSION: The ultrafast protocol showed potential to discriminate between malignant and benign breast lesions with high accuracy using MS.}, } @article {pmid37028455, year = {2023}, author = {Lin, Y and Amkul, K and Laosatit, K and Liu, J and Yimram, T and Chen, J and Yuan, X and Chen, X and Somta, P}, title = {Fine mapping of QTL conferring resistance to calcareous soil in mungbean reveals VrYSL3 as candidate gene for the resistance.}, journal = {Plant science : an international journal of experimental plant biology}, volume = {332}, number = {}, pages = {111698}, doi = {10.1016/j.plantsci.2023.111698}, pmid = {37028455}, issn = {1873-2259}, mesh = {Quantitative Trait Loci/genetics ; *Vigna/genetics/metabolism ; Genome-Wide Association Study ; Soil ; Iron/metabolism ; *Iron Deficiencies ; }, abstract = {Iron is a crucial nutrient for biological functions in plants. High-pH and calcareous soil is a major stress causing iron deficiency chlorosis (IDC) symptoms and yield losses in crops. Use of calcareous soil-tolerance genetic resources is the most effective preventative method to combat the effects of high-pH and calcareous soils. A previous study using a mungbean recombinant inbred line (RIL) population of the cross Kamphaeg Saen 2 (KPS2; IDC susceptible) × NM-10-12 identified a major quantitative trait locus (QTL), qIDC3.1, which controls resistance and explains more than 40% of IDC variation. In this study, we fine-mapped qIDC3.1 and identified an underlying candidate gene. A genome wide association analysis (GWAS) using 162 mungbean accessions identified single nucleotide polymorphisms (SNPs) on chromosome 6; several SNPs were associated with soil plant analysis development (SPAD) values and IDC visual scores of mungbeans planted on calcareous soil, respectively. These SNPs corresponded to qIDC3.1. Using the same RIL population as in the previous study and an advanced backcross population developed from KPS2 and IDC-resistant inbred line RIL82, qIDC3.1 was further confirmed and fine-mapped to an interval of 217 kilobases harboring five predicted genes, including LOC106764181 (VrYSL3), which encodes a yellow stripe1-like-3 (YSL3) protein, YSL3 is involved in iron deficiency resistance. Gene expression analysis revealed that VrYSL3 was highly expressed in mungbean roots. In calcareous soil, expression of VrYSL3 was significantly up-regulated, and it was more obviously upregulated in the roots of RIL82, than in those of KPS2. Sequence comparison of VrYSL3 between the RIL82 and KPS2 revealed four SNPs that result in amino acid changes in the VrYSL3 protein and a 20-bp insertion/deletion in the promoter where a cis-regulatory element resides. Transgenic Arabidopsis thaliana plants overexpressing VrYSL3 showed enhanced iron and zinc contents in the leaves. Taken together, these results indicate that VrYSL3 is a strong candidate gene responsible for calcareous soil resistance in mungbean.}, } @article {pmid37028182, year = {2023}, author = {Yahaya, JJ and Ngaiza, AI and Morgan, ED and Abraham, ZS and Othieno, E}, title = {Invasive ductal carcinoma of breast in a 73-year old male: A rare case report and literature review.}, journal = {International journal of surgery case reports}, volume = {105}, number = {}, pages = {108121}, pmid = {37028182}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Male breast cancers despite being similar to female breast cancers in various aspects; however, they have important distinctive characteristics such as molecular biology, increased tendency for axillary lymph node metastasis and late age at presentation.

PRESENTATION OF CASE: We present the case of a 73-year old indigenous African male who had a 3-year history of right breast swelling which was associated with episodes of pain and tenderness. The assigned clinical stage for the patient was T2aNoMo. The mass was histologically confirmed to be invasive ductal carcinoma, not specified type (NST) without axillary lymph node involvement or distant metastasis. Immunohistochemistry also showed positive results for ER and PR hormonal receptors but negative for HER2.

CLINICAL DISCUSSION: Considering the rarity nature of male breast cancers, this contributes to lack of evidence of the specific treatment approaches despite the noticeable difference in clinical presentation and even biological characteristics of male breast cancers, which are more likely to contribute to poor prognosis.

CONCLUSION: The prevalence of male breast cancers has been reported to be less than 1 % of all male cancers. This contributes to the lack of analytical large studies that address the comprehensive data regarding the clinical outcomes of breast cancer among men and their predictors. Therefore, having prospective multicenter studies in future would help in providing high level of evidence on prognosis.}, } @article {pmid37020090, year = {2023}, author = {Kawaguchi, S and Kinowaki, K and Tamura, N and Masumoto, T and Nishikawa, A and Shibata, A and Tanaka, K and Kobayashi, Y and Ogura, T and Sato, J and Kawabata, H}, title = {High-accuracy prediction of axillary lymph node metastasis in invasive lobular carcinoma using focal cortical thickening on magnetic resonance imaging.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {30}, number = {4}, pages = {637-646}, pmid = {37020090}, issn = {1880-4233}, mesh = {Humans ; Female ; Middle Aged ; Aged ; *Breast Neoplasms/pathology ; Lymphatic Metastasis/diagnostic imaging/pathology ; *Carcinoma, Lobular/diagnostic imaging/surgery/pathology ; Retrospective Studies ; *Carcinoma, Ductal, Breast/pathology ; Lymph Nodes/pathology ; Magnetic Resonance Imaging ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) grows diffusely in a single-cell fashion, sometimes presenting only subtle changes in preoperative imaging; therefore, axillary lymph node (ALN) metastases of ILC are difficult to detect using magnetic resonance imaging (MRI). Preoperative underestimation of nodal burden occurs more frequently in ILC than in invasive ductal carcinoma (IDC), however, the morphological assessment for metastatic ALNs of ILC have not fully been investigated. We hypothesized that the high false-negative rate in ILC is caused by the discrepancy in the MRI findings of ALN metastases between ILC and IDC and aimed to identify the MRI finding with a strong correlation with ALN metastasis of ILC.

METHOD: This retrospective analysis included 120 female patients (mean ± standard deviation age, 57.2 ± 11.2 years) who underwent upfront surgery for ILC at a single center between April 2011 and June 2022. Of the 120 patients, 35 (29%) had ALN metastasis. Using logistic regression, we constructed prediction models based on MRI findings: primary tumor size, focal cortical thickening (FCT), cortical thickness, long-axis diameter (LAD), and loss of hilum (LOH).

RESULTS: The area under the curves were 0.917 (95% confidence interval [CI] 0.869-0.968), 0.827 (95% CI 0.758-0.896), 0.754 (95% CI 0.671-0.837), and 0.621 (95% CI 0.531-0.711) for the FCT, cortical thickness, LAD, and LOH models, respectively.

CONCLUSIONS: FCT may be the most relevant MRI finding for ALN metastasis of ILC, and although its prediction model may lead to less underestimation of the nodal burden, rigorous external validation is required.}, } @article {pmid37017594, year = {2023}, author = {Zheng, L and Wu, H and Wen, N and Zhang, Y and Wang, Z and Peng, X and Tan, Y and Qiu, L and Qu, F and Tan, W}, title = {Aptamer-Functionalized Nanovaccines: Targeting In Vivo DC Subsets for Enhanced Antitumor Immunity.}, journal = {ACS applied materials & interfaces}, volume = {15}, number = {15}, pages = {18590-18597}, doi = {10.1021/acsami.2c20846}, pmid = {37017594}, issn = {1944-8252}, mesh = {Humans ; *Cancer Vaccines ; Immunotherapy/methods ; T-Lymphocytes ; Antigens, Neoplasm/genetics ; *Neoplasms/therapy ; Adjuvants, Immunologic ; Adjuvants, Pharmaceutic ; Dendritic Cells ; }, abstract = {Cancer vaccines, which directly pulsed in vivo dendritic cells (DCs) with specific antigens and immunostimulatory adjuvants, showed great potential for cancer immunoprevention. However, most of them were limited by suboptimal outcomes, mainly owing to overlooking the complex biology of DC phenotypes. Herein, based on adjuvant-induced antigen assembly, we developed aptamer-functionalized nanovaccines for in vivo DC subset-targeted codelivery of tumor-related antigens and immunostimulatory adjuvants. We chose two aptamers, iDC and CD209, and tested their performance on DC targeting. Our results verified that these aptamer-functionalized nanovaccines could specifically recognize circulating classical DCs (cDCs), a subset of DCs capable of priming naïve T cells, noting that iDC outperformed CD209 in this regard. With excellent cDC-targeting capability, the iDC-functionalized nanovaccine induced potent antitumor immunity, leading to effective inhibition of tumor occurrence and metastasis, thus providing a promising platform for cancer immunoprevention.}, } @article {pmid37015704, year = {2024}, author = {Haq, AU and Li, JP and Khan, I and Agbley, BLY and Ahmad, S and Uddin, MI and Zhou, W and Khan, S and Alam, I}, title = {DEBCM: Deep Learning-Based Enhanced Breast Invasive Ductal Carcinoma Classification Model in IoMT Healthcare Systems.}, journal = {IEEE journal of biomedical and health informatics}, volume = {28}, number = {3}, pages = {1207-1217}, doi = {10.1109/JBHI.2022.3228577}, pmid = {37015704}, issn = {2168-2208}, mesh = {Humans ; Female ; *Deep Learning ; Benchmarking ; *Breast Neoplasms/diagnostic imaging ; Delivery of Health Care ; *Carcinoma, Ductal ; }, abstract = {Accurate breast cancer (BC) diagnosis is a difficult task that is critical for the proper treatment of BC in IoMT (Internet of Medical Things) healthcare systems. This paper proposes a convolutional neural network (CNN)-based diagnosis method for detecting early-stage breast cancer. In developing the proposed method, we incorporated the CNN model for the invasive ductal carcinoma (IDC) classification using breast histology image data. We have incorporated transfer learning (TL) and data augmentation (DA) mechanisms to improve the CNN model's predictive outcomes. For the fine-tuning process, the CNN model was trained with breast histology image data. Furthermore, the held-out cross-validation method for best model selection and hyper-parameter tuning was incorporated. In addition, various performance evaluation metrics for model performance assessment were computed. The experimental results confirmed that the proposed model outperformed the baseline models across all evaluation metrics, achieving 99.04% accuracy. We recommend the proposed method for early recognition of BC in IoMT healthcare systems due to its high performance.}, } @article {pmid37013774, year = {2023}, author = {Oh, J and Oh, JM and Cho, SY}, title = {METTL3-mediated downregulation of splicing factor SRSF11 is associated with carcinogenesis and poor survival of cancer patients.}, journal = {European review for medical and pharmacological sciences}, volume = {27}, number = {6}, pages = {2561-2570}, doi = {10.26355/eurrev_202303_31793}, pmid = {37013774}, issn = {2284-0729}, mesh = {Humans ; *Adenocarcinoma of Lung ; Carcinogenesis ; *Colonic Neoplasms ; Down-Regulation ; *Lung Neoplasms/genetics/pathology ; *Methyltransferases/genetics ; *Serine-Arginine Splicing Factors/genetics ; }, abstract = {OBJECTIVE: N6-methyladenosine (m6A) is one of the most abundant post-transcriptional modifications in eukaryotic RNA. As m6A modifications play an important role in RNA processing, abnormal m6A regulation caused by aberrant expression of m6A regulators is closely related to carcinogenesis. In this study, we aimed to determine the role of METTL3 expression in carcinogenesis, regulation of splicing factor expression by METTL3, and their effects in survival period and cancer-related metabolisms.

MATERIALS AND METHODS: We investigated the correlation between each splicing factor and METTL3 in breast invasive ductal carcinoma (BRCA), colon adenocarcinoma (COAD), lung adenocarcinoma (LUAD) and gastric adenocarcinoma (STAD). Survival analysis was performed based on the expression of each splicing factor. To determine the molecular mechanism of SRSF11 in carcinogenesis, gene set enrichment analysis using RNA sequencing data was performed according to SRSF11 expression.

RESULTS: Among the 64 splicing factors used for correlation analysis, 13 splicing factors showed a positive correlation with METTL3 in all four cancer types. We found that when METTL3 expression was decreased, the expression of SRSF11 was also decreased in all four types of cancer tissue when compared to that in normal tissue. Decreased SRSF11 expression was associated with poor survival in patients with BRCA, COAD, LUAD, and STAD. Gene set enrichment analysis according to SRSF11 expression showed that the p53/apoptosis, inflammation/immune response, and ultraviolet/reactive oxygen species stimulus-response pathways were enriched in cancers with decreased SRSF11 expression.

CONCLUSIONS: These results suggest that METTL3 regulates SRSF11 expression, which could influence mRNA splicing in m6A modified cancer cells. METTL3-mediated downregulation of SRSF11 expression in cancer patients correlates with poor prognosis.}, } @article {pmid37011225, year = {2023}, author = {Thomas, R and Umar, T and Borumandi, F}, title = {Intraductal Carcinoma: The Carcinoma In Situ of the Salivary Gland.}, journal = {The Journal of craniofacial surgery}, volume = {34}, number = {5}, pages = {e432-e434}, doi = {10.1097/SCS.0000000000009287}, pmid = {37011225}, issn = {1536-3732}, mesh = {Humans ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/surgery ; *Salivary Gland Neoplasms/diagnostic imaging/surgery ; *Carcinoma in Situ ; Biopsy, Fine-Needle ; Parotid Gland/pathology ; *Parotid Neoplasms/diagnostic imaging/surgery ; }, abstract = {Intraductal carcinoma of the salivary gland (IDC) is a rare in situ neoplasm of the salivary gland with similar features to the ductal carcinoma in situ of the breast. This report aims to present the clinical presentation and histological features of IDC. The authors present a 90-year-old gentleman with an indurated and painless tumor within the right parotid. Preoperative diagnostics, including fine needle aspiration cytology, ultrasound scan, and magnetic resonance imaging, were suggestive of Warthin tumor. The tumour was excised by extracapsular dissection. The patient is disease free within the follow-up period of 33 months. Intraductal carcinoma is an indolent phenotype with only a few reported cases with nodal metastases, and to the best of our knowledge, no cases have been reported with distant metastases. Complete surgical excision is recommended to prevent a recurrence. The knowledge of this underreported salivary gland malignancy is important to prevent misdiagnosis and insufficient treatment.}, } @article {pmid37010596, year = {2023}, author = {Danzinger, S and Pöckl, K and Kronawetter, G and Pfeifer, C and Behrendt, S and Gscheidlinger, P and Harrasser, L and Mühlböck, H and Dirschlmayer, W and Schauer, C and Reitsamer, R and Uher, H and Schönau, K and Delmarko, I and Singer, CF}, title = {Axillary lymph node status and invasive lobular breast cancer : Analysis of the Clinical Tumor Register of the AGO Austria.}, journal = {Wiener klinische Wochenschrift}, volume = {135}, number = {17-18}, pages = {463-471}, pmid = {37010596}, issn = {1613-7671}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnosis ; Austria/epidemiology ; *Carcinoma, Ductal, Breast/diagnosis/pathology/surgery ; *Carcinoma, Lobular/diagnosis/pathology/surgery ; Retrospective Studies ; Lymph Nodes/pathology ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) represents the second most common type of invasive breast cancer (BC). Although ILC generally have good prognostic properties (positive estrogen receptor, ER, low tumor grade), they are generally diagnosed at a more advanced stage. The data on the axillary lymph node status in ILC compared to invasive ductal carcinoma (IDC) are considered controversial. Therefore, the aim of this study was to compare the pathological node stage (pN) between ILC and IDC in an Austria-wide register.

METHODS: Data of the Clinical Tumor Register (Klinisches TumorRegister, KTR) of the Austrian Association for Gynecological Oncology (AGO) were retrospectively analyzed. Patients with primary early BC, invasive lobular or ductal, diagnosed between January 2014 and December 2018, and primary surgery were included. A total of 2127 tumors were evaluated and compared in 2 groups, ILC n = 303, IDC n = 1824.

RESULTS: A total of 2095 patients were analyzed in the study. In the multivariate analysis, pN2 and pN3 were observed significantly more frequently in ILC compared with IDC (odds ratio, OR 1.93; 95% confidence interval, CI 1.19-3.14; p = 0.008 and OR 3.22; 95% CI: 1.47-7.03; p = 0.003; respectively). Other factors associated with ILC were tumor grades 2 and 3, positive ER, and pathological tumor stage (pT) 2 and pT3. In contrast, concomitant ductal carcinoma in situ, overexpression of the human epidermal growth factor receptor 2 (HER2), and a moderate and high proliferation rate (Ki67) were found less frequently in ILC.

CONCLUSION: The data show an increased risk of extensive axillary lymph node metastasis (pN2/3) in ILC.}, } @article {pmid37010048, year = {2023}, author = {Geitung, JT}, title = {Editorial for "Feasibility of Quantitative MRI using 3D-QALAS for Discriminating Immunohistochemical Status in Invasive Ductal Carcinoma of the Breast".}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {58}, number = {6}, pages = {1760-1761}, doi = {10.1002/jmri.28712}, pmid = {37010048}, issn = {1522-2586}, mesh = {Humans ; Female ; Feasibility Studies ; Breast/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; *Carcinoma, Ductal ; *Breast Neoplasms/diagnostic imaging ; *Carcinoma, Ductal, Breast/pathology ; }, } @article {pmid37008917, year = {2023}, author = {Kender, Z and Jende, JME and Kurz, FT and Tsilingiris, D and Schimpfle, L and Sulaj, A and von Rauchhaupt, E and Bartl, H and Mooshage, C and Göpfert, J and Nawroth, P and Herzig, S and Szendroedi, J and Bendszus, M and Kopf, S}, title = {Sciatic nerve fractional anisotropy and neurofilament light chain protein are related to sensorimotor deficit of the upper and lower limbs in patients with type 2 diabetes.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1046690}, pmid = {37008917}, issn = {1664-2392}, mesh = {Humans ; *Diabetes Mellitus, Type 2/pathology ; Anisotropy ; Intermediate Filaments ; Sciatic Nerve/diagnostic imaging/pathology ; *Diabetic Neuropathies/complications ; Lower Extremity/diagnostic imaging ; Biomarkers ; }, abstract = {BACKGROUND: Diabetic sensorimotor polyneuropathy (DSPN) is one of the most prevalent and poorly understood diabetic microvascular complications. Recent studies have found that fractional anisotropy (FA), a marker for microstructural nerve integrity, is a sensitive parameter for the structural and functional nerve damage in DSPN. The aim of this study was to investigate the significance of proximal sciatic nerve's FA on different distal nerve fiber deficits of the upper and lower limbs and its correlation with the neuroaxonal biomarker, neurofilament light chain protein (NfL).

MATERIALS AND METHODS: Sixty-nine patients with type 2 diabetes (T2DM) and 30 healthy controls underwent detailed clinical and electrophysiological assessments, complete quantitative sensory testing (QST), and diffusion-weighted magnetic resonance neurography of the sciatic nerve. NfL was measured in the serum of healthy controls and patients with T2DM. Multivariate models were used to adjust for confounders of microvascular damage.

RESULTS: Patients with DSPN showed a 17% lower sciatic microstructural integrity compared to healthy controls (p<0.001). FA correlated with tibial and peroneal motor nerve conduction velocity (NCV) (r=0.6; p<0.001 and r=0.6; p<0.001) and sural sensory NCV (r=0.50; p<0.001). Participants with reduced sciatic nerve´s FA showed a loss of function of mechanical and thermal sensation of upper (r=0.3; p<0.01 and r=0.3; p<0.01) and lower (r=0.5; p<0.001 and r=0.3; p=<0.01) limbs and reduced functional performance of upper limbs (Purdue Pegboard Test for dominant hand; r=0.4; p<0.001). Increased levels of NfL and urinary albumin-creatinine ratio (ACR) were associated with loss of sciatic nerve´s FA (r=-0.5; p<0.001 and r= -0.3, p= 0.001). Of note, there was no correlation between sciatic FA and neuropathic symptoms or pain.

CONCLUSION: This is the first study showing that microstructural nerve integrity is associated with damage of different nerve fiber types and a neuroaxonal biomarker in DSPN. Furthermore, these findings show that proximal nerve damage is related to distal nerve function even before clinical symptoms occur. The microstructure of the proximal sciatic nerve and is also associated with functional nerve fiber deficits of the upper and lower limbs, suggesting that diabetic neuropathy involves structural changes of peripheral nerves of upper limbs too.}, } @article {pmid37006812, year = {2023}, author = {Su, X and Wang, G and Zheng, S and Ge, C and Kong, F and Wang, C}, title = {Comprehensive Explorations of CCL28 in Lung Adenocarcinoma Immunotherapy and Experimental Validation.}, journal = {Journal of inflammation research}, volume = {16}, number = {}, pages = {1325-1342}, pmid = {37006812}, issn = {1178-7031}, abstract = {BACKGROUND: Chemokines have been reported to play an important role in cancer immunotherapy. This study aimed to explore the chemokines involved in lung cancer immunotherapy.

METHODS: All the public data were downloaded from The Cancer Genome Atlas Program database. Quantitative real time-PCR was used to detect the mRNA level of specific molecules and Western blot was used for the protein level. Other experiments used include luciferase reporter experiments, flow cytometric analysis, Chromatin immunoprecipitation assay, ELISA and co-cultured system.

RESULTS: We found that the CCL7, CCL11, CCL14, CCL24, CCL25, CCL26, CCL28 had a higher level, while the CCL17, CCL23 had a lower level in immunotherapy non-responders. Also, we found that immunotherapy non-responders had a higher level of CD56dim NK cells, NK cells, Th1 cells, Th2 cells and Treg, yet a lower level of iDC and Th17 cells. Biological enrichment analysis indicated that in the patients with high Treg infiltration, the pathways of pancreas beta cells, KRAS signaling, coagulation, WNT BETA catenin signaling, bile acid metabolism, interferon alpha response, hedgehog signaling, PI3K/AKT/mTOR signaling, apical surface, myogenesis were significantly enriched in. CCL7, CCL11, CCL26 and CCL28 were selected for further analysis. Compared with the patients with high CCL7, CCL11, CCL26 and CCL28 expression, the patients with low CCL7, CCL11, CCL26 and CCL28 expression had a better performance of immunotherapy response and this effect might partly be due to Treg cells. Furthermore, biological exploration and clinical correlation of CCL7, CCL11, CCL26 and CCL28 were conducted, Finally, CCL28 was selected for validation. Experiments showed that under the hypoxia condition, HIF-1α was upregulated, which can directly bind to the promoter region of CCL28 and lead to its higher level. Also, CCL28 secreted by lung cancer cells could induce Tregs infiltration.

CONCLUSION: Our study provides a novel insight focused on the chemokines in lung cancer immunotherapy. Also, CCL28 was identified as an underlying biomarker for lung cancer immunotherapy.}, } @article {pmid36999966, year = {2023}, author = {Tan, HJ and Tan, PH and Leong, LCH and Tan, VKM and Tan, BKT and Lim, SZ and Preetha, M and Wong, CY and Yong, WS and Sim, Y}, title = {Encapsulated papillary carcinoma of the breast: An institutional case series and literature review.}, journal = {Cancer medicine}, volume = {12}, number = {10}, pages = {11408-11416}, pmid = {36999966}, issn = {2045-7634}, mesh = {Humans ; Female ; *Carcinoma, Papillary/surgery/pathology ; Breast/pathology ; *Carcinoma in Situ ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Prognosis ; *Breast Neoplasms/diagnosis/therapy ; *Carcinoma, Ductal, Breast/pathology ; Retrospective Studies ; }, abstract = {BACKGROUND: Encapsulated papillary carcinoma of the breast is rare, making difficult diagnosis and resulting in patients undergoing excision biopsy before definitive surgery. Evidence-based guidelines are sparse. We would like to further elucidate the clinicopathological, treatment and survival outcomes.

MATERIALS AND METHODS: 54 patients identified, with a median follow up duration of 48 months. Patients' demographics, radiological and clinicopathological characteristics, treatment, adjuvant therapies as well as survival data were analysed.

RESULTS: 18 (33.3%) cases were pure EPC, 12 (22.2%) were EPC associated with ductal carcinoma in situ (DCIS) and 24 (44.4%) cases had concurrent invasive ductal carcinoma. EPCs were more likely to present as a solid-cystic mass on sonography (63.8%), regular-shaped (oval or round) (97.9%), lack spiculations (95.7%) and lack suspicious microcalcifications (95.6%). Median tumour size was largest in the EPC with IDC group (18.5 mm). 2 patients developed loco-regional recurrence. Overall survival is good for EPCs of all subtypes.

CONCLUSION: EPC is a rare tumour with excellent prognosis.}, } @article {pmid36993608, year = {2023}, author = {Joshi, U and Budhathoki, P and Gaire, S and Yadav, SK and Shah, A and Adhikari, A and Choong, G and Couzi, R and Giridhar, K and Leon-Ferre, R and Boughey, JC and Hieken, TJ and Mutter, R and Ruddy, KJ and Haddad, TC and Goetz, MP and Couch, FJ and Yadav, S}, title = {Clinical Outcomes and Prognostic Factors in Triple-Negative Invasive Lobular Carcinoma of the Breast.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {36993608}, issn = {2693-5015}, support = {K12 CA090628/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; }, abstract = {Purpose: Triple-negative invasive lobular carcinoma (TN-ILC) of breast cancer is a rare disease and the clinical outcomes and prognostic factors are not well-defined. Methods: Women with stage I-III TN-ILC or triple-negative invasive ductal carcinoma (TN-IDC) of the breast undergoing mastectomy or breast-conserving surgery between 2010 and 2018 in the National Cancer Database were included. Kaplan-Meier curves and multivariate Cox proportional hazard regression were used to compare overall survival (OS) and evaluate prognostic factors. Multivariate logistic regression was performed to analyze the factors associated with pathological response to neoadjuvant chemotherapy. Results: The median age at diagnosis for women with TN-ILC was 67 years compared to 58 years in TN-IDC (p<0.001). There was no significant difference in the OS between TN-ILC and TN-IDC in multivariate analysis (HR 0.96, p=0.44). Black race and higher TNM stage were associated with worse OS, whereas receipt of chemotherapy or radiation was associated with better OS in TN-ILC. Among women with TN-ILC receiving neoadjuvant chemotherapy, the 5-year OS was 77.3% in women with a complete pathological response (pCR) compared to 39.8% in women without any response. The odds of achieving pCR following neoadjuvant chemotherapy were significantly lower in women with TN-ILC compared to TN-IDC (OR 0.53, p<0.001). Conclusion: Women with TN-ILC are older at diagnosis but have similar OS compared to TN-IDC after adjusting for tumor and demographic characteristics. Administration of chemotherapy was associated with improved OS in TN-ILC, but women with TN-ILC were less likely to achieve complete response to neoadjuvant therapy compared to TN-IDC.}, } @article {pmid36990811, year = {2023}, author = {Hong, F and Li, N and Feng, Z and Zhang, F}, title = {A case of male breast encapsulated papillary carcinoma with ductal carcinoma in situ and invasive ductal carcinoma.}, journal = {Asian journal of surgery}, volume = {46}, number = {9}, pages = {3777-3778}, doi = {10.1016/j.asjsur.2023.03.101}, pmid = {36990811}, issn = {0219-3108}, mesh = {Male ; Humans ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; *Carcinoma, Papillary/pathology ; *Carcinoma, Ductal, Breast/pathology ; Lymphatic Metastasis ; *Breast Neoplasms ; }, } @article {pmid36989828, year = {2023}, author = {Trillo, P and Sandoval, J and Trapani, D and Nicolò, E and Zagami, P and Giugliano, F and Tarantino, P and Vivanet, G and Ascione, L and Friedlaender, A and Esposito, A and Criscitiello, C and Curigliano, G}, title = {Evolution of biological features of invasive lobular breast cancer: Comparison between primary tumour and metastases.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {185}, number = {}, pages = {119-130}, doi = {10.1016/j.ejca.2023.02.028}, pmid = {36989828}, issn = {1879-0852}, mesh = {Humans ; Female ; *Triple Negative Breast Neoplasms ; *Carcinoma, Ductal, Breast/drug therapy ; Retrospective Studies ; *Carcinoma, Lobular/drug therapy ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Neoplasm Recurrence, Local/metabolism ; *Breast Neoplasms/drug therapy ; Prognosis ; Receptors, Progesterone/metabolism ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) has unique clinical-biological features. Phenotypical differences between primary tumours (PTs) and metastases (M) have been described for invasive ductal carcinoma, but data on ILC are limited.

METHODS: We retrospectively analysed patients with recurrent ILC from our institution from 2013 to 2020. We evaluated the discordance of the oestrogen receptor (ER), progesterone receptor (PgR) and HER2 between PT and M, to understand prognostic and therapeutic implications.

RESULTS: Thirteen percent (n = 91) of all patients had ILC. We observed 15%, 44% and 5% of ER, PgR and HER2 status discordance between PT and M. ER/PgR discordance was related to receptor loss and HER2 mainly due to gain. PT presented a luminal-like phenotype (93%); 6% and 1% were triple-negative (TNBC) and HER2-positive. In M, there was an increase in TNBC (16%) and HER2-positive (5%). Metastasis-free survival and overall survival (OS) were different according to clinical phenotype, with poorer prognosis for HER2+ and TNBC (p < 0.001); OS after metastatic progression did not differ across phenotypes (p = 0.079). In luminal-like ILC (n = 85) at diagnosis, we found that OS after relapse was poorer in patients experiencing a phenotype switch to TNBC but improved in patients with HER2 gain (p = 0.0028). Poorer survival was reported in patients with a PgR and/or ER expression loss of ≥25%. There was HER2-low enrichment in M1 (from 37% to 58%): this change was not associated with OS (p > 0.05).

CONCLUSION: Our results suggest that phenotype switch after metastatic progression may be associated with patients' outcomes. Tumour biopsy in recurrent ILC could drive treatment decision-making, with prognostic implications.}, } @article {pmid36976351, year = {2023}, author = {Aiello, EN and D'Iorio, A and Solca, F and Torre, S and Bonetti, R and Scheveger, F and Colombo, E and Maranzano, A and Maderna, L and Morelli, C and Doretti, A and Amboni, M and Vitale, C and Verde, F and Ferrucci, R and Barbieri, S and Zirone, E and Priori, A and Pravettoni, G and Santangelo, G and Silani, V and Ticozzi, N and Ciammola, A and Poletti, B}, title = {Clinimetrics and feasibility of the Italian version of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease patients.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {130}, number = {5}, pages = {687-696}, pmid = {36976351}, issn = {1435-1463}, mesh = {Humans ; *Parkinson Disease/complications/diagnosis/psychology ; Reproducibility of Results ; Cross-Sectional Studies ; Feasibility Studies ; Neuropsychological Tests ; *Cognitive Dysfunction/etiology/complications ; Language ; }, abstract = {BACKGROUND: This study aimed at assessing the cross-sectional and longitudinal clinimetrics and feasibility of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease (PD) patients.

METHODS: N = 109 PD patients underwent the FAB and the Montreal Cognitive Assessment (MoCA). A subsample of patients further underwent a thorough motor, functional and behavioral evaluation (the last including measures of anxiety, depression and apathy). A further subsample was administered a second-level cognitive battery tapping on attention, executive functioning, language, memory, praxis and visuo-spatial abilities. The following properties of the FAB were tested: (1) concurrent validity and diagnostics against the MoCA; (2) convergent validity against the second-level cognitive battery; (4) association with motor, functional and behavioral measures; (5) capability to discriminate patients from healthy controls (HCs; N = 96); (6) assessing its test-retest reliability, susceptibility to practice effects and predictive validity against the MoCA, as well as deriving reliable change indices (RCIs) for it, at a ≈ 6-month interval, within a subsample of patients (N = 33).

RESULTS: The FAB predicted MoCA scores at both T0 and T1, converged with the vast majority of second-level cognitive measures and was associated with functional independence and apathy. It accurately identified cognitive impairment (i.e., a below-cut-off MoCA score) in patients, also discriminating patients from HCs. The FAB was reliable at retest and free of practice effects; RCIs were derived according to a standardized regression-based approach.

DISCUSSION: The FAB is a clinimetrically sound and feasible screener for detecting dysexecutive-based cognitive impairment in non-demented PD patients.}, } @article {pmid36974780, year = {2023}, author = {Buonomo, OC and Pellicciaro, M and Materazzo, M and Berardi, S and Gigliotti, PE and Caspi, J and Meucci, R and Perretta, T and Portarena, I and Dauri, M and Pistolese, CA and Vanni, G}, title = {Surgical Treatments for Ductal Carcinoma In Situ (DCIS) in Elderly Patients.}, journal = {Anticancer research}, volume = {43}, number = {4}, pages = {1555-1562}, doi = {10.21873/anticanres.16305}, pmid = {36974780}, issn = {1791-7530}, mesh = {Humans ; Female ; Aged ; *Carcinoma, Intraductal, Noninfiltrating/surgery/pathology ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; Lymphatic Metastasis ; *Breast Neoplasms/surgery ; *Carcinoma, Ductal, Breast/pathology ; }, abstract = {BACKGROUND/AIM: Despite an aging population, there is no consensus regarding ductal carcinoma in situ (DCIS) treatment for elderly women. Breast surgery can be well tolerated even in elderly patients. The aim of this study is to evaluate the surgical management of DCIS in elderly patients.

PATIENTS AND METHODS: We retrospectively analyzed patients with DCIS from 2016 to 2022 at our Breast Unit and divided our population according to age.

RESULTS: Out of 231 patients with DCIS, 45 (19.5%) were elderly. The Charlson comorbidity index and American Society of Anesthesiology (ASA) score was significantly higher in the elderly (p<0.001 for both). Among the elderly, 10 (22.2%) patients received upstaging diagnoses, versus 18 (9.7%) in the control (p=0.048). Twelve (26.7%) of the elderly patients underwent sentinel lymph node biopsy, versus 93 (50%) in the control group (p=0.005). No difference was reported between groups in terms of breast conserving surgeries performed. A higher incidence of surgeries performed using local anesthesia was reported in the elderly group (p=0.041). Thirty-day surgical complications, according to Clavien-Dindo, did not show significant differences.

CONCLUSION: Despite higher comorbidity and ASA score, breast surgery is safe and feasible in elderly patients. Due to the higher risk of upstaging to invasive ductal carcinoma, surgery should be performed but sentinel lymph node biopsy should be omitted, owing to the low risk of lymph node metastasis and lower use of adjuvant treatments.}, } @article {pmid36973739, year = {2023}, author = {Cheng, X and Jia, X and Wang, C and Zhou, S and Chen, J and Chen, L and Chen, J}, title = {Hyperglycemia induces PFKFB3 overexpression and promotes malignant phenotype of breast cancer through RAS/MAPK activation.}, journal = {World journal of surgical oncology}, volume = {21}, number = {1}, pages = {112}, pmid = {36973739}, issn = {1477-7819}, support = {2021Y29//Medical science and technology program in Ningbo/ ; }, mesh = {Female ; Humans ; Phosphofructokinase-2/genetics/metabolism ; Cell Proliferation ; Cell Line, Tumor ; *MicroRNAs/genetics ; *Hyperglycemia/complications/genetics ; Phenotype ; *Carcinoma, Ductal/genetics ; Cell Movement ; Gene Expression Regulation, Neoplastic ; }, abstract = {BACKGROUND: Breast cancer is the most common tumor in women worldwide. Diabetes mellitus is a global chronic metabolic disease with increasing incidence. Diabetes mellitus has been reported to positively regulate the development of many tumors. However, the specific mechanism of hyperglycemic environment regulating breast cancer remains unclear. PFKFB3 (6-phosphofructose-2-kinase/fructose-2, 6-bisphosphatase 3) is a key regulatory factor of the glycolysis process in diabetes mellitus, as well as a promoter of breast cancer. So, we want to explore the potential link between PFKFB3 and the poor prognosis of breast cancer patients with hyperglycemia in this study.

METHODS: Cell culture was utilized to construct different-glucose breast cancer cell lines. Immunohistochemistry was adopted to analyze the protein level of PFKFB3 in benign breast tissues, invasive ductal carcinoma with diabetes and invasive ductal carcinoma without diabetes. The Kaplan-Meier plotter database and GEO database (GSE61304) was adopted to analyze the survival of breast cancer patients with different PFKFB3 expression. Western blot was adopted to analyze the protein level of PFKFB3, epithelial-mesenchymal transition (EMT)-related protein and extracellular regulated protein kinases (ERK) in breast cancer cells. Gene Set Cancer Analysis (GSCA) was utilized to investigate the potential downstream signaling pathways of PFKFB3. TargetScan and OncomiR were utilized to explore the potential mechanism of PFKFB3 overexpression by hyperglycemia. Transfections (including siRNAs and miRNA transfection premiers) was utilized to restrain or mimic the expression of the corresponding RNA. Cell functional assays (including cell counting, MTT, colony formation, wound-healing, and cell migration assays) were utilized to explore the proliferation and migration of breast cancer cells.

RESULTS: In this study, we demonstrated that the expression of PFKFB3 in breast cancer complicated with hyperglycemia was higher than that in breast cancer with euglycemia through cell experiment in vitro and histological experiment. PFKFB3 overexpression decreased the survival period of breast cancer patients and was correlated with a number of clinicopathological parameters of breast cancer complicated with diabetes. PFKFB3 promoted the proliferation and migration of breast cancer in a hyperglycemic environment and might be regulated by miR-26. In addition, PFKFB3 stimulated epithelial-mesenchymal transition of breast cancer in a hyperglycemic environment. In terms of downstream mechanism exploration, we predicted and verified the cancer-promoting effect of PFKFB3 in breast cancer complicated with hyperglycemia through RAS/MAPK pathway.

CONCLUSIONS: In conclusion, PFKFB3 could be overexpressed by hyperglycemia and might be a potential therapeutic target for breast cancer complicated with diabetes.}, } @article {pmid36973678, year = {2023}, author = {Tong, S and Jiang, N and Wan, JH and Chen, CR and Wang, SH and Wu, CY and Guo, Q and Xiao, XY and Huang, H and Zhou, T}, title = {The effects of the prognostic biomarker SAAL1 on cancer growth and its association with the immune microenvironment in lung adenocarcinoma.}, journal = {BMC cancer}, volume = {23}, number = {1}, pages = {275}, pmid = {36973678}, issn = {1471-2407}, mesh = {Humans ; Cyclin D1 ; Prognosis ; *Lung Neoplasms/pathology ; *Adenocarcinoma of Lung/genetics ; Biomarkers, Tumor/genetics ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Inhibition of Serum Amyloid A-like 1 (SAAL1) expression could inhibit cancer progression and improve the prognosis of cancer patients. At present, the correlation between SAAL1 and lung adenocarcinoma (LAC) remains unclear. Therefore, this study surveyed the worth and pathway of SAAL1 in LAC progression and immunity.

METHODS: Bioinformatics and immunohistochemistry were used to identify the SAAL1 expression in LAC. The roles of SAAL1 expression in the existence values of LAC patients were explored, and the nomograms were constructed. Clinical values of SAAL1 co-expressed genes were evaluated by COX regression, survival, and Receiver operating characteristic (ROC) analysis. EDU and western blotting methods were used to inquiry the functions and pathways of the SAAL1 in cell growths. The correlation between the SAAL1 level and immune microenvironment was visualized using correlation research.

RESULTS: SAAL1 level was elevated in LAC tissues, and was observed in cancer tissues of dead patients. SAAL1 overexpression had something to do with shorter overall survival, progression-free interval, and disease-specific survival in LAC. The area under the curve of SAAL1 was 0.902 in normal tissues and cancer tissues. Inhibition of SAAL1 expression could inhibit cancer cell proliferation, which may be related to the decreased expression of cyclin D1 and Bcl-2 proteins. In LAC, SAAL1 level had something to do with stromal, immune, and estimate scores, and correlated with macrophages, T cells, Th2 cells, CD8 T cells, NK CD56dim cells, DC, eosinophils, NK CD56bright cells, pDC, iDC, cytotoxic cells, Tgd, aDC cells, B cells, Tcm, and TFH levels. SAAL1 overexpression had something to do with existence values and the immunity in LAC.

CONCLUSIONS: Inhibition of SAAL1 expression could regulate cancer growth via cyclin D1 and Bcl-2. SAAL1 is a promising prognostic biomarker in LAC patients.}, } @article {pmid36970720, year = {2022}, author = {Glencer, AC and Miller, PN and Greenwood, H and Maldonado Rodas, CK and Freimanis, R and Basu, A and Mukhtar, RA and Brabham, C and Kim, P and Hwang, ES and Rosenbluth, JM and Hirst, GL and Campbell, MJ and Borowsky, AD and Esserman, LJ}, title = {Identifying Good Candidates for Active Surveillance of Ductal Carcinoma In Situ: Insights from a Large Neoadjuvant Endocrine Therapy Cohort.}, journal = {Cancer research communications}, volume = {2}, number = {12}, pages = {1579-1589}, pmid = {36970720}, issn = {2767-9764}, support = {T32 CA251070/CA/NCI NIH HHS/United States ; U01 CA111234/CA/NCI NIH HHS/United States ; U01 CA196406/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging ; Retrospective Studies ; *Carcinoma, Ductal, Breast/pathology ; Neoadjuvant Therapy ; Watchful Waiting ; *Breast Neoplasms/diagnostic imaging ; }, abstract = {UNLABELLED: Ductal carcinoma in situ (DCIS) is a biologically heterogenous entity with uncertain risk for invasive ductal carcinoma (IDC) development. Standard treatment is surgical resection often followed by radiation. New approaches are needed to reduce overtreatment. This was an observational study that enrolled patients with DCIS who chose not to pursue surgical resection from 2002 to 2019 at a single academic medical center. All patients underwent breast MRI exams at 3- to 6-month intervals. Patients with hormone receptor-positive disease received endocrine therapy. Surgical resection was strongly recommended if clinical or radiographic evidence of disease progression developed. A recursive partitioning (R-PART) algorithm incorporating breast MRI features and endocrine responsiveness was used retrospectively to stratify risk of IDC. A total of 71 patients were enrolled, 2 with bilateral DCIS (73 lesions). A total of 34 (46.6%) were premenopausal, 68 (93.2%) were hormone-receptor positive, and 60 (82.1%) were intermediate- or high-grade lesions. Mean follow-up time was 8.5 years. Over half (52.1%) remained on active surveillance without evidence of IDC with mean duration of 7.4 years. Twenty patients developed IDC, of which 6 were HER2 positive. DCIS and subsequent IDC had highly concordant tumor biology. Risk of IDC was characterized by MRI features after 6 months of endocrine therapy exposure; low-, intermediate-, and high-risk groups were identified with respective IDC rates of 8.7%, 20.0%, and 68.2%. Thus, active surveillance consisting of neoadjuvant endocrine therapy and serial breast MRI may be an effective tool to risk-stratify patients with DCIS and optimally select medical or surgical management.

SIGNIFICANCE: A retrospective analysis of 71 patients with DCIS who did not undergo upfront surgery demonstrated that breast MRI features after short-term exposure to endocrine therapy identify those at high (68.2%), intermediate (20.0%), and low risk (8.7%) of IDC. With 7.4 years mean follow-up, 52.1% of patients remain on active surveillance. A period of active surveillance offers the opportunity to risk-stratify DCIS lesions and guide decisions for operative management.}, } @article {pmid36970436, year = {2023}, author = {Yoshida, K and Kotsuma, T and Takaoka, Y and Tamenaga, S and Yamazaki, H and Nose, T and Murakami, N and Inaba, K and Akiyama, H and Masui, K and Takenaka, T and Kubota, H and Tselis, N and Masuda, N and Yasojima, H and Takeda, M and Mano, M and Nakamura, S and Utsunomiya, K and Tanigawa, N and Tanaka, E}, title = {HDR-brachytherapy for accelerated partial breast irradiation: Long-term experience from a Japanese institution.}, journal = {Journal of contemporary brachytherapy}, volume = {15}, number = {1}, pages = {1-8}, pmid = {36970436}, issn = {1689-832X}, abstract = {PURPOSE: We investigated the long-term oncological outcome of high-dose-rate (HDR) multicatheter interstitial brachytherapy (MIB) for adjuvant accelerated partial breast irradiation (APBI) after breast conserving surgery in Japanese patients.

MATERIAL AND METHODS: Between June 2002 and October 2011, 86 breast cancer patients were treated at National Hospital Organization Osaka National Hospital (trial number of the local institutional review board, 0329). Median age was 48 years (range, 26-73 years). Eighty patients had invasive and 6 patients non-invasive ductal carcinoma. Tumor stage distribution was pT0 in 2, pTis in 6, pT1 in 55, pT2 in 22, and pT3 in one patient, respectively. Twenty-seven patients had close/positive resection margins. Total physical HDR dose was 36-42 Gy in 6-7 fractions.

RESULTS: At a median follow-up of 119 months (range, 13-189 months), the 10-year local control (LC) and overall survival rate was 93% and 88%, respectively. Concerning the 2009 Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology risk stratification scheme, the 10-year LC rate was 100%, 100%, and 91% for patients considered as low-risk, intermediate-risk, and high-risk, respectively. According to the 2018 American Brachytherapy Society risk stratification scheme, the 10-year LC rate was 100% and 90% for patients 'acceptable' and 'unacceptable' for APBI, respectively. Wound complications were observed in 7 patients (8%). Risk factors for wound complications were the omission of prophylactic antibiotics during MIB, open cavity implantation, and V100 ≥ 190 cc. No grade ≥ 3 late complications (CTCVE version 4.0) were observed.

CONCLUSIONS: Adjuvant APBI using MIB is associated with favorable long-term oncological outcomes in Japanese patients for low-risk, intermediate-risk, and acceptable groups of patients.}, } @article {pmid36969041, year = {2023}, author = {Xu, J and Xu, Y and Xu, C and Wang, C}, title = {Morphological and molecular pathological features of the breast carcinoma with choriocarcinomatous features: A case report and a literature review.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {984425}, pmid = {36969041}, issn = {2234-943X}, abstract = {Here we present a rare case of breast cancer with both invasive ductal carcinoma and choriocarcinoma components in a 55-year-old woman. Firstly, the serum human chorionic gonadotropin level showed 15.9mIU/ml preoperatively. And adequate immunohistochemical tests were performed on the specimen. Secondly, High-throughput sequencing was performed to detect the molecular characteristics of the two components, respectively. Then, DNA short tandem repeat (STR) analysis confirmed the homology of the two components, indicating the somatic origin of choriocarcinoma components. Finally, the clinical course and pathological characteristics of the case were reviewed and a literature search for other cases was performed.}, } @article {pmid36959807, year = {2023}, author = {Huang, Q and Nong, W and Tang, X and Gao, Y}, title = {An ultrasound-based radiomics model to distinguish between sclerosing adenosis and invasive ductal carcinoma.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1090617}, pmid = {36959807}, issn = {2234-943X}, abstract = {OBJECTIVES: We aimed to develop an ultrasound-based radiomics model to distinguish between sclerosing adenosis (SA) and invasive ductal carcinoma (IDC) to avoid misdiagnosis and unnecessary biopsies.

METHODS: From January 2020 to March 2022, 345 cases of SA or IDC that were pathologically confirmed were included in the study. All participants underwent pre-surgical ultrasound (US), from which clinical information and ultrasound images were collected. The patients from the study population were randomly divided into a training cohort (n = 208) and a validation cohort (n = 137). The US images were imported into MaZda software (Version 4.2.6.0) to delineate the region of interest (ROI) and extract features. Intragroup correlation coefficient (ICC) was used to evaluate the consistency of the extracted features. The least absolute shrinkage and selection operator (LASSO) logistic regression and cross-validation were performed to obtain the radiomics score of the features. Based on univariate and multivariate logistic regression analyses, a model was developed. 56 cases from April 2022 to December 2022 were included for independent validation of the model. The diagnostic performance of the model and the radiomics scores were evaluated by performing the receiver operating characteristic (ROC) analysis. The calibration curve and decision curve analysis (DCA) were used for calibration and evaluation. Leave-One-Out Cross-Validation (LOOCV) was used for the stability of the model.

RESULTS: Three predictors were selected to develop the model, including radiomics score, palpable mass and BI-RADS. In the training cohort, validation cohort and independent validation cohort, AUC of the model and radiomics score were 0.978 and 0.907, 0.946 and 0.886, 0.951 and 0.779, respectively. The model showed a statistically significant difference compared with the radiomics score (p<0.05). The Kappa value of the model was 0.79 based on LOOCV. The Brier score, calibration curve, and DCA showed the model had a good calibration and clinical usefulness.

CONCLUSIONS: The model based on radiomics, ultrasonic features, and clinical manifestations can be used to distinguish SA from IDC, which showed good stability and diagnostic performance. The model can be considered a potential candidate diagnostic tool for breast lesions and can contribute to effective clinical diagnosis.}, } @article {pmid36952359, year = {2023}, author = {Wang, DY and Li, SF and Gao, SL and Yuan, P and Zhang, BL}, title = {Differences in clinical characteristics and prognosis between breast neuroendocrine carcinoma and breast invasive ductal carcinoma: A multicentre population-based study from China.}, journal = {Cancer medicine}, volume = {12}, number = {8}, pages = {9644-9649}, pmid = {36952359}, issn = {2045-7634}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/diagnosis/epidemiology/therapy ; *Breast Neoplasms/diagnosis/epidemiology/therapy ; Prognosis ; China/epidemiology ; *Carcinoma, Neuroendocrine/diagnosis/epidemiology/therapy ; }, abstract = {AIM: We constructed a multicentre cohort in China to analyse the differences in clinical characteristics, treatment strategies and prognoses between breast neuroendocrine carcinoma (NEC) and invasive ductal carcinoma (IDC) of the breast.

METHODS: All patients with early-stage breast cancer who attended three hospitals in Beijing from 2000 to 2018 were included in the study. We used propensity score matching to make a 1:3 match between NEC and IDC.

RESULTS: After propensity score matching, 153 patients with IDC and 51 patients with NEC were analysed. Multivariate Cox regression showed that compared to patients with IDC, patients with NEC had a worse disease-free survival (HR = 2.94, 95% CI: 1.69-5.12, p < 0.001).

CONCLUSION: NEC patients have a worse disease-free survival than IDC patients.}, } @article {pmid36951614, year = {2023}, author = {Amano, M and Fujita, S and Takei, N and Sano, K and Wada, A and Sato, K and Kikuta, J and Kuwatsuru, Y and Tachibana, R and Sekine, T and Horimoto, Y and Aoki, S}, title = {Feasibility of Quantitative MRI Using 3D-QALAS for Discriminating Immunohistochemical Status in Invasive Ductal Carcinoma of the Breast.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {58}, number = {6}, pages = {1752-1759}, doi = {10.1002/jmri.28683}, pmid = {36951614}, issn = {1522-2586}, mesh = {Humans ; Female ; Ki-67 Antigen ; Feasibility Studies ; Magnetic Resonance Imaging/methods ; Breast ; *Carcinoma, Ductal ; *Breast Neoplasms/diagnostic imaging ; Retrospective Studies ; *Carcinoma, Ductal, Breast/diagnostic imaging ; }, abstract = {BACKGROUND: Two-dimensional synthetic MRI of the breast has limited spatial coverage. Three-dimensional (3D) synthetic MRI could provide volumetric quantitative parameters that may reflect the immunohistochemical (IHC) status in invasive ductal carcinoma (IDC) of the breast.

PURPOSE: To evaluate the feasibility of 3D synthetic MRI using an interleaved Look-Locker acquisition sequence with a T2 preparation pulse (QALAS) for discriminating the IHC status, including hormone receptor (HR), human epidermal growth factor receptor 2 (HER 2), and Ki-67 expression in IDC.

STUDY TYPE: Prospective observational study.

POPULATION: A total of 33 females with IDC of the breast (mean, 52.3 years).

FIELD STRENGTH/SEQUENCE: A 3-T, 3D-QALAS gradient-echo and fat-suppressed T1-weighted 3D fast spoiled gradient-echo sequences.

ASSESSMENT: Two radiologists semiautomatically delineated 3D regions of interest (ROIs) of the whole tumors on the dynamic MRI that was registered to the synthetic T1-weighted images acquired from 3D-QALAS. The mean T1 and T2 were measured for each IDC.

STATISTICAL TESTS: Intraclass correlation coefficient for assessing interobserver agreement. Mann-Whitney U test to determine the relationship between the mean T1 or T2 and the IHC status. Multivariate logistic regression analysis followed by receiver operating characteristics (ROC) analysis for discriminating IHC status. A P value <0.05 was considered statistically significant.

RESULTS: The interobserver agreement was good to excellent. There was a significant difference in the mean T1 between HR-positive and HR-negative lesions, while the mean T2 value differed between HR-positive and HR-negative lesions, between the triple-negative and HR-positive or HER2-positive lesions, and between the Ki-67 level > 14% and ≤ 14%. Multivariate analysis showed that the mean T2 was higher in HR-negative IDC than in HR-positive IDC. ROC analysis revealed that the mean T2 was predictive for discriminating HR status, triple-negative status, and Ki-67 level.

DATA CONCLUSION: 3D synthetic MRI using QALAS may be useful for discriminating IHC status in IDC of the breast.

EVIDENCE LEVEL: 1.

TECHNICAL EFFICACY: Stage 2.}, } @article {pmid36949078, year = {2023}, author = {Gorman, C and Punzo, D and Octaviano, I and Pieper, S and Longabaugh, WJR and Clunie, DA and Kikinis, R and Fedorov, AY and Herrmann, MD}, title = {Interoperable slide microscopy viewer and annotation tool for imaging data science and computational pathology.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {1572}, pmid = {36949078}, issn = {2041-1723}, support = {HHSN2612015000031//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; }, mesh = {Humans ; *Microscopy/methods ; *Data Science ; Reproducibility of Results ; }, abstract = {The exchange of large and complex slide microscopy imaging data in biomedical research and pathology practice is impeded by a lack of data standardization and interoperability, which is detrimental to the reproducibility of scientific findings and clinical integration of technological innovations. We introduce Slim, an open-source, web-based slide microscopy viewer that implements the internationally accepted Digital Imaging and Communications in Medicine (DICOM) standard to achieve interoperability with a multitude of existing medical imaging systems. We showcase the capabilities of Slim as the slide microscopy viewer of the NCI Imaging Data Commons and demonstrate how the viewer enables interactive visualization of traditional brightfield microscopy and highly-multiplexed immunofluorescence microscopy images from The Cancer Genome Atlas and Human Tissue Atlas Network, respectively, using standard DICOMweb services. We further show how Slim enables the collection of standardized image annotations for the development or validation of machine learning models and the visual interpretation of model inference results in the form of segmentation masks, spatial heat maps, or image-derived measurements.}, } @article {pmid36939947, year = {2023}, author = {Maggi, G and D'Iorio, A and Aiello, EN and Poletti, B and Ticozzi, N and Silani, V and Amboni, M and Vitale, C and Santangelo, G}, title = {Correction to: Psychometrics and diagnostics of the Italian version of the Beck Depression Inventory-II (BDI-II) in Parkinson's disease.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {7}, pages = {2631}, doi = {10.1007/s10072-023-06746-4}, pmid = {36939947}, issn = {1590-3478}, } @article {pmid36939123, year = {2023}, author = {Mareti, E and Vavoulidis, E and Papanastasiou, A and Maretis, T and Tsampazis, N and Margioula-Siarkou, C and Chatzinikolaou, F and Giasari, S and Nasioutziki, M and Daniilidis, A and Zepiridis, L and Dinas, K}, title = {Evaluating the potential role of human papilloma virus infection in breast carcinogenesis via real-time polymerase chain reaction analyzes of breast fine needle aspiration samples from Greek patients.}, journal = {Diagnostic cytopathology}, volume = {51}, number = {7}, pages = {414-422}, doi = {10.1002/dc.25130}, pmid = {36939123}, issn = {1097-0339}, mesh = {Biopsy, Fine-Needle ; Human papillomavirus 18 ; *Papillomavirus Infections ; *Breast Neoplasms/pathology ; Female ; Carcinogenesis ; Human Papillomavirus Viruses ; Humans ; Greece/epidemiology ; Papillomaviridae/genetics ; Real-Time Polymerase Chain Reaction ; }, abstract = {BACKGROUND: Human papilloma virus (HPV), in addition to its known clinical contribution to cervical cancer is probably actively involved in the development of breast tumors in various populations worldwide. Predominant HPV types in breast cancer patients vary geographically. The present study further examines HPV incidence in Greece, based on molecular analysis of clinical cytological samples.

METHODS: Greek patient fine needle aspiration (FNA) biopsy samples were examined using RT-PCR and immunohistological staining. FNA biopsy samples were collected from 114 female patients, diagnosed between the years 2018 and 2021, 57 with C5 diagnosed breast cancer lesions and 57 diagnosed with benign diseases.

RESULTS: A total of three different HPV types were identified within the patient sample. HPV-39 was found only in the control group, in 1.8% of patients, while HPV-59 was present in both control and study groups in 1.8% and 3.5% respectively. HPV-16, on the other hand, was present only in the study group in 12.3% of cases. HPV type presence was statistically differentiated between histological groups. HPV-16 was exclusively in IDC, HPV-39 was present in one cyst diagnosed sample and HPV-59 was present in 3 samples that included fibroadenoma, IDC and LN diagnosis.

CONCLUSION: More international comparative studies are required to investigate population differences and HPV genotype distribution to offer definite answers to the effect that certain HPV types might have a role in breast cancer, as this study also supports, albeit in a cofactory role.}, } @article {pmid36937402, year = {2023}, author = {Zheng, C and Fu, C and Wen, Y and Liu, J and Lin, S and Han, H and Han, Z and Xu, C}, title = {Clinical characteristics and overall survival prognostic nomogram for metaplastic breast cancer.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1030124}, pmid = {36937402}, issn = {2234-943X}, abstract = {BACKGROUND: Metaplastic breast cancer (MBC) is a rare breast tumor and the prognostic factors for survival in patients still remain controversial. This study aims to develop and validate a nomogram to predict the overall survival (OS) of patients with MBC.

METHODS: We searched the Surveillance, Epidemiology, and End Results (SEER) database for data about patients including metaplastic breast cancer and infiltrating ductal carcinoma (IDC) from 2010 to 2018. The survival outcomes of patients between MBC and IDC were analyzed and compared with the Kaplan-Meier (KM) method. MBC patients were randomly allocated to the training set and validation I set by a ratio of eight to two. Meanwhile, the performance of this model was validated again by the validation II set, which consisted of MBC patients from the Union Hospital of Fujian Medical University between 2010 and 2018. The independent prognostic factors were selected by univariate and multivariate Cox regression analyses. The nomogram was constructed to predict individual survival outcomes for MBC patients. The discriminative power, calibration, and clinical effectiveness of the nomogram were evaluated by the concordance index (C-index), the receiver operating characteristic (ROC) curve, and the decision curve analysis (DCA).

RESULTS: MBC had a significantly higher T stage (T2 and above accounting for 75.1% vs 39.9%), fewer infiltrated lymph nodes (N0 accounted for 76.2% vs 67.7%), a lower proportion of ER (22.2% vs 81.2%), PR (13.6% vs 71.4%), and HER-2(6.7% vs 17.7%) positive, radiotherapy(51.6% vs 58.0%) but more chemotherapy(67.5% vs 44.7%), and a higher rate of mastectomy(53.2% vs 36.8%), which was discovered when comparing the clinical baseline data between MBC and IDC. Age at diagnosis, T, N, and M stage, as well as surgery and radiation treatment, were all significant independent prognostic factors for overall survival (OS). In the validation I cohort, the nomogram's C-index (0.769 95% CI 0.710 -0.828) was indicated to be considerably higher than the standard AJCC model's (0.700 95% CI 0.644 -0.756). Nomogram's great predictive capability capacity further was supported by the comparatively high C-index of the validation II sets (0.728 95%CI 0.588-0.869).

CONCLUSIONS: Metaplastic breast cancer is more aggressive, with a worse clinical prognosis than IDC. This nomogram is recommended for patients with MBC, both American and Chinese, which can help clinicians make more accurate individualized survival analyses.}, } @article {pmid36934657, year = {2023}, author = {Varun, K and Zoltan, K and Alba, S and Manuel, B and Elisabeth, K and Dimitrios, T and Jan B, G and Maik, B and Khurrum, S and Berend, I and Stephen, H and Thomas, F and Julia, S and Peter, N and Stefan, K}, title = {Elevated markers of DNA damage and senescence are associated with the progression of albuminuria and restrictive lung disease in patients with type 2 diabetes.}, journal = {EBioMedicine}, volume = {90}, number = {}, pages = {104516}, pmid = {36934657}, issn = {2352-3964}, mesh = {Mice ; Animals ; *Diabetes Mellitus, Type 2/complications ; Follow-Up Studies ; Interleukin-6 ; *Prediabetic State ; Albuminuria/complications ; Cross-Sectional Studies ; Prospective Studies ; *Lung Diseases ; Fibrosis ; DNA Damage ; Cellular Senescence ; }, abstract = {BACKGROUND: This study was conducted to investigate the cascade involving DNA damage, senescence, and senescence-associated secretory phenotype (SASP) in experimental diabetes and in a four-year follow-up study in patients with pre-diabetes and type 2 diabetes.

METHODS: Kidney, lung, and liver were studied in 4 months diabetic db/db mice and age-matched controls for the presence of DNA damage and fibrosis. DNA damage (comet-tail-length and ɤH2Ax-positivity in white blood cells), urinary p21-excretion, and plasma IL-6 and TGF-β1 were determined from 115 healthy participants, 34 patients with pre-diabetes and 221 with type 2 diabetes. Urinary albumin-creatinine-ratio, lung function, and transient elastography of the liver were performed in a prospective follow-up study over 4 years.

FINDINGS: db/db mice showed an increased nuclear ɤH2AX signal in all tissues as compared to the background control. Markers for DNA damage, senescence, and SASP were increased in patients with diabetes. The presence of nephropathy, restrictive lung disease (RLD), and increased liver stiffness was in a cross-sectional design associated with increased markers for DNA damage, senescence, and SASP. The progression of nephropathy over 4 years was predicted by increased DNA damage, senescence, and SASP, while the progression of RLD was associated with increased DNA damage and IL-6 only. The progression of liver stiffness was not associated with any of these parameters. HbA1c was not predictive for progression.

INTERPRETATION: In db/db mice, the cascade of DNA damage is associated with diabetes-related complications. In patients with diabetes, the progression of complications in the kidney and lung is predicted by markers reflecting DNA damage, and senescence-triggered organ fibrosis.

FUNDING: This work was supported by the German Research Foundation (DFG) in the CRC 1118 and CRC 1158, by the GRK DIAMICOM, by the German Center for Diabetes Research (DZD e.V.), and by the Ministry of Science, Research and the Arts, Baden-Württemberg (Kompetenznetzwerk Präventivmedizin).}, } @article {pmid36933533, year = {2023}, author = {Tahir, N and Zahid, M and Jillani, A and Tahir, S and Yaseen, M and Abbas, Q and Abdul Shakoor, R and Hussain, SZ and Shahid, I}, title = {Impact of alternate Mn doping in ternary nanocomposites on their structural, optical and antimicrobial properties: Comparative analysis of photocatalytic degradation and antibacterial activity.}, journal = {Journal of environmental management}, volume = {337}, number = {}, pages = {117706}, doi = {10.1016/j.jenvman.2023.117706}, pmid = {36933533}, issn = {1095-8630}, mesh = {*Molybdenum ; Light ; Anti-Bacterial Agents/pharmacology ; Sunlight ; *Nanocomposites/chemistry ; Catalysis ; }, abstract = {The present study was done to investigate and compare the photocatalytic and antibacterial activity of two in situ Manganese doped ternary nanocomposites. The dual ternary hybrid systems comprised Mn-doped Ag2WO4 coupled with MoS2-GO and Mn-doped MoS2 coupled with Ag2WO4-GO. Both hierarchical alternate Mn-doped ternary heterojunctions formed efficient plasmonic catalysts for wastewater treatment. The novel nanocomposites were well-characterized using XRD, FTIR, SEM-EDS, HR-TEM, XPS, UV-VIS DRS, and PL techniques confirming the successful insertion of Mn[+2] ions in respective host substrates. The bandgap of the ternary nanocomposites evaluated by the tauc plot showed them visible light-active nanocomposites. The photocatalytic ability of both Mn-doped coupled nanocomposites was investigated against the dye methylene blue. Both ternary nanocomposites showed excellent sunlight harvesting ability for dye degradation in 60 min. The maximum catalytic efficiency of both photocatalysts was obtained at a solution pH value of 8, photocatalyst dose and oxidant dose of 30 mg/100 mL and 1 mM for Mn-Ag2WO4/MoS2-GO, 50 mg/100 mL, 3 mM for Mn-MoS2/Ag2WO4-GO keeping IDC of 10 ppm for all photocatalysts. The nanocomposites showed excellent photocatalytic stability after five successive cycles. The response surface methodology was used as a statistical tool for the evaluation of the photocatalytic response of several interacting parameters for dye degradation by ternary composites. The antibacterial activity was determined by the inactivation of gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria by support-based doped ternary hybrids.}, } @article {pmid36933394, year = {2023}, author = {Vormittag-Nocito, E and Acosta, AM and Agarwal, S and Narayan, KD and Kumar, R and Al Rasheed, MRH and Kajdacsy-Balla, A and Behm, FG and Mohapatra, G}, title = {In-Depth Comparison of Genetic Variants Demonstrates a Close Relationship Between Invasive and Intraductal Components of Prostate Cancer.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {36}, number = {6}, pages = {100130}, doi = {10.1016/j.modpat.2023.100130}, pmid = {36933394}, issn = {1530-0285}, mesh = {Male ; Humans ; *Prostatic Intraepithelial Neoplasia/genetics/pathology ; *Prostatic Neoplasms/pathology ; Prostate/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Prostatectomy ; }, abstract = {Intraductal carcinoma (IDC) of the prostate is often associated with concurrent high-grade invasive prostate cancer (PCa) and poor clinical outcomes. In this context, IDC is thought to represent the retrograde spread of invasive prostatic adenocarcinoma into the acini and ducts. Prior studies have demonstrated a concordance of PTEN loss and genomic instability between the IDC and high-grade invasive components of PCa, but larger genomic association studies to solidify our understanding of the relationship between these 2 lesions are lacking. Here, we evaluate the genomic relationship between duct-confined (high-grade prostatic intraepithelial neoplasia and IDC) and invasive components of high-grade PCa using genetic variants generated by whole exome sequencing. High-grade prostatic intraepithelial neoplasia and IDC were laser-microdissected, and PCa and nonneoplastic tissue was manually dissected from 12 radical prostatectomies. A targeted next-generation sequencing panel was used to identify disease-relevant variants. Additionally, the degree of overlap between adjacent lesions was determined by comparing exome-wide variants detected using whole exome sequencing data. Our results demonstrate that IDC and invasive high-grade PCa components show common genetic variants and copy number alterations. Hierarchical clustering of genome-wide variants suggests that in these tumors, IDC is more closely related to the high-grade invasive components of the tumor compared with high-grade prostatic intraepithelial neoplasia. In conclusion, this study reinforces the concept that, in the context of high-grade PCa, IDC likely represents a late event associated with tumor progression.}, } @article {pmid36932870, year = {2023}, author = {Rastin, M and Mahmoudi, M and Tabasi, N and Kia, N and Hajavi, J and Esmaeili, SA}, title = {The Evaluation of the Effect of Tolerogenic Probiotics on the Maturation of Healthy Dendritic Cells versus Immature Dendritic Cells.}, journal = {Iranian journal of immunology : IJI}, volume = {20}, number = {1}, pages = {26-35}, doi = {10.22034/iji.2023.91783.2131}, pmid = {36932870}, issn = {1735-367X}, mesh = {*Interleukin-10 ; Cell Differentiation ; Cells, Cultured ; Interleukin-12 ; Dendritic Cells ; *Probiotics ; }, abstract = {BACKGROUND: Dendritic cells, (DCs) as one of the important immune cell populations, are responsible for the initiation, development, and control of acquired immune responses. Myeloid dendritic cells can be used as a vaccine for several autoimmune diseases and cancers. Tolerogenic probiotics with regulatory properties can affect the maturation and development of immature dendritic cells (IDC) into mature DCs with certain immunomodulatory effects.

OBJECTIVE: To assess the immunomodulatory effect of Lactobacillus rhamnosus and Lactobacillus delbrueckii, as two tolerogenic probiotics, in the differentiation and maturation of myeloid dendritic cells.

METHODS: The IDCs were derived from the healthy donors in GM-CSF and IL 4 medium. Mature DCs (MDC) were produced with L. delbrueckii, L. rhamnosus, and LPS from IDCs. Real-Time PCR and flow cytometry were used to confirm the DC maturation and to determine DC markers as well as IDO, IL10, and IL12 expression levels, respectively.

RESULTS: Probiotic-derived DCs showed a significant reduction in the level of HLA-DR (P≤0.05), CD86 (P≤0.05), CD80 (P≤0.001), CD83 (P≤0.001), and CD1a. Also, the expression of IDO (P≤0.001) and IL10 increased while IL12 expression decreased (P≤0.001).

CONCLUSION: Our findings revealed that tolerogenic probiotics could induce regulatory DCs by reducing co-stimulatory molecules along with increasing the expression of IDO and IL10 during the differentiation process. Therefore, the induced regulatory DCs probably can be used in the treatment of various inflammatory diseases.}, } @article {pmid36931261, year = {2023}, author = {Cardona Barberán, A and Bonte, D and Boel, A and Thys, V and Paredis, R and Machtelinckx, F and De Sutter, P and De Croo, I and Leybaert, L and Stoop, D and Coucke, P and Vanden Meerschaut, F and Heindryckx, B}, title = {Assisted oocyte activation does not overcome recurrent embryo developmental problems.}, journal = {Human reproduction (Oxford, England)}, volume = {38}, number = {5}, pages = {872-885}, doi = {10.1093/humrep/dead051}, pmid = {36931261}, issn = {1460-2350}, mesh = {Pregnancy ; Child ; Humans ; Male ; Female ; Animals ; Mice ; *Sperm Injections, Intracytoplasmic/methods ; *Calcium ; Ionomycin ; Calcimycin ; Prospective Studies ; Semen ; Pregnancy Rate ; Oocytes ; Embryonic Development ; Retrospective Studies ; Adaptor Proteins, Signal Transducing ; Apoptosis Regulatory Proteins ; }, abstract = {STUDY QUESTION: Can recurrent embryo developmental problems after ICSI be overcome by assisted oocyte activation (AOA)?

SUMMARY ANSWER: AOA did not improve blastocyst formation in our patient cohort with recurrent embryo developmental problems after ICSI.

WHAT IS KNOWN ALREADY: The use of AOA to artificially induce calcium (Ca2+) rises by using Ca2+ ionophores (mainly calcimycin and ionomycin) has been reported as very effective in overcoming fertilization failure after ICSI, especially in patients whose Ca2+ dynamics during fertilization are deficient. However, there is only scarce and contradictory literature on the use of AOA to overcome embryo developmental problems after ICSI, and it is not clear whether abnormal Ca2+ patterns during fertilization disturb human preimplantation embryo development. Moreover, poor embryo development after ICSI has also been linked to genetic defects in the subcortical maternal complex (SCMC) genes.

STUDY DESIGN, SIZE, DURATION: This prospective cohort single-center study compared ICSI-AOA cycles and previous ICSI cycles in couples with normal fertilization rates (≥60%) but impaired embryonic development (≤15% blastocyst formation) in at least two previous ICSI cycles. In total, 42 couples with embryo developmental problems were included in this study from January 2018 to January 2021.

Of the 42 couples included, 17 underwent an ICSI-AOA cycle consisting of CaCl2 injection and double ionomycin exposure. Fertilization, blastocyst development, pregnancy, and live birth rates after ICSI-AOA were compared to previous ICSI cycles. In addition, the calcium pattern induced by the male patient's sperm was investigated by mouse oocyte calcium analysis. Furthermore, all 42 couples underwent genetic screening. Female patients were screened for SCMC genes (TLE6, PADI6, NLRP2, NLRP5, NLRP7, and KHDC3L) and male patients were screened for the sperm-oocyte-activating factor PLCZ1.

We compared 17 AOA cycles to 44 previous ICSI cycles from the same patient cohort. After AOA, a total fertilization rate of 68.95% (131/190), a blastocyst development rate of 13.74% (18/131), a pregnancy rate of 29.41% (5/17), and a live birth rate of 23.53% (4/17) were achieved, which was not different from the previous ICSI cycles (76.25% (321/421, P-value = 0.06); 9.35% (30/321, P-value = 0.18), 25.00% (11/44, P-value = 0.75), and 15.91% (7/44, P-value = 0.48), respectively). Calcium analysis showed that patient's sperm induced calcium patterns similar to control sperm samples displaying normal embryo developmental potential. Genetic screening revealed 10 unique heterozygous variants (in NLRP2, NLRP5, NLRP7, TLE6, and PADI6) of uncertain significance (VUS) in 14 females. Variant NLRP5 c.623-12_623-11insTTC (p.?) was identified in two unrelated individuals and variant NLRP2 c.1572T>C (p.Asp524=) was identified in four females. Interestingly, we identified a previously reported homozygous mutation PLCZ1, c.1499C>T (p.Ser500Leu), in a male patient displaying impaired embryonic development, but not showing typical fertilization failure.

Our strict inclusion criteria, requiring at least two ICSI cycles with impaired embryo development, reduced cycle-to-cycle variability, while the requirement of a lower blastocyst development not influenced by a poor fertilization excluded couples who otherwise would be selective cases for AOA; however, these criteria limited the sample size of this study. Targeted genetic screening might be too restricted to identify a genetic cause underlying the phenotype of poor embryo development for all patients. Moreover, causality of the identified VUS should be further determined.

Strong evidence for AOA overcoming impaired embryonic development is still lacking in the literature. Thus far, only one article has reported a beneficial effect of AOA (using calcimycin) compared to previous ICSI cycles in this patient population, whilst two more recent sibling-oocyte control studies (one using calcimycin and the other ionomycin) and our research (using ionomycin) could not corroborate these findings. Although no major abnormalities have been found in children born after AOA, this technique should be reserved for couples with a clear Ca2+-release deficiency. Finally, genetic screening by whole-exome sequencing may reveal novel genes and variants linked to embryo developmental problems and allow the design of more personalized treatment options, such as wild-type complementary RNA or recombinant protein injection.

This study was supported by the Flemish Fund for Scientific Research (grant FWO.OPR.2015.0032.01 to B.H. and grant no. 1298722N to A.B.). A.C.B., D.B., A.B., V.T., R.P., F.M., I.D.C., L.L., D.S., P.D.S., P.C., and F.V.M. have nothing to disclose. B.H. reports a research grant from the Flemish Fund for Scientific Research and reports being a board member of the Belgian Society for Reproductive Medicine and the Belgian Ethical Committee on embryo research.

TRIAL REGISTRATION NUMBER: NCT03354013.}, } @article {pmid36927911, year = {2023}, author = {Mitsuyoshi, A and Yanagawa, T and Kikumori, K and Hori, A and Oshima, K and Shinke, G and Katsuyama, S and Ikeshima, R and Hiraki, M and Ohmura, Y and Sugimura, K and Masuzawa, T and Hata, T and Takeda, Y and Murata, K}, title = {[A Case of De Novo Stage Ⅳ Breast Cancer with Umbilical Metastasis and Peritoneal Dissemination].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {3}, pages = {366-368}, pmid = {36927911}, issn = {0385-0684}, mesh = {Female ; Humans ; Middle Aged ; Peritoneum ; *Breast Neoplasms/surgery/pathology ; Positron Emission Tomography Computed Tomography ; Umbilicus/surgery/pathology ; *Carcinoma, Ductal ; }, abstract = {The patient was a 48-year-old woman. At the time of consultation, a hard mass of 30 mm in size was palpated in area A of the right breast, and a firm mass of about 10 mm was seen in the umbilical region. Histological diagnosis of the breast mass was invasive ductal carcinoma. PET-CT scan showed accumulation in the right breast, as well as suspicion of umbilical metastasis and peritoneal dissemination, uterine mass, and left ovarian cancer. Since this is an atypical metastatic site for invasive ductal carcinoma of the breast, and the possibility of peritoneal dissemination due to gynecological cancer complications cannot be ruled out, resection of the umbilical mass and laparoscopy was performed. The review laparoscopy revealed no evidence of primary cancer in the uterine body or left ovary, and a white nodular lesion of suspected seeding in the peritoneum around the left ovary. The histology and immunostaining results of the umbilical mass and left peri-ovarian nodule both showed glandular luminal structures similar to those of the primary breast cancer, and the left peri-ovarian nodule was ER positive, GATA3 positive, and PAX8 negative, leading to the diagnosis of umbilical metastasis and peritoneal seeding derived from breast cancer. Umbilical metastasis is often referred to as Sister Mary Joseph's nodule in the case of visceral malignancies and is often associated with peritoneal dissemination and is often caused by invasive metastasis of peritoneal dissemination lesions on the dorsal side of the umbilical region. In this case, histological examination of the umbilical specimen showed no disseminated lesion on the peritoneal side, so it was not considered to be an invasive metastasis due to peritoneal dissemination.}, } @article {pmid36927901, year = {2023}, author = {Miyazaki, S and Iwasaki, K and Narita, T and Yoneda, G and Takei, H and Jibiki, N}, title = {[A Case of Bilateral HER2-Positive Invasive Ductal Carcinoma with Complete Response on One Side with Trastuzumab Deruxtecan].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {3}, pages = {327-331}, pmid = {36927901}, issn = {0385-0684}, mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/drug therapy/surgery/pathology ; Erb-b2 Receptor Tyrosine Kinases ; Mastectomy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Neoplasm Recurrence, Local/surgery ; Trastuzumab ; *Carcinoma, Ductal/drug therapy ; Camptothecin/analogs & derivatives ; Immunoconjugates ; }, abstract = {A 52-year-old female with stage Ⅳ, bilateral, HER2-positive, breast cancer as well as bilateral axillary lymph node(LN) metastasis and bilateral pulmonary metastasis was administered trastuzumab plus pertuzumab plus docetaxel as a standard chemotherapy. After this treatment the right breast cancer, right axillary LN metastasis, and bilateral pulmonary metastases contracted, while the left breast cancer and left axillary LN metastasis expanded. Trastuzumab emtansine was then administered, and the left axillary LN metastasis contracted, however, the left breast cancer expanded, resulting in marked breast engorgement. When trastuzumab deruxtecan(T-DXd)was administered, the left breast cancer contracted for the first time during the overall treatment process, and the signs of breast inflammation disappeared. Other lesions showed no recrudescence. T-DXd was administered seven times, and, at the stage of maximum contraction during the treatment period, a total left mastectomy and left axillary LN dissection were performed. Pathological examination then confirmed that tumor cells were no longer present in the left breast and left axillary LN. In this case T-DXd was highly effective for the local treatment of intractable, HER2-positive, breast cancer.}, } @article {pmid36927792, year = {2023}, author = {Onkar, S and Cui, J and Zou, J and Cardello, C and Cillo, AR and Uddin, MR and Sagan, A and Joy, M and Osmanbeyoglu, HU and Pogue-Geile, KL and McAuliffe, PF and Lucas, PC and Tseng, GC and Lee, AV and Bruno, TC and Oesterreich, S and Vignali, DAA}, title = {Immune landscape in invasive ductal and lobular breast cancer reveals a divergent macrophage-driven microenvironment.}, journal = {Nature cancer}, volume = {4}, number = {4}, pages = {516-534}, pmid = {36927792}, issn = {2662-1347}, support = {R35 CA263850/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; R01 CA252378/CA/NCI NIH HHS/United States ; T32 CA082084/CA/NCI NIH HHS/United States ; R35 GM146989/GM/NIGMS NIH HHS/United States ; R01 CA203689/CA/NCI NIH HHS/United States ; P01 AI108545/AI/NIAID NIH HHS/United States ; }, mesh = {Female ; Humans ; *Carcinoma, Lobular/drug therapy ; *Breast Neoplasms/drug therapy ; *Carcinoma, Ductal, Breast/drug therapy ; Treatment Outcome ; Disease-Free Survival ; Tumor Microenvironment ; }, abstract = {T cell-centric immunotherapies have shown modest clinical benefit thus far for estrogen receptor-positive (ER[+]) breast cancer. Despite accounting for 70% of all breast cancers, relatively little is known about the immunobiology of ER[+] breast cancer in women with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). To investigate this, we performed phenotypic, transcriptional and functional analyses for a cohort of treatment-naive IDC (n = 94) and ILC (n = 87) tumors. We show that macrophages, and not T cells, are the predominant immune cells infiltrating the tumor bed and the most transcriptionally diverse cell subset between IDC and ILC. Analysis of cellular neighborhoods revealed an interplay between macrophages and T cells associated with longer disease-free survival in IDC but not ILC. Our datasets provide a rich resource for further interrogation into immune cell dynamics in ER[+] IDC and ILC and highlight macrophages as a potential target for ER[+] breast cancer.}, } @article {pmid36926632, year = {2023}, author = {Tower, A and Hughes, J and Moore, L and Srivastava, K}, title = {Mixed metaplastic carcinoma of the breast: a case report.}, journal = {Journal of surgical case reports}, volume = {2023}, number = {3}, pages = {rjad144}, pmid = {36926632}, issn = {2042-8812}, abstract = {A 68 year-old woman with no significant medical history discovered a lump incidentally in her left breast. The patient's initial imaging revealed a 4.6-cm irregular mass at 11:00 categorized as a BI-RADS 5 as well as an enlarged axillary lymph node and an area of 2.5 cm of heterogeneous calcifications in the 3 o'clock position. The 4.6-cm lesion was revealed to be infiltrating ductal carcinoma with a squamous component, mixed metaplastic carcinoma, which was strongly ER (100+)/PR (100+) positive, HER-2/Neu negative on FISH. The 2.5-cm calcifications were ductal carcinoma in situ. The patient completed neoadjuvant chemotherapy, and had an excellent response. After further discussion, the patient elected for breast conservation therapy and underwent a left wireless localized partial mastectomy with a left axillary dissection. Surgical pathology revealed a near complete pathologic response with only 8-mm residual tumour as well as a negative conversion of the clipped axillary node.}, } @article {pmid36926394, year = {2023}, author = {Wang, YJ and Huang, CP and Hong, ZJ and Liao, GS and Yu, JC}, title = {Invasive breast carcinoma with osteoclast-like stromal giant cells: A case report.}, journal = {World journal of clinical cases}, volume = {11}, number = {7}, pages = {1521-1527}, pmid = {36926394}, issn = {2307-8960}, abstract = {BACKGROUND: Invasive breast carcinoma with osteoclast-like stromal giant cells (OGCs) is an extremely rare morphology of breast carcinomas. To the best of our knowledge, the most recent case report describing this rare pathology was published six years ago. The mechanism controlling the development of this unique histological formation is still unknown. Further, the prognosis of patients with OGC involvement is also controversial.

CASE SUMMARY: We report the case of a 48-year-old woman, who presented to the outpatient department with a palpable, growing, painless mass in her left breast for about one year. Sonography and mammography revealed a 26.5 mm × 18.8 mm asymmetric, lobular mass with circumscribed margin and the Breast Imaging Reporting and Data System was category 4C. Sono-guided aspiration biopsy revealed invasive ductal carcinoma. The patient underwent breast conserving surgery and was diagnosed with invasive breast carcinoma with OGCs, grade II, with intermediate grade of ductal carcinoma in situ (ER: 80%, 3+, PR: 80%, 3+, HER-2: negative, Ki 67: 30%). Adjuvant chemotherapy and post-operation radiotherapy were initiated thereafter.

CONCLUSION: As a rare morphology of breast cancer, breast carcinoma with OGC occurs most often in relatively young women, has less lymph node involvement, and its occurrence is not race-dependent.}, } @article {pmid36926252, year = {2023}, author = {Song, G and Zhang, Y}, title = {Clinicopathological characteristics, treatments, and prognosis of breast ductal carcinoma in situ with microinvasion: A narrative review.}, journal = {Chronic diseases and translational medicine}, volume = {9}, number = {1}, pages = {5-13}, pmid = {36926252}, issn = {2589-0514}, abstract = {BACKGROUND: Ductal carcinoma in situ with microinvasion (DCIS-MI) is defined as ductal carcinoma in situ (DCIS) with a microscopic invasive focus ≤1 mm in the longest diameter. The current literature is controversial concerning the clinical prognostic features and management of DCIS-MI. This narrative review described recently reported literature regarding the characteristics, treatment, and prognosis of it.

METHODS: Searching PubMed for relevant articles covering the period of 1982 to 2021 using the following terms by MeSH and free-word: breast cancer, microinvasion, DCIS, DCIS-MI, and invasive ductal carcinoma (IDC).

RESULTS: DCIS-MI tends to express more aggressive pathological features such as necrosis, HER2+, ER- or PR-, and high nuclear grade. The overall prognosis of DCIS-MI is typically good, however, some indicators such as young age, HR-, HER2+ and multimicroinvasive lesions, were associated with worse prognoses. And there are also conflicting results on the differences between the prognoses of DCIS-MI and DCIS or T1a-IDC. Postoperative chemotherapy and anti-HER2 therapy still have uncertain benefits and are more likely to be used to treat high-risk patients who are HR- orHER2+ to improve the prognosis.

CONCLUSION: DCIS-MI has more aggressive pathological features, which may suggest its biological behavior is worse than that of DCIS and similar to early IDC. Although the overall prognosis of DCIS-MI is good, when making decisions about adjuvant therapy clinicians need to give priority to the hormone receptor status, HER2 expression and axillary lymph node status of patients, because these may affect the prognosis and treatment response.}, } @article {pmid36923390, year = {2023}, author = {Surabhi, DM and Wilson, JC and Singh, M and Green, L}, title = {Recognizing invasive breast carcinoma of no special type with medullary pattern.}, journal = {Radiology case reports}, volume = {18}, number = {5}, pages = {1788-1792}, pmid = {36923390}, issn = {1930-0433}, abstract = {Invasive breast carcinoma of no special type (IBC-NST) with medullary pattern is an uncommon histologic type of invasive breast carcinoma. It is associated with high-grade, poorly differentiated tumor cells that form large sheets of irregular confluent tumor cells associated with a prominent lymphocytic infiltrate. Patients with IBC-NST with medullary pattern are often postmenopausal women with a high body mass index and multiparity. We report the case of a 71-year-old woman who presented for routine screening mammography and breast mass suspicious for malignancy, initially thought to be invasive ductal carcinoma with an associated prominent lymphoid infiltrate. However, it was ultimately diagnosed as IBC-NST with medullary pattern, and radiologic imaging (particularly ultrasound and mammography) along with pathology review were critical in making the diagnosis. We make the case of the importance of radiographic imaging in diagnosing this condition, as the prognosis of IBC-NST with medullary pattern is typically more favorable compared to IBC-NST.}, } @article {pmid36914070, year = {2023}, author = {Tholany, J and Suzuki, H and Livorsi, DJ and Perencevich, EN and Goto, M}, title = {The association of infectious diseases consultation and 30-day mortality rates among veterans with enterococcal bacteraemia: a propensity score-matched retrospective cohort study.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {29}, number = {8}, pages = {1039-1044}, doi = {10.1016/j.cmi.2023.03.009}, pmid = {36914070}, issn = {1469-0691}, mesh = {Humans ; *Veterans ; *Gram-Positive Bacterial Infections/mortality ; *Bacteremia/mortality ; Retrospective Studies ; Logistic Models ; Vancomycin/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; *Referral and Consultation ; Male ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Enterococcaceae ; }, abstract = {OBJECTIVES: Infectious disease consultation (IDC) has been associated with improved outcomes in several infections, but the benefit of IDC among patients with enterococcal bacteraemia has not been fully evaluated.

METHODS: We performed a 1:1 propensity score-matched retrospective cohort study evaluating all patients with enterococcal bacteraemia at 121 Veterans Health Administration acute-care hospitals from 2011 to 2020. The primary outcome was 30-day mortality. We performed conditional logistic regression to calculate the OR to determine the independent association of IDC and 30-day mortality adjusted for vancomycin susceptibility and the primary source of bacteraemia.

RESULTS: A total of 12,666 patients with enterococcal bacteraemia were included; 8400 (63.3%) had IDC, and 4266 (36.7%) did not have IDC. Two thousand nine hundred seventy-two patients in each group were included after propensity score matching. Conditional logistic regression revealed that IDC was associated with a significantly lower 30-day mortality rate compared with patients without IDC (OR = 0.56; 95% CI, 0.50-0.64). The association of IDC was observed irrespective of vancomycin susceptibility, and when the primary source of bacteraemia was a urinary tract infection, or from an unknown primary source. IDC was also associated with higher appropriate antibiotic use, blood culture clearance documentation, and the use of echocardiography.

DISCUSSION: Our study suggests that IDC was associated with improved care processes and 30-day mortality rates among patients with enterococcal bacteraemia. IDC should be considered for patients with enterococcal bacteraemia.}, } @article {pmid36905704, year = {2023}, author = {Öztürk, Ç and Okcu, O and Öztürk, SD and Aşkan, G and Şen, B and Bedir, R}, title = {A new practical method of estimating tumoral microenvironment parameters of possible prognostic significance in patients with invasive breast carcinoma: Combined microenvironment score.}, journal = {Annals of diagnostic pathology}, volume = {64}, number = {}, pages = {152128}, doi = {10.1016/j.anndiagpath.2023.152128}, pmid = {36905704}, issn = {1532-8198}, mesh = {Humans ; Female ; Prognosis ; *Tumor Microenvironment ; *Breast Neoplasms/pathology ; Lymph Nodes/pathology ; }, abstract = {BACKGROUND AND OBJECTIVE: In recent years, the tumor microenvironment has become increasingly recognized as an influential factor in breast cancer development and growth. The parameters that form the microenvironment are the tumor stroma ratio and tumor infiltrating lymphocytes. In addition, tumor budding, which shows the ability of the tumor to metastasize, gives information about the progression of the tumor. In this study, the combined microenvironment score (CMS) was determined with these parameters, and the relationship between CMS and prognostic parameters and survival was evaluated.

MATERIALS AND METHODS: In our study, tumor stroma ratio, tumor infiltrating lymphocytes, and tumor budding were evaluated in hematoxylin-eosin sections of 419 patients with invasive ductal carcinoma. Patients were scored separately for each of these parameters, and these scores were summed to determine the CMS. The patients were divided into 3 groups according to CMS and the relationship between CMS and prognostic parameters and the survival of the patients was studied.

RESULTS: The patients with CMS 3 had higher histological grade and Ki67 proliferation index compared to CMS 1 and 2. Additionally, lymphovascular invasion, axillary lymph node and distant metastasis were more common. Disease-free, and overall survival were significantly shortened in the CMS 3 group. CMS was found as an independent risk factor for DFS (HR: 2.144 (95 % CI: 1.219-3.77) p: 0.008), but not an independent risk factor for OS.

CONCLUSION: CMS is a prognostic parameter that can be easily evaluated and does not require extra time and cost. Evaluating the morphological parameters of the microenvironment with a single scoring system will contribute to routine pathology practice and predict patient prognosis.}, } @article {pmid36902676, year = {2023}, author = {Ruan, Z and Quan, Q and Wang, Q and Jiang, J and Peng, R}, title = {New Staging System and Prognostic Model for Malignant Phyllodes Tumor Patients without Distant Metastasis: A Development and Validation Study.}, journal = {Journal of clinical medicine}, volume = {12}, number = {5}, pages = {}, pmid = {36902676}, issn = {2077-0383}, support = {2022A1515012387//Basic and Applied Basic Research Fund of Guangdong Province/ ; }, abstract = {PURPOSE: To build a new staging system and new prognostic models for MPTB.

METHODS: We performed a comprehensive analysis of the data from the SEER database.

RESULTS: We discussed the characteristics of MPTB by comparing 1085 MPTB cases with 382,718 invasive ductal carcinoma cases. We established a new stage- and age-stratification system for MPTB patients. Furthermore, we built two prognostic models for MPTB patients. The validity of these models was confirmed through multifaceted and multidata verification.

CONCLUSIONS: Our study provided a staging system and prognostic models for MPTB patients, which can not only help to predict patient outcomes, but also enhance the understanding of the prognostic factors associated with MPTB.}, } @article {pmid36901095, year = {2023}, author = {Shenkman, G}, title = {The Mediating Role of Insecure Attachment in the Gap in Parenthood Desire between Lesbian and Gay Individuals and Their Heterosexual Counterparts.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {5}, pages = {}, pmid = {36901095}, issn = {1660-4601}, mesh = {Humans ; Male ; Female ; Heterosexuality ; Homosexuality, Male ; *Homosexuality, Female ; *Sexual and Gender Minorities ; Parenting ; }, abstract = {Previous studies have shown that lesbian and gay (LG) individuals, in comparison to their heterosexual counterparts, tend to report lower levels of parenthood desire. While numerous variables have been suggested to explain this gap in parenthood aspirations, no study has investigated the mediating role of avoidant attachment in the association between sexual orientation and parenthood desire. For that purpose, a sample of 790 cisgender Israelis aged 18-49 years (M = 28.27, SD = 4.76) was recruited using convenience sampling. Among the participants, 345 self-reported as predominantly or exclusively lesbian or gay and 445 self-reported as exclusively heterosexual. Participants completed online questionnaires assessing their sociodemographic characteristics, parenthood desire, and avoidant and anxious attachment styles. Mediation analyses were performed using the PROCESS macro, and the results revealed that LG individuals reported lower parenthood desire, higher avoidant attachment, and higher anxious attachment compared to heterosexual individuals. Moreover, avoidant attachment had a significant mediation effect in the association between sexual orientation and parenthood desire. The findings suggest that LG individuals are more likely to report higher avoidant attachment due to possible rejection and discrimination from family members and peers, and this may be associated with lower parenthood desire. The results contribute to the growing body of research on family formation and parenthood aspirations among LG individuals, and specifically studies aimed at delineating the factors that contribute to the gap in parenthood aspirations between sexual minority individuals and their heterosexual counterparts.}, } @article {pmid36900347, year = {2023}, author = {Lee, JH and Ryu, JM and Lee, SK and Chae, BJ and Lee, JE and Kim, SW and Nam, SJ and Yu, J}, title = {Clinical Characteristics and Prognosis of Metaplastic Breast Cancer Compared with Invasive Ductal Carcinoma: A Propensity-Matched Analysis.}, journal = {Cancers}, volume = {15}, number = {5}, pages = {}, pmid = {36900347}, issn = {2072-6694}, abstract = {BACKGROUND: Metaplastic breast cancer (MpBC) is an aggressive histologic type of breast cancer. Although MpBC has a poor prognosis and is responsible for a large proportion of breast cancer mortalities, the clinical features of MpBC compared with invasive ductal carcinoma (IDC) are not well known, and the optimal treatment has not been identified.

METHODS: We retrospectively reviewed medical records of 155 MpBC patients and 16,251 IDC cases who underwent breast cancer surgery in a single institution between January 1994 and December 2019. The two groups were matched 1:4 by age, tumor size, nodal status, hormonal receptor status, and HER2 status using propensity-score matching (PSM). Finally, 120 MpBC patients were matched with 478 IDC patients. Disease-free survival and overall survival of MpBC and IDC patients both before and after PSM were analyzed by Kaplan-Meier survival, and multivariable Cox regression analysis was performed to identify variables affecting long-term prognosis.

RESULTS: The most common subtype of MpBC was triple-negative breast cancer, and nuclear and histologic grades were higher than those of IDC. Pathologic nodal staging of the metaplastic group was significantly lower than that of the ductal group, and more frequent adjuvant chemotherapy was performed in the metaplastic group. Multivariable Cox regression analysis indicated that MpBC was an independent prognostic factor for disease-free survival (HR = 2.240; 95% CI, 1.476-3.399, p = 0.0002) and overall survival (HR = 1.969; 95% CI, 1.147-3.382, p = 0.0140). However, survival analysis revealed no significant difference between MpBC and IDC patients in disease-free survival (HR = 1.465; 95% CI, 0.882-2.432, p = 0.1398) or overall survival (hazard ratio (HR) = 1.542; 95% confidential interval (CI), 0.875-2.718, p = 0.1340) after PSM.

CONCLUSION: Although the MpBC histologic type had poor prognostic factors compared with IDC, it can be treated according to the same principles as aggressive IDC.}, } @article {pmid36900164, year = {2023}, author = {Osiecki, R and Kozikowski, M and Sarecka-Hujar, B and Pyzlak, M and Dobruch, J}, title = {Prostate Cancer Morphologies: Cribriform Pattern and Intraductal Carcinoma Relations to Adverse Pathological and Clinical Outcomes-Systematic Review and Meta-Analysis.}, journal = {Cancers}, volume = {15}, number = {5}, pages = {}, pmid = {36900164}, issn = {2072-6694}, abstract = {The present study aimed to assess the association between the cribriform pattern (CP)/intraductal carcinoma (IDC) and the adverse pathological and clinical outcomes in the radical prostatectomy (RP) cohort. A systematic search was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement (PRISMA). The protocol from this review was registered on the PROSPERO platform. We searched PubMed[®], the Cochrane Library and EM-BASE[®] up to the 30th of April 2022. The outcomes of interest were the extraprostatic extension (EPE), seminal vesicle invasion (SVI), lymph node metastasis (LNS met), risk of biochemical recurrence (BCR), distant metastasis (MET) and disease-specific death (DSD). As a result, we identified 16 studies with 164 296 patients. A total of 13 studies containing 3254 RP patients were eligible for the meta-analysis. The CP/IDC was associated with adverse outcomes, including EPE (pooled OR = 2.55, 95%CI 1.23-5.26), SVI (pooled OR = 4.27, 95%CI 1.90-9.64), LNs met (pooled OR = 6.47, 95%CI 3.76-11.14), BCR (pooled OR = 5.09, 95%CI 2.23-11.62) and MET/DSD (pooled OR = 9.84, 95%CI 2.75-35.20, p < 0.001). In conclusion, the CP/IDC belong to highly malignant prostate cancer patterns which have a negative impact on both the pathological and clinical outcomes. The presence of the CP/IDC should be included in the surgical planning and postoperative treatment guidance.}, } @article {pmid36897545, year = {2023}, author = {Kikuchi, M and Gomi, N and Ueki, A and Osako, T and Terauchi, T}, title = {Effectiveness and tasks of breast MRI surveillance for high-risk women with cancer susceptibility genes other than BRCA1/2: a single institution study.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {30}, number = {4}, pages = {577-583}, pmid = {36897545}, issn = {1880-4233}, mesh = {*Breast Neoplasms/diagnostic imaging/genetics/pathology ; Magnetic Resonance Imaging ; Risk ; *Genetic Predisposition to Disease ; Japan ; Ataxia Telangiectasia Mutated Proteins/genetics ; Fanconi Anemia Complementation Group N Protein/genetics ; Antigens, CD/genetics ; Cadherins/genetics ; Tumor Suppressor Protein p53/genetics ; *Early Detection of Cancer/methods ; *Genes, Neoplasm ; Neoplasm Staging ; Humans ; Female ; Adult ; Middle Aged ; Aged ; }, abstract = {BACKGROUND: In Japan, with the introduction of multigene panel testing, there is an urgent need to build a new medical system for hereditary breast cancer patients that covers pathogenic variants other than BRCA1/2. The aim of this study was to reveal the current status of breast MRI surveillance for high-risk breast cancer susceptibility genes other than BRCA1/2 and the characteristics of detected breast cancer.

METHODS: We retrospectively examined 42 breast MRI surveillance with contrast performed on patients with hereditary tumors other than BRCA1/2 pathogenic variants at our hospital from 2017 to 2021. MRI exams were evaluated independently by two radiologists. Final histopathological diagnosis for malignant lesions were obtained from surgical specimen.

RESULTS: A total of 16 patients included TP53, CDH1, PALB2, ATM pathogenic variants and 3 variant of unknown significance. 2 patients with TP53 pathogenic variants were detected breast cancer by annual MRI surveillance. The rate of cancer detection was 12.5% (2/16). One patient was detected synchronous bilateral breast cancer and unilateral multiple breast cancers (3 lesions in 1 patient), so there were 4 malignant lesions in total. Surgical pathology of 4 lesions were 2 ductal carcinoma in situ, 1 invasive lobular carcinoma, and 1 invasive ductal carcinoma. MRI findings of 4 malignant lesions were detected as 2 non mass enhancement, 1 focus and 1 small mass. All of 2 patients with PALB2 pathogenic variants had previously developed breast cancer.

CONCLUSIONS: Germline TP53 and PALB2 were strongly associated with breast cancer, suggesting that MRI surveillance is essential for breast cancer-related hereditary predisposition.}, } @article {pmid36896205, year = {2023}, author = {Terasaki, A and Bando, H and Ueda, A and Okazaki, M and Hashimoto, S and Iguchi-Manaka, A and Kondo, Y and Hara, H}, title = {Local recurrence of breast cancer histologically resembling Paget disease presumably due to needle tract seeding: a case report.}, journal = {International cancer conference journal}, volume = {12}, number = {2}, pages = {143-148}, pmid = {36896205}, issn = {2192-3183}, abstract = {Seeding of cancer cells along the needle tract during core needle biopsy is a well-known phenomenon, with a reported frequency of between 22 and 50% [Hoorntje et al. in Eur J Surg Oncol 30:520-525, 2004;Liebens et al. in Maturitas 62:113-123, 2009;Diaz et al. in AJR Am J Roentgenol 173:1303-1313, 1999;]. Local recurrence due to needle tract seeding is rare because the immune system eliminates the cancer cells in most cases. In addition, most local recurrences due to needle tract seeding occur as invasive carcinoma after diagnosis of invasive ductal carcinoma of the breast or mucinous carcinoma, and needle tract seeding due to noninvasive carcinoma is uncommon. We herein report a rare case of local breast cancer recurrence histologically resembling Paget disease, presumably due to needle tract seeding after core needle biopsy for diagnosis of ductal carcinoma in situ of the breast. After receiving a diagnosis of ductal carcinoma in situ, the patient underwent skin-sparing mastectomy and breast reconstruction with a latissimus dorsi musculocutaneous flap. The pathological study showed ER/PgR-negative ductal carcinoma in situ, and no postoperative radiation therapy or systemic therapy was administered. Six months after the surgery, the patient had a breast cancer recurrence histologically resembling Paget disease, presumably in the scar of her core needle biopsy. The pathological study showed Paget disease localized in the epidermis, no invasive carcinoma, and no lymph node metastasis. It was morphologically similar to the primary lesion and was diagnosed as a local recurrence due to needle tract seeding.}, } @article {pmid36893606, year = {2023}, author = {Göransson, S and Chen, S and Olofsson, H and Larsson, O and Strömblad, S}, title = {An extracellular matrix stiffness-induced breast cancer cell transcriptome resembles the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC).}, journal = {Biochemical and biophysical research communications}, volume = {654}, number = {}, pages = {73-79}, doi = {10.1016/j.bbrc.2023.03.001}, pmid = {36893606}, issn = {1090-2104}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology ; Transcriptome ; Extracellular Matrix/genetics/pathology ; *Breast Neoplasms/genetics/pathology ; *Carcinoma in Situ ; }, abstract = {Identifying mechanisms driving the transition from ductal carcinoma in situ (DCIS) to invasive breast cancer remains a challenge in breast cancer research. Breast cancer progression is accompanied by remodelling and stiffening of the extracellular matrix, leading to increased proliferation, survival, and migration. Here, we studied stiffness-dependent phenotypes in MCF10CA1a (CA1a) breast cancer cells cultured on hydrogels with stiffness corresponding to normal breast and breast cancer. This revealed a stiffness-associated morphology consistent with acquisition of an invasive phenotype in breast cancer cells. Surprisingly, this strong phenotypic switch was accompanied by relatively modest transcriptome-wide alterations in mRNA levels, as independently quantified using both DNA-microarrays and bulk RNA sequencing. Strikingly, however, the stiffness-dependent alterations in mRNA levels overlapped with those contrasting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). This supports a role of matrix stiffness in driving the pre-invasive to invasive transition and suggests that mechanosignalling may be a target for prevention of invasive breast cancer.}, } @article {pmid36891453, year = {2023}, author = {Wadhwa, S and Ashwini, RK and Khadri, SIS}, title = {A Diagnostic Revelation: Case of a Mucinous Carcinoma of the Breast.}, journal = {Indian journal of surgical oncology}, volume = {14}, number = {1}, pages = {144-149}, pmid = {36891453}, issn = {0975-7651}, abstract = {Mucinous or colloid cancers are a rare subtype of invasive ductal carcinoma, making up only 2-3% of infiltrating carcinomas. Prevalence of pure mucinous breast cancer(PMBC) among infiltrating duct carcinomas in less than 60 year olds is 2-7%, and in less than 35 year olds, it is 1%. Mucinous carcinoma of the breast is divided into 2 subtypes, the pure type and mixed type. PMBC is characterized by a lower incidence of nodal involvement, favourable histological grade, and higher ER/PR expression. Axillary metastases are rare, though found in 12-14%. It has a better prognosis than infiltrative ductal cancer with 10-year survival being more than 90%. Here is the case of a 70-year-old female who presented with lump in the left breast since 3 years. On examination, we detected a left breast lump occupying the whole breast except lower outer quadrant, measuring 10 × 8 cm with overlying skin stretched with puckering and engorged veins seen, nipple displaced laterally and higher by 1 cm, firm to hard in consistency, and mobile with breast tissue. Sonomammography, mammography, FNAC and biopsy were suggestive of benign phyllodes tumour. Patient was hence posted for simple mastectomy on the left side with removal of attached lymph nodes (near axillary tail). Histopathological examination revealed pure mucinous breast carcinoma with nine lymph nodes, free from tumour and showing reactive hyperplasia. Immunohistochemistry studies demonstrated ER + , PR + , HER-2-NEU-. The patient was started on hormonal therapy. Therefore, mucinous carcinoma of the breast is a rare entity with imaging features sometimes mimicking a benign tumour such as Phyllodes tumour, hence making it important to include it as a differential diagnosis in our daily practice. It is especially important in the subtyping of carcinoma of the breast since it carries a favourable risk profile with less chances of lymph node involvement, higher hormone receptor positivity and good response to endocrine treatment.}, } @article {pmid36891420, year = {2023}, author = {Rateria, N and Naidu, PG and Tewari, M}, title = {Invasive Cancer in Accessory Axillary Breast: a Rare Presentation.}, journal = {Indian journal of surgical oncology}, volume = {14}, number = {1}, pages = {40-41}, pmid = {36891420}, issn = {0975-7651}, abstract = {Accessory breast tissue has an incidence of 0.3-6% and primary cancer arising in it is even rarer 0.2-0.6%. It may have aggressive course with tendency for early metastasis. Due to its rarity, variety of differentials, and lack of clinical awareness, treatment is usually delayed. We present here an interesting case of a 65-year-old lady with a 8 × 7-cm hard lump in right axillary region for 3 years with fungation for 3 months and with no concomitant breast lesion or axillary lymphadenopathy. Biopsy revealed invasive ductal carcinoma with no systemic metastasis. Management of accessory breast cancer follows same guidelines with primary treatment being wide excision and lymphadenectomy. Adjuvant therapies include radiotherapy and hormonal therapy.}, } @article {pmid36890060, year = {2023}, author = {Verspyck, E and Attal, N}, title = {Diagnosing nociplastic pain in cancer survivors: a major step forward.}, journal = {British journal of anaesthesia}, volume = {130}, number = {5}, pages = {515-518}, doi = {10.1016/j.bja.2023.02.006}, pmid = {36890060}, issn = {1471-6771}, mesh = {Humans ; *Cancer Survivors ; Pain ; *Fibromyalgia/complications/diagnosis/therapy ; Headache ; Pain Management ; *Neoplasms/complications ; }, abstract = {Nociplastic pain syndromes include particular fibromyalgia, irritable bowel syndrome, headache, complex regional pain syndrome, and idiopathic orofacial pain. Several mechanisms have been proposed to account for nociplastic pain including central sensitisation, alterations of pain modulatory controls, epigenetic changes, and peripheral mechanisms. Importantly, nociplastic pain might also be present in patients with cancer pain, particularly those with pain related to complications of cancer treatment. Increased awareness of nociplastic pain associated with cancer should have important implications for monitoring and managing such patients.}, } @article {pmid36884000, year = {2023}, author = {Thapa, P and Singh, V and Gupta, K and Shrivastava, A and Kumar, V and Kataria, K and Mishra, PR and Mehta, DS}, title = {Point-of-care devices based on fluorescence imaging and spectroscopy for tumor margin detection during breast cancer surgery: Towards breast conservation treatment.}, journal = {Lasers in surgery and medicine}, volume = {55}, number = {4}, pages = {423-436}, doi = {10.1002/lsm.23651}, pmid = {36884000}, issn = {1096-9101}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery ; Point-of-Care Systems ; Spectrum Analysis ; Optical Imaging ; *Carcinoma, Ductal ; }, abstract = {OBJECTIVE: Fluorescence-based methods are highly specific and sensitive and have potential in breast cancer detection. Simultaneous fluorescence imaging and spectroscopy during intraoperative procedures of breast cancer have great advantages in detection of tumor margin as well as in classification of tumor to healthy tissues. Intra-operative real-time confirmation of breast cancer tumor margin is the aim of surgeons, and therefore, there is an urgent need for such techniques and devices which fulfill the surgeon's priorities.

METHODS: In this article, we propose the development of fluorescence-based smartphone imaging and spectroscopic point-of-care multi-modal devices for detection of invasive ductal carcinoma in tumor margin during removal of tumor. These multimodal devices are portable, cost-effective, noninvasive, and user-friendly. Molecular level sensitivity of fluorescence process shows different behavior in normal, cancerous and marginal tissues. We observed significant spectral changes, such as, red-shift, full-width half maximum (FWHM), and increased intensity as we go towards tumor center from normal tissue. High contrast in fluorescence images and spectra are also recorded for cancer tissues compared to healthy tissues. Preliminary results for the initial trial of the devices are reported in this article.

RESULTS: A total 44 spectra from 11 patients of invasive ductal carcinoma (11 spectra for invasive ductal carcinoma and rest are normal and negative margins) are used. Principle component analysis is used for the classification of invasive ductal carcinoma with an accuracy of 93%, specificity of 75% and sensitivity of 92.8%. We obtained an average 6.17 ± 1.66 nm red shift for IDC with respect to normal tissue. The red shift and maximum fluorescence intensity indicates p < 0.01. These results described here are supported by histopathological examination of the same sample.

CONCLUSION: In the present manuscript, simultaneous fluorescence-based imaging and spectroscopy is accomplished for the classification of IDC tissues and breast cancer margin detection.}, } @article {pmid36883497, year = {2023}, author = {}, title = {Yassir Alaa Muhammed Hassan Shubbar CORRELATION BETWEEN DIFFERENT CLINICOPATHOLOGICAL PARAMETERS AND MOLECULAR SUBTYPES OF FEMALE BREAST CARCINOMA IN SOUTH REGION OF IRAQ.}, journal = {Wiadomosci lekarskie (Warsaw, Poland : 1960)}, volume = {76}, number = {1}, pages = {97-107}, doi = {10.36740/WLek202301114}, pmid = {36883497}, issn = {0043-5147}, mesh = {Female ; Humans ; *Breast Neoplasms/chemistry/metabolism/pathology ; Iraq ; Ki-67 Antigen/analysis/metabolism ; Receptors, Estrogen/analysis/metabolism ; Receptors, Progesterone/analysis/metabolism ; *Carcinoma, Ductal, Breast/chemistry/metabolism/pathology ; Erb-b2 Receptor Tyrosine Kinases/analysis/metabolism ; Immunohistochemistry ; }, abstract = {OBJECTIVE: The aim: To correlate variable clincopathological parameters with molecular subtypes of the breast carcinoma, which affect the prognosis and management of breast malignancy.

PATIENTS AND METHODS: Materials and methods: In this study a total of 511 female patients with breast carcinoma were included, ranging from 32 to 85 years of age, with 35.8% premenopausal and 64.1% being post-menopausal. The sample slides were stained immunohistochemically for estrogen receptors (ER), progesterone receptors (PR), ki67 and HER2, the tumors were graded histologically using the Nottingham criteria system.

RESULTS: Results: Most tumors (72.8%) ranged between 2 and 5 cm in size; the most common histological type of breast carcinoma (49.7%) was invasive ductal carcinoma of no special type, with grade 2 presented in 51.8% cases; most frequent stage at time of presentation was stage 3A, found in 39.9%; the most frequent molecular subtype was ER and/or PR+, Her2- with low proliferation rate ki67<14% subtype in 48.5%, and those group were more likely (statistically significant) to be older, have stage 3 breast cancer, present with tumor size between 2 and 5 cm and tend to be well differentiated histological grade (grade1), mostly with lymph node positive, and most likely have tumor type of invasive ductal carcinoma of no special type.

CONCLUSION: Conclusions: the most common histological type of breast carcinoma in Iraq south was invasive ductal carcinoma of no special type and most cases showed (ER and/or PR+, HER 2-, low ki67) as the most common molecular subtype.}, } @article {pmid36883168, year = {2023}, author = {Heller, B and Amir, A and Waxman, R and Maaravi, Y}, title = {Hack your organizational innovation: literature review and integrative model for running hackathons.}, journal = {Journal of innovation and entrepreneurship}, volume = {12}, number = {1}, pages = {6}, pmid = {36883168}, issn = {2192-5372}, abstract = {This article aims to offer a comprehensive overview of the existing literature on the hackathon phenomenon to offer scholars a common ground for future research and managers and practitioners research-based guidelines on best planning and running a hackathon. A review of the most relevant literature on hackathons was conducted to serve as the research basis for our integrative model and guidelines. This article synthesizes the research on hackathons to offer comprehensible guidelines for practitioners while also providing questions for future hackathon researchers. We differentiate between the different design characteristics of hackathons while noting their advantages and disadvantages, discuss tools and methodologies for successful hackathon setup and execution step-by-step, and provide recommendations to encourage project continuity.}, } @article {pmid36883155, year = {2022}, author = {Ali Khadem, Z and Abdul Wadood Al-Shammaree, S}, title = {Prognostic Value of Intracellular Transcription of Factors HIF-1α and p53 and Their Relation to Estradiol and TNM Parameters of Breast Cancer Tissues in Women with Invasive Ductal Carcinoma in Thi-Qar Province, Iraq.}, journal = {Archives of Razi Institute}, volume = {77}, number = {4}, pages = {1341-1348}, pmid = {36883155}, issn = {2008-9872}, mesh = {Adolescent ; Adult ; Female ; Humans ; Young Adult ; *Breast Neoplasms/chemistry/genetics/metabolism/pathology ; *Carcinoma, Ductal, Breast/chemistry/genetics/metabolism/pathology ; *Estradiol/analysis/genetics/metabolism ; *Hypoxia-Inducible Factor 1, alpha Subunit/analysis/genetics/metabolism ; Iraq/epidemiology ; Prognosis ; *Tumor Suppressor Protein p53/analysis/genetics/metabolism ; }, abstract = {Breast cancer is the most common malignancy affecting women's health, with an increasing incidence worldwide. This study aimed to measure the intracellular concentration of the hypoxia-inducible factor 1 α (HIF-1α), tumor suppression protein p53, and estradiol (E2) in tumor tissues of adult females with breast cancer and their relation to tumor grade, tumor size, and lymph node metastases (LNM). The study was conducted on 65 adult female participants with breast mass admitted to the operating theater in Al-Hussein Teaching Hospital and Al-Habboby Teaching Hospital in Nasiriyah, Iraq, from January to November 2021. Fresh breast tumor tissues were collated and homogenized for intracellular biochemical analysis using the enzyme-linked immunosorbent assay method. In total, 44 (58%) out of 65 patients, in the age range of 18-42 years and the mean±SD age of 32.55±6.40 years, had fibroadenomas, and other 21 (42%) cases, in the age range of 32-80 years and the mean±SD age of 56±14.4 years had invasive ductal carcinoma (IDC) breast cancer. Intracellular levels of HIF-1α, p53, and E2 were elevated significantly (P<0.001) in IDC cases compared to the benign group. The most malignant tumors of IDC cases were in grade III and sizes T2 and T3. The tissue concentrations of HIF-1α, P53, and E2 were significantly elevated in patients with tumor stage T3 compared to T2 and T1. A significant elevation was found in the levels of HIF-1α, p53, and E2 in the positive LNM subgroup compared to the negative LNM group. Based on the obtained results, the prognostic value of the intracellular HIF-1α is considered to be a useful prognostic factor in Iraqi women with ICD and the combination of a HIF-1α protein with the nonfunctional p53 and E2 tends to indicate the proliferation, invasiveness, and metastases of the breast tumors.}, } @article {pmid36880192, year = {2023}, author = {Zhao, Y and Chai, N and Li, S and Yan, L and Zhou, C and He, J and Zhang, H}, title = {Evaluation of the efficacy of chemotherapy for tubular carcinoma of the breast: A Surveillance, Epidemiology, and End Results cohort study.}, journal = {Cancer medicine}, volume = {12}, number = {9}, pages = {10326-10339}, pmid = {36880192}, issn = {2045-7634}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/pathology ; Cohort Studies ; *Breast Neoplasms/drug therapy/epidemiology ; *Adenocarcinoma ; Propensity Score ; }, abstract = {BACKGROUND: The use of systematic treatment for tubular carcinoma (TC) of the breast remained controversial. This study aimed to explore the efficacy of chemotherapy on TC to develop individualized treatment strategies.

METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, 6486 eligible cases with TC and 309,304 with invasive ductal carcinoma (IDC) were collected. Breast cancer-specific survival (BCSS) was assessed through multivariable Cox analyses and Kaplan-Meier analyses. Differences between groups were balanced using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW).

RESULTS: Compared with IDC patients, TC patients had a more favorable long-term BCSS after PSM (hazard ratio = 0.62, p = 0.004) and IPTW (hazard ratio = 0.61, p < 0.001). Chemotherapy was an unfavorable predictor of BCSS for TC (hazard ratio = 3.20, p < 0.001). After stratifying by hormone receptor (HR) and lymph node (LN) status, chemotherapy was correlated with worse BCSS in the HR+/LN- subgroup (hazard ratio = 6.95, p = 0.001) but showed no impact on BCSS in the HR+/LN+ (hazard ratio = 0.75, p = 0.780) and HR-/LN- (hazard ratio = 7.87, p = 0.150) subgroups.

CONCLUSIONS: Tubular carcinoma is a low-grade malignant tumor with favorable clinicopathological features and excellent long-term survival. Adjuvant chemotherapy was not recommended for TC regardless of HR and LN status, while the therapy regimens should be carefully individualized.}, } @article {pmid36876593, year = {2023}, author = {Wang, L and Luo, R and Chen, Y and Liu, H and Guan, W and Li, R and Zhang, Z and Duan, S and Wang, D}, title = {Breast Cancer Growth on Serial MRI: Volume Doubling Time Based on 3-Dimensional Tumor Volume Assessment.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {58}, number = {4}, pages = {1303-1313}, doi = {10.1002/jmri.28670}, pmid = {36876593}, issn = {1522-2586}, mesh = {Humans ; Female ; Middle Aged ; Aged ; *Breast Neoplasms/diagnostic imaging/pathology ; Tumor Burden ; Retrospective Studies ; Magnetic Resonance Imaging ; Breast/diagnostic imaging/pathology ; Diffusion Magnetic Resonance Imaging/methods ; }, abstract = {BACKGROUND: The volume doubling time (VDT) of breast cancer was most frequently calculated using the two-dimensional (2D) diameter, which is not reliable for irregular tumors. It was rarely investigated using three-dimensional (3D) imaging with tumor volume on serial magnetic resonance imaging (MRI).

PURPOSE: To investigate the VDT of breast cancer using 3D tumor volume assessment on serial breast MRIs.

STUDY TYPE: Retrospective.

SUBJECTS: Sixty women (age at diagnosis: 57 ± 10 years) with breast cancer, assessed by two or more breast MRI examinations. The median interval time was 791 days (range: 70-3654 days).

FIELD STRENGTH/SEQUENCE: 3-T, fast spin-echo T2-weighted imaging (T2WI), single-shot echo-planar diffusion-weighted imaging (DWI), and gradient echo dynamic contrast-enhanced imaging.

ASSESSMENT: Three radiologists independently reviewed the morphological, DWI, and T2WI features of lesions. The whole tumor was segmented to measure the volume on contrast-enhanced images. The exponential growth model was fitted in the 11 patients with at least three MRI examinations. The VDT of breast cancer was calculated using the modified Schwartz equation.

STATISTICAL TESTS: Mann-Whitney U test, Kruskal-Wallis test, Chi-squared test, intraclass correlation coefficients, and Fleiss kappa coefficients. A P-value <0.05 was considered statistically significant. The exponential growth model was evaluated using the adjusted R[2] and root mean square error (RMSE).

RESULTS: The median tumor diameter was 9.7 mm and 15.2 mm on the initial and final MRI, respectively. The median adjusted R[2] and RMSE of the 11 exponential models were 0.97 and 15.8, respectively. The median VDT was 540 days (range: 68-2424 days). For invasive ductal carcinoma (N = 33), the median VDT of the non-luminal type was shorter than that of the luminal type (178 days vs. 478 days). On initial MRI, breast cancer manifesting as a focus or mass lesion showed a shorter VDT than that of a non-mass enhancement (NME) lesion (median VDT: 426 days vs. 665 days).

DATA CONCLUSION: A shorter VDT was observed in breast cancer manifesting as focus or mass as compared to an NME lesion.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.}, } @article {pmid36876173, year = {2023}, author = {Akbari, ME and Akbari, A and Khayamzadeh, M and Salmanian, R and Akbari, M}, title = {Ten-Year Survival of Breast Cancer in Iran: A National Study (Retrospective Cohort Study).}, journal = {Breast care (Basel, Switzerland)}, volume = {18}, number = {1}, pages = {12-21}, pmid = {36876173}, issn = {1661-3791}, abstract = {PURPOSE: This study aimed to estimate the 5- and 10-year survival rates of breast cancer in Iran.

METHODS: This retrospective cohort study was performed in 2019 on breast cancer patients registered in the national cancer registry system of Iran during 2007-2014. The patients were contacted to collect their information and status (alive or dead). Age and pathological type of tumor were categorized into five groups, and the place of residence was divided into 13 regions. The Kaplan-Meier method and the Cox proportional hazards model were used for data analysis.

RESULTS: A total of 87,902 patients were diagnosed with breast cancer during the study, 22,307 of whom were followed-up. The 5- and 10-year survival rates of the patients were 80% and 69%, respectively. The mean age of the patients was 50.68 ± 12.76 years (median age, 49 years). About 2.3% of the patients were male. The 5- and 10-year survival rates were 69% and 50% in men, respectively. The highest survival rate was reported in the age group of 40-49 years, and the lowest rate was found in the age group of ≥70 years. Of all pathological types, 88% were found in the invasive ductal carcinoma group; the highest survival rate was reported in the noninvasive carcinoma group. The highest survival rate was reported in the Tehran region and the lowest in the Hamedan region. Based on the results, the Cox proportional hazards model, sex, age group, and pathological type were statistically significant differences.

CONCLUSION: This nationwide study performed on breast cancer patients indicated an improvement in the overall survival rate of these patients over the past years (the 5-year survival rate increased from 71% in 2011 to 80% in the present study), which might be attributed to advances in cancer management.}, } @article {pmid36868097, year = {2023}, author = {Aktan, Ç and Küçükaslan, AŞ and Türk, BA and Yildirim, I}, title = {Expression analysis of novel long non-coding RNAs for invasive ductal and invasive lobular breast carcinoma cases.}, journal = {Pathology, research and practice}, volume = {244}, number = {}, pages = {154391}, doi = {10.1016/j.prp.2023.154391}, pmid = {36868097}, issn = {1618-0631}, mesh = {Female ; Humans ; *RNA, Long Noncoding/genetics ; *Carcinoma, Ductal, Breast/genetics/pathology ; *Carcinoma, Lobular/genetics/pathology ; Treatment Outcome ; *Breast Neoplasms/pathology ; }, abstract = {AIM: Long non-coding RNAs (LncRNAs) serve as important regulatory molecules of gene expression and protein functionality at multiple biological levels, and their deregulation plays a key role in tumorigenesis including in breast cancer metastasis. Therefore, in this study, we aim to compare the expression of novel lncRNAs in the landscape of invasive ductal carcinoma (IDC) and invasive lobular (ILC) carcinoma of breast.

MAIN METHODS: We have designed an in-silico approach to find the lncRNAs that regulate the breast cancer. Then, we used the clinical samples to carry out the verification of our in silico finding. In the present study, the tissues of breast cancer were deparaffinized. RNA was extracted by the TRIzole method. After synthesizing cDNA from the extracted RNA, expression levels of lncRNAs were analyzed by qPCR using primers specifically designed and validated for the targeted lncRNAs. In this study, breast biopsy materials from 41 female patients with IDC and 10 female patients with ILC were examined histopathological and expression changes of candidate lncRNAs were investigated in line with the findings. The results were analyzed using IBM SPSS Statistics 25 version.

RESULTS: The mean age of the cases was 53.78 ± 14.96. The minimum age was 29, while the maximum age was 87. While 27 of the cases were pre-menopausal, 24 cases were post-menopausal. The number of hormone receptor-positive cases was found to be 40, 35, and 27 for ER, PR, and cerb2/neu, respectively. While the expressions of LINC00501, LINC00578, LINC01209, LINC02015, LINC02584, ABCC5-AS1, PEX5L-AS2, SHANK2-AS3 and SOX2-OT showed significant differences (p < 0.05), the expressions of LINC01206, LINC01994, SHANK2-AS1, and TPRG1-AS2 showed no significant differences (p > 0.05). In addition, it was determined that the regulation of all lncRNAs could be able to involve in the development of cancer such as the NOTCH1, NFKB, and estrogen receptor signalings.

CONCLUSION: As a result, it was thought that the discovery of novel lncRNAs might be an important player in the diagnosis, prognosis and therapeutic development of breast cancer.}, } @article {pmid36868037, year = {2023}, author = {Abate, F and Russo, M and Ricciardi, C and Tepedino, MF and Romano, M and Erro, R and Pellecchia, MT and Amboni, M and Barone, P and Picillo, M}, title = {Wearable sensors for assessing disease severity and progression in Progressive Supranuclear Palsy.}, journal = {Parkinsonism & related disorders}, volume = {109}, number = {}, pages = {105345}, doi = {10.1016/j.parkreldis.2023.105345}, pmid = {36868037}, issn = {1873-5126}, mesh = {Humans ; *Supranuclear Palsy, Progressive/diagnosis ; Patient Acuity ; Severity of Illness Index ; Gait ; *Wearable Electronic Devices ; Disease Progression ; }, abstract = {INTRODUCTION: Progressive supranuclear palsy (PSP) is an atypical parkinsonism characterized by prominent gait and postural impairment. The PSP rating scale (PSPrs) is a clinician-administered tool to evaluate disease severity and progression. More recently, digital technologies have been used to investigate gait parameters. Therefore, object of this study was to implement a protocol using wearable sensors evaluating disease severity and progression in PSP.

METHODS: Patients were evaluated with the PSPrs as well as with three wearable sensors located on the feet and lumbar area. Spearman coefficient was used to assess the relationship between PSPrs and quantitative measurements. Furthermore, sensor parameters were included in a multiple linear regression model to assess their ability in predicting the PSPrs total score and sub-scores. Finally, differences between baseline and three-month follow-up were calculated for PSPrs and each quantitative variable. The significance level in all analyses was set at ≤ 0.05.

RESULTS: Fifty-eight evaluations from thirty-five patients were analyzed. Quantitative measurements showed multiple significant correlations with the PSPrs scores (r between 0.3 and 0.7; p < 0.05). Linear regression models confirmed the relationships. After three months visit, significant worsening from baseline was observed for cadence, cycle duration and PSPrs item 25, while PSPrs item 10 showed a significant improvement.

CONCLUSION: We propose wearable sensors can provide an objective, sensitive quantitative evaluation and immediate notification of gait changes in PSP. Our protocol can be easily introduced in outpatient and research settings as a complementary tool to clinical measures as well as an informative tool on disease severity and progression in PSP.}, } @article {pmid36866842, year = {2023}, author = {Abdollahpour, N and Helali, F and Rasoulzadeh, Y and Hassankhani, H}, title = {Barriers and Challenges to Human Factors/Ergonomics Knowledge Transfer to Small Business Enterprises in an Industrially Developing Country.}, journal = {IISE transactions on occupational ergonomics and human factors}, volume = {11}, number = {1-2}, pages = {14-31}, doi = {10.1080/24725838.2023.2179687}, pmid = {36866842}, issn = {2472-5846}, mesh = {Humans ; *Developing Countries ; *Small Business ; Ergonomics ; }, abstract = {OCCUPATIONAL APPLICATIONWe found that small business enterprises (SBEs) face intra- and extra-organizational barriers in different dimensions related to their work system to practically implement human factors/ergonomics (HFE) knowledge transfer and to achieve its benefits in an industrially developing country. Utilizing a three-zone lens, we evaluated the feasibility of overcoming the barriers identified by stakeholders, especially ergonomists. To overcome the identified barriers in practice, three types of macroergonomics interventions (top-down, middle-out, and bottom-up) were distinguished through macroergonomics theory. The bottom-up approach of macroergonomics, as a participatory HFE intervention, was considered as the entry point to overcome the perceived barriers in the first zone of the lens, which included such themes as lack of competence, lack of involvement and interaction, and inefficient training and learning approaches. This approach focused on improving emotional literacy as a care zone among the small business enterprise personnel.}, } @article {pmid36863342, year = {2023}, author = {Aggius-Vella, E and Chebat, DR and Maidenbaum, S and Amedi, A}, title = {Activation of human visual area V6 during egocentric navigation with and without visual experience.}, journal = {Current biology : CB}, volume = {33}, number = {7}, pages = {1211-1219.e5}, doi = {10.1016/j.cub.2023.02.025}, pmid = {36863342}, issn = {1879-0445}, mesh = {Humans ; *Auditory Perception ; *Movement/physiology ; Motion ; Hearing ; Eye Movements ; }, abstract = {V6 is a retinotopic area located in the dorsal visual stream that integrates eye movements with retinal and visuo-motor signals. Despite the known role of V6 in visual motion, it is unknown whether it is involved in navigation and how sensory experiences shape its functional properties. We explored the involvement of V6 in egocentric navigation in sighted and in congenitally blind (CB) participants navigating via an in-house distance-to-sound sensory substitution device (SSD), the EyeCane. We performed two fMRI experiments on two independent datasets. In the first experiment, CB and sighted participants navigated the same mazes. The sighted performed the mazes via vision, while the CB performed them via audition. The CB performed the mazes before and after a training session, using the EyeCane SSD. In the second experiment, a group of sighted participants performed a motor topography task. Our results show that right V6 (rhV6) is selectively involved in egocentric navigation independently of the sensory modality used. Indeed, after training, rhV6 of CB is selectively recruited for auditory navigation, similarly to rhV6 in the sighted. Moreover, we found activation for body movement in area V6, which can putatively contribute to its involvement in egocentric navigation. Taken together, our findings suggest that area rhV6 is a unique hub that transforms spatially relevant sensory information into an egocentric representation for navigation. While vision is clearly the dominant modality, rhV6 is in fact a supramodal area that can develop its selectivity for navigation in the absence of visual experience.}, } @article {pmid36856731, year = {2023}, author = {Cao, S and Kalin, ML and Huang, X}, title = {EPISOL: A software package with expanded functions to perform 3D-RISM calculations for the solvation of chemical and biological molecules.}, journal = {Journal of computational chemistry}, volume = {44}, number = {17}, pages = {1536-1549}, doi = {10.1002/jcc.27088}, pmid = {36856731}, issn = {1096-987X}, mesh = {Thermodynamics ; Solvents/chemistry ; Solutions ; Computer Simulation ; *Software ; }, abstract = {Integral equation theory (IET) provides an effective solvation model for chemical and biological systems that balances computational efficiency and accuracy. We present a new software package, the expanded package for IET-based solvation (EPISOL), that performs 3D-reference interaction site model (3D-RISM) calculations to obtain the solvation structure and free energies of solute molecules in different solvents. In EPISOL, we have implemented 22 different closures, multiple free energy functionals, and new variations of 3D-RISM theory, including the recent hydrophobicity-induced density inhomogeneity (HI) theory for hydrophobic solutes and ion-dipole correction (IDC) theory for negatively charged solutes. To speed up the convergence and enhance the stability of the self-consistent iterations, we have introduced several numerical schemes in EPISOL, including a newly developed dynamic mixing approach. We show that these schemes have significantly reduced the failure rate of 3D-RISM calculations compared to AMBER-RISM software. EPISOL consists of both a user-friendly graphic interface and a kernel library that allows users to call its routines and adapt them to other programs. EPISOL is compatible with the force-field and coordinate files from both AMBER and GROMACS simulation packages. Moreover, EPISOL is equipped with an internal memory control to efficiently manage the use of physical memory, making it suitable for performing calculations on large biomolecules. We demonstrate that EPISOL can efficiently and accurately calculate solvation density distributions around various solute molecules (including a protein chaperone consisting of 120,715 atoms) and obtain solvent free energy for a wide range of organic compounds. We expect that EPISOL can be widely applied as a solvation model for chemical and biological systems. EPISOL is available at https://github.com/EPISOLrelease/EPISOL.}, } @article {pmid36856291, year = {2023}, author = {Johnson, HM and Valero, V and Yang, WT and Smith, BD and Krishnamurthy, S and Shen, Y and Lin, H and Lucci, A and Rauch, GM and Kuerer, HM}, title = {Eliminating Breast Surgery for Invasive Cancer with Exceptional Response to Neoadjuvant Systemic Therapy: Prospective Multicenter Clinical Trial Planned Initial Feasibility Endpoint.}, journal = {Journal of the American College of Surgeons}, volume = {237}, number = {1}, pages = {101-108}, pmid = {36856291}, issn = {1879-1190}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; UL1 RR024148/RR/NCRR NIH HHS/United States ; }, mesh = {Female ; Humans ; Middle Aged ; Aged ; Neoadjuvant Therapy/methods ; *Triple Negative Breast Neoplasms/drug therapy ; Prospective Studies ; Feasibility Studies ; Neoplasm Recurrence, Local/prevention & control ; *Breast Neoplasms/surgery/drug therapy ; Erb-b2 Receptor Tyrosine Kinases/metabolism/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; }, abstract = {BACKGROUND: Response to neoadjuvant systemic therapy (NST) for breast cancer enables tailoring of subsequent therapy. Image-guided breast biopsy after NST can accurately predict a pathologic complete response (pCR). The feasibility phase of the clinical trial reported here assesses omission of breast surgery followed by radiotherapy in terms of local recurrence before trial expansion.

STUDY DESIGN: Women with unicentric, cT1-2 N0-1 M0 triple-negative (TNBC) or human epidermal growth factor receptor 2-positive breast cancer (HER2+BC) cancer with <2 cm residual disease on post-NST imaging were eligible to enroll. If no residual invasive or in situ disease was identified by image-guided, vacuum-assisted core biopsy (VACB), breast surgery was omitted, and radiotherapy delivered. The primary endpoint for the feasibility phase was ipsilateral breast tumor recurrence at 6 months. If any recurrence occurred during the feasibility phase the trial would halt.

RESULTS: Thirteen patients were enrolled from March 2017 to October 2018. The mean age was 60.8 years (range 51 to 75) and most patients were White (69.2%) and non-Hispanic/Latino (84.6%). All patients had invasive ductal carcinoma (6 TNBC, 7 HER2+BC). Mean tumor size was 2.4 cm (range 0.9 to 5.0) before NST and 0.7 cm (range 0 to 1.8) after NST. Seven patients (53.8%) had residual disease identified on VACB; the remaining 6 (46.2%) comprised the feasibility cohort. At a median follow-up of 44.3 months (range 41.3 to 51.3) there was no ipsilateral breast tumor recurrence in this cohort.

CONCLUSIONS: These early data suggest that omission of breast surgery in patients with invasive TNBC and HER2+BC with no evidence of residual disease on standardized VACB after NST is potentially feasible. Results from the expansion phase of this clinical trial will be reported per protocol prespecified analyses.}, } @article {pmid36853294, year = {2023}, author = {Montazer, F and Boozari, B and Alizadeh-Navaei, R}, title = {Evaluation of LGR5 Cancer Stem Cell Marker Expression in Breast Cancer and Its Relationship with Hormonal Profile and Clinical Pathological Features.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {24}, number = {2}, pages = {467-470}, pmid = {36853294}, issn = {2476-762X}, mesh = {Aged ; Female ; Humans ; Middle Aged ; *Breast Neoplasms ; Cross-Sectional Studies ; Cytoplasm ; Iran/epidemiology ; Neoplastic Stem Cells ; Receptors, G-Protein-Coupled ; Adult ; }, abstract = {BACKGROUND: Due to the high prevalence of breast cancer and the importance of evaluating new prognostic criteria for effective treatment of these patients, this study was performed to investigate the role of LGR5 in breast cancer and its relationship with hormonal and clinicalopathological features of the disease.

METHODS: This cross-sectional study was performed on breast cancer tissue samples in the archives of the pathology department of Firoozabadi Hospital in Tehran between 2019 and 2021. Inclusion criteria included invasive ductal carcinoma and exclusion criteria were preoperative chemotherapy. Blocks were examined for LGR5 marker expression by IHC method using LGR5 monoclonal antibody kits (Abcam). The expression pattern of LGR5 marker was cytoplasmic and cells presenting brown staining in the cytoplasm were considered positive for this marker and in terms of distribution and severity of staining were divided into three groups: mild, moderate and severe.

RESULTS: This study was performed on 60 patients with breast cancer with a mean age of 55.5±9.7. Most of the patients (55%) were in grade II. The KI67 marker was positive in 45 cases (75%) and the HER2 marker in 14 cases (23.3%) and 8 cases (13.3%) were triple-negative. The expression severity of staining of LGR5 marker in 41 cases (68.3%) was moderate and the distribution of marker expression in 31 cases (51.7%) was moderate. No significant relationship was observed between LGR5 expression severity and tumor characteristics.

CONCLUSION: LGR5 marker is expressed in a remarkable percentage of breast cancer patients and has no significant relationship with tumor characteristics.}, } @article {pmid36850582, year = {2023}, author = {Russo, M and Amboni, M and Barone, P and Pellecchia, MT and Romano, M and Ricciardi, C and Amato, F}, title = {Identification of a Gait Pattern for Detecting Mild Cognitive Impairment in Parkinson's Disease.}, journal = {Sensors (Basel, Switzerland)}, volume = {23}, number = {4}, pages = {}, pmid = {36850582}, issn = {1424-8220}, support = {FARB2019//University of Salerno/ ; }, mesh = {Humans ; Bayes Theorem ; *Parkinson Disease/diagnosis ; Gait ; Gait Analysis ; *Cognitive Dysfunction/diagnosis ; }, abstract = {The aim of this study was to determine a gait pattern, i.e., a subset of spatial and temporal parameters, through a supervised machine learning (ML) approach, which could be used to reliably distinguish Parkinson's Disease (PD) patients with and without mild cognitive impairment (MCI). Thus, 80 PD patients underwent gait analysis and spatial-temporal parameters were acquired in three different conditions (normal gait, motor dual task and cognitive dual task). Statistical analysis was performed to investigate the data and, then, five ML algorithms and the wrapper method were implemented: Decision Tree (DT), Random Forest (RF), Naïve Bayes (NB), Support Vector Machine (SVM) and K-Nearest Neighbour (KNN). First, the algorithms for classifying PD patients with MCI were trained and validated on an internal dataset (sixty patients) and, then, the performance was tested by using an external dataset (twenty patients). Specificity, sensitivity, precision, accuracy and area under the receiver operating characteristic curve were calculated. SVM and RF showed the best performance and detected MCI with an accuracy of over 80.0%. The key features emerging from this study are stance phase, mean velocity, step length and cycle length; moreover, the major number of features selected by the wrapper belonged to the cognitive dual task, thus, supporting the close relationship between gait dysfunction and MCI in PD.}, } @article {pmid36848617, year = {2023}, author = {Esserman, LJ and Ali, H and McKenzie, T}, title = {When Less Can Be More: How the 10-Year Updated Results From the Randomized Controlled AMAROS Trial Should Affect Axillary Management in the Setting of a Positive Node.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {41}, number = {12}, pages = {2144-2150}, doi = {10.1200/JCO.22.02070}, pmid = {36848617}, issn = {1527-7755}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery/drug therapy ; Axilla/pathology ; Mastectomy ; *Lymphedema ; Mastectomy, Segmental ; Randomized Controlled Trials as Topic ; }, abstract = {The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.It is important to reflect on how far we as a medical community have come when treating breast cancer. Ongoing research, clinical trials, and better understanding of biology have transformed our understanding and treatment of breast cancer. There is still much to learn. Although progress was slow for decades, treatments have evolved more quickly in the recent past. The Halsted radical mastectomy, first popularized in 1894, was performed for almost a century, and although it decreased local recurrence, it did not improve survival. This well-intentioned surgery disfigured women and was abandoned as better systemic therapies were introduced and less aggressive surgical procedures were found to be equivalent in clinical trials. The evolution of trials in the modern era has taught us an important lesson. De-escalation of surgical interventions in the setting of improved systemic therapy can lead to better patient outcomes. We present a case of a clinician with an early-stage invasive ductal carcinoma responsive to neoadjuvant endocrine therapy and who subsequently underwent a partial mastectomy with axillary sentinal lymph node biopsy. Although clinically node-negative, she was pathologically node-positive, and concerned about both optimizing her outcomes and minimizing the risk of lymphedema. The release of 10-year follow-up data from the AMAROS trial furthers our knowledge and understanding of the impact of local control measures of the axilla. The concepts illustrated by the findings of AMAROS may be applied in clinical practice and ultimately help us make rational treatment choices and support shared decision making for patients like ours.}, } @article {pmid36843866, year = {2023}, author = {Mansoor, NS and Arifin, F and Kornain, NKM and Razalli, MM}, title = {A rare invasive male breast cancer of nonspecific type presenting at a primary care clinic: Importance of early diagnosis and management.}, journal = {Journal of family & community medicine}, volume = {30}, number = {1}, pages = {65-67}, pmid = {36843866}, issn = {1319-1683}, abstract = {Male breast cancer is a rare disease with an incidence rate of <1% of all breast cancer cases, and only 1% of all male malignancies. Men tend to present at an older age and with more advanced stages compared to women. We report a case of a 74-year-old man who presented at a primary care clinic with a right subareolar painless breast mass. A mammogram and core biopsy were performed. A diagnosis of right invasive breast carcinoma was rendered. The patient underwent a right total mastectomy with ipsilateral axillary lymph node dissection, which revealed an invasive ductal carcinoma of no special type (NST). Chemotherapy, radiotherapy, and hormonal therapy were included in the adjuvant treatment plan. In this report, we discuss the important role of the primary care physician (PCP) in early diagnosis and referral for definitive management. The PCP also plays an essential role in the holistic care of male breast cancer patients, including the management of physical, psychological, social, and underlying chronic diseases.}, } @article {pmid36827339, year = {2023}, author = {Kelly, HK and Geller, S and Swami, V and Shenkman, G and Levy, S and Ridge, D}, title = {A relational investigation of Israeli gay fathers' experiences of surrogacy, early parenthood, and mental health in the context of the COVID-19 pandemic.}, journal = {PloS one}, volume = {18}, number = {2}, pages = {e0282330}, pmid = {36827339}, issn = {1932-6203}, mesh = {Male ; Pregnancy ; Infant ; Child ; Female ; Humans ; Fathers/psychology ; Mental Health ; Israel ; Pandemics ; Gestational Carriers/psychology ; *COVID-19 ; Parenting/psychology ; *Sexual and Gender Minorities ; }, abstract = {Perinatal distress affects approximately 10% of fathers, but little is known about how gay fathers experience the challenges surrounding childbirth and early parenting of a child. This study explored gay fathers' experiences of having a baby via transnational surrogacy, raising that baby as a gay parent, and the context of the COVID-19 pandemic. In-depth qualitative interviews were conducted with 15 Israeli men to understand their experiences of surrogacy and early parenthood, focusing on the impact on their mental health and the relational factors involved. Secondary narrative analysis revealed that fathers constructed surrogacy as a perilous quest that required strong intentionality to undertake. The first year of parenthood was conceptualised alternately as a joyful experience and/or one that challenged fathers' identities and mental health. A relational framework was applied to better conceptualise the fathers' narratives, revealing that actual connections-and the potentials for links-considerably shaped experiences of surrogacy, perinatal distress and recovery. Implications for research and policy are discussed.}, } @article {pmid36819928, year = {2023}, author = {Rounds, AK and Tractenberg, RE and Groah, SL and Frost, JK and Ljungberg, IH and Navia, H and Pham, CT}, title = {Urinary Symptoms Are Unrelated to Leukocyte Esterase and Nitrite Among Indwelling Catheter Users.}, journal = {Topics in spinal cord injury rehabilitation}, volume = {29}, number = {1}, pages = {82-93}, pmid = {36819928}, issn = {1945-5763}, mesh = {Humans ; *Urinary Tract Infections/diagnosis ; Nitrites ; Urinary Bladder ; Prospective Studies ; Predictive Value of Tests ; Catheters, Indwelling ; *Spinal Cord Injuries ; *Spinal Cord Diseases ; Carboxylic Ester Hydrolases ; }, abstract = {OBJECTIVES: To explore the association between dipstick results and urinary symptoms.

METHOD: This was a prospective 12-month observational study of real-time self-administered urine dipstick results and symptoms in a community setting that included 52 spinal cord injury/disease (SCI/D) participants with neurogenic lower urinary tract dysfunction (NLUTD) who use an indwelling catheter. Symptoms were collected using the Urinary Symptom Questionnaire for Neurogenic Bladder-Indwelling Catheter (USQNB-IDC). The USQNB-IDC includes actionable (A), bladder (B1), urine quality (B2), and other (C) symptoms; analyses focused on A, B1, and B2 symptoms. Dipstick results include nitrite (NIT +/-), and leukocyte esterase (LE; negative, trace, small, moderate, or large). Dipstick outcomes were defined as strong positive (LE = moderate/large and NIT+), inflammation positive (LE = moderate/large and NIT-), negative (LE = negative/trace and NIT-), and indeterminate (all others).

RESULTS: Nitrite positive dipsticks and moderate or large LE positive dipsticks were each observed in over 50% of the sample in every week. Strong positive dipstick results were observed in 35% to 60% of participants in every week. A, B1, or B2 symptoms co-occurred less than 50% of the time with strong positive dipsticks, but they also co-occurred with negative dipsticks. Participants were asymptomatic with a strong positive dipstick an average of 30.2% of the weeks. On average, 73% of the time a person had a negative dipstick, they also had no key symptoms (95% CI, .597-.865).

CONCLUSION: No association was observed between A, B1, and B2 symptoms and positive dipstick. A negative dipstick with the absence of key symptoms may better support clinical decision-making.}, } @article {pmid36819793, year = {2022}, author = {Wuraola, FO and Olasehinde, O and Di Bernardo, M and Akinkuolie, AA and Adisa, AO and Aderounmu, AA and Mohammed, TO and Omoyiola, OZ and Kingham, TP and Alatise, OI}, title = {Breast cancer in elderly patients: a clinicopathological review of a Nigerian database.}, journal = {Ecancermedicalscience}, volume = {16}, number = {}, pages = {1484}, pmid = {36819793}, issn = {1754-6605}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Breast cancer in the elderly population has not been evaluated in the Nigerian context. With the rising incidence of breast cancer and the changing demographics, it is likely that an increasing number of elderly patients will be managed in the coming years in Nigeria. This review describes the clinicopathological profile of elderly patients with breast cancer in a Nigerian database.

METHOD: From a prospective institutional database, elderly patients (65 years and above) managed for breast cancer over a 9-year period were reviewed. Details of their socio-demographic characteristics, patterns of presentation, pathology, treatment and outcome were obtained and analysed.

RESULTS: Of the 607 patients managed during the study period, there were 87 older patients accounting for 14.3% of the total. There was a progressive rise in the number of patients with breast cancer towards the latter part of the study. Expectedly, they were all post-menopausal, with their ages ranging from 65 to 92 years, with a mean of 71 ± 6.58 years. Systemic hypertension was the commonest co-morbidity (29.8%). The mean tumour size at presentation was 10 cm, with the majority presenting with stage 3 disease. Invasive ductal carcinoma was the predominant histological type 83 (95.4%); 44.4% of those who had immunohistochemistry were oestrogen receptor-positive. Approximately half underwent mastectomy (52.8%), 63 (72.4%) had chemotherapy, 8 (44.4%) had hormonal therapy and only 6 (6.9%) had combined multimodal therapy in addition to surgery. Overall 5-year survival was 42.1%.

CONCLUSION: The pattern of presentation and outcomes of care in this elderly cohort is similar to the general population. Early presentation and use of multimodal treatment is still the mainstay of survival.}, } @article {pmid36816390, year = {2022}, author = {Balsak, S and Yozgat, CY and Yuzkan, S and Uyar, A}, title = {Comparison of ultrasonographic and mammographic features of extremely rare papillary carcinoma and invasive ductal carcinoma.}, journal = {Contemporary oncology (Poznan, Poland)}, volume = {26}, number = {4}, pages = {275-281}, pmid = {36816390}, issn = {1428-2526}, abstract = {INTRODUCTION: This study aimed to investigate and compare ultrasonographic and mammographic findings of papillary breast carcinoma and invasive ductal carcinoma in breast masses that were diagnosed as pathological.

MATERIAL AND METHODS: This retrospective study included 88 patients with breast lesions, who underwent ultrasonography, mediolateral oblique-craniocaudal, and tomosynthesis imaging in the Picture Archiving and Communication System between January 2010 and March 2019.

RESULTS: 44 histopathologically diagnosed papillary carcinoma patients and 44 invasive ductal carcinoma patients were divided into groups according to contour, shape, internal structure, calcific-cystic component, echogenicity, posterior acoustic change, skin orientation, and environmental echogenic halo. There was a statistically significant difference between the groups in mammography contour, U/S contour, U/S shape, U/S posterior acoustics, and U/S internal structure. Logistic regression analysis showed that the presence of homogenous appearance (p < 0.001) and absence of shading in the posterior acoustic U/S (p = 0.001) were the most pertinent findings for determining papillary carcinoma. In the U/S, the likelihood of a homogenous tumour being a papillary carcinoma was 16.869 times higher than that of invasive ductal carcinoma, whereas the same probability was 0.1101 times less for a tumour with posterior acoustic shadowing.

CONCLUSIONS: It is challenging to differentiate between invasive ductal carcinoma and papillary carcinoma of the breast without histopathological diagnosis both on ultrasound and mammography. The results of our study demonstrated that the ultrasonographic and mammographic findings of invasive ductal carcinoma and papillary carcinoma were like each other. Therefore, it is still not possible to distinguish between these 2 types of cancer only in accordance with these 2 criteria.}, } @article {pmid36809741, year = {2023}, author = {Kor, A and Shoshani, A}, title = {Moderating the impact of the COVID-19 pandemic on children's and adolescents' substance use, digital media use, and mental health: A randomized positive psychology addiction prevention program.}, journal = {Addictive behaviors}, volume = {141}, number = {}, pages = {107660}, pmid = {36809741}, issn = {1873-6327}, mesh = {Humans ; Child ; Adolescent ; Mental Health ; Pandemics ; *COVID-19 ; Internet ; Psychology, Positive ; *Substance-Related Disorders/prevention & control ; Propylamines ; }, abstract = {OBJECTIVE: Previous research suggests that well-being interventions are effective in moderating substance and digital media use and improving mental health. This study evaluated the feasibility and preliminary efficacy of a school-based Positive Psychology Addiction Prevention (PPAP) intervention aimed at reducing substance and digital media use and increasing the mental health of school children during the COVID-19 pandemic.

METHODS: The sample was composed of 1,670 children and adolescents (Mean age = 12.96, SD = 2.01) from six elementary and secondary schools in Israel who were randomly assigned to the PPAP intervention (n = 833) or the waiting-list control conditions (n = 837). A three-year longitudinal repeated-measures randomized control design was used to examine modifications in substance use, digital media use, and psychological symptoms in the intervention and control groups assessed on the pre-test (before the outbreak of COVID-19, September 2019), the post-test (May 2021), and the 12-month follow-up (May 2022).

RESULTS: The 12-month prevalence of tobacco use, alcohol use, and cannabis use decreased significantly from the pre- to the follow-up period in the intervention group, and increased significantly in the control group. Daily digital media use increased during the pandemic period in both groups, with a significantly higher increase in the control group. The intervention group reported significantly lower psychological symptoms and negative emotions, and greater positive emotions and life satisfaction after the intervention and at follow-up compared to the control group.

CONCLUSIONS: The COVID-19 pandemic has profoundly disrupted the lives of children and adolescents. Well-being and addiction prevention interventions may be effective in improving the mental health of school children during pandemics and crisis periods.}, } @article {pmid36805386, year = {2023}, author = {Kwong, A and Co, M and Fukuma, E}, title = {Prospective Clinical Trial on Expanding Indications for Cryosurgery for Early Breast Cancers.}, journal = {Clinical breast cancer}, volume = {23}, number = {4}, pages = {363-368}, doi = {10.1016/j.clbc.2023.01.007}, pmid = {36805386}, issn = {1938-0666}, mesh = {Humans ; Middle Aged ; Female ; *Breast Neoplasms/surgery/pathology ; *Cryosurgery/adverse effects ; Neoplasm, Residual/surgery ; Prospective Studies ; *Carcinoma, Intraductal, Noninfiltrating/surgery/pathology ; }, abstract = {INTRODUCTION: This is a prospective single arm clinical trial on cryosurgery for early breast cancers, to evaluate the expanded criteria to tumors larger than 1.5 cm and non-luminal breast cancers.

METHODS: Inclusion criteria include Solitary T1 breast cancers of any immunohistotypes. Cryosurgery was performed using the IceCure ProSense Cryoablation System. Lumpectomy of the cryoablated tumor was then performed 8 weeks after cryosurgery.

RESULTS: Fifteen patients underwent cryosurgery followed by lumpectomy (BCS). Median age was 53 years old 5 (33.3%) patients had ductal carcinoma in situ (DCIS), while 10 (66.7%) patients had invasive ductal carcinoma (IDC), of which 5 (50%) patients had luminal type cancers of which 3 (60%) were luminal A and 2 (40%) luminal B, 3 (30%) patients had HER2 enriched invasive carcinoma and 2 (20%) patients had triple negative IDC. Median tumor size was 13mm (Range 8.6-18mm). Seven (46.7%) patients were found to have residual cancer in the post-cryosurgery lumpectomy specimen. All residual cancers were found at the periphery of the cryoablated breast tissue. All breast cancers were otherwise completely ablated centrally as confirmed by routine histopathology, immunochemistry and TUNEL assay for evaluation of cell viability. None of the tumor factors such as tumor biology, as well as surgical factors such as ablation time and iceball size, were associated with risk of residual cancer. None of the 15 patients developed post-operative complications.

CONCLUSION: Residual cancer occurs at the periphery of the cryoablation site, careful pre-operative planning and intra-operative monitoring is crucial to ensure complete cryoablation.}, } @article {pmid36803091, year = {2023}, author = {Maybank, AK and Curtis, H and Topp, T and Barnes, PJ}, title = {Metastatic Mammary Carcinoma Presenting as a Large Cystic Axillary Mass: A Report of an Unusual Case.}, journal = {International journal of surgical pathology}, volume = {31}, number = {7}, pages = {1409-1413}, doi = {10.1177/10668969231152574}, pmid = {36803091}, issn = {1940-2465}, mesh = {Female ; Humans ; Middle Aged ; Lymphatic Metastasis/pathology ; Neoplasm Recurrence, Local/pathology ; Breast/pathology ; *Breast Neoplasms/pathology ; *Carcinoma/pathology ; Lymph Nodes/pathology ; Axilla/pathology ; }, abstract = {The differential diagnosis of cystic axillary masses is broad and includes intranodal lesions. Cystic metastatic tumor deposits are rare, and have been reported in a few tumor types, most commonly in the head and neck region, but rarely described with metastatic mammary carcinoma. We report a case of a 61-year-old female who presented with a large right axillary mass. Imaging studies revealed a cystic axillary mass and ipsilateral breast mass. She was managed with breast conservation surgery and axillary dissection for invasive ductal carcinoma, no special type, Nottingham grade 2 (21 mm). One of nine lymph nodes contained a cystic nodal deposit (52 mm), which resembled a benign inclusion cyst. Oncotype DX recurrence score for the primary tumor was low (8), conferring a low risk of disease recurrence despite the large size of the nodal metastatic deposit. A cystic pattern of metastatic mammary carcinoma is rare and important to recognize for accurate staging and management decisions.}, } @article {pmid36798680, year = {2023}, author = {Aghajanzadeh, M and Torabi, H and Najafi, B and Talebi, P and Shirini, K}, title = {Intermammary breast cancer: A rare case of cancer with origin of breast cells in an unusual location.}, journal = {SAGE open medical case reports}, volume = {11}, number = {}, pages = {2050313X231154996}, pmid = {36798680}, issn = {2050-313X}, abstract = {The most common type of cancer among the female population is breast cancer. The most common site for the occurrence of breast cancer is the upper outer quadrant; the upper inner quadrant is the second site, and both the lower outer and the lower inner quadrants are in the third place. This problem is rarely seen in the central portion. Intermammary metastasis due to breast cancer is an infrequent finding. This article presents a 62-year-old lady who presented to the surgical ward with intermammary swelling that appeared suddenly 3 months ago. Ultrasound examination showed a hypoechoic micro-lobulated mass with internal vascularity on the chest wall. Although core needle biopsy suspected invasive ductal carcinoma, both right and left axillary lymph nodes were normal and free. The patient was consulted by an oncologist who recommended radiotherapy before surgery and chemotherapy before and after surgery. This study aims to report and discuss a rare case of intermammary cancer with the origin of breast cells without breast and axillary lymph node involvement. Although the intermammary region is an extremely rare location where breast cancer could occur, its management strategy is the same as other breast cancers.}, } @article {pmid36797734, year = {2023}, author = {Arias Ramos, D and Alzate, JA and Moreno Gómez, GA and Hoyos Pulgarín, JA and Olaya Gómez, JC and Cortés Bonilla, I and Vargas Mosquera, C}, title = {Empirical treatment and mortality in bacteremia due to extended spectrum β-lactamase producing Enterobacterales (ESβL-E), a retrospective cross-sectional study in a tertiary referral hospital from Colombia.}, journal = {Annals of clinical microbiology and antimicrobials}, volume = {22}, number = {1}, pages = {13}, pmid = {36797734}, issn = {1476-0711}, mesh = {Humans ; Retrospective Studies ; Cross-Sectional Studies ; *Escherichia coli Infections/drug therapy ; Tertiary Care Centers ; Colombia/epidemiology ; beta-Lactamases/genetics ; Anti-Bacterial Agents/therapeutic use ; Risk Factors ; *Bacteremia/drug therapy/microbiology ; }, abstract = {BACKGROUND: Infections caused by extended spectrum β-lactamase (ESβL) producing bacteria are common and problematic. When they cause bloodstream infections, they are associated with significant morbidity and mortality.

METHODS: A retrospective cross-sectional observational study was conducted in a single center in Pereira, Colombia. It included people hospitalized with bacteremia due to gram-negative bacilli with the extended-spectrum β-lactamase producing phenotype. A logistic regression analysis was constructed. Clinical characteristics and risk factors for death from sepsis were established.

RESULTS: The prevalence of bacteremia due to Enterobacterales with extended-spectrum β-lactamase producing phenotype was 17%. 110 patients were analyzed. Most patients were men (62%) with a median age of 58 years, hospital mortality was 38%. Admission to intensive care was 45%. The following risk factors for mortality were established: shock requiring vasoactive support, Pitt score > 3 points, and not having an infectious disease consultation (IDC).

CONCLUSIONS: bacteremia due to Enterobacterales with extended-spectrum β-lactamase producing phenotype have a high mortality. Early recognition of sepsis, identification of risk factors for antimicrobial resistance, and prompt initiation of appropriate empiric antibiotic treatment are important. An infectious disease consultation may help improve outcomes.}, } @article {pmid36797689, year = {2023}, author = {Al-Keilani, MS and Bdeir, R and Elstaty, RI and Alqudah, MA}, title = {Expression of substance P, neurokinin 1 receptor, Ki-67 and pyruvate kinase M2 in hormone receptor negative breast cancer and evaluation of impact on overall survival.}, journal = {BMC cancer}, volume = {23}, number = {1}, pages = {158}, pmid = {36797689}, issn = {1471-2407}, support = {20170380//Deanship of scientific research, jordan university of science and technology, Jordan/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Substance P ; Receptors, Neurokinin-1/metabolism ; Ki-67 Antigen/metabolism ; Pyruvate Kinase ; *Triple Negative Breast Neoplasms ; Hormones ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Chronic inflammation is a hallmark of cancer, and it can be stimulated by many factors. Substance P (SP), through binding to neurokinin 1 receptor (NK1R), and pyruvate kinase M2 (PKM2) play critical roles in cancer development and progression via modulating the tumor microenvironment. This study aimed to investigate the prognostic significance of SP and PKM2 in combination with NK1R and Ki-67 in hormone receptor negative (HR-ve) breast cancer.

METHODS: Immunohistochemical expression levels of SP, NK1R, PKM2, and Ki-67 were measured in 144 paraffin-embedded breast cancer tissues (77 h -ve and 67 h + ve). SP, NK1R, and PKM2 were scored semiquantitatively, while Ki-67 was obtained by the percentage of total number of tumor cells with nuclear staining. The optimal cutoff value for SP, NK1R, PKM2, and Ki-67 were assessed by Cutoff Finder.

RESULTS: High SP expression in HR -ve breast cancer was associated with TNM stage (p = 0.020), pT stage (p = 0.035), pN stage (p = 0.002), axillary lymph node metastasis (p = 0.003), and NK1R expression level (p = 0.010). In HR + ve breast cancer, SP expression was associated with HER2 status (p = 0.001) and PKM2 expression level (p = 0.012). Regarding PKM2 expression level, it significantly associated with HER2 status (p = 0.001) and history of DCIS (p = 0.046) in HR-ve tumors, and with HER2 status (p < 0.001) and SP expression level (p = 0.012) in HR + ve tumors. Survival analysis revealed that high SP level negatively impacted overall survival in HR-ve tumors that had low NK1R level (p = 0.021). Moreover, high SP negatively impacted overall survival in HR-ve tumors that had low Ki-67 level (p = 0.005). High PKM2 negatively impacted overall survival in HR-ve cases with low SP (p = 0.047).

CONCLUSION: Combined expression levels of SP with NK1R or Ki-67, and PKM2 with SP could be used to predict survival in breast cancer patients with HR-ve tumors. Our findings suggest a role of SP/NK1R pathway and PKM2 in HR-ve breast cancer pathogenesis which should be further investigated to unveil the underlying molecular mechanisms.}, } @article {pmid36788935, year = {2023}, author = {Shenkman, G and Bos, HMW and D'Amore, S and Carone, N}, title = {Mental Health Disparities Between Lesbian Mothers and Heterosexual Parents: the Mediating Role of Positivity.}, journal = {Sexuality research & social policy : journal of NSRC : SR & SP}, volume = {}, number = {}, pages = {1-11}, pmid = {36788935}, issn = {1868-9884}, abstract = {INTRODUCTION: Previous evidence has shown better mental health outcomes for lesbian mothers, in comparison with heterosexual parents. The present study explored the mediating role of positivity (i.e., the tendency to view life with a positive outlook) in determining these mental health differences.

METHODS: Seventy-two Israeli lesbian mothers by donor insemination (from 36 families) were compared with 72 Israeli heterosexual parents by assisted reproduction (without donated gametes; from 36 families) on positivity, life satisfaction, and depressive symptomatology. All parents were cisgender and had at least one child born through assisted reproduction, aged 3-10 years. Data were collected between December 2019 and February 2021.

RESULTS: Mediational analyses indicated that lesbian mothers reported greater positivity, which was, in turn, associated with greater life satisfaction and less depressive symptomatology.

CONCLUSIONS: The results pinpoint the possible protective and strengthening role of positivity for lesbian mothers in the pronatalist and familistic environment of Israel. The research contributes to the literature on the mental health of parents with diverse sexual orientations living outside of the USA and Europe. Policy Implications Policymakers and mental health professional should be knowledgeable about the importance of improving positivity as a strategy for reducing depressive symptomatology and promoting life satisfaction among lesbian mothers. Moreover, policy makers and legislators are called to ease the access of sexual minority individuals to parenthood, as in this population parenthood associates with heightened mental health outcomes.}, } @article {pmid36788122, year = {2023}, author = {Huang, K and Dufresne, M and Baksh, M and Nussbaum, S and Abbaszadeh Kasbi, A and Mohammed, A and Advani, P and Morozov, A and Bagaria, S and McLaughlin, S and Gabriel, E}, title = {How Well Does Non-mass Enhancement Correlate With DCIS/Invasive Cancer?.}, journal = {The American surgeon}, volume = {89}, number = {12}, pages = {5414-5420}, doi = {10.1177/00031348231156776}, pmid = {36788122}, issn = {1555-9823}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/surgery ; Retrospective Studies ; *Breast Neoplasms/surgery ; *Triple Negative Breast Neoplasms ; Breast ; Correlation of Data ; Pathologic Complete Response ; *Carcinoma, Ductal, Breast/surgery ; }, abstract = {INTRODUCTION: Contiguous non-mass enhancement (NME) often coexists with a solid tumor component on MRI, but it can be challenging to predict whether NME represents invasive breast cancer, ductal carcinoma in situ (DCIS), benign disease, or biopsy site reaction. The purpose of this study was to determine the association between the size/extent of NME and the presence of invasive cancer and/or DCIS on final pathology.

METHODS: This was a single institution retrospective analysis of a prospectively maintained breast cancer registry (2010-2020). Female patients who underwent surgical resection were included if they had a diagnosis of invasive breast cancer (with or without DCIS) and had an MRI showing both a solid mass and contiguous NME. The size of NME on MRI was compared with the size of invasive cancer and/or DCIS on the final pathology.

RESULTS: From a total of 3443 patients, 225 patients were included. 86.2% had invasive ductal carcinoma (IDC), and 12.0% had invasive lobular carcinoma 76.9% were ER+, 16.4% were HER2+, and 13.3% were triple negative breast cancer (TNBC). 18.7% received neoadjuvant chemotherapy (NCT) of whom 31% achieved a complete radiographic/pathologic response. Pearson correlation coefficients (r) between the size of NME and invasive cancer/DCIS showed a strong and positive correlation of MRI NME with DCIS on pathology in patients without NCT. Subgroup analysis showed the strongest correlations for NME and DCIS among non-white (r = .70) and HER2 + patients (r = .74) who did not receive NCT.

CONCLUSIONS: Strong correlations between NME and DCIS were found for HER2 + disease and non-white patients, but only modest correlations were found for other patient/disease characteristics. These correlations may impact decisions in surgical approach.}, } @article {pmid36787199, year = {2023}, author = {Ochiai, S and Chiba, N and Gunji, T and Kobayashi, T and Sano, T and Tomita, K and Shigoka, M and Tabuchi, S and Hidaka, E and Wakiya, M and Nakatsugawa, M and Kawachi, S}, title = {Efficacy of CT Value Along Portal Vein for Preoperative Prediction of Portal Vein Resection in Pancreatic Head Cancer.}, journal = {The American surgeon}, volume = {89}, number = {12}, pages = {5442-5449}, doi = {10.1177/00031348231156772}, pmid = {36787199}, issn = {1555-9823}, mesh = {Humans ; Retrospective Studies ; *Portal Vein/diagnostic imaging/surgery/pathology ; Neoplasm Invasiveness/pathology ; *Pancreatic Neoplasms/diagnostic imaging/surgery/pathology ; Pancreaticoduodenectomy/methods ; Tomography, X-Ray Computed/methods ; }, abstract = {BACKGROUND: It is important for surgeons to determine whether combined portal vein (PV) resection (PVR) is necessary before surgery. The present study aimed to determine the ability of computed tomography (CT) value along the PV in predicting the necessity for concomitant PVR.

METHODS: A total of 107 consecutive patients who underwent pancreaticoduodenectomy (PD) for invasive ductal carcinoma of the pancreatic head at our institute between September 2007 and September 2020 were reviewed retrospectively. Univariate analysis to predict PVR was performed with preoperative radiological valuables acquired by Synapse Vincent. The resected specimen near the PV or the PV notch was analyzed by histopathological findings.

RESULTS: Only the CT value of the PV was independently associated with PVR (Mann-Whitney U test; P = .045, logistic regression test; P = .039). The outer boundary of the PV was unclear in the cases without pathological PV invasion and PVR due to the development of smooth muscle in the outer membrane of the PV and the proliferation of collagen fibers. The elastic fibers were arranged regularly in the notch portion of the PV in cases wherein PVR was not performed.

DISCUSSION: The CT value along the PV was independently associated with PVR and is the only predictor of PVR. These results were very useful in predicting PVR preoperatively and were histopathologically supportive.}, } @article {pmid36786227, year = {2023}, author = {Salzano, S and Zappullo, I and Senese, VP and Conson, M and Finelli, C and Mikulincer, M and Shaver, PR}, title = {Validation and psychometric properties of the Italian version of the Power Behavioural System Scale.}, journal = {Research in psychotherapy (Milano)}, volume = {26}, number = {1}, pages = {}, pmid = {36786227}, issn = {2239-8031}, abstract = {The power behavioural system is a neurobehavioral system that motivates a person to acquire and control resources that are important for survival and reproductive success. When activated, its function is to protect or restore the sense of power, influence, or dominance. Repeated experiences of failure in achieving this goal may result in hyperactivation or deactivation of power-oriented behaviours (analogous to the secondary strategies observed with respect to the attachment behavioural system). Gaining a reliable and valid measure of hyperactivation and deactivation of the power system can be important for understanding an individual's responses to different social contexts and, in clinical settings, can help the therapist identify the client's difficulties that may undermine the therapeutic process. In the present study, we developed the Italian version of the Power Behavioural System Scale (PBSS), a self-report measure developed by Shaver et al. (2011) to assess individual differences in hyperactivation and deactivation of the power system. Results indicated an adequate fit to the expected two-factor model, and the measure proved to be reliable and had good convergent and structural validity, allowing the quantification of individual differences in power system hyperactivation and deactivation.}, } @article {pmid36781838, year = {2023}, author = {Sekido, N and Matsuoka, M and Takahashi, R and Sengoku, A and Nomi, M and Matsuyama, F and Murata, T and Kitta, T and Mitsui, T}, title = {Cross-sectional internet survey exploring symptomatic urinary tract infection by type of urinary catheter in persons with spinal cord lesion in Japan.}, journal = {Spinal cord series and cases}, volume = {9}, number = {1}, pages = {3}, pmid = {36781838}, issn = {2058-6124}, mesh = {Humans ; *Urinary Catheters/adverse effects ; Cross-Sectional Studies ; Urinary Catheterization/adverse effects ; Japan/epidemiology ; *Urinary Tract Infections/epidemiology/etiology ; Spinal Cord ; }, abstract = {STUDY DESIGN: Cross-sectional study by members of patient advocacy groups.

OBJECTIVES: To evaluate the incidence and frequency of symptomatic urinary tract infection (sUTI) in persons with spinal cord lesion (SCL) using different types of catheters based on an internet survey in Japan.

SETTING: An internet survey.

METHODS: We conducted an Internet survey of persons with SCL who were considered to be able to perform intermittent self-catheterization (ISC). We evaluated the incidence and frequency of sUTI over the last year in persons performing ISC and those managed by indwelling catheterization (IDC). We also compared the same parameters between persons in the ISC group using reusable silicone catheters and single-use catheters and those with and without a concomitant use of intermittent balloon catheters (i-IDC).

RESULTS: Two-hundred and eighty-two persons were analyzed. In the ISC and IDC groups, sUTI occurred in 52.2% and 31.4% of persons (p = 0.021), respectively, in the last year, and the frequencies were 2.8 and 3.5 times a year (p = 0.127), respectively. There were no significant differences in the incidence or frequency of sUTI between persons using reusable catheters and single-use catheters or those with and without the concomitant use of i-IDC.

CONCLUSIONS: sUTI occurred in about 1 in 2 persons with SCL performing ISC, which was significantly higher than in the IDC group, and the frequency of sUTI in persons performing ISC was about 3 times a year. The different types of catheters used for ISC were not associated with the incidence or frequency of sUTI. Sponsorship Coloplast Japan Inc.}, } @article {pmid36777854, year = {2023}, author = {Ma, R and Tang, Z and Wang, J}, title = {PTTG1IP (PBF) is a prognostic marker and correlates with immune infiltrate in ovarian cancer.}, journal = {American journal of translational research}, volume = {15}, number = {1}, pages = {27-46}, pmid = {36777854}, issn = {1943-8141}, abstract = {OBJECTIVE: An oncogenic protein, pituitary tumor transforming gene 1 binding factor (PTTG1IP, also called PBF), has been found to be expressed in various cancers. However, few studies have explored its prognostic significance and biologic function in epithelial ovarian cancer (EOC).

METHODS: Based on the Cancer Genome Atlas (TCGA) database, this study determined the differential expression of PBF at the mRNA level in EOC and normal tissues, which was then verified using real-time PCR and western blotting. Moreover, the Kaplan-Meier method and the Cox regression method were adopted to assess the clinical value of PBF in EOC. A nomogram model was constructed to evaluate the prognostic performance of PBF in EOC. Gene set enrichment analysis (GSEA) was employed to evaluate the signaling and pathway enrichment of PBF in EOC. The association between PBF expression and tumor-infiltrating immune cells (TIICs) in EOC was examined by single-sample GSEA and TIMER.

RESULTS: PBF was significantly higher in EOC than normal tissues as shown through TCGA database, and this result was verified by qRT-PCR and western blotting of EOC tissues and different cell lines. High PBF was associated with tumor size and lymphatic metastasis status. Kaplan-Meier (KM) analysis indicated that high PBF expression correlated with poor prognosis in patients with EOC (P < 0.0001). Moreover, multivariate Cox regression analysis was used to verify that PBF is an independent prognostic factor for EOC. The nomogram model exhibited moderate predictive accuracy and clinical utility in predicting EOC prognosis. The GSEA revealed that the expression of signaling pathways, such DNA damage replication, p53 pathway, Akt phosphorylation pathway, and estrogen-dependent nuclear pathway, were increased in the phenotype with high PBF expression. PBF expression was associated with neutrophil cells, iDC cells, NK cells, and Tem cells.

CONCLUSION: As a prognostic biomarker for EOC, PBF was found to be correlated with immune infiltration, and may therefore be a promising target for immunotherapy for EOC.}, } @article {pmid36769184, year = {2023}, author = {Górnicki, T and Lambrinow, J and Mrozowska, M and Romanowicz, H and Smolarz, B and Piotrowska, A and Gomułkiewicz, A and Podhorska-Okołów, M and Dzięgiel, P and Grzegrzółka, J}, title = {Expression of RBMS3 in Breast Cancer Progression.}, journal = {International journal of molecular sciences}, volume = {24}, number = {3}, pages = {}, pmid = {36769184}, issn = {1422-0067}, mesh = {Humans ; Female ; *Breast Neoplasms/metabolism ; Breast/metabolism ; *Carcinoma, Ductal, Breast/pathology ; MCF-7 Cells ; RNA, Messenger/genetics ; Cell Line, Tumor ; Trans-Activators/metabolism ; RNA-Binding Proteins/metabolism ; }, abstract = {The aim of the study was to evaluate the localization and intensity of RNA-binding motif single-stranded-interacting protein 3 (RBMS3) expression in clinical material using immunohistochemical (IHC) reactions in cases of ductal breast cancer (in vivo), and to determine the level of RBMS3 expression at both the protein and mRNA levels in breast cancer cell lines (in vitro). Moreover, the data obtained in the in vivo and in vitro studies were correlated with the clinicopathological profiles of the patients. Material for the IHC studies comprised 490 invasive ductal carcinoma (IDC) cases and 26 mastopathy tissues. Western blot and RT-qPCR were performed on four breast cancer cell lines (MCF-7, BT-474, SK-BR-3 and MDA-MB-231) and the HME1-hTERT (Me16C) normal immortalized breast epithelial cell line (control). The Kaplan-Meier plotter tool was employed to analyze the predictive value of overall survival of RBMS3 expression at the mRNA level. Cytoplasmatic RBMS3 IHC expression was observed in breast cancer cells and stromal cells. The statistical analysis revealed a significantly decreased RBMS3 expression in the cancer specimens when compared with the mastopathy tissues (p < 0.001). An increased expression of RBMS3 was corelated with HER2(+) cancer specimens (p < 0.05) and ER(-) cancer specimens (p < 0.05). In addition, a statistically significant higher expression of RBMS3 was observed in cancer stromal cells in comparison to the control and cancer cells (p < 0.0001). The statistical analysis demonstrated a significantly higher expression of RBMS3 mRNA in the SK-BR-3 cell line compared with all other cell lines (p < 0.05). A positive correlation was revealed between the expression of RBMS3, at both the mRNA and protein levels, and longer overall survival. The differences in the expression of RBMS3 in cancer cells (both in vivo and in vitro) and the stroma of breast cancer with regard to the molecular status of the tumor may indicate that RBMS3 could be a potential novel target for the development of personalized methods of treatment. RBMS3 can be an indicator of longer overall survival for potential use in breast cancer diagnostic process.}, } @article {pmid36765396, year = {2023}, author = {Sui, Y and Li, S and Fu, XQ and Zhao, ZJ and Xing, S}, title = {Bioinformatics analyses of combined databases identify shared differentially expressed genes in cancer and autoimmune disease.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {109}, pmid = {36765396}, issn = {1479-5876}, mesh = {Humans ; *Lupus Erythematosus, Systemic/genetics ; Janus Kinases/therapeutic use ; *Neoplasms ; Carcinogenesis ; Computational Biology ; RNA, Messenger/metabolism ; }, abstract = {BACKGROUND: Inadequate immunity caused by poor immune surveillance leads to tumorigenesis, while excessive immunity due to breakdown of immune tolerance causes autoimmune genesis. Although the function of immunity during the onset of these two processes appears to be distinct, the underlying mechanism is shared. To date, gene expression data for large bodies of clinical samples are available, but the resemblances of tumorigenesis and autoimmune genesis in terms of immune responses remains to be summed up.

METHODS: Considering the high disease prevalence, we chose invasive ductal carcinoma (IDC) and systemic lupus erythematosus (SLE) to study the potential commonalities of immune responses. We obtained gene expression data of IDC/SLE patients and normal controls from five IDC databases (GSE29044, GSE21422, GSE22840, GSE15852, and GSE9309) and five SLE databases (GSE154851, GSE99967, GSE61635, GSE50635, and GSE17755). We intended to identify genes differentially expressed in both IDC and SLE by using three bioinformatics tools including GEO2R, the limma R package, and Weighted Gene Co-expression Network Analysis (WGCNA) to perform function enrichment, protein-protein network, and signaling pathway analyses.

RESULTS: The mRNA levels of signal transducer and activator of transcription 1 (STAT1), 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase like (OASL), and PML nuclear body scaffold (PML) were found to be differentially expressed in both IDC and SLE by using three different bioinformatics tools of GEO2R, the limma R package and WGCNA. From the combined databases in this study, the mRNA levels of STAT1 and OAS1 were increased in IDC while reduced in SLE. And the mRNA levels of OASL and PML were elevated in both IDC and SLE. Based on Kyoto Encyclopedia of Genes and Genomes pathway analysis and QIAGEN Ingenuity Pathway Analysis, both IDC and SLE were correlated with the changes of multiple components involved in the Interferon (IFN)-Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway.

CONCLUSION: The expression levels of STAT1 and OAS1 manifest the opposite expression tendency across cancer and autoimmune disease. They are components in the IFN-JAK-STAT signaling pathway related to both tumorigenesis and autoimmune genesis. STAT1 and OAS1-associated IFN-JAK-STAT signaling could explain the commonalities during tumorigenesis and autoimmune genesis and render significant information for more precise treatment from the point of immune homeostasis.}, } @article {pmid36763857, year = {2023}, author = {Langley, RG and Sofen, H and Dei-Cas, I and Reich, K and Sigurgeirsson, B and Warren, RB and Paul, C and Szepietowski, JC and Tsai, TF and Hampele, I and You, R and Charef, P and Papavassilis, C}, title = {Secukinumab long-term efficacy and safety in psoriasis through to year 5 of treatment: results of a randomized extension of the phase III ERASURE and FIXTURE trials.}, journal = {The British journal of dermatology}, volume = {188}, number = {2}, pages = {198-207}, doi = {10.1093/bjd/ljac040}, pmid = {36763857}, issn = {1365-2133}, mesh = {Humans ; Quality of Life ; *Nasopharyngitis/chemically induced ; Antibodies, Monoclonal, Humanized/adverse effects ; *Psoriasis/drug therapy ; *Respiratory Tract Infections ; Treatment Outcome ; Severity of Illness Index ; Double-Blind Method ; }, abstract = {BACKGROUND: In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of secukinumab (a fully human anti-interleukin-17A monoclonal antibody) was demonstrated to have been maintained through to year 3 of treatment in moderate-to-severe plaque psoriasis.

OBJECTIVES: To assess the efficacy and safety of secukinumab through to year 5 of treatment in moderate-to-severe plaque psoriasis.

METHODS: Responders with ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) from two core trials - ERASURE and FIXTURE - were randomized 2 : 1 at year 1 (end of core trials) to either the same dose (300 or 150 mg, continuous treatment) or placebo (treatment withdrawal) every 4 weeks, until year 3 or relapse (> 50% reduction in maximal PASI from core study baseline). Partial responders (achieving PASI 50 but not PASI 75) at year 1 continued at the same dose as in the core trials. At year 3, all patients received open-label secukinumab treatment, with those on secukinumab 300 mg continuing on their dose, while those on secukinumab 150 mg or placebo received secukinumab 150 or 300 mg based on the physician's discretion. The study is registered on ClinicalTrials.gov with the identifier NCT01544595.

RESULTS: Most patients randomized to placebo at year 1 relapsed, but the response was rapidly recaptured upon reinitiation of treatment. PASI responses were sustained with secukinumab through to year 5. The PASI responses for the 300 mg responders + partial responders group at year 1 (PASI 75/90/100: 86.8%/72.8%/45.9%) trended downwards until year 3 (PASI 75/90/100: 82.3%/58.4%/32.7%) and then remained stable through year 4 (PASI 75/90/100: 83.3%/60.1%/32.2%) until year 5 (PASI 75/90/100: 81.1%/62.8%/35.1%). Dermatology Life Quality Index showed sustained benefit up to year 5. Absolute PASI responses were maintained throughout the study. The most common adverse events (AEs) were infections and infestations, nasopharyngitis, and upper respiratory tract infections (URTIs). The overall exposure-adjusted incidence rate (EAIR; with 95% confidence interval) for all AEs was 139.9 (130.3-149.9). EAIRs for Crohn's disease and neutropenia were 0.1 (0.0-0.3) and 0.5 (0.3-0.8), respectively.

CONCLUSIONS: The 4-year extension of two pivotal phase III trials demonstrated that secukinumab treatment was effective through to year 5 and improved quality of life in patients with moderate-to-severe plaque psoriasis. The most common AEs were infections and infestations, nasopharyngitis, and URTIs. The safety profile was consistent with that in the secukinumab phase II/III clinical development programme.}, } @article {pmid36762811, year = {2023}, author = {Joe, WH and Lee, CY and Kim, CH and Ko, YS and Kim, SP and Kwon, SM}, title = {Breast Cancer to Meningioma: A Rare Case of Tumor-to-Tumor Metastasis.}, journal = {Brain tumor research and treatment}, volume = {11}, number = {1}, pages = {73-78}, pmid = {36762811}, issn = {2288-2405}, support = {2020R1G1A1013289//National Research Foundation of Korea/Korea ; }, abstract = {Tumor-to-tumor metastasis (TTM) is defined as the hematogenous metastasis within a primary host tumor from a donor neoplasm. Since there is insufficient evidence regarding the pathophysiology, clinical course, and management of TTM, there are no precise guidelines for its management. A 73-year-old female patient diagnosed with breast cancer was found to have convexity meningioma. Since the size of tumor and peritumoral brain edema increased during follow-up period, the meningioma was treated with surgical resection. Postoperatively, histopathologic examination confirmed metastasis of invasive ductal carcinoma within a secretory meningioma. The final diagnosis was TTM of breast cancer in meningioma. Here, we report a rare case of intra-meningioma metastasis and a review of literature to provide a better understanding of this rare phenomenon.}, } @article {pmid36755863, year = {2022}, author = {Zhu, S and Wang, H and Lin, L and Fei, X and Wu, J}, title = {Primary breast osteosarcoma in a patient previously treated for ipsilateral invasive ductal carcinoma: An unusual case report with clinical and genomic features.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {1013653}, pmid = {36755863}, issn = {2234-943X}, abstract = {Primary breast osteosarcoma is a rare subtype of breast malignancy with limited clinical evidence, inadequate biological understanding, and unmet treatment consensus. Here, we report an unusual case of primary breast osteosarcoma developing in the same quadrant of the breast 2 years after initial dissection and radiation of invasive ductal carcinoma. Thorough evaluations of imaging and pathology were conducted while genomic alterations of both primary and secondary tumors, as well as peripheral blood samples, were explored through the next-generation sequencing technique. A comprehensive review of the current literature was also performed on this rare malignancy.}, } @article {pmid36754375, year = {2023}, author = {Goubar, A and Martin, FC and Sackley, C and Foster, NE and Ayis, S and Gregson, CL and Cameron, ID and Walsh, NE and Sheehan, KJ}, title = {Development and Validation of Multivariable Prediction Models for In-Hospital Death, 30-Day Death, and Change in Residence After Hip Fracture Surgery and the "Stratify-Hip" Algorithm.}, journal = {The journals of gerontology. Series A, Biological sciences and medical sciences}, volume = {78}, number = {9}, pages = {1659-1668}, pmid = {36754375}, issn = {1758-535X}, support = {MR/S032819/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Aged ; Hospital Mortality ; *Hip Fractures/surgery ; Algorithms ; England/epidemiology ; }, abstract = {BACKGROUND: To develop and validate the stratify-hip algorithm (multivariable prediction models to predict those at low, medium, and high risk across in-hospital death, 30-day death, and residence change after hip fracture).

METHODS: Multivariable Fine-Gray and logistic regression of audit data linked to hospital records for older adults surgically treated for hip fracture in England/Wales 2011-14 (development n = 170 411) and 2015-16 (external validation, n = 90 102). Outcomes included time to in-hospital death, death at 30 days, and time to residence change. Predictors included age, sex, pre-fracture mobility, dementia, and pre-fracture residence (not for residence change). Model assumptions, performance, and sensitivity to missingness were assessed. Models were incorporated into the stratify-hip algorithm assigning patients to overall low (low risk across outcomes), medium (low death risk, medium/high risk of residence change), or high (high risk of in-hospital death, high/medium risk of 30-day death) risk.

RESULTS: For complete-case analysis, 6 780 of 141 158 patients (4.8%) died in-hospital, 8 693 of 149 258 patients (5.8%) died by 30 days, and 4 461 of 119 420 patients (3.7%) had residence change. Models demonstrated acceptable calibration (observed:expected ratio 0.90, 0.99, and 0.94), and discrimination (area under curve 73.1, 71.1, and 71.5; Brier score 5.7, 5.3, and 5.6) for in-hospital death, 30-day death, and residence change, respectively. Overall, 31%, 28%, and 41% of patients were assigned to overall low, medium, and high risk. External validation and missing data analyses elicited similar findings. The algorithm is available at https://stratifyhip.co.uk.

CONCLUSIONS: The current study developed and validated the stratify-hip algorithm as a new tool to risk stratify patients after hip fracture.}, } @article {pmid36753450, year = {2023}, author = {Taylor, DB and Burrows, S and Dessauvagie, BF and Saunders, CM and Ives, A}, title = {Accuracy and precision of contrast enhanced mammography versus MRI for predicting breast cancer size: how "good" are they really?.}, journal = {The British journal of radiology}, volume = {96}, number = {1144}, pages = {20211172}, pmid = {36753450}, issn = {1748-880X}, mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/pathology ; Prospective Studies ; Contrast Media ; Mammography/methods ; Magnetic Resonance Imaging/methods ; }, abstract = {OBJECTIVE: To evaluate and compare the accuracy and precision of contrast-enhanced mammography (CEM) vs MRI to predict the size of biopsy-proven invasive breast cancer.

METHODS: Prospective study, 59 women with invasive breast cancer on needle biopsy underwent CEM and breast MRI. Two breast radiologists read each patient's study, with access limited to one modality. CEM lesion size was measured using low-energy and recombined images and on MRI, the first post-contrast series. Extent of abnormality per quadrant was measured for multifocal lesions. Reference standards were size of largest invasive malignant lesion, invasive (PathInvasive) and whole (PathTotal). Pre-defined clinical concordance ±10 mm.

RESULTS: Mean patient age 56 years, 42 (71%) asymptomatic. Lesions were invasive ductal carcinoma 40 (68%) with ductal carcinoma in situ (31/40) in 78%, multifocal in 12 (20%). Median lesion size was 17 mm (invasive) and 27 mm (total), range (5-125 mm). Lin's concordance correlation coefficients for PathTotal 0.75 (95% CI 0.6, 0.84) and 0.71 (95% CI 0.56, 0.82) for MRI and contrast-enhanced spectral mammography (CESM) respectively. Mean difference for total size, 3% underestimated and 4% overestimated, and for invasive 41% and 50% overestimate on MRI and CESM respectively. LOAs for PathTotal varied from 60% under to a 2.4 or almost threefold over estimation. MRI was concordant with PathTotal in 36 (64%) cases compared with 32 (57%) for CESM. Both modalities concordant in 26 (46%) cases respectively.

CONCLUSION: Neither CEM nor MRI have sufficient accuracy to direct changes in planned treatment without needle biopsy confirmation.

ADVANCES IN KNOWLEDGE: Despite small mean differences in lesion size estimates using CEM or MRI, the 95% limits of agreement do not meet clinically acceptable levels.}, } @article {pmid36753185, year = {2019}, author = {Lima-Ribeiro, I and Lima-Ribeiro, I and Da Silva Santa Rosa, JG and Do Céu-Clara Costa, I}, title = {[Healthy eating, schoolchildren perception about themselves].}, journal = {Revista de salud publica (Bogota, Colombia)}, volume = {21}, number = {3}, pages = {381-386}, doi = {10.15446/rsap.V21n3.54047}, pmid = {36753185}, issn = {2539-3596}, mesh = {Child ; Humans ; *Feeding Behavior ; *Diet, Healthy ; Parents ; Vegetables ; Perception ; Diet ; }, abstract = {OBJECTIVE: To evaluate the perception of schoolchildren between 7-10 years of a public school in Natal-RN about healthy eating.

METHOD: Descriptive study, with quantitative and qualitative approach by focus group interviews with 29 students whose average age was 8.8 years. The analysis was aided by IRAMUTEQ software and supported the concept of perception of Merleau-Ponty.

RESULTS: Children's perception about healthy eating was associated with fresh foods and culinary preparations. We identified concepts acquired at school on the topic, as well as teachers criticizing the consumption of ultra-processed foods. There were reports of predilection for certain school meals and rejection of others. In addition, children have cited the presence of unhealthy foods served at school. Regarding the role of families, parents were cited in the role of guide for a healthy consumption at the same time they encouraged to consumption of processed foods at home or they provided money to buy them. Many children did not consume healthy foods, mainly fruits and vegetables because they consider unpalatable.

CONCLUSION: The perception of children about healthy foods was influenced by school, family and media. Although they possessed sense of what would be a healthy feed, the pleasure in eating processed foods led to unhealthy practices. The findings show the need for a look magnified by the professionals involved in this role to stimulate and drive healthy practices.}, } @article {pmid36752370, year = {2023}, author = {Miceli, R and Gao, Y and Qian, K and Heller, SL}, title = {Predicting Upgrade of Ductal Carcinoma In Situ to Invasive Breast Cancer at Surgery With Ultrafast Imaging.}, journal = {AJR. American journal of roentgenology}, volume = {221}, number = {1}, pages = {34-43}, doi = {10.2214/AJR.22.28698}, pmid = {36752370}, issn = {1546-3141}, mesh = {Humans ; Middle Aged ; Female ; *Breast Neoplasms/diagnostic imaging/surgery/pathology ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/surgery/pathology ; Mammography ; Magnetic Resonance Imaging/methods ; Sentinel Lymph Node Biopsy ; *Carcinoma, Ductal, Breast/diagnostic imaging/surgery/pathology ; Retrospective Studies ; }, abstract = {BACKGROUND. Biopsy-proven ductal carcinoma in situ (DCIS) lesions are often upgraded to invasive cancer at surgery. Therefore, accurate prediction of the likelihood of invasion is helpful for surgical planning, including the need for sentinel lymph node biopsy (SLNB). OBJECTIVE. The purpose of the present study was to investigate whether kinetic features of clinically available ultrafast MRI (UF-MRI) can predict upgrade of biopsy-proven DCIS to invasive cancer at surgical excision. METHODS. Consecutive patients with biopsy-proven pure DCIS lesions who underwent UF-MRI with conventional dynamic contrast-enhanced MRI (DCE-MRI) and subsequently underwent surgery between August 2019 and January 2021 were identified. Patient and lesion characteristics, biopsy method and pathology, and lesion features on mammography, ultrasound, DCE-MRI, and UF-MRI were assessed to determine predictors of upgrade to invasive cancer. The Fisher exact test and Kruskal-Wallis test were used for association analysis. RESULTS. In 68 patients (median age, 52.0 years; range, 31-79 years) with 68 biopsy-proven pure DCIS lesions, 26 lesions (38%) were upgraded from in situ to invasive cancer. An upgrade of DCIS to invasive cancer was significantly associated with a shorter time to enhancement (TTE) on preoperative UF-MRI (p = .03), with a threshold of 11 seconds providing maximum specificity (50%) and sensitivity (76%) for upgrade. Larger lesion size on DCE-MRI (p = .001) and mammography (p = .04) was also significantly associated with upgrade; an optimal predictive threshold of 4.4 cm on DCE-MRI yielded sensitivity of 88% and specificity of 56%. No other specific variables were significantly associated with upgrade after surgery. Logistic regression of selected features combined with TTE produced a higher AUC (0.85) in predicting upgrade to invasive disease than did each factor alone, but this result was not statistically significant. CONCLUSION. Preoperative UF-MRI TTE and lesion size on DCE-MRI and mammography show potential in predicting upgrade of DCIS to invasive cancer at surgery. CLINICAL IMPACT. UF-MRI provides useful information that can be used in surgical planning, including determination of the need to perform SLNB.}, } @article {pmid36747860, year = {2023}, author = {Ricks-Santi, LJ and Fredenburg, K and Rajaei, M and Esnakula, A and Naab, T and McDonald, JT and Kanaan, Y}, title = {Characterization of GATA3 and Mammaglobin in breast tumors from African American women.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {36747860}, issn = {2693-5015}, support = {R15 CA239100/CA/NCI NIH HHS/United States ; }, abstract = {GATA3 and Mammaglobin are often used in the clinic to identify metastases of mammary origin due to their robust and diffuse expression in mammary tissue. However, the expression of these markers has not been well characterized in tumors from African American women. The goal of this study was to characterize and evaluate the expression of GATA3 and mammaglobin breast tumors from African American women and determine their association with clinicopathological outcomes including breast cancer subtypes. Tissue microarrays (TMAs) were constructed from well preserved, morphologically representative tumors in archived formalin-fixed, paraffin-embedded (FFPE) surgical blocks from 202 patients with primary invasive ductal carcinoma. Mammaglobin, and GATA3 expression was assessed using immunohistochemistry (IHC). Univariate analysis was carried out to determine the association between expression of GATA3, mammaglobin and clinicopathological characteristics. Kaplan-Meier estimates of overall survival and disease-free survival were also plotted and a log-rank test performed to compare estimates among groups. GATA3 expression showed statistically significant association with lower grade (p<0.001), ER-positivity (p<0.001), PR-positivity (p<0.001), and the luminal subtype (p<0.001). Mammaglobin expression was also significantly associated with lower grade (p=0.031), ER-positivity (p=0.007), and PR-positivity (p=0.022). There was no association with recurrence-free or overall survival. Our results confirm that GATA3 and mammaglobin demonstrate expression predominantly in luminal breast cancers from African American women. Markers with improved specificity and sensitivity are warranted given the high prevalence of triple negative breast cancer in the group.}, } @article {pmid36742232, year = {2022}, author = {Ghalkhani, E and Akbari, MT and Izadi, P and Mahmoodzadeh, H and Kamali, F}, title = {The Expression Levels of Circulating miR-129 and miR-203a in Association with Breast Cancer and Related Metastasis.}, journal = {Iranian journal of public health}, volume = {51}, number = {12}, pages = {2808-2816}, pmid = {36742232}, issn = {2251-6093}, abstract = {BACKGROUND: A significant part of deaths related to breast cancer is the result of invasion to other organs. It is essential to discover new non-invasive biomarkers to improve anticipation of recurrence risk in breast cancer patients. In this study, the plasma levels of miR-129 and miR-203a were evaluated to investigate their diagnostic potential in breast cancer and its metastasis.

METHODS: In this case-control study, conducted in Tarbiat Modares University, Tehran, Iran, in 2019, Invasive Ductal Carcinoma blood samples were divided into 3 groups based on their stages as I, II/III, IV. Each group contained 30 individuals. We also recruited 30 normal individuals as a control group. Real-Time PCR was conducted to evaluate miR-129 and miR-203a expression levels. The discriminatory ability of the evaluated plasma miRNAs was assessed by ROC (Receiver Operating Characteristic) curves in breast cancer diagnosis and its metastasis.

RESULTS: MiR-129 and miR-203a expression levels were significantly downregulated in breast cancer. Reducing tendency was observed in the mentioned miRNAs from less to more invasive stages. The expression level of miR-129 was decreased in metastatic than non-metastatic patients and it was significantly related to metastasis. A significant association between miR-129 expression level and lymph node status was also observed (P=0.04). Evaluation of ROC curves revealed that miR-129 and miR-203a were able to discriminate breast cancer fairly and poorly respectively. The ability of miR-129 in the diagnosis of breast cancer metastasis was poor.

CONCLUSION: MiR-129 and miR-203a may both act as tumor suppressor miRNAs. Our results need further evidence in a large population to be confirmed as diagnostic markers.}, } @article {pmid36742153, year = {2023}, author = {Liu, W and Wan, Q and Zhou, E and He, P and Tang, L}, title = {LncRNA LINC01833 is a Prognostic Biomarker and Correlates with Immune Infiltrates in Patients with Lung Adenocarcinoma by Integrated Bioinformatics Analysis.}, journal = {Journal of oncology}, volume = {2023}, number = {}, pages = {3965198}, pmid = {36742153}, issn = {1687-8450}, abstract = {Due to the absence of accurate tools for early detection and successful treatment, lung adenocarcinoma (LUAD) is one of the most aggressive tumors with high morbidity and mortality globally. It is absolutely necessary to investigate the process behind its development and search for new biomarkers that could aid in the early detection of LUAD. There is a correlation between the immune microenvironment of the tumor and the prognosis of lung cancer as well as the efficacy of immunotherapy. Long noncoding RNAs (lncRNAs) have been identified as potential prognostic biomarkers linked to immunological activities. In this study, we identified 1 downregulated lncRNA and 76 upregulated lncRNAs in LUAD samples from TCGA datasets. Among the 77 dysregulated lncRNAs, our attention focused on lncRNA LINC01833 (LINC01833). When compared with nontumor specimens, the level of expression of LINC01833 was shown to be significantly elevated in LUAD samples. In addition, the data of the ROC study revealed that LUAD patients with high LINC01833 expression had an AUC value of 0.840 (95% confidence interval: 0.804 to 0.876). There was a correlation between high LINC01833 expression and an advanced clinical stage. Patients who had a high expression of LINC01833 were shown to have a lower overall survival rate (p < 0.001) and a lower disease-specific survival rate (p = 0.004) in comparison to patients who were in the low LINC01833 group, according to the data on survival. In addition, the results of the multivariate analysis revealed that high LINC01833 expression was an independent predictor of poor survival in LUAD. Moreover, the immune analysis revealed that we found that the expression of LINC01833 was positively associated with Th2 cells, aDC, and Tgd, while negatively associated with Mast cells, Tcm, Eosinophils, iDC, DC, Tem, Th17 cells, and pDC. Overall, our data point to the possibility that the unique lncRNA LINC01833 might be employed as a diagnostic and prognostic marker, and as a result, it has a significant impact on clinical practice.}, } @article {pmid36738975, year = {2023}, author = {Okubo, Y and Sato, S and Hasegawa, C and Koizumi, M and Suzuki, T and Yamamoto, Y and Yoshioka, E and Ono, K and Washimi, K and Yokose, T and Kishida, T and Miyagi, Y}, title = {Cribriform pattern and intraductal carcinoma of the prostate can have a clinicopathological impact, regardless of their percentage and/or number of cores.}, journal = {Human pathology}, volume = {135}, number = {}, pages = {99-107}, doi = {10.1016/j.humpath.2023.01.008}, pmid = {36738975}, issn = {1532-8392}, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/surgery ; *Adenocarcinoma/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Lymphatic Metastasis/pathology ; Prostatectomy ; Neoplasm Grading ; *Prostate/surgery ; Retrospective Studies ; Biopsy ; Middle Aged ; Aged ; Treatment Outcome ; }, abstract = {Cribriform pattern and intraductal carcinoma of the prostate (IDC-P) are widely accepted as poor prognostic factors in prostate cancer. However, it remains unclear to what extent the presence of these morphological features in prostate biopsy specimens, as diagnosed by hematoxylin-eosin-stained specimens only, affects the clinicopathological impact. In this study, we summarized the characteristics of the cribriform pattern and IDC-P in 850 prostate biopsy cases. The results showed a statistically significant increase in the incidence of cribriform pattern and IDC-P as grade group (GG) increased (especially in cases ≥ GG4, Chi-square test P < 0.001). The independent risk factors for cribriform pattern and IDC-P in biopsy specimens in the multivariate logistic regression analysis were the former GG, presence of IDC-P, lesion length of the highest GG core, latter GG, presence of the cribriform pattern, number of biopsies obtained, and number of highest GG core. Overall, 125 cases in which radical prostatectomy was conducted after biopsy were selected for further analysis. Multivariate logistic regression analysis using biopsy and surgical specimens confirmed that the presence of the cribriform pattern and IDC-P in biopsy specimens were independent risk factors for lymph node metastasis (odds ratios [95% confidence interval] were 6.54 [1.15-37.05] for the cribriform pattern and 23.71 [1.74-322.42] for IDC-P). The presence of the cribriform pattern and/or IDC-P in a biopsy specimen was a significant factor, even if only partially present, indicating lymph node metastasis. However, further validation is required to predict poor prognostic factors more accurately.}, } @article {pmid36733163, year = {2022}, author = {Oshima, K and Mitsuyoshi, A and Kikumori, K and Hori, A and Yanagawa, T and Shinke, G and Katsuyama, S and Ikeshima, R and Hiraki, M and Ohmura, Y and Sugimura, K and Masuzawa, T and Hata, T and Takeda, Y and Murata, K}, title = {[A Case of Locally Advanced Breast Cancer That Responded to Paclitaxel plus Bevacizumab and Underwent Radical Surgery].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {49}, number = {13}, pages = {1645-1647}, pmid = {36733163}, issn = {0385-0684}, mesh = {Female ; Humans ; Aged ; *Breast Neoplasms/drug therapy/surgery/pathology ; Paclitaxel ; Bevacizumab/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Combined Modality Therapy ; }, abstract = {The patient is a 69-year-old female. She was aware of a right breast mass about a year ago, but left it alone. In March 2021, she visited our hospital with a 11 cm mass occupying the right breast and self-destruction due to skin invasion. The diagnosis of invasive ductal carcinoma of the breast(ER-positive, PgR-positive, HER2-negative), cT4bN1M0, Stage ⅢB was made, and preoperative chemotherapy was decided. We expected a high response rate for bevacizumab(Bv)because it was predicted that the skin defect would increase at surgical resection if a response to chemotherapy was not achieved, and in April 2021, paclitaxel(PTX)plus Bv therapy was initiated. After 4 courses, the mass had shrunk to 5 cm and a marked response had been achieved. However, she was unable to continue the treatment due to peripheral neuropathy. Therefore, considering the period of delayed wound healing due to Bv, we decided on AC therapy followed by surgery. In December 2021, Bt plus Ax was performed and the wound could be closed without skin grafting. Since PTX plus Bv therapy is expected to have a high response rate, we considered it to be one of the effective treatment options for locally advanced breast cancer.}, } @article {pmid36733146, year = {2022}, author = {Hojo, S and Yoshioka, S and Wakabayashi, Y}, title = {[A Case Performed Mastectomy to Tumor Progression of Breast Cancer Omitting Surgery after Neoadjuvant Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {49}, number = {13}, pages = {1594-1596}, pmid = {36733146}, issn = {0385-0684}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/drug therapy/surgery/pathology ; Mastectomy ; Neoadjuvant Therapy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Trastuzumab/therapeutic use ; }, abstract = {We report a case performed mastectomy to tumor progression of breast cancer omitting surgery after neoadjuvant chemotherapy. A 62-year-old female patient visited our hospital for left breast tumor. A tumor of the size of 26×24 mm was found at between lower and upper outer quadrant, and we diagnosed it as breast cancer(cT1, cN2, M0, Stage ⅢA, ER positive/HER2 positive). Neoadjuvant chemotherapy by triweekly trastuzumab and weekly paclitaxel followed by EC chemotherapy were performed. However, she rejected surgery after neoadjuvant chemotherapy, and although we consequently restarted a regimen of triweekly trastuzumab which she also refused to continue after 9 cycles. 32 months later, she noticed induration on her left breast, and we diagnosed it as tumor progression of breast cancer. After obtaining informed consent, we performed total mastectomy and axillary lymph node dissection. Histological diagnosis revealed invasive ductal carcinoma, ER negative/HER2 positive, and no axillary lymph node metastasis. So far omission of surgery after neoadjuvant chemotherapy to breast cancer is not defined yet, and we expect early definition of evidence.}, } @article {pmid36733112, year = {2022}, author = {Satoh, E and Hara, M and Uehira, D and Yonekura, K and Murakata, A and Ohinata, R and Toyofuku, Y and Tanami, H and Osanai, T and Sugano, N and Sakoma, T}, title = {[A Case of Recurrent Breast Cancer with Multiple Bone Metastasis Effectively Treated by CDK4/6 Inhibitor in Addition to Aromatase Inhibitor].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {49}, number = {13}, pages = {1491-1493}, pmid = {36733112}, issn = {0385-0684}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/drug therapy/surgery/pathology ; Aromatase Inhibitors/therapeutic use ; Letrozole ; Mastectomy ; Lymph Node Excision ; Cyclin-Dependent Kinase 4 ; }, abstract = {We report a case of recurrent breast cancer with multiple bone metastasis in a 62-year-old woman. Her breast cancer (invasive ductal carcinoma, T2N0M0, Stage ⅡA)was resected in 2001(partial mastectomy plus axillary lymph node dissection) with adjuvant chemotherapy(UFT)and irradiation to her left remnant breast. In February 2018, she complained of severe pain in right femoral joint and hip. CT scan showed a left cystic breast tumor(17 cm)and multiple bone metastasis. The core needle biopsy of the costal bone lesion and left mastectomy were performed. These pathological findings were recurrence of the breast cancer(ER+). The endocrine therapy(exemestane, aromatase inhibitor), the administration of denosumab and irradiation to painful bone lesions were performed, but it did not suppress tumor progression. The treatment of letrozole plus palbociclib(CDK4/6 inhibitor)were continued for 3 months from May 2018, and this therapy made her bone lesions smaller, but palbociclib were stopped due to its severe neutropenia. After that, the single administration of letrozole was continued, but the tumor marker did not become normal. In February 2019, abemaciclib was administered in addition to letrozole. One year later, her symptoms improved and her bone metastases have showed partial response.}, } @article {pmid36730303, year = {2023}, author = {Chang, H and Hu, T and Hu, J and Ding, T and Wang, Q and Cheng, J}, title = {Complete response in patient with liver metastasis of HER2-positive breast cancer following therapy with margetuximab: a case report.}, journal = {Anti-cancer drugs}, volume = {34}, number = {7}, pages = {883-887}, pmid = {36730303}, issn = {1473-5741}, mesh = {Female ; Humans ; Aged ; *Breast Neoplasms/pathology ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Trastuzumab ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; *Liver Neoplasms/drug therapy/etiology ; Antibodies, Monoclonal ; }, abstract = {Metastatic human epidermal growth factor receptor 2 (HER2) positive breast cancer has a poor prognosis and few effective targeted therapies. However, several anti-HER2 agents are emerging in conjunction with chemotherapy, which may lead to increased rates of pathological complete response in patients with HER2-positive metastatic breast cancer. Among them, margetuximab demonstrated a significant improvement in progression-free survival compared with trastuzumab, when combined with chemotherapy in pretreated patients. Here we present a case of a 67-year-old female patient who was diagnosed with HER2-positive, histological grade III and invasive ductal carcinoma of the left breast in September 2018. She received postoperative adjuvant therapy with EC-TH plus radiotherapy, followed by therapy with HER2-targeted trastuzumab for 1 year (till December 2019). In May 2020, routine reexamination showed a supraclavicular lymph node and bone metastasis. Patient was then treated with pyrotinib, capecitabine and bisphosphonate for a period of 3 months. In December 2020, liver MRI revealed multiple liver metastases. The patient received eight cycles of second-line therapy (vinorelbine plus margetuximab) from January 2021. Since the ninth cycle, the patient was continued with only margetuximab. In March 2021, MRI showed a 70% decrease in the liver metastasis lesions. By June 2021, liver lesions were totally disappeared. During therapy, patient experienced only grade-1 anemia. This case demonstrates that margetuximab plus chemotherapy is safe and might bring clinical benefits for patients with HER2-positive breast cancer with liver metastasis. Further studies evaluating the efficacy and safety of margetuximab in Chinese HER2-positive breast cancer patients are needed.}, } @article {pmid36729856, year = {2023}, author = {Li, J and Lu, Q and Zhou, H and Xu, F and Huang, J and Hong, R and Wang, S}, title = {Significant response to margetuximab in Chinese HER2-positive metastatic breast cancer patient who progressed after second-line targeted therapy.}, journal = {Anti-cancer drugs}, volume = {34}, number = {7}, pages = {892-895}, pmid = {36729856}, issn = {1473-5741}, mesh = {Female ; Humans ; Antibodies, Monoclonal/therapeutic use ; *Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/pathology ; East Asian People ; Erb-b2 Receptor Tyrosine Kinases ; Trastuzumab ; Acrylamides ; Aminoquinolines ; }, abstract = {Activation of the antibody-dependent cellular cytotoxicity is one of the key mechanisms of anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody treatment. Margetuximab is a fragment C (Fc)-modified chimeric anti-HER2 immunoglobulin G1 monoclonal antibody that shares epitope specificity with trastuzumab. In this case, we reported that margetuximab plus chemotherapy was effective as later-line therapy in a postmenopausal Chinese woman with metastatic diseases, who was diagnosed with estrogen receptor -, progesterone receptor (PR)-, HER2+ invasive ductal carcinoma. This patient used paclitaxel-albumin plus trastuzumab and pertuzumab as the first-line therapy with progression-free survival (PFS) of 14 months, and pyrotinib in combined with vinorelbine as the second-line therapy with a PFS of 17 months. Then she received margetuximab plus capecitabine as the third-line treatment, the metastatic lesions in the liver were obviously shrunk, indicating clinical partial response and the PFS was 7 months. This case revealed that margetuximab plus chemotherapy may be an appropriate option for the patients who progressed after treating with anti-HER2 monoclonal antibodies and pyrotinib.}, } @article {pmid36715845, year = {2023}, author = {Kada Mohammed, S and Billa, O and Ladoire, S and Jankowski, C and Desmoulins, I and Poillot, ML and Coutant, C and Beltjens, F and Dabakuyo, S and Arnould, L}, title = {HER2-positive invasive lobular carcinoma: a rare breast cancer which may not necessarily require anti-HER2 therapy. A population-based study.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {30}, number = {3}, pages = {343-353}, pmid = {36715845}, issn = {1880-4233}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular ; *Carcinoma, Ductal, Breast ; Treatment Outcome ; Disease-Free Survival ; }, abstract = {BACKGROUND: HER2-positive (HER2 +) invasive lobular breast cancer (ILC) is rare and poorly characterised. In particular, patient outcomes compared to those associated with HER2 + invasive ductal cancer (IDC) and HER2-negative (HER2 -) ILC, as well as the benefits of anti-HER2 therapy, are not well established.

METHODS: We analysed the data from the Côte d'Or Registry of Breast and Gynaecological Cancers (France) for all patients diagnosed with early-stage HER2 + ILC (62 cases), HER2 + IDC (833 cases) and HER2 - ILC (685 cases) between 1998 and 2015 to compare overall and disease-free survival (OS and DFS) between these groups in correlation with anti-HER2 therapy.

RESULTS: ILCs were associated with older age, larger tumours, lower histological grades, higher hormonal receptor positivity rates and multifocality, and more common endocrine therapy. OS and DFS between the three groups did not differ. We found that anti-HER2 therapy was associated with a survival benefit in patients with HER2 + IDC. In contrast, the survival of HER2 + ILC patients was not improved by anti-HER2 treatment, remaining close to that of HER2 - ILC patients.

CONCLUSION: HER2 + ILC seems not to be associated with better outcomes than HER2 + IDC but may not differ from HER2 - ILC in terms of survival.}, } @article {pmid36708642, year = {2023}, author = {Maggi, G and Vitale, C and Cerciello, F and Santangelo, G}, title = {Sleep and wakefulness disturbances in Parkinson's disease: A meta-analysis on prevalence and clinical aspects of REM sleep behavior disorder, excessive daytime sleepiness and insomnia.}, journal = {Sleep medicine reviews}, volume = {68}, number = {}, pages = {101759}, doi = {10.1016/j.smrv.2023.101759}, pmid = {36708642}, issn = {1532-2955}, mesh = {Humans ; *REM Sleep Behavior Disorder/etiology/complications ; *Parkinson Disease/complications/epidemiology/drug therapy ; Wakefulness ; *Sleep Initiation and Maintenance Disorders/epidemiology/complications ; Quality of Life ; Prevalence ; Sleep ; *Disorders of Excessive Somnolence/epidemiology/diagnosis ; *Sleep Wake Disorders ; }, abstract = {Sleep disorders (SDs) are common non-motor symptoms of Parkinson's disease (PD) with wide variability in their prevalence rates. The etiology of SDs in PD is multifactorial because the degenerative processes underlying the disease and their interaction with drugs and clinical features may promote REM sleep behavior disorder (RBD), excessive daytime sleepiness (EDS) and insomnia. Therefore, we designed a meta-analytic study to provide a reliable estimate of the prevalence and associated clinical and neuropsychiatric aspects of SDs in PD. A systematic literature search was performed up to February 2022. Pooled RBD prevalence was 46%, and its occurrence was associated with older age, lower education, longer disease duration, higher levodopa equivalent daily dose (LEDD), worse motor and autonomic manifestations, poorer quality of life and autonomy, and more severe neuropsychiatric symptoms. The pooled prevalence of EDS was 35% and was associated with older age, longer disease duration, worse motor and autonomic symptoms, higher LEDD, reduced autonomy, and more severe neuropsychiatric symptoms. Insomnia was reported in 44% of PD patients and was related to longer disease duration, higher LEDD, and more severe depression. SDs are associated with a more severe PD clinical phenotype; further studies should explore the pathophysiological mechanisms underlying SDs and develop targeted therapeutic strategies.}, } @article {pmid36703942, year = {2022}, author = {Zarchi, G and Sherman, M and Gady, O and Herzig, T and Idan, Z and Greenbaum, D}, title = {Blockchains as a means to promote privacy protecting, access availing, incentive increasing, ELSI lessening DNA databases.}, journal = {Frontiers in digital health}, volume = {4}, number = {}, pages = {1028249}, pmid = {36703942}, issn = {2673-253X}, abstract = {Not all blockchains are created equal, and many cannot accommodate all of the primary characteristics of big data: Variety, Velocity, Volume and Veracity. Currently, public blockchains are slow and clunky, it can be expensive to keep up with the velocity of genomic data production. Further, the transparent and universally accessible nature of public blockchain doesn't necessarily accommodate all of the variety of sequence data, including very private information. Bespoke private permissioned blockchains, however, can be created to optimally accommodate all of the big data features of genomic data. Further, private permissioned chains can be implemented to both protect the privacy and security of the genetic information therein, while also providing access to researchers. An NFT marketplace associated with that private chain can provide the discretized sale of anonymous and encrypted data sets while also incentivizing individuals to share their data through payments mediated by smart contracts. Private blockchains can provide a transparent chain of custody for each use of the customers' data, and validation that this data is not corrupted. However, even with all of these benefits there remain some concerns with the implementation of this new technology including the ethical, legal and social implications typically associated with DNA databases.}, } @article {pmid36703131, year = {2024}, author = {Shenkman, G and Itzhak, SB}, title = {Estimated likelihood of parenthood among sexual minority individuals associates with interpersonal vulnerability and traumatic outlook.}, journal = {Journal of reproductive and infant psychology}, volume = {42}, number = {4}, pages = {636-652}, doi = {10.1080/02646838.2023.2171563}, pmid = {36703131}, issn = {1469-672X}, mesh = {Humans ; Female ; Male ; Adult ; *Sexual and Gender Minorities/psychology ; Young Adult ; Adolescent ; Middle Aged ; Israel ; Surveys and Questionnaires ; Parents/psychology ; Homosexuality, Female/psychology ; Interpersonal Relations ; Homosexuality, Male/psychology ; }, abstract = {BACKGROUND: Lesbian women and gay men (LG) tend to report lower levels of parenthood aspiration than their heterosexual counterparts. While several variables have been suggested to explain this phenomenon, no study has investigated the potential mediating role of interpersonal vulnerability and subjective traumatic outlook in the association between sexual orientation and the estimated likelihood of parenthood.

OBJECTIVE: To investigate whether interpersonal vulnerability and subjective traumatic outlook mediate the association between sexual orientation and a lower estimated likelihood of parenthood.

METHODS: A sample of 435 childfree, cisgender Israeli participants, aged 18-49 years (M = 27.82, SD = 4.47), were recruited through convenience sampling. 192 participants self-reported as LG (64 lesbian women and 128 gay men). Participants completed online questionnaires assessing their estimated likelihood of parenthood, interpersonal vulnerability, and subjective traumatic outlook. Mediation analyses were performed using the PROCESS macro.

RESULTS: LG individuals reported a lower estimated likelihood of parenthood than their heterosexual counterparts. Interpersonal vulnerability and subjective traumatic outlook significantly mediated the association between sexual orientation and a lower estimated likelihood of parenthood.

CONCLUSIONS: Despite improvement in the socio-political climate relating to sexual minority rights and access to fertility technologies, LG individuals are still more likely to report a lower estimated likelihood of parenthood in comparison to heterosexual individuals. Moreover, this gap appears to be partially mediated by interpersonal vulnerability and subjective traumatic outlook. The results contribute to the growing body of international research exploring family formation among sexual minority individuals and are relevant for researchers, clinicians, and policymakers.}, } @article {pmid36694444, year = {2023}, author = {Da Prat, V and Galli, L and Cichero, P and Castiglioni, B and Oltolini, C and Tassan Din, C and Andolina, A and Bruzzesi, E and Poli, A and Moro, M and Mancini, N and Clementi, M and Tresoldi, M and Castagna, A and Scarpellini, P and Ripa, M}, title = {Antibiotic appropriateness for Gram-negative bloodstream infections: impact of infectious disease consultation.}, journal = {Infectious diseases (London, England)}, volume = {55}, number = {4}, pages = {255-262}, doi = {10.1080/23744235.2023.2169345}, pmid = {36694444}, issn = {2374-4243}, mesh = {Humans ; Anti-Bacterial Agents/therapeutic use ; Retrospective Studies ; *Bacteremia/diagnosis ; Referral and Consultation ; *Sepsis/drug therapy ; *Communicable Diseases/drug therapy ; *Gram-Negative Bacterial Infections ; }, abstract = {BACKGROUND: We investigated the role of infectious disease consultation (IDC) on therapeutic appropriateness in Gram-negative bloodstream infections (GNBSIs) in a setting with a high proportion of antibiotic resistance. Secondary outcomes were in-hospital mortality and the impact of rapid diagnostic tests (RDTs).

METHODS: Retrospective study on hospitalised patients with GNBSIs. Therapy was deemed appropriate if it had the narrowest spectrum considering infection and patients' characteristics. Interventional-IDC (I-IDC) group included patients with IDC-advised first appropriate or last non-appropriate therapy. Time to first appropriate therapy and survival were evaluated by Kaplan-Meier curves. Factors associated with therapy appropriateness were assessed by multivariate Cox proportional-hazard models.

RESULTS: 471 patients were included. High antibiotic resistance rates were detected: quinolones 45.5%, third-generation cephalosporins 37.4%, carbapenems 7.9%. I-IDC was performed in 31.6% of patients (149/471), RDTs in 70.7% (333/471). The 7-day probability of appropriate treatment was 91.9% (95% confidence interval [95%CI]: 86.4-95.8%) vs. 75.8% (95%CI: 70.9-80.4%) with and without I-IDC, respectively (p-value = 0.0495); 85.5% (95%CI: 81.3-89.1%) vs. 69.4% (95%CI: 61.3-77.2%) with and without RDTs, respectively (p-value = 0.0023). Compared to RDTs alone, the combination with I-IDC was associated with a higher proportion of appropriate therapies at day 7: 81.9% (95%CI: 76.4-86.7%) vs. 92.6% (95%CI: 86.3-96.7%). At multivariate analysis, I-IDC and RDTs were associated with time to first appropriate therapy [adjusted hazard-ratio 1.292 (95%CI: 1.014-1.647) and 1.383 (95%CI: 1.080-1.771), respectively], with no impact on mortality.

CONCLUSIONS: In a setting with a high proportion of antibiotic resistance, IDC and RDTs were associated with earlier prescription of appropriate therapy in GNBSIs, without impact on mortality.}, } @article {pmid36693540, year = {2023}, author = {Allegrini, M and Gaillard, C and Brousse, S and Levêque, J and Nyangoh-Timoh, K}, title = {A chyle leak following a tumorectomy and an axillary sentinel lymph node dissection: Case report.}, journal = {Journal of gynecology obstetrics and human reproduction}, volume = {52}, number = {3}, pages = {102544}, doi = {10.1016/j.jogoh.2023.102544}, pmid = {36693540}, issn = {2468-7847}, mesh = {Female ; Humans ; Aged ; Sentinel Lymph Node Biopsy ; Axilla/pathology ; *Chyle ; Lymph Node Excision ; *Breast Neoplasms/pathology ; }, abstract = {A chyle leak following a tumorectomy is a rare complication of surgery for breast cancer. We report a case of chylous leakage after axillary sentinel lymph node dissection. A 78-year-old woman with a left breast invasive ductal carcinoma underwent a breast-conserving surgery and had two sentinel lymph nodes removed. Ten days after surgery she came back with a swelling the left breast and the axilla, the drainage fluid was "milky". She underwent a second surgery for positive margins, during which time we did a mass ligature in the axilla and placed a drain that was remove when it wasn't productive anymore.}, } @article {pmid36684641, year = {2023}, author = {Tuan, HX and Duc, NM and Huy, NA and Tri, CM and Quyen, HD and Truc, BT and Trung, NT and Dieu, AN and Dung, PX}, title = {A rare case of breast invasive cribriform carcinoma.}, journal = {Radiology case reports}, volume = {18}, number = {3}, pages = {1049-1052}, pmid = {36684641}, issn = {1930-0433}, abstract = {Although invasive ductal carcinoma accounts for 75% of all primary breast cancers diagnosed, there are other, more uncommon kinds, including invasive cribriform carcinoma (ICC). Invasive cribriform carcinoma has 2 subtypes: pure and mixed. Ultrasonography and magnetic resonance imaging are the best imaging methods for assessing the characteristics of breast ICC (MRI). Our goal in this article was to report a rare instance of breast ICC in a 38-year-old Vietnamese woman. During a clinical examination, a spherical mass in the left breast without ipsilateral axillary lymph nodes was seen. On ultrasonography, the lesion was classified as BI-RADS 4C. The lesion was with an apparent diffusion coefficient value of 0.46 × 10[-3] mm[2]/s. Lesion showed a quick initial increase on dynamic T1-weighted imaging with contrast enhancement, followed by a wash-out in the delayed phase. The final histopathological findings confirmed the presence of ICC.}, } @article {pmid36684123, year = {2022}, author = {Li, B and Liu, J and Wu, G and Zhu, Q and Cang, S}, title = {Evaluation of adjuvant therapy for T1-2N1miM0 breast cancer without further axillary lymph node dissection.}, journal = {Frontiers in surgery}, volume = {9}, number = {}, pages = {905437}, pmid = {36684123}, issn = {2296-875X}, abstract = {BACKGROUND: For breast cancer (BC) with sentinel lymph node micrometastases (SLNMs), there are limited data to guide the selection of postoperative adjuvant therapy. This study aimed to identify target populations who might benefit most from adjuvant therapy and examine prognostic factors among patients with T1-2N1miM0 BC with one or two SLNMs who underwent sentinel lymph node biopsy (SLNB) alone.

METHODS: There were 7,423 patients diagnosed with T1-2N1miM0 BC between 2010 and 2015, and patients with one or two SLNMs were extracted from the Surveillance, Epidemiology, and End Results database. All the patients underwent SLNB alone without further axillary lymph node dissection, and they were stratified according to adjuvant therapy. The statistical significance of categorical variables was analyzed using the χ [2] test. Univariable and multivariable Cox analyses were used to analyze characteristics predictive of Breast-cancer-specific survival and overall survival (OS). Kaplan-Meier methods with the log-rank test was analyzed to compare survival difference between the different treatments.

RESULTS: Adjuvant chemotherapy and radiotherapy improved 5-year OS rates. Multivariate analysis revealed that age ≥70 years, high grade, T2 stage, triple-negative subtype, and absence of radiotherapy were poor prognostic factors for OS. Patients who received breast-conserving surgery (BCS), and those with invasive ductal carcinoma (IDC), luminal A, luminal B, or basal-like subtype, and T1c or T2 stage benefited from adjuvant radiotherapy. Patients who received BCS, and those with IDC, luminal A subtype, and T1b, T1c, or T2 stage benefited from adjuvant chemotherapy.

CONCLUSION: Our findings provide a clinical evaluation of treatment choice after surgery, which may help clinicians make individualized clinical decisions.}, } @article {pmid36678422, year = {2023}, author = {Feredj, E and Audureau, E and Boueilh, A and Fihman, V and Fourati, S and Lelièvre, JD and Gallien, S and Grimbert, P and Matignon, M and Melica, G}, title = {Impact of a Dedicated Pretransplant Infectious Disease Consultation on Respiratory Tract Infections in Kidney Allograft Recipients: A Retrospective Study of 516 Recipients.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, pmid = {36678422}, issn = {2076-0817}, abstract = {BACKGROUND: Respiratory tract infections (RTIs) are a leading cause of death after kidney transplant. Preventive strategies may be implemented during a dedicated infectious disease consultation (IDC) before transplantation. Impact of IDC on RTIs after transplant has not been determined.

METHODS: We conducted a monocentric retrospective cohort analysis including all kidney transplant recipients from January 2015 to December 2019. We evaluated the impact of IDC on RTIs and identified risk and protective factors associated with RTIs.

RESULTS: We included 516 kidney transplant recipients. Among these, 145 had an IDC before transplant. Ninety-five patients presented 123 RTIs, including 75 (61%) with pneumonia. Patient that benefited from IDC presented significantly less RTIs (p = 0.049). RTIs were an independent risk factor of mortality (HR = 3.64 (1.97-6.73)). Independent risk factors for RTIs included HIV (OR = 3.33 (1.43-7.74)) and HCV (OR = 3.76 (1.58-8.96)). IDC was identified as an independent protective factor (OR = 0.48 (0.26-0.88)). IDC prior to transplantation is associated with diminished RTIs and is an independent protective factor. RTIs after kidney transplant are an independent risk factor of death. Implementing systematic IDC may have an important impact on reducing RTIs and related morbidity and mortality.}, } @article {pmid36674966, year = {2023}, author = {Hölken, JM and Teusch, N}, title = {The Monocytic Cell Line THP-1 as a Validated and Robust Surrogate Model for Human Dendritic Cells.}, journal = {International journal of molecular sciences}, volume = {24}, number = {2}, pages = {}, pmid = {36674966}, issn = {1422-0067}, support = {281A308C18.//Federal Ministry of Food and Agriculture/ ; }, mesh = {Humans ; Cell Line ; *Dendritic Cells/metabolism ; Cell Differentiation ; }, abstract = {We have implemented an improved, cost-effective, and highly reproducible protocol for a simple and rapid differentiation of the human leukemia monocytic cell line THP-1 into surrogates for immature dendritic cells (iDCs) or mature dendritic cells (mDCs). The successful differentiation of THP-1 cells into iDCs was determined by high numbers of cells expressing the DC activation markers CD54 (88%) and CD86 (61%), and the absence of the maturation marker CD83. The THP-1-derived mDCs are characterized by high numbers of cells expressing CD54 (99%), CD86 (73%), and the phagocytosis marker CD11b (49%) and, in contrast to THP-1-derived iDCs, CD83 (35%) and the migration marker CXCR4 (70%). Treatment of iDCs with sensitizers, such as NiSO4 and DNCB, led to high expression of CD54 (97%/98%; GMFI, 3.0/3.2-fold induction) and CD86 (64%/96%; GMFI, 4.3/3.2-fold induction) compared to undifferentiated sensitizer-treated THP-1 (CD54, 98%/98%; CD86, 55%/96%). Thus, our iDCs are highly suitable for toxicological studies identifying potential sensitizing or inflammatory compounds. Furthermore, the expression of CD11b, CD83, and CXCR4 on our iDC and mDC surrogates could allow studies investigating the molecular mechanisms of dendritic cell maturation, phagocytosis, migration, and their use as therapeutic targets in various disorders, such as sensitization, inflammation, and cancer.}, } @article {pmid36671532, year = {2023}, author = {Yang, Y and Luo, D and Gao, W and Wang, Q and Yao, W and Xue, D and Ma, B}, title = {Combination Analysis of Ferroptosis and Immune Status Predicts Patients Survival in Breast Invasive Ductal Carcinoma.}, journal = {Biomolecules}, volume = {13}, number = {1}, pages = {}, pmid = {36671532}, issn = {2218-273X}, support = {81602337//National Natural Science Foundation of China/ ; 81702564//National Natural Science Foundation of China/ ; 81570579//National Natural Science Foundation of China/ ; UNPYSCT-2017062//Education Department of Heilongjiang Province/ ; LH2021H050//Natural Science Foundation of Heilongjiang Province/ ; }, mesh = {Humans ; *Ferroptosis/genetics ; Algorithms ; Cell Death ; Iron ; *Carcinoma, Ductal ; }, abstract = {Ferroptosis is a new form of iron-dependent cell death and plays an important role during the occurrence and development of various tumors. Increasingly, evidence shows a convincing interaction between ferroptosis and tumor immunity, which affects cancer patients' prognoses. These two processes cooperatively regulate different developmental stages of tumors and could be considered important tumor therapeutic targets. However, reliable prognostic markers screened based on the combination of ferroptosis and tumor immune status have not been well characterized. Here, we chose the ssGSEA and ESTIMATE algorithms to evaluate the ferroptosis and immune status of a TCGA breast invasive ductal carcinoma (IDC) cohort, which revealed their correlation characteristics as well as patients' prognoses. The WGCNA algorithm was used to identify genes related to both ferroptosis and immunity. Univariate COX, LASSO regression, and multivariate Cox regression models were used to screen prognostic-related genes and construct prognostic risk models. Based on the ferroptosis and immune scores, the cohort was divided into three groups: a high-ferroptosis/low-immune group, a low-ferroptosis/high-immune group, and a mixed group. These three groups exhibited distinctive survival characteristics, as well as unique clinical phenotypes, immune characteristics, and activated signaling pathways. Among them, low-ferroptosis and high-immune statuses were favorable factors for the survival rates of patients. A total of 34 differentially expressed genes related to ferroptosis-immunity were identified among the three groups. After univariate, Lasso regression, and multivariate stepwise screening, two key prognostic genes (GNAI2, PSME1) were identified. Meanwhile, a risk prognosis model was constructed, which can predict the overall survival rate in the validation set. Lastly, we verified the importance of model genes in three independent GEO cohorts. In short, we constructed a prognostic model that assists in patient risk stratification based on ferroptosis-immune-related genes in IDC. This model helps assess patients' prognoses and guide individualized treatment, which also further eelucidatesthe molecular mechanisms of IDC.}, } @article {pmid36655741, year = {2023}, author = {Zavaglio, F and Rivela, F and Cassaniti, I and Arena, F and Gabanti, E and Asti, AL and Lilleri, D and Rampino, T and Baldanti, F and Gregorini, M}, title = {ELISPOT assays with pp65 peptides or whole HCMV antigen are reliable predictors of immune control of HCMV infection in seropositive kidney transplant recipients.}, journal = {Journal of medical virology}, volume = {95}, number = {2}, pages = {e28507}, pmid = {36655741}, issn = {1096-9071}, mesh = {Humans ; Cytomegalovirus ; Enzyme-Linked Immunospot Assay ; CD8-Positive T-Lymphocytes ; *Kidney Transplantation ; *Cytomegalovirus Infections ; Antigens, Viral ; Antiviral Agents/therapeutic use ; Cytokines ; }, abstract = {Human cytomegalovirus (HCMV) infection represents a major complication for solid organ transplant recipients. The aim of this study was to verify if the measurement of HCMV-specific T-cells could help to identify patients protected against HCMV disease cytokine flow cytometry using infected dendritic cells as stimulus (CFC-iDC, which discriminates between CD4[+] and CD8[+] T cells), and ELISPOT, using infected cell lysate (ELISPOT-iCL) or pp65 (ELISPOT-pp65) as stimulus, were adopted. Among the 47 kidney transplant recipients (KTR) enrolled, 29 had a self-resolving HCMV infection (Controllers) and 18 required antiviral treatment (Non-Controllers). HCMV-specific T-cell frequency at the peak of HCMV infection identified Controllers and Non-Controllers, although the diagnostic performance of CD8[+] CFC-iDC (area under the curve [AUC] of the receiver-operator characteristic curve: 0.65) was lower than that of CD4[+] CFC-iDC (AUC: 0.83), ELISPOT-iCL (AUC: 0.83) and ELISPOT-pp65 (AUC: 0.80). CFC-iDC detected a protective immune reconstitution significantly earlier (median time: 38 days) than ELISPOT-iCL and ELISPOT-pp65 (median time: 126 and 133 days, respectively). Time to protective immune reconstitution in Non-Controllers was significantly longer than in Controllers with the ELISPOT and the CD4[+] CFC-iDC assays, but not with CD8[+] CFC-iDC. The majority of patients did not require antiviral treatment after protective immune reconstitution, with the exception of five patients according to CFC-iDC assay, one patient according to ELISPOT-iCL assay and three patients according to ELISPOT-pp65 assay. Monitoring the HCMV-specific immunological reconstitution with is effective in discriminating KTR at risk of or protected from HCMV disease and the ELISPOT assays are suitable for implementation in the clinical setting.}, } @article {pmid36653542, year = {2023}, author = {Maggi, G and D'Iorio, A and Aiello, EN and Poletti, B and Ticozzi, N and Silani, V and Amboni, M and Vitale, C and Santangelo, G}, title = {Psychometrics and diagnostics of the Italian version of the Beck Depression Inventory-II (BDI-II) in Parkinson's disease.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {5}, pages = {1607-1612}, pmid = {36653542}, issn = {1590-3478}, mesh = {Humans ; Psychometrics ; *Depression/diagnosis/etiology ; *Parkinson Disease/complications/diagnosis/psychology ; Quality of Life ; Reproducibility of Results ; Psychiatric Status Rating Scales ; }, abstract = {INTRODUCTION: Depression is one of the most disabling neuropsychiatric manifestations of Parkinson's disease (PD) and requires proper screening and diagnosis because it affects the overall prognosis and quality of life of patients. This study aimed to assess the psychometric and diagnostic properties of the Beck Depression Inventory-II (BDI-II) in an Italian PD cohort.

MATERIALS AND METHODS: Fifty consecutive outpatients with PD underwent the Italian version of the BDI-II and other questionnaires to evaluate anxiety and apathetic symptoms. Patients' caregivers completed the depression/dysphoria domain of the Neuropsychiatric Inventory (NPI-D). We evaluated the internal consistency, convergent and divergent validity, and factorial structure of BDI-II. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios were computed using ROC analyses, and an optimal cutoff was defined using the Youden index.

RESULTS: The BDI-II proved to be internally consistent (Cronbach's α = 0.840) and substantially met the bi-factorial structure. Regarding construct validity, the BDI-II was substantially related to anxiety measures, but not to apathy. With the combination of the NPI-D and anxiety score used as the gold standard, the BDI-II overall showed good accuracy (AUC = 0.859) with adequate sensitivity (75%) and specificity (87%). The optimal cutoff point was defined at 14.50.

CONCLUSIONS: We provide evidence of the psychometric and diagnostic properties of the Italian version of the BDI-II as a screening tool for depression in patients with PD. The BDI-II was found to be reliable and valid for the measurement of depression in patients with PD; therefore, it is available for use in clinical research and practice.}, } @article {pmid36645627, year = {2023}, author = {Yashima, Y and Fujioka, T and Kubota, K and Mori, M and Sato, A and Oda, G and Nakagawa, T and Onishi, I and Tanaka, M and Tateishi, U}, title = {Comparison of the clinical and pathological characteristics of ultrasound-guided biopsy for breast masses and non-mass lesions between 16-gauge spring-loaded core needle biopsy and 12-gauge spring-loaded vacuum-assisted biopsy.}, journal = {Journal of medical ultrasonics (2001)}, volume = {50}, number = {2}, pages = {205-212}, pmid = {36645627}, issn = {1613-2254}, mesh = {Humans ; Female ; Biopsy, Large-Core Needle/methods ; Retrospective Studies ; *Breast/diagnostic imaging/pathology ; Image-Guided Biopsy/methods ; Ultrasonography, Interventional/methods ; *Breast Neoplasms/diagnostic imaging/pathology ; }, abstract = {PURPOSE: To retrospectively compare the clinical and pathological characteristics of breast masses and non-mass lesions that underwent ultrasound (US)-guided 16-gauge spring-loaded core needle biopsy (CNB) or 12-gauge spring-loaded vacuum-assisted biopsy (VAB).

METHODS: We retrospectively compared the results from US-guided diagnostic breast biopsy performed with a 16-gauge CNB (Magnum™) or a 12-gauge VAB (Celero[®]). The patients' backgrounds and pathological features for each device were examined.

RESULTS: In 453 patients with 500 lesions, 373 lesions underwent CNB and 127 underwent VAB. The positive biopsy rate (positive predictive value 3) was significantly higher for VAB (92/127; 72.4%) than for CNB (231/373; 61.9%) (P = 0.032). Non-mass lesions were biopsied more frequently with VAB (57/127; 47.4%) than with CNB (27/378; 7.14%) (P = 0.000). The upgrade rate from high-risk to malignant lesions was significantly higher for CNB (5/19; 26.3%) than for VAB (1/8; 12.5%) (P = 0.043). There were five (1.34%) specimen failures with CNB and one (0.78%) with VAB, 18 (4.82%) re-biopsies with CNB and three (2.36%) with VAB, and 11/21 (52.4%) upgrades from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) with CNB and 11/30 (36.7%) with VAB. Although these rates tended to be higher with CNB than with VAB, the difference was not significant.

CONCLUSION: Although VAB had a significantly higher rate of non-mass lesion biopsies, the upgrade rate from high-risk to malignant lesions was significantly lower for VAB than for CNB. US-guided 12-gauge spring-loaded VAB may be more appropriate for biopsy of non-mass lesions.}, } @article {pmid36644191, year = {2022}, author = {Zuo, C and Xie, J}, title = {Mixed primary mucinous cystadenocarcinoma and invasive ductal carcinoma of the breast: a case report and literature review.}, journal = {Translational cancer research}, volume = {11}, number = {12}, pages = {4455-4464}, pmid = {36644191}, issn = {2219-6803}, abstract = {BACKGROUND: Mucinous cystadenocarcinoma (MCA) mainly occurs in the ovary, pancreas, and appendix, whereas the breast is a rare primary site of occurrence. Invasive ductal carcinoma (IDC) is the most common breast malignancy. Only 31 cases of the breast MCA have been reported in the English literature, and the coexistence of MCA and IDC in the breast are rare.

CASE DESCRIPTION: Here, we describe a 61-year-old postmenopausal woman with no family history of breast cancer or other breast-related diseases, who presented with a palpable mass in her left breast lasting for 2 months. On ultrasonography examination, the tumor was a cystic-solid lesion with clear boundary. Magnetic resonance imaging (MRI) showed a mass with low signal intensity on T1 weighted imaging and high signal intensity on T2 weighted imaging. Intraoperative frozen sections revealed metastatic tumor cells in one sentinel lymph node (1/4). She then underwent left modified radical mastectomy with axillary dissection. The post-operative pathological examination showed the tumor consisted mostly of MCA (60%), with a small proportion of intermediate-grade IDC. The MCA had a well-demarcated cystic structure with papillary projections and abundant mucoid material. The epithelium lining cystic spaces was tall columnar, with mucin-producing cells that had basally located nuclei. The degree of cytological atypia varied considerably. Axillary lymph nodes were normal (0/15). The MCA was triple-negative for estrogen receptor (ER), progesterone receptor (PR), and HER2, and positive for CK7 but negative for CK20. Through next-generation sequencing, no mutations in the BRCA1 and BRCA2 genes were identified in our case, which was not highlighted in prior cases. After surgery, the patient underwent eight cycles of chemotherapy, and she has been disease-free during the 10-month follow-up. In addition to detailing this instance of mixed MCA and IDC of the breast, we reviewed relevant literature and compare our findings with other patients who had breast MCAs.

CONCLUSIONS: Our results improved the understanding of mixed MCA and IDC, especially MCA, and provided a basis for its diagnosis and differential diagnosis from other metastatic diseases.}, } @article {pmid36641657, year = {2022}, author = {Manginstar, C and Oley, MH and Oley, MC and Merung, M and Langi, FLFG and Kepel, BJ and Rusli, LV and Islam, AA and Faruk, M}, title = {Correlation analysis of HIF-1α and Ca15-3 in response to neoadjuvant chemotherapy in locally advanced breast cancer: A cohort study in Indonesia.}, journal = {Breast disease}, volume = {41}, number = {1}, pages = {481-487}, doi = {10.3233/BD-229004}, pmid = {36641657}, issn = {1558-1551}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Prognosis ; Biomarkers, Tumor/metabolism ; Cohort Studies ; Neoadjuvant Therapy ; Prospective Studies ; Hypoxia-Inducible Factor 1, alpha Subunit/therapeutic use ; Indonesia ; Hypoxia ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide and a leading cause of death in Indonesia. The primary treatment of locally advanced BC is neoadjuvant chemotherapy (NAC). The rapid proliferation of tumor cells in a neoplastic microenvironment is largely due to hypoxia, which also encourages the development of chemoresistant BC. The master regulator of the hypoxia response is hypoxia-inducible factor-1α (HIF-1α). The response evaluation criteria in solid tumors (RECIST) is an objective response metric that demonstrates the efficacy of a NAC based mostly on the size of the tumor. Ca15-3 is the protein product of the MUC1 gene and is the most widely used serum marker in BC. The purpose of this study is to investigate the relationship between HIF-1α and RECIST and between Ca15-3 and RECIST and to assess the relationship among all of them in BC.

METHODS: This observational study used the prospective cohort method included 11 patients with histopathologically confirmed BC, specifically invasive ductal carcinoma. We evaluated the changes in HIF-1α and Ca15-3 serum levels using ELISA and measured tumor lesions with RECIST. The procedure was carried out twice. Serum levels were measured at baseline, and after receiving two cycles of NAC (5 weeks).

RESULTS: Among the 11 patients included in this study, HIF-1α, Ca15-3, and RECIST decreased significantly after NAC. The changes in RECIST correlated with Ca15-3: each unit decrease in RECIST score was associated with a 0.3-unit decrease in Ca15-3 levels (p = 0.019).

CONCLUSIONS: There was a decrease in HIF-1α, followed by a decrease in Ca15-3 and RECIST in response to chemotherapy. There was a statistically significant correlation between Ca15-3 and response to chemotherapy. This study evidences the relationship between factors that shape the local tumor microenvironment.}, } @article {pmid36641655, year = {2022}, author = {Kridis, WB and Feki, A and Khmiri, S and Toumi, N and Chaabene, K and Daoud, J and Ayedi, I and Khanfir, A}, title = {Prognostic factors in inflammatory breast cancer: A single-center study.}, journal = {Breast disease}, volume = {41}, number = {1}, pages = {461-469}, doi = {10.3233/BD-220034}, pmid = {36641655}, issn = {1558-1551}, mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/diagnosis/genetics ; Hormones ; *Inflammatory Breast Neoplasms/diagnosis/genetics ; Neoplasm Recurrence, Local ; Prognosis ; Erb-b2 Receptor Tyrosine Kinases/genetics/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Adult ; Aged ; Aged, 80 and over ; }, abstract = {BACKGROUND: Previous studies have shown that poor prognostic indicators of inflammatory breast cancer (IBC) include younger age at diagnosis, poorer tumor grade, negative estrogen receptor, lesser degree of pathological response in the breast and lymph nodes.

METHODS: This is a retrospective study conducted over a period of 12 years between January 2008 and December 2019 at the medical oncology department at Habib Bourguiba University Hospital in Sfax. We included in this study women with confirmed IBC. We excluded patients with no histological evidence, those whose medical records were unusable. Data collection was done from patient files. The aim of this study was to analyze the factors of poor prognosis of this entity.

RESULTS: During a period of 12 years (2008-2019), 2879 cases of breast cancer were treated at Habib Bourguiba hospital in Sfax. 81 IBC were included. The incidence of IBC was 3%. The average age was 52.4 years (26-87 years). Invasive ductal carcinoma was the most frequent histological type (85.7%). Hormone receptor were positive in 64%. Human Epidermal Growth Factor Receptor-2 (HER2) was overexpressed in 35.9% of cases. The proliferation index Ki-67 was analyzed in 34 cases. It was >20% in 24 cases. Luminal A, luminal B, HER2+++, triple negative were found in 13%, 50.7%, 16% and 20% respectively. Metastases at diagnosis were found in 38%. Poor prognostic factors significantly influencing overall survival in univariate analysis were metastatic stage, high SBR grade, lymph node involvement, in particular greater than 3 nodes, negative hormone receptors, triple-negative molecular profile and occurrence of relapse.

CONCLUSION: Number of positive lymph nodes greater than 3 and the occurrence of relapse were independent prognostic factors in case of localized IBC. Metastatic stage was associated with a very poor prognosis.}, } @article {pmid36641174, year = {2023}, author = {Moghaddam, FD and Heidari, G and Zare, EN and Djatoubai, E and Paiva-Santos, AC and Bertani, FR and Wu, A}, title = {Carbohydrate polymer-based nanocomposites for breast cancer treatment.}, journal = {Carbohydrate polymers}, volume = {304}, number = {}, pages = {120510}, doi = {10.1016/j.carbpol.2022.120510}, pmid = {36641174}, issn = {1879-1344}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy ; Polymers/therapeutic use/chemistry ; *Nanocomposites/therapeutic use/chemistry ; Carbohydrates ; }, abstract = {Breast cancer is known as the most common invasive malignancy in women with the highest mortality rate worldwide. This concerning disease may be presented in situ (relatively easier treatment) or be invasive, especially invasive ductal carcinoma which is highly worrisome nowadays. Among several strategies used in breast cancer treatment, nanotechnology-based targeted therapy is currently being investigated, as it depicts advanced technological features able of preventing drugs' side effects on normal cells while effectively acting on tumor cells. In this context, carbohydrate polymer-based nanocomposites have gained particular interest among the biomedical community for breast cancer therapy applications due to their advantage features, including abundance in nature, biocompatibility, straightforward fabrication methods, and good physicochemical properties. In this review, the physicochemical properties and biological activities of carbohydrate polymers and their derivate nanocomposites were discussed. Then, various methods for the fabrication of carbohydrate polymer-based nanocomposites as well as their application in breast cancer therapy and future perspectives were discussed.}, } @article {pmid36637351, year = {2023}, author = {Zhi, R and Wu, K and Zhang, J and Liu, H and Niu, C and Li, S and Fu, L}, title = {PRMT3 regulates the progression of invasive micropapillary carcinoma of the breast.}, journal = {Cancer science}, volume = {114}, number = {5}, pages = {1912-1928}, pmid = {36637351}, issn = {1349-7006}, support = {31870860//National Natural Science Foundation of China/ ; 81872164//National Natural Science Foundation of China/ ; 82173344//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/metabolism ; Breast/pathology ; *Breast Neoplasms/pathology ; Histones ; *Carcinoma, Papillary/metabolism ; Protein-Arginine N-Methyltransferases/genetics/metabolism ; }, abstract = {Invasive micropapillary carcinoma (IMPC) is a special histopathological subtype of breast cancer. Clinically, IMPC exhibits a higher incidence of lymphovascular invasion and lymph node metastasis compared with that of invasive ductal carcinoma (IDC), the most common type. However, the metabolic characteristics and related mechanisms underlying malignant IMPC biological behaviors are unknown. We performed large-scale targeted metabolomics analysis on resected tumors obtained from chemotherapy-naïve IMPC (n = 25) and IDC (n = 26) patients to investigate metabolic alterations, and we integrated mass spectrometry analysis, RNA sequencing, and ChIP-sequencing data to elucidate the potential molecular mechanisms. The metabolomics revealed distinct metabolic profiles between IMPC and IDC. For IMPC patients, the metabolomic profile was characterized by significantly high levels of arginine methylation marks, and protein arginine methyltransferase 3 (PRMT3) was identified as a critical regulator that catalyzed the formation of these arginine methylation marks. Notably, overexpression of PRMT3 was an independent risk factor for poor IMPC prognosis. Furthermore, we demonstrated that PRMT3 was a key regulator of breast cancer cell proliferation and metastasis both in vitro and in vivo, and treatment with a preclinical PRMT3 inhibitor decreased the xenograft tumorigenic capacity. Mechanistically, PRMT3 regulated the endoplasmic reticulum (ER) stress signaling pathway by facilitating histone H4 arginine 3 asymmetric dimethylation (H4R3me2a), which may endow breast cancer cells with great proliferative and metastatic capacity. Our findings highlight PRMT3 importance in regulating the malignant biological behavior of IMPC and suggest that small-molecule inhibitors of PRMT3 activity might be promising breast cancer treatments.}, } @article {pmid36636972, year = {2022}, author = {Mareev, VY and Orlova, YA and Plisuk, AG and Pavlikova, EP and Akopyan, ZA and Matskeplishvili, ST and Malahov, PS and Krasnova, TN and Seredenina, EM and Potapenko, AV and Agapov, МA and Asratyan, DA and Dyachuk, LI and Samokhodskaya, LM and Mershina, EM and Sinitsyn, VE and Mareev, YV and Shatokhina, EA and Begrambekova, YL and Kamalov, AA}, title = {Proactive anti-inflammatory therapy in the advanced stages of a new coronavirus infection. Main results of the inpatient phase of the COLORIT study (Colchicin vs. Ruxolitinib and secukinumab in an open, prospective, randomized trial in patients with novel coronavirus infection COVID-19).}, journal = {Kardiologiia}, volume = {62}, number = {12}, pages = {11-22}, doi = {10.18087/cardio.2022.12.n2316}, pmid = {36636972}, issn = {0022-9040}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Inpatients ; Prospective Studies ; RNA, Viral ; Inflammation ; Colchicine ; Anti-Inflammatory Agents ; Treatment Outcome ; Cytokines ; Nitriles ; Pyrazoles ; Pyrimidines ; Antibodies, Monoclonal, Humanized ; }, abstract = {Aim To evaluate clinical efficacy of the proactive anti-inflammatory therapy in patients hospitalized for COVID-19 with pneumonia and a risk of "cytokine storm".Material and methods The COLORIT study was a comparative study with randomization into 4 groups: colchicine (n=21) 1 mg for the first 3 days followed by 0.5 mg/day through day 12 or discharge from the hospital; secukinumab 300 mg/day, s.c., as a single dose (n=20); ruxolitinib 5 mg, twice a day (n=10); and a control group with no anti-inflammatory therapy (n=22). The effect was evaluated after 12±2 days of inpatient treatment or upon discharge, what comes first. For ethical reasons, completely randomized recruitment to the control group was not possible. Thus, for data analysis, 17 patients who did not receive any anti-inflammatory therapy for various reasons not related with inclusion into the study were added to the control group of 5 randomized patients. Inclusion criteria: presence of coronavirus pneumonia (positive PCR test for SARS-CoV-2 RNA or specific clinical presentation of pneumonia; IDC-10 codes U07.1 and U07.2); C-reactive protein (CRP) concentration >60 mg/l or its threefold increase from baseline; at least 2 of 4 symptoms (fever >37.5 °C, persistent cough, shortness of breath with inspiratory rate >20 per min or blood saturation with oxygen <94 % by the 7th-9th day of disease. The study primary endpoint was changes in COVID Clinical Condition Scale (CCS-COVID) score. The secondary endpoints were the dynamics of CRP and changes in the area of lung lesion according to data of computed tomography (CT) of the lungs from the date of randomization to 12±2 days.Results All three drugs significantly reduced inflammation, improved the clinical course of the disease, and decreased the disease severity as evaluated by the CCS score: in the ruxolitinib group, by 5.5 (p=0.004); in the secukinumab group, by 4 (p=0.096); in the colchicine group, by 4 (p=0.017), and in the control group, by 2 (р=0.329). In all three groups, the CCS-COVID score was 2-3 by the end of observation period, which corresponded to a mild process, while in the control group, the score was 7 (р=0.005). Time-related changes in CRP were significant in all three anti-inflammatory treatment groups with no statistical difference between the groups. By the end of the study, changes in CT of the lungs were nonsignificant.Conclusion In severe СOVID-19 with a risk of "cytokine storm", the proactive therapy with ruxolitinib, colchicine, and secukinumab significantly reduces the inflammation severity, prevents the disease progression, and results in clinical improvement.}, } @article {pmid36633721, year = {2023}, author = {Han, S and Lee, SB and Gong, G and Lee, J and Chae, SY and Oh, JS and Moon, DH}, title = {Prognostic significance of pretreatment [18]F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with T2N1 hormone receptor-positive, ERBB2-negative breast cancer who underwent adjuvant chemotherapy.}, journal = {Breast cancer research and treatment}, volume = {198}, number = {2}, pages = {207-215}, pmid = {36633721}, issn = {1573-7217}, support = {HI18C2383//Ministry of Health and Welfare/ ; }, mesh = {Humans ; Female ; Positron Emission Tomography Computed Tomography/methods ; *Breast Neoplasms/diagnostic imaging/drug therapy ; Fluorodeoxyglucose F18 ; Prognosis ; *Triple Negative Breast Neoplasms ; Cohort Studies ; Positron-Emission Tomography/methods ; Chemotherapy, Adjuvant ; Radiopharmaceuticals ; Retrospective Studies ; Erb-b2 Receptor Tyrosine Kinases ; }, abstract = {PURPOSE: To determine whether tumor uptake of [18]F-fluorodeoxyglucose ([18]F-FDG) is associated with invasive disease-free survival (IDFS) in patients with hormone receptor (HR)-positive ERBB2-negative early-stage breast cancer treated with adjuvant chemotherapy.

METHODS: This is a single-center cohort study of women with breast cancer who underwent surgery between 2008 and 2015 at Asan Medical Center, Seoul, Korea. Patients were enrolled if they were diagnosed with HR-positive ERBB2-negative breast cancer with histology of invasive ductal carcinoma, had an American Joint Committee on Cancer pathologic tumor stage of T2N1 with 1-3 positive axillary nodes, underwent preoperative [18]F-FDG positron emission tomography/computed tomography (PET/CT), and underwent breast cancer surgery followed by anthracycline- or taxane-based adjuvant chemotherapy. The primary outcome measure was IDFS. The maximum standardized uptake value (SUVmax) was dichotomized using a predefined cut-off of 4.14.

RESULTS: A total of 129 patients were included. The median follow-up period for IDFS in those without recurrence was 82 months (interquartile range, 65-106). Multivariable Cox analysis showed that SUVmax was independently associated with IDFS [adjusted hazard ratio 2.49; 95% confidence interval (CI), 1.06-5.84]. Ten-year IDFS estimates via the Kaplan-Meier method were 0.60 (95% CI, 0.42-0.74) and 0.82 (95% CI, 0.65-0.91) for high and low SUVmax groups, respectively. The overall association between SUVmax and IDFS appeared to be consistent across subgroups divided according to age, progesterone receptor status, histologic grade, or presence of lymphovascular invasion.

CONCLUSION: High SUVmax on preoperative [18]F-FDG PET/CT was independently associated with reduced long-term IDFS in T2N1 HR-positive ERBB2-negative breast cancer patients who underwent adjuvant chemotherapy.}, } @article {pmid36633438, year = {2023}, author = {Ganbold, E and Kim, ES and Li, Y and Yin, F and Sharma, PK and Jeon, JB and Oh, JM and Lee, DN and Kim, NY}, title = {Highly Sensitive Interdigitated Capacitive Humidity Sensors Based on Sponge-Like Nanoporous PVDF/LiCl Composite for Real-Time Monitoring.}, journal = {ACS applied materials & interfaces}, volume = {15}, number = {3}, pages = {4559-4568}, doi = {10.1021/acsami.2c20499}, pmid = {36633438}, issn = {1944-8252}, abstract = {In this study, a sponge-like poly(vinylidene fluoride) (PVDF)/lithium chloride (LiCl) nanocomposite-entrenched interdigitated capacitive (IDC) sensor was developed for real-time humidity-sensing applications. Here, we demonstrated a sponge-like nanoporous structure ranging from 200 nm to 2 μm size holes, the PVDF/LiCl structure fabricated on an interdigitated capacitor (IDC) electrode functioning as a high-performance sensor because of the presence of ionized LiCl. The nanoporous PVDF/LiCl composite-based humidity sensor exhibited a high sensitivity of 12.6 nF/% relative humidity (RH), a linearity of 0.990, and a low hysteresis of 2.6% in the range of 25-95% RH. The composite film exhibited a response time of 17.7 s, a recovery time of 21 s, and an intensified increase of 8.02 nF/s (a decrease of 6.7 nF/s). The sensor designed demonstrates ultra-high sensing characteristics with 10 times higher sensitivity, i.e., 12.678.96 pF/%RH as compared to other polymer-based composite humidity sensors. Owing to the sensing performance and portability, the proposed nanoporous PVDF/LiCl composite-based IDC sensor is expected to be a promising platform for a wide range of humidity-sensing applications, including real-time breath monitoring and non-contact sensing.}, } @article {pmid36631536, year = {2023}, author = {Hogenhout, R and Remmers, S and van Leenders, GJLH and Roobol, MJ}, title = {The transition from transrectal to transperineal prostate biopsy without antibiotic prophylaxis: Cancer detection rates and complication rates.}, journal = {Prostate cancer and prostatic diseases}, volume = {26}, number = {3}, pages = {581-587}, pmid = {36631536}, issn = {1476-5608}, mesh = {Male ; Humans ; *Prostate/pathology ; *Prostatic Neoplasms/diagnosis/pathology ; Anti-Bacterial Agents/therapeutic use ; Image-Guided Biopsy/adverse effects ; Magnetic Resonance Imaging ; }, abstract = {BACKGROUND: Currently, transperineal prostate biopsy (TPB) is preferred over transrectal biopsy (TRB) because of less infectious complications and improved clinically significant prostate cancer (csPCa) detection. However, literature on omitting antibiotic prophylaxis (AP) is limited. Furthermore, previous studies did not include invasive cribriform growth/intraductal carcinoma (CR/IDC) in the definition of csPCa. Therefore, we compared the infectious complication rates between TPB without AP and TRB with AP, and we compared the csPCa detection rates between TPB and TRB including CR/IDC in the definition of csPCa.

METHODS: We included 729 men who were referred to Erasmus MC Cancer Institute between 2013-2019 for MRI/TRUS fusion-guided prostate biopsy. Up to 2019, TRB was performed with AP, thereafter TPB was performed without AP. Data on complications were collected prospectively. We compared csPCa detection rates between the biopsy routes using multivariable logistic regressions for men without previous PCa diagnosis and mixed logistic regression for men on active surveillance. To compare the csPCa detection rates in anterior and apical lesions, and the complications rates between the biopsy routes, we used the chi-square test.

RESULTS: Overall, we found no difference in csPCa detection between TPB and TRB (odds ratio 1.0, 95%-confidence interval (CI) 0.62-1.76, p = 0.9; for men on active surveillance: odds ratio 1.05, 95%-CI 0.58-1.88, p = 0.9). This was confirmed in anterior and apical lesions although absolute numbers were low. TPB reduced infectious complications with fever compared to TRB (1.1% vs 5.1%, difference = 4.0%, 95%-CI 1.0-7.9, p = 0.010).

CONCLUSIONS: TPB has no different csPCa detection rate from TRB taking CR/IDC into account. TPB is, however, preferable because of less infectious complications, even if AP is omitted.}, } @article {pmid36626910, year = {2023}, author = {Quagliarotti, C and Cortesi, M and Coloretti, V and Fantozzi, S and Gatta, G and Bonifazi, M and Zamparo, P and Piacentini, MF}, title = {The Effects of a Wetsuit on Biomechanical, Physiological, and Perceptual Variables in Experienced Triathletes.}, journal = {International journal of sports physiology and performance}, volume = {18}, number = {2}, pages = {171-179}, doi = {10.1123/ijspp.2022-0029}, pmid = {36626910}, issn = {1555-0273}, mesh = {Humans ; Biomechanical Phenomena ; *Respiration ; *Swimming/physiology ; Arm/physiology ; }, abstract = {PURPOSE: Wetsuits have been shown to change swim biomechanics and, thus, increase performance, but not all athletes are comfortable with their use because of possible modifications in motor coordination. The aim of this study was to evaluate the effects of wetsuit use on biomechanical, physiological, and perceptual variables.

METHODS: Eleven national- and international-level triathletes, familiar with wetsuit use, performed 7 × 200-m front crawl at constant preset speed twice, with and without a full wetsuit. The trunk incline (TI) and index of coordination (IdC) were measured stroke by stroke using video analysis. Stroke, breaths, and kick count, and timing (as breathing/kick action per arm-stroke cycle); stroke length (SL); and underwater length were analyzed using inertial-measurement-unit sensors. Heart rate (HR), rating of perceived exertion (RPE), and swimming comfort were monitored during the task.

RESULTS: A lower TI; IdC; number of strokes, kicks, and breaths; HR; and RPE for each 200 m were found in wetsuit compared with swimsuit condition. Higher values of SL and underwater length were found in wetsuit, whereas no differences were found in swimming comfort and timing of kicks and breaths. An increase for swimsuit condition in number of strokes and breaths, HR, and RPE was found during the task compared with the first 200 m.

CONCLUSION: Wetsuit use reduces TI and, thus, drag; increases propelling proficiency; and shows lower fatigability, without modifying motor coordination, compared with swimsuit use at the same speed. The use of a wetsuit during training sessions is recommended to increase comfort and the positive effects on performance.}, } @article {pmid36624021, year = {2023}, author = {Zhang, J and Liu, Y and Fan, H and Wang, W and Shao, W and Cao, G and Shi, X}, title = {Prediction of Clinical Molecular Typing of Breast Invasive Ductal Carcinoma Using [18]F-FDG PET/CT Dual-Phase Imaging.}, journal = {Academic radiology}, volume = {30 Suppl 2}, number = {}, pages = {S82-S92}, doi = {10.1016/j.acra.2022.12.036}, pmid = {36624021}, issn = {1878-4046}, mesh = {Female ; Humans ; Fluorodeoxyglucose F18 ; Positron Emission Tomography Computed Tomography ; Retrospective Studies ; Ki-67 Antigen ; *Triple Negative Breast Neoplasms ; Positron-Emission Tomography/methods ; *Carcinoma, Ductal ; *Breast Neoplasms/diagnostic imaging ; Radiopharmaceuticals ; *Carcinoma, Ductal, Breast/diagnostic imaging ; }, abstract = {RATIONALE AND OBJECTIVES: To investigate the diagnostic value of Fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography ([18]F-FDG PET/CT) dual-phase imaging for the different molecular subtypes of invasive ductal carcinoma of the breast.

MATERIALS AND METHODS: Clinical imaging data of 164 women with invasive ductal carcinoma of the breast confirmed by pathology who underwent [18]F-FDG PET/CT dual-phase imaging were retrospectively analyzed. The maximum standard uptake values (SUVmax) of the early and delayed phases of the lesion were measured and recorded as SUVmax1 and SUVmax2, respectively, and the retention index (RI) was calculated. We analyzed the change rule of SUVmax1, SUVmax2, and RI for the different molecular subtypes and molecular marker expression groups. The diagnostic threshold of different molecular marker expression status was determined using receiver operating characteristic curve analysis.

RESULTS: SUVmax1 and SUVmax2 were highest in the TNBC group and lowest in the luminal A group (p<0.001). TNBC and HER2 overexpression groups had higher RI than the luminal A and B groups (p<0.001), with no significant difference between the TNBC and HER2 overexpression groups or between the luminal A and B groups (p=0.640 and 0.345, respectively). The ER- and PR-negative groups had significantly higher SUVmax1, SUVmax2, and RI than the PR-positive group (p<0.001). The HER2-positive group had higher SUVmax1 and SUVmax2 than the negative group (p<0.001). The Ki67 overexpression group had higher SUVmax1 and SUVmax2 levels than the low expression group (p<0.001). There was no significant difference in RI between HER2-positive and negative groups or between Ki67 high and low expression groups (p=0.904 and 0.216, respectively). For ER-negative and positive expression status, the maximum area under the curve (AUC) of SUVmax2 was 0.852, diagnostic threshold was 10.87, sensitivity was 79.6%, and specificity was 74.5%. For PR-negative and positive expression status, the AUC of SUVmax2 was 0.858, diagnostic threshold was 10.45, sensitivity was 83.1%, and specificity was 75.3%. For HER2-negative and positive expression status, the AUC of SUVmax1 was 0.714, diagnostic threshold was 9.28, sensitivity was 79.6%, and specificity was 60.9%. For Ki67 high- and low expression status, the AUC of SUVmax2 was 0.915 at maximum, diagnostic threshold was 10.21, sensitivity was 83.4%, and specificity was 93.9%.

CONCLUSION: [18]F-FDG PET/CT dual-phase imaging facilitates the prediction of the expression of molecular markers and subtypes of invasive ductal carcinoma of the breast and the development of more tailored treatment plans for patients with this disease.}, } @article {pmid36617494, year = {2023}, author = {Matta, L and Blaas, L and de Faria, CC}, title = {From honeymoon to dysfunction: brown fat remodelling in obesity.}, journal = {The Journal of physiology}, volume = {601}, number = {4}, pages = {711-713}, doi = {10.1113/JP284187}, pmid = {36617494}, issn = {1469-7793}, mesh = {Humans ; Animals ; Mice ; *Adipose Tissue, Brown ; *Obesity ; Diet, High-Fat ; Mice, Inbred C57BL ; }, } @article {pmid36616805, year = {2022}, author = {Ahmad, S and Khosravi, R and Iyer, AK and Mirzavand, R}, title = {Wireless Capacitive Liquid-Level Detection Sensor Based on Zero-Power RFID-Sensing Architecture.}, journal = {Sensors (Basel, Switzerland)}, volume = {23}, number = {1}, pages = {}, pmid = {36616805}, issn = {1424-8220}, support = {NA//Natural Sciences and Engineering Research Council/ ; NA//Future Energy Systems/ ; }, abstract = {In this paper, a new method for the wireless detection of liquid level is proposed by integrating a capacitive IDC-sensing element with a passive three-port RFID-sensing architecture. The sensing element transduces changes in the liquid level to corresponding fringe-capacitance variations, which alters the phase of the RFID backscattered signal. Variation in capacitance also changes the resonance magnitude of the sensing element, which is associated with a high phase transition. This change in the reactive phase is used as a sensing parameter by the RFID architecture for liquid-level detection. Practical measurements were conducted in a real-world scenario by placing the sensor at a distance of approximately 2 m (with a maximum range of about 7 m) from the RFID reader. The results show that the sensor node offers a high sensitivity of 2.15°/mm to the liquid-level variation. Additionally, the sensor can be used within or outside the container for the accurate measurement of conductive- or non-conductive-type liquids due to the use of polyethylene coating on the sensitive element. The proposed sensor increases the reliability of the current level sensors by eliminating the internal power source as well as complex signal-processing circuits, and it offers real-time response, linearity, high sensitivity, and excellent repeatability, which are suitable for widespread deployment of sensor node applications.}, } @article {pmid36613131, year = {2023}, author = {Norouzi, N and Angel, JL}, title = {Intergenerational Day Centers: A New Wave in Adult and Child Day Care.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {1}, pages = {}, pmid = {36613131}, issn = {1660-4601}, mesh = {Child ; Humans ; Aged ; *Child Care ; *Child Day Care Centers ; }, abstract = {Intergenerational Day Centers (IDCs) are an innovation that addresses two important societal challenges, the continuing need for childcare and the emerging demand for older-adult supportive services that help them remain independent in their homes. These facilities provide care, and specialized resources and activities for both older adults and children in one location. While the importance and benefits of these programs have been proven, there is scant information in the literature and best-practice guidelines on the planning and development of these programs. This qualitative study focuses on the research, planning, and building development for new IDCs in metropolitan areas. It is based on a case example of the process of establishing an IDC in the City of Austin, which was an element of the Age-Friendly Austin Plan. It examines the applicable literature and the extensive involvement of experts in architecture, community planning, and public health policy as well as data collected from community engagement workshops to facilitate the IDC's creation and operation. This study offers a developmental strategy method that can be adopted and utilized by other cities, developers, and designers who are interested in building IDCs.}, } @article {pmid36611608, year = {2023}, author = {Kim, KY and Jang, CW and Chung, SY and Kim, M and Cho, SR and Cho, HE}, title = {Usefulness of YouTube in Sharing Information about New Gene Therapy for Spinal Muscular Atrophy: A Content Analysis.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {1}, pages = {}, pmid = {36611608}, issn = {2227-9032}, abstract = {This study aimed to objectively assess YouTube videos' quality, reliability, and information delivery capability regarding novel spinal muscular atrophy treatments. Using the keywords "nusinersen", "spinraza", "ridisplam", "evrysdi", "onasemnogene abeparvovec", and "zolgensma", we were able to retrieve and screen 360 videos before settling on a final sample of 99 on 25 September 2022. Then, two independent raters used the mDISCERN and GQS instruments to evaluate the videos' reliability and quality and the Information Delivery Capability (IDC) score to assess the videos' accuracy and patient-friendliness. The quality, reliability, and information delivery capability of the videos about the new treatment for SMA were quite heterogeneous, with an average mDISCERN, GQS, and IDC score of 3.172 ± 0.899, 2.980 ± 1.025, and 4.141 ± 1.747, respectively. In-depth analysis showed that healthcare expert videos that explained contents while showing infographic supplements had good quality, reliability, and information delivery capability. As YouTube is already a dominant media platform, the public may obtain new information about novel therapeutics for SMA through YouTube. It is necessary to consider how SMA patients and caregivers can choose trusted sources with reliable information on YouTube, and our results can provide clues. Additionally, experts should strive to provide more accurate, reliable, and patient-oriented videos.}, } @article {pmid36608855, year = {2023}, author = {Aune, T and Hamiel, D and Wolmer, L}, title = {Does emotion regulation mediate the effect of stressful life events on depressive symptoms in adolescents?.}, journal = {Journal of affective disorders}, volume = {325}, number = {}, pages = {354-359}, doi = {10.1016/j.jad.2022.12.158}, pmid = {36608855}, issn = {1573-2517}, mesh = {Humans ; Female ; Adolescent ; Male ; *Depression/psychology ; *Emotional Regulation ; Life Change Events ; Cross-Sectional Studies ; Emotions/physiology ; }, abstract = {INTRODUCTION: Adolescents' exposure to stressful life events (SLEs) is highly prevalent and increases their risk of developing depression considerably. A small number of studies have addressed the extent to which resilience factors, such as the ability to emotionally regulate, mediate the relationship between SLEs and depression. This study examined whether emotion regulation mediates and significantly attenuates the direct path between SLEs and depressive symptoms in a nonclinical sample of adolescents.

METHOD: A sample of 235 first- and second-year high-school students completed the Depression Anxiety Stress Scale, the Risk Factor Questionnaire, and the Difficulties in Emotion Regulation Scale. Mean age was 16.9 (SD = 1.8) years, and 65 % (n = 152) of the participants were female. To assess for mediation, a regression-based path analysis approach was used.

RESULTS: SLEs were significantly (t = 5.13, p < 0.001) associated with depressive symptoms, explaining 59.1 % of the total variance. Controlling for the mediation variable (emotion regulation), we found a reduced but statistically significant direct effect (t = 2.87, p = 0.005) between SLEs and depressive symptoms. A statistically significant indirect effect explaining 64.6 % of the total effect demonstrated partial mediation from stressful life events to depressive symptoms via emotion regulation.

LIMITATIONS: Our analyses are based on correlational and cross-sectional data and thus exclude statistical examination of temporal causal relationships, and assessments of whether reported affects are stable over time.

CONCLUSIONS: Our results indicate that interventions that can modify the ability to regulate emotions may help reduce depressive symptoms in at-risk adolescents.}, } @article {pmid36607851, year = {2023}, author = {Hadano, Y and Suyama, A and Hijikata, T and Miura, A and Fujii, S and Suzuki, Y and Tomoda, Y and Awaya, Y}, title = {The importance of infectious disease specialists consulting on a weekly basis in a Japanese tertiary care hospital: A retrospective observational study.}, journal = {Medicine}, volume = {102}, number = {1}, pages = {e32628}, pmid = {36607851}, issn = {1536-5964}, mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use ; Cefepime ; Meropenem ; Tertiary Care Centers ; Retrospective Studies ; East Asian People ; Referral and Consultation ; *Communicable Diseases/diagnosis ; Piperacillin, Tazobactam Drug Combination ; }, abstract = {Limited data are available regarding part-time infectious disease consultations (IDCs) and their importance in tertiary care teaching hospitals in Japan. This is a retrospective review of IDCs from June 2016 to March 2021 and describes IDC services provided by part-time infectious disease specialists once a week for 4 hours, and their impact on the quality of medical care, including antimicrobial stewardship. Data, such as the requesting department, requesting reasons, and final diagnoses, were analyzed. In April 2018, part-time infectious disease specialists launched consultation services and attended an antimicrobial stewardship team conference. Meropenem, tazobactam/piperacillin, and cefepime monthly days of therapy (DOT) were calculated to assess the effect of each intervention; a pre-post analysis was conducted using the Kruskal-Wallis test. Additional quality improvement (QI) projects related to infectious diseases were implemented. There were 237 IDCs during the study period. Consultations were mostly requested by the General Internal Medicine, Emergency Medicine, and Cardiology departments. The most common diagnoses were bone/joint, respiratory, and genitourinary infections. Infectious disease services, even on a part-time basis, achieve good outcomes in patient management, antimicrobial stewardship, and QI projects. DOT/1000 patient-days were reduced for meropenem and cefepime, while it increased for tazobactam/piperacillin. The DOT/1000 patient-days for the 3-antipseudomonal agents significantly decreased during this period. After implementing the QI tetanus vaccination project in the Emergency Room, the number of tetanus toxoid vaccinations per month increased.}, } @article {pmid36604587, year = {2023}, author = {Nasrazadani, A and Li, Y and Fang, Y and Shah, O and Atkinson, JM and Lee, JS and McAuliffe, PF and Bhargava, R and Tseng, G and Lee, AV and Lucas, PC and Oesterreich, S and Wolmark, N}, title = {Mixed invasive ductal lobular carcinoma is clinically and pathologically more similar to invasive lobular than ductal carcinoma.}, journal = {British journal of cancer}, volume = {128}, number = {6}, pages = {1030-1039}, pmid = {36604587}, issn = {1532-1827}, support = {P30 CA047904/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Carcinoma, Lobular/drug therapy ; Retrospective Studies ; *Carcinoma, Ductal, Breast/pathology ; *Breast Neoplasms/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; }, abstract = {BACKGROUND: Mixed invasive ductal lobular carcinoma (mDLC) remains a poorly understood subtype of breast cancer composed of coexisting ductal and lobular components.

METHODS: We sought to describe clinicopathologic characteristics and determine whether mDLC is clinically more similar to invasive ductal carcinoma (IDC) or invasive lobular carcinoma (ILC), using data from patients seen at the University of Pittsburgh Medical Center.

RESULTS: We observed a higher concordance in clinicopathologic characteristics between mDLC and ILC, compared to IDC. There is a trend for higher rates of successful breast-conserving surgery after neoadjuvant chemotherapy in patients with mDLC compared to patients with ILC, in which it is known to be lower than in those with IDC. Metastatic patterns of mDLC demonstrate a propensity to develop in sites characteristic of both IDC and ILC. A meta-analysis evaluating mDLC showed shared features with both ILC and IDC with significantly more ER-positive and fewer high grades in mDLC compared to IDC, although mDLCs were significantly smaller and included fewer late-stage tumours compared to ILC.

CONCLUSIONS: These findings support clinicopathologic characteristics of mDLC driven by individual ductal vs lobular components and given the dominance of lobular pathology, mDLC features are often more similar to ILC than IDC. This study exemplifies the complexity of mixed disease.}, } @article {pmid36602069, year = {2022}, author = {Serrano-Quintero, A and Sequeda-Juárez, A and Pérez-Hernández, CA and Sosa-Delgado, SM and Mendez-Tenorio, A and Ramón-Gallegos, E}, title = {Immunogenic analysis of epitope-based vaccine candidate induced by photodynamic therapy in MDA-MB-231 triple-negative breast cancer cells.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {40}, number = {}, pages = {103174}, doi = {10.1016/j.pdpdt.2022.103174}, pmid = {36602069}, issn = {1873-1597}, mesh = {Humans ; Female ; Photosensitizing Agents ; *Photochemotherapy/methods ; Calreticulin/metabolism/therapeutic use ; Epitopes/therapeutic use ; *Triple Negative Breast Neoplasms/drug therapy ; *Breast Neoplasms ; Chromatography, Liquid ; Tandem Mass Spectrometry ; *Vaccines/therapeutic use ; Cytokines/metabolism ; Cell Line, Tumor ; }, abstract = {BACKGROUND: Photodynamic therapy (PDT) is used to treat tumors through selective cytotoxic effects. PDT induces damage-associated molecular patterns (DAMPs) expression, which can cause an immunogenic death cell (IDC). In this study we identified potential immunogenic epitopes generated by PDT on triple-negative breast cancer cell line (MDA-MB-231).

METHODS: MDA-MB-231 cells were exposed to PDT using ALA (160 µg/mL)/630 nm at 8 J/cm[2]. Membrane proteins were extracted and separated by 2D PAGE. Proteins overexpressed were identified by LC-MS/MS and analyzed in silico through a peptide-HLA docking in order to identify the epitopes with more immunogenicity and antigenicity properties, as well as lower allergenicity and toxicity activity. The selected peptides were evaluated in response to macrophage activation and cytokine release by flow cytometry.

RESULTS: Differential proteins were overexpressed in the cells treated with PDT. A group of 16 peptides were identified from them, established in a rigorous selection by measuring antigenicity, immunogenicity, allergenicity, and toxicity in silico. The final selection was based on molecular dynamics, where 2 peptides showed the highest stability regarding to the RMSD value. These peptides were obtained from the proteins calreticulin and HSP90. The cytokine analysis evidenced macrophage activation by the releasing of TNF.

CONCLUSION: Two peptides were identified from calreticulin and HSP90; proteins induced by PDT in MDA-MB-231 cells. Both epitopes showed immunogenic potential as a peptide-based vaccine for triple-negative breast cancer.}, } @article {pmid36600790, year = {2022}, author = {Kimchy, AV and Umoren, MD and Rosenberg, JJ and Ilagan, C and Nithagon, P and Shafa, S and Jennings, JJ}, title = {Breast Cancer Metastasis to the Gastrointestinal Tract With Unusual Endoscopic and Histologic Presentations.}, journal = {ACG case reports journal}, volume = {9}, number = {12}, pages = {e00938}, pmid = {36600790}, issn = {2326-3253}, abstract = {The gastrointestinal (GI) tract is an infrequent site of breast cancer metastasis, but it often poses a diagnostic challenge when it occurs. The symptoms of GI metastases are often nonspecific, and the endoscopic manifestations are variable, requiring tissue biopsies for histologic examination. We report 2 cases of breast cancer metastasizing to the GI tract: a case of human epidermal growth factor receptor 2-positive invasive ductal carcinoma that metastasized to the stomach, a rare location for this histologic subtype, and another case of invasive lobular cell carcinoma that metastasized to the colon with unusual findings of mucosal pallor and edema on colonoscopy.}, } @article {pmid36600314, year = {2023}, author = {Park, HL and Lee, SW and Hong, JH and Lee, J and Lee, A and Kwon, SJ and Park, SY and Yoo, IR}, title = {Prognostic impact of [18]F-FDG PET/CT in pathologic stage II invasive ductal carcinoma of the breast: re-illuminating the value of PET/CT in intermediate-risk breast cancer.}, journal = {Cancer imaging : the official publication of the International Cancer Imaging Society}, volume = {23}, number = {1}, pages = {2}, pmid = {36600314}, issn = {1470-7330}, mesh = {Humans ; Female ; Positron Emission Tomography Computed Tomography ; *Breast Neoplasms/pathology ; Fluorodeoxyglucose F18/metabolism ; Prognosis ; Retrospective Studies ; *Carcinoma, Ductal, Breast/diagnostic imaging/therapy/metabolism ; Radiopharmaceuticals ; }, abstract = {BACKGROUND: The aim of this study is to investigate the impact of [18]F-FDG PET/CT on prognosis of stage II invasive ductal carcinoma (IDC) of the breast primarily treated with surgery.

METHODS: The clinical records of 297 consecutive IDC with preoperative PET/CT and pathologically staged II in surgery from 2013 to 2017 were retrospectively reviewed. The maximum standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), tumor-to-liver ratio (TLR), and metabolic tumor volume (MTV) were measured. Association of clinicopathologic factors (age, T stage, N stage, AJCC pathologic stage of IIA or IIB, pathologic prognostic stage, grade, hormonal receptor status, HER2 status, Ki-67, and adjuvant therapy) and PET parameters with DFS was assessed using the Cox proportional hazards model.

RESULTS: There were 35 recurrences and 10 deaths at a median follow-up of 49 months (range 0.8 ~ 87.3). All PET parameters were significantly associated with DFS in univariate analysis but in multivariate analysis, SUVpeak was the only factor significantly associated with DFS (hazard ratio 2.58, 95% confidence interval 1.29-5.15, P = 0.007). In cohorts with higher values of SUVpeak or TLR, patients who received adjuvant chemotherapy had significantly superior DFS.

CONCLUSION: Metabolic parameters derived from preoperative PET/CT was significantly associated with recurrence in stage II IDC primarily treated with surgery. PET/CT can be a powerful prognostic tool in conjunction with novel staging systems and current biomarkers for patients undergoing contemporary therapy. Our results urge to reconsider the currently underestimated value of PET/CT confined to diagnostic aspect and to newly recognize its prognostic impact in these intermediate-risk breast cancer.}, } @article {pmid36599340, year = {2022}, author = {Kim, MH and Suh, J and Kong, HJ and Oh, SJ}, title = {Maximum Voided Volume Is a Better Clinical Parameter for Bladder Capacity Than Maximum Cystometric Capacity in Patients With Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia: A Prospective Cohort Study.}, journal = {International neurourology journal}, volume = {26}, number = {4}, pages = {317-324}, pmid = {36599340}, issn = {2093-4777}, support = {04-2019-0390//Seoul National University Hospital/ ; }, abstract = {PURPOSE: Bladder capacity is an important parameter in the diagnosis of lower urinary tract dysfunction. We aimed to determine whether the maximum bladder capacity (MCC) measured during a urodynamic study was affected by involuntary detrusor contraction (IDC) in patients with Lower Urinary Tract Symptoms (LUTS)/Benign Prostatic Hyperplasia (BPH).

METHODS: Between March 2020 and April 2021, we obtained maximum voided volume (MVV) from a 3-day frequency-volume chart, MCC during filling cystometry, and maximum anesthetic bladder capacity (MABC) during holmium laser enucleation of the prostate under spinal or general anesthesia in 139 men with LUTS/BPH aged >50 years. Patients were divided according to the presence of IDC during filling cystometry. We assumed that the MABC is close to the true value of the MCC, as it is measured under the condition of minimizing neural influence over the bladder.

RESULTS: There was no difference in demographic and clinical characteristics between the non-IDC (n=20) and IDC groups (n=119) (mean age, 71.5±7.4) (P>0.05). The non-IDC group had greater bladder volume to feel the first sensation, first desire, and strong desire than the IDC group (P<0.001). In all patients, MABC and MVV were correlated (r=0.41, P<0.001); however, there was no correlation between MCC and MABC (r=0.19, P=0.02). There was no significant difference in MABC between the non-IDC and IDC groups (P=0.19), but MVV and MCC were significantly greater in the non-IDC group (P<0.001). There was no significant difference between MABC and MVV (MABC-MVV, P=0.54; MVV/MABC, P=0.07), but there was a significant difference between MABC and MCC between the non-IDC and IDC groups (MABC-MCC, P<0.001; MCC/MABC, P<0.001).

CONCLUSION: Maximum bladder capacity from a urodynamic study does not represent true bladder capacity because of involuntary contractions.}, } @article {pmid36596982, year = {2023}, author = {Watson, JF and Radic, R and Frost, R and Paton, S and Kessell, MA and Dessauvagie, BF and Taylor, DB}, title = {Vacuum-assisted excision biopsy for definitive diagnosis of breast lesions of uncertain malignant potential (B3 lesions) on core biopsy - A single centre Western Australian experience.}, journal = {Journal of medical imaging and radiation oncology}, volume = {67}, number = {4}, pages = {365-376}, doi = {10.1111/1754-9485.13502}, pmid = {36596982}, issn = {1754-9485}, mesh = {Female ; Humans ; *Mammography ; Australia ; Breast/diagnostic imaging/pathology ; Biopsy, Needle ; Biopsy ; Image-Guided Biopsy ; *Breast Neoplasms/diagnostic imaging/pathology ; }, abstract = {INTRODUCTION: In Australia, the usual approach to breast lesions where core biopsy returns an uncertain result ("B3" breast lesion) is to perform surgical diagnostic open biopsy (DOB). This is associated with patient time off work, costs of hospital admission, risks of general anaesthesia and surgical complications. The majority of B3 lesions return benign results following surgery. Vacuum assisted excision biopsy (VAEB) is a less invasive, lower cost alternative, and is standard of care for selected B3 lesions in the United Kingdom. Similar use of VAEB in Australia, could save many women unnecessary surgery. The aim of this study was to document our experience during the introduction of VAEB as an alternative to DOB for diagnosis of selected B3 lesions.

METHODS: The multidisciplinary team developed an agreed VAEB pathway for selected B3 lesions. Technically accessible papillary lesions, mucocele-like lesions and radial scars without atypia measuring ≤ 15mm were selected.

RESULTS: Over a 7 month period, 18 women with 20 B3 lesions were offered VAEB. 16 women (18 lesions) chose VAEB over DOB. Papillomas were the commonest lesion type. All lesions were successfully sampled: 17/18 were benign. One lesion (6%) was upgraded to malignancy (ductal carcinoma in situ on VAEB, invasive ductal carcinoma at surgery). No major complications occurred. Patient satisfaction was high: 15/16 respondents would again choose VAEB over surgery.

CONCLUSION: VAEB is a patient-preferred, safe, well-tolerated, lower-cost alternative to DOB for definitive diagnosis of selected B3 breast lesions.}, } @article {pmid36591521, year = {2022}, author = {Yang, Y and Zhang, W and Wan, L and Tang, Z and Zhang, Q and Bai, Y and Zhang, D}, title = {Construction and validation of a clinical predictive nomogram for intraductal carcinoma of the prostate based on Chinese multicenter clinical data.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {1074478}, pmid = {36591521}, issn = {2234-943X}, abstract = {INTRODUCTION: Intraductal carcinoma of the prostate (IDC-P) is a special pathological type of prostate cancer that is highly aggressive with poor prognostic outcomes.

OBJECTIVE: To establish an effective predictive model for predicting IDC-P.

METHODS: Data for 3185 patients diagnosed with prostate cancer at three medical centers in China from October 2012 to April 2022 were retrospectively analyzed. One cohort (G cohort) consisting of 2384 patients from Zhejiang Provincial People's Hospital was selected for construction (Ga cohort) and internal validate (Gb cohort)of the model. Another cohort (I cohort) with 344 patients from Quzhou People's Hospital and 430 patients from Jiaxing Second People's Hospital was used for external validation. Univariate and multivariate binary logistic regression analyses were performed to identify the independent predictors. Then, the selected predictors were then used to establish the predictive nomogram. The apparent performance of the model was evaluated via externally validated. Decision curve analysis was also performed to assess the clinical utility of the developed model.

RESULTS: Univariate and multivariate logistic regression analyses showed that alkaline phosphatase (ALP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), prostate specific antigen (PSA) and lactate dehydrogenase were independent predictors of IDC-P. Therefore, a predictive nomogram of IDC-P was constructed. The nomogram had a good discriminatory power (AUC = 0.794). Internal validation (AUC = 0.819)and external validation (AUC = 0.903) also revealed a good predictive ability. Calibration curves showed good agreement between the predicted and observed incidences of IDC-P.

CONCLUSION: We developed a clinical predictive model composed of alkaline phosphatase (ALP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), prostate specific antigen (PSA) and lactate dehydrogenase (LDH) with a high precision and universality. This model provides a novel calculator for predicting the diagnosis of IDC-P and different treatment options for patients at an early stage.}, } @article {pmid36590775, year = {2022}, author = {Abur, PP and Yusufu, LM and Odigie, VI and Emeka, NS}, title = {Metachronous Contralateral Breast Cancer in Ahmadu Bello University Teaching Hospital, Zaria, Northwestern Nigeria.}, journal = {Journal of the West African College of Surgeons}, volume = {12}, number = {4}, pages = {52-55}, pmid = {36590775}, issn = {2276-6944}, abstract = {BACKGROUND: Breast cancer is the most frequent cancer of women. Metachronous contralateral breast cancer (MCBC) is a cancer in the contralateral breast after 6 months of the initial diagnosis of the first breast cancer. It is an important public health issue because of an increased incidence of a primary breast cancer and improved survival. There is a paucity of data in the Northwestern region of the country. The study was to document the incidence, the method of detection, clinicopathological features, and the treatment of MCBC in our hospital.

PATIENTS AND METHODS: It was a 7-year prospective study from January 2011 to December 2017. Patients who had treatment for nonmetastatic breast cancer, American Joint Committee on Cancer (AJCC) Stages 1-111, were followed up. Those that developed MCBC were studied. Age, the method of detection, stage at presentation, pathological types, hormone receptor status, and treatment were documented. Data obtained were analysed using SPSS version 21.0. Results were presented as simple percentages and charts.

RESULTS: Of 1285 women with nonmetastatic breast cancer, 47 had MCBC (incidence of 3.7%); 30 (63.8%) were aged 21-50 years; 23 (48.9%) detected by self-breast examination; 13 (27.7%) by clinical breast examination; seven (14.9%) by mammography; and four (8.5%) by breast ultrasound scan. Fourteen (29.8%) were AJCC stage I; 23 (48.9%), stage II; seven (14.9%), stage III; and three (6.4%), stage IV. Thirty-nine (83%) were invasive ductal carcinoma; 22 (50.0%) were estrogen receptor/progesterone receptor (ER/PR) positive, human epidermal receptor (HER)-2 neu negative; nine were (20.5%) ER/PR and HER-2 neu positive; six (13.6%) were ER/PR negative, HER-2 neu positive, whereas seven (15.9%) were triple negative. Forty-three (91.5%) had modified radical mastectomy and 19 (40.4%) had cytotoxics.

CONCLUSION: With an average of six cases in a year, MCBC is common in our hospital. Majority (63.8%) were young. The commonest method of detection was by self-breast examination. Majority (78.3%) presented at an early stage. Most (91.5%) still had modified radical mastectomy.}, } @article {pmid38384043, year = {2023}, author = {Soman, PS and Hemalatha, A and Sreeramulu, PN}, title = {Expression of BRCA1 by immunohistochemistry and its association with ER, PR, Her2neu status in infiltrative ductal carcinoma of breast.}, journal = {Journal of cancer research and therapeutics}, volume = {19}, number = {Suppl 2}, pages = {S706-S711}, doi = {10.4103/jcrt.jcrt_639_22}, pmid = {38384043}, issn = {1998-4138}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Immunohistochemistry ; Erb-b2 Receptor Tyrosine Kinases/genetics/metabolism ; Mastectomy ; *Carcinoma, Ductal, Breast/genetics/therapy/metabolism ; Biomarkers, Tumor/genetics/metabolism ; BRCA1 Protein/genetics ; }, abstract = {BACKGROUND: Breast cancer is a heterogeneous disease, which differs in its clinical behaviors and responses to treatment and outcome. The prognosis of breast cancer depends on histopathological parameters and molecular subtypes. Among more than 300 genes, which are involved in the pathogenesis of breast cancer tumor suppressor gene such as BRCA1 is known to play a significant role in hereditary cancers. However, its role in sporadic cases of infiltrating ductal carcinoma is yet to be established.

AIMS AND OBJECTIVES: To evaluate the expression of BRCA1 in infiltrative ductal carcinoma and to analyze the association of BRCA1 with histopathological parameters and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (Her2) neu expression.

MATERIALS AND METHODS: This was a laboratory-based exploratory study in which 56 patients with infiltrative ductal carcinoma who underwent radical mastectomy from October 2019 to July 2021 were included. Patients with chemotherapy and radiotherapy, trucut biopsies, and incomplete patient details were excluded. Immunostaining for BRCA1 was performed. Individual clinicopathological parameters were compared with the BRCA1 mutation. Statistical analysis was done using SPSS 22. A P value of < 0.05 was considered statistically significant.

RESULTS: Among 56 cases of IDC, 18 cases (32.1%) showed BRCA1 mutation. BRCA1 mutation was associated with postmenopausal age, larger tumor size, lower tumor grade, and higher tumor staging. When we analyzed the biomarkers with BRCA1 mutation, it showed a negative association with ER, PR, and Her2 neu and a high Ki67 proliferation index. No family history of breast carcinoma was seen in 34/56 patients where history was available.

CONCLUSION: Our study showed BRCA1 mutation in 32.1% and associated with postmenopausal age group, larger tumor size, and higher staging and negative hormonal status of breast carcinoma.}, } @article {pmid38384039, year = {2023}, author = {Kathimanda, ST and Hussain, N and Bugalia, A and Sarangi, S}, title = {Role of breast ultrasonography in predicting accurate tumor dimensions in correlation with histopathology and its impact on staging of breast carcinoma.}, journal = {Journal of cancer research and therapeutics}, volume = {19}, number = {Suppl 2}, pages = {S682-S684}, doi = {10.4103/jcrt.jcrt_938_22}, pmid = {38384039}, issn = {1998-4138}, mesh = {Female ; Humans ; *Ultrasonography, Mammary ; Cross-Sectional Studies ; *Breast Neoplasms/diagnostic imaging/surgery/drug therapy ; Ultrasonography ; Physical Examination ; Neoplasm Staging ; }, abstract = {BACKGROUND AND OBJECTIVES: Estimation of the preoperative size of a breast tumor is of primary importance in deciding the treatment modality. Hence, clinical examination of the lump aided by the imaging is necessary. Our study is instrumental in correlating the size of breast tumor by high-resolution ultrasonography (USG) with the morphological size and also in comparing clinical staging of breast carcinoma against the gold standard pathological staging.

METHODS: It is a cross-sectional study of correlating the size of tumor on USG with the morphological size of biopsy proven invasive ductal carcinoma when received after excision. The size of the tumor was measured grossly and was compared with the USG measurements and palpatory findings.

RESULTS: Seventy percent of cases had good correlation between the USG and morphological size. In 50% of cases, the size on physical examination corroborated with the USG findings and only in 40% of the cases size on physical examination matched with morphological findings. In 65% of cases, the clinical staging of the breast carcinoma matched with the pathological staging. Our study reflected that USG promised to be the most useful radiological tool in predicting the accurate preoperative size of the tumor.

INTERPRETATION AND CONCLUSION: We observed that USG has proved to be a very useful conjunct to clinical examination as only palpation was not found to be very accurate in predicting the actual tumor size. It proved to be safer and cheaper and effectively instrumental in meting out an effective management at pre- and postoperative level to the patient.}, } @article {pmid38375814, year = {2023}, author = {Huang, T and Lu, C and Zhang, Y and Lin, BY and Zhang, ZJ and Zhu, D and Wang, L and Lu, Y}, title = {Effect of activating cancer-associated fibroblasts biomarker TNC on immune cell infiltration and prognosis in breast cancer.}, journal = {Annals of medicine}, volume = {55}, number = {2}, pages = {2250987}, pmid = {38375814}, issn = {1365-2060}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics ; *Cancer-Associated Fibroblasts/metabolism/pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Prognosis ; Biomarkers/metabolism ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Cancer-associated fibroblasts (CAFs) are the most important components of the tumor microenvironment (TME). CAFs are heterogeneous and involved in tumor tumorigenesis and drug resistance, contributing to TME remodeling and predicting clinical outcomes as prognostic factors. However, the effect of CAFs the TME and the prognosis of patients with breast cancer (BC) is not fully understood. This study investigated the correlation between CAFs-activating biomarkers immune cell infiltration and survival in patients with breast cancer.

METHODS: RNA sequencing data and survival information for patients with breast cancer were downloaded from The Cancer Genome Atlas (TCGA) using R software. We then analyzed the correlation between CAFs-expressing biomarkers and immune cells using the clusterProfiler package, and evaluated the prognostic role of appealing genes using the Survminer package. Immunohistochemical (IHC) staining was used to determine the expression levels of TNC in 160 breast cancer samples pathologically diagnosed as invasive ductal carcinoma that were not otherwise specified (IDC-NOS).

RESULTS: Data analysis showed that CAFs-expressing genes was higher than in normal tissues (p < 0.05). Pathway enrichment revealed that the overexpression of CAFs-related genes was mainly enriched in the focal adhesion and phosphoinositol-3 kinase-serine/threonine kinase (PI3K-AKT) signaling pathways. Immune infiltration analysis suggested that high expression of CAFs-related genes was significantly positively correlated with the infiltration of naive B cells and resting dendritic cells and inversely correlated with macrophages cell infiltration. In addition, high TNC expression in tumor cells was associated with the most adverse clinicopathological features and reduced metastasis-free survival (MFS) (hazard ratio (HR) 0.574, 95% confidence interval (CI) 0.404-0.815, p = 0.035).

CONCLUSIONS: This study found that CAFs may participate in immunosuppression and regulate tumor cell proliferation and invasion. High TNC expression is associated with several adverse clinicopathological features, and high TNC expression in tumor cells has been identified as an independent prognostic factor for IDC-NOS.}, } @article {pmid36587134, year = {2023}, author = {Levy-Jurgenson, A and Tekpli, X and Kristensen, VN and Yakhini, Z}, title = {Analysis of Spatial Molecular Data.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2614}, number = {}, pages = {349-356}, pmid = {36587134}, issn = {1940-6029}, mesh = {Humans ; *Neoplasms/diagnosis/genetics ; Phenotype ; Algorithms ; Microscopy/methods ; }, abstract = {Digital analysis of pathology whole-slide images has been recently gaining interest in the context of cancer diagnosis and treatment. In particular, deep learning methods have demonstrated significant potential in supporting pathology analysis, recently detecting molecular traits never before recognized in pathology H&E whole-slide images (WSIs). Alongside these advancements in the digital analysis of WSIs, it is becoming increasingly evident that both spatial and overall tumor heterogeneity may be significant determinants of cancer prognosis and treatment outcome. In this chapter, we describe methods that aim to support these two elements. We describe both an end-to-end deep learning pipeline for producing limited spatial transcriptomics from WSIs with associated bulk gene expression data, as well as an algorithm for quantifying spatial tumor heterogeneity based on the results of this pipeline.}, } @article {pmid36586492, year = {2023}, author = {Ward, MC and Recht, A and Vicini, F and Al-Hilli, Z and Asha, W and Chadha, M and Abraham, A and Thaker, N and Khan, AJ and Keisch, M and Shah, C}, title = {Cost-Effectiveness Analysis of Ultra-Hypofractionated Whole Breast Radiation Therapy Alone Versus Hormone Therapy Alone or Combined Treatment for Low-Risk ER-Positive Early Stage Breast Cancer in Women Aged 65 Years and Older.}, journal = {International journal of radiation oncology, biology, physics}, volume = {116}, number = {3}, pages = {617-626}, doi = {10.1016/j.ijrobp.2022.12.028}, pmid = {36586492}, issn = {1879-355X}, mesh = {Female ; Humans ; Aged ; *Breast Neoplasms/radiotherapy/pathology ; Cost-Effectiveness Analysis ; Anastrozole ; Breast/pathology ; Aromatase Inhibitors ; Cost-Benefit Analysis ; Hormones ; }, abstract = {PURPOSE: The optimal management of early-stage, low-risk, hormone-positive breast cancer in older women remains controversial. Recent trials have shown that 5-fraction ultrahypofractionated whole-breast irradiation (U-WBI) has similar outcomes to longer courses, reducing the cost and inconvenience of treatment. We performed a cost-utility analysis to compare U-WBI to hormone therapy alone or their combination.

METHODS AND MATERIALS: We simulated 3 different treatment approaches for women age 65 years or older with pT1-2N0 ER-positive invasive ductal carcinoma treated with lumpectomy with negative margins using a Markov microsimulation model. The strategies were U-WBI performed with a 3-dimensional conformal technique over 5 fractions without a boost ("radiation therapy [RT] alone"), adjuvant hormone therapy (anastrozole for 5 years) without RT ("aromatase-inhibitor [AI] alone"), or the combination of the 2. The combination strategy was calibrated to match trial results, and the relative effectiveness of the RT alone and AI alone strategies were inferred from previous randomized trials. The primary endpoint was the cost-effectiveness of the 3 strategies over a lifetime horizon as measured by the incremental cost-effectiveness ratio (ICER), with a value of $100,000/quality-adjusted life-year deemed "cost-effective."

RESULTS: The model results compared with the prespecified target outcomes. On average, RT alone was the least expensive strategy ($14,775), with AI alone slightly more ($14,998), and combination therapy the costliest ($19,802). RT alone dominated AI alone (the incremental cost-effectiveness ratio [ICER] -$5089). Combination therapy, compared with RT alone, was slightly more expensive than our definition of cost-effective (ICER $113,468) but was cost-effective compared with AI alone (ICER $54,451). Probabilistic sensitivity analysis demonstrated RT alone to be cost-effective in 50% of trials, with combination therapy in 36% and AI alone in 14%.

CONCLUSIONS: U-WBI alone appears the more cost-effective de-escalation strategy for these low-risk patients, compared with AI alone. Combining U-WBI and AI appears more costly but may be preferred by some patients.}, } @article {pmid36584059, year = {2022}, author = {Farouk, O and Ezzat, M and El-Badrawy, A and Fady, T and El-Kashef, W and Shams, N and Senbel, A}, title = {Charcoal Localization for Surgical Resection of Non-Palpable Suspicious Breast Lesions.}, journal = {Chirurgia (Bucharest, Romania : 1990)}, volume = {117}, number = {6}, pages = {671-680}, doi = {10.21614/chirurgia.2802}, pmid = {36584059}, issn = {1221-9118}, mesh = {Humans ; Adult ; Female ; *Breast Neoplasms/diagnostic imaging/surgery ; Mammography/methods ; Charcoal ; Prospective Studies ; Mastectomy ; Treatment Outcome ; Mastectomy, Segmental ; }, abstract = {Background: Breast cancer is more frequently detected as radiographic non-palpable lesions with the increased utilization of national screening programs. Moreover, the sizes of tumors detected have decreased in recent years, increasing the need for accurate image-directed localization for surgical excision in a significant portion of cases. Although Wire guided localization has been the most commonly used method for many years, inherent problems remain and limit its practice. Radio-guided occult lesion localization (ROLL) is currently the standard method of localization, however, it is unavailable in most low resource communities. This encourages us to use charcoal localization which is a simple and cheap method of surgical localization of non-palpable suspicious breast lesions. Methods: This prospective study included 34 patients who presented with non-palpable suspicious breast lesions (BIRADS 4 or 5). All patients were injected 1-3 ml of sterilized 3% aqueous suspension of charcoal granules under the guidance of ultrasound at the superficial border of the suspicious lesion and the track between the lesion and the needle entry point in the skin which will occur at the future incision. This method was carried out in most patients one day before the operation, however, two patients underwent surgical excision after 6 days of localization without any interruption. Results: Thirty-four patients had 36 Lesions. The median age was 43 years. The mean diameter of lesions was 10.9 mm. Of 36 lesions; the BIRADS as follow10 (4a), 12 (4b), 8 (4c), and 6 (5). Postoperative investigations revealed 16 malignant lesions and 20 benign lesions. All 20 benign lesions were managed by wide local excision; All 14 BIRADS 4a lesions were proved to be benign. Sixteen malignant lesions were managed as the following; nine patients had breast-conserving surgery, five patients had modified radical mastectomy (three patients had past history of modified radical mastectomy, one patient had Multicentric IDC and one patient had infiltrated safety margins on conservation), and one patient had Nipple Sparing Mastectomy with immediate breast reconstruction by Latissimus Dorsi Flap. There was no reaction or infection reported in our study. Conclusion: Charcoal localization has many advantages and helps surgical localization.}, } @article {pmid36577560, year = {2023}, author = {Lerner, G and Tang, H and Singh, K and Golestani, R and St Claire, S and Humphrey, PA and Lannin, D and Janostiak, R and Harigopal, M}, title = {AMACR Expression is a Potential Diagnostic Marker in Apocrine Lesions of Breast, and is Associated with High Histologic Grade and Lymph Node Metastases in Some Invasive Apocrine Breast Cancers.}, journal = {Clinical breast cancer}, volume = {23}, number = {2}, pages = {199-210}, doi = {10.1016/j.clbc.2022.11.012}, pmid = {36577560}, issn = {1938-0666}, mesh = {Humans ; Female ; *Breast Neoplasms/metabolism ; *Triple Negative Breast Neoplasms/diagnosis ; Lymphatic Metastasis ; Biomarkers, Tumor/metabolism ; Neoplasm Recurrence, Local ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Receptors, Progesterone/metabolism ; Receptors, Estrogen/metabolism ; Racemases and Epimerases ; }, abstract = {BACKGROUND: Carcinoma with apocrine differentiation (AC) is a subtype of breast carcinoma with apocrine features in >90% of the tumor. Molecular studies demonstrate AC has high expression of androgen receptor (AR) mRNA. Pure AC lack estrogen receptor (ER), progesterone receptor (PR), and express AR, with variable human epidermal growth factor 2 (HER2) status. Currently, in triple negative AC, no targetable therapies or specific diagnostic markers exist.

MATERIALS AND METHODS: α-Methylacyl CoA racemase (AMACR) expression was investigated as a marker of apocrine differentiation using a single-plex immunoperoxidase stain, and a novel AMACR/p63 dual stain in a subset of cases, across 1) benign apocrine lesions (apocrine metaplasia, adenosis) 2) apocrine DCIS (ADCIS), 3) AC/ invasive ductal carcinoma (IDC) with apocrine features, 4) non-apocrine triple negative breast cancer (TNBC) and 5) IDC, no special type. A sub-set of cases were evaluated by tissue microarray.

RESULTS: AMACR expression was increased in both AC and ADCIS, with minimal expression in benign breast tissue, TNBC and IDC, NST cases. In invasive cases, those with positive AMACR (>5% positivity) were significantly associated with higher histologic grade (P = .006), initial N stage (chi squared 0.044), and lack of ER or PR expression (both P < .001), with no correlation with overall survival. Analysis of TCGA breast cancer datasets revealed AMACR expression was significantly higher in molecularly defined apocrine carcinomas relative to basal and luminal subtypes. Moreover, high AMACR expression predicted worse relapse-free and distant-metastasis free survival, among both ER-/PR-/Her2- and ER-/PR-/Her2+ breast cancer cohorts (log-rank P = .081 and .00011, respectively).

CONCLUSION: AMACR represents a promising diagnostic and prognostic marker in apocrine breast lesions. Further study is needed to determine the biologic and clinical significance of this protein in AC.}, } @article {pmid36577332, year = {2023}, author = {Lemel, R and Shalev, L and Nitsan, G and Ben-David, BM}, title = {Listen up! ADHD slows spoken-word processing in adverse listening conditions: Evidence from eye movements.}, journal = {Research in developmental disabilities}, volume = {133}, number = {}, pages = {104401}, doi = {10.1016/j.ridd.2022.104401}, pmid = {36577332}, issn = {1873-3379}, mesh = {Young Adult ; Humans ; *Speech Perception/physiology ; Eye Movements ; *Attention Deficit Disorder with Hyperactivity ; Quality of Life ; Word Processing ; Speech Disorders ; }, abstract = {BACKGROUND: Cognitive skills such as sustained attention, inhibition and working memory are essential for speech processing, yet are often impaired in people with ADHD. Offline measures have indicated difficulties in speech recognition on multi-talker babble (MTB) background for young adults with ADHD (yaADHD). However, to-date no study has directly tested online speech processing in adverse conditions for yaADHD.

AIMS: Gauging the effects of ADHD on segregating the spoken target-word from its sound-sharing competitor, in MTB and working-memory (WM) load.

METHODS AND PROCEDURES: Twenty-four yaADHD and 22 matched controls that differ in sustained attention (SA) but not in WM were asked to follow spoken instructions presented on MTB to touch a named object, while retaining one (low-load) or four (high-load) digit/s for later recall. Their eye fixations were tracked.

OUTCOMES AND RESULTS: In the high-load condition, speech processing was less accurate and slowed by 140ms for yaADHD. In the low-load condition, the processing advantage shifted from early perceptual to later cognitive stages. Fixation transitions (hesitations) were inflated for yaADHD.

CONCLUSIONS AND IMPLICATIONS: ADHD slows speech processing in adverse listening conditions and increases hesitation, as speech unfolds in time. These effects, detected only by online eyetracking, relate to attentional difficulties. We suggest online speech processing as a novel purview on ADHD. WHAT THIS PAPER ADDS?: We suggest speech processing in adverse listening conditions as a novel vantage point on ADHD. Successful speech recognition in noise is essential for performance across daily settings: academic, employment and social interactions. It involves several executive functions, such as inhibition and sustained attention. Impaired performance in these functions is characteristic of ADHD. However, to date there is only scant research on speech processing in ADHD. The current study is the first to investigate online speech processing as the word unfolds in time using eyetracking for young adults with ADHD (yaADHD). This method uncovered slower speech processing in multi-talker babble noise for yaADHD compared to matched controls. The performance of yaADHD indicated increased hesitation between the spoken word and sound-sharing alternatives (e.g., CANdle-CANdy). These delays and hesitations, on the single word level, could accumulate in continuous speech to significantly impair communication in ADHD, with severe implications on their quality of life and academic success. Interestingly, whereas yaADHD and controls were matched on WM standardized tests, WM load appears to affect speech processing for yaADHD more than for controls. This suggests that ADHD may lead to inefficient deployment of WM resources that may not be detected when WM is tested alone. Note that these intricate differences could not be detected using traditional offline accuracy measures, further supporting the use of eyetracking in speech tasks. Finally, communication is vital for active living and wellbeing. We suggest paying attention to speech processing in ADHD in treatment and when considering accessibility and inclusion.}, } @article {pmid36574856, year = {2023}, author = {Ying, Z and van Eenige, R and Beerepoot, R and Boon, MR and Kloosterhuis, NJ and van de Sluis, B and Bartelt, A and Rensen, PCN and Kooijman, S}, title = {Mirabegron-induced brown fat activation does not exacerbate atherosclerosis in mice with a functional hepatic ApoE-LDLR pathway.}, journal = {Pharmacological research}, volume = {187}, number = {}, pages = {106634}, doi = {10.1016/j.phrs.2022.106634}, pmid = {36574856}, issn = {1096-1186}, mesh = {Animals ; Humans ; Mice ; *Adipose Tissue, Brown ; Adrenergic Agonists/metabolism/pharmacology ; Apolipoproteins E/genetics/metabolism ; *Atherosclerosis/drug therapy/metabolism ; Cholesterol/metabolism ; Fatty Acids/metabolism ; Lipoproteins, LDL/metabolism ; Liver/metabolism ; Triglycerides ; Receptors, LDL/metabolism ; Acetanilides ; Thiazoles ; }, abstract = {Activation of brown adipose tissue (BAT) with the β3-adrenergic receptor agonist CL316,243 protects mice from atherosclerosis development, and the presence of metabolically active BAT is associated with cardiometabolic health in humans. In contrast, exposure to cold or treatment with the clinically used β3-adrenergic receptor agonist mirabegron to activate BAT exacerbates atherosclerosis in apolipoprotein E (ApoE)- and low-density lipoprotein receptor (LDLR)-deficient mice, both lacking a functional ApoE-LDLR pathway crucial for lipoprotein remnant clearance. We, therefore, investigated the effects of mirabegron treatment on dyslipidemia and atherosclerosis development in APOE*3-Leiden.CETP mice, a humanized lipoprotein metabolism model with a functional ApoE-LDLR clearance pathway. Mirabegron activated BAT and induced white adipose tissue (WAT) browning, accompanied by selectively increased fat oxidation and attenuated fat mass gain. Mirabegron increased the uptake of fatty acids derived from triglyceride (TG)-rich lipoproteins by BAT and WAT, which was coupled to increased hepatic uptake of the generated cholesterol-enriched core remnants. Mirabegron also promoted hepatic very low-density lipoprotein (VLDL) production, likely due to an increased flux of fatty acids from WAT to the liver, and resulted in transient elevation in plasma TG levels followed by a substantial decrease in plasma TGs. These effects led to a trend toward lower plasma cholesterol levels and reduced atherosclerosis. We conclude that BAT activation by mirabegron leads to substantial metabolic benefits in APOE*3-Leiden.CETP mice, and mirabegron treatment is certainly not atherogenic. These data underscore the importance of the choice of experimental models when investigating the effect of BAT activation on lipoprotein metabolism and atherosclerosis.}, } @article {pmid36572997, year = {2023}, author = {Bendarkawi, Y and Cherif Chefchaouni, A and Lkhoyaali, S and Bechar, H and Boudina, Y and Abercha, Y and Belahcen, MJ and Rahali, Y}, title = {Tamoxifen induced hands deformities.}, journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners}, volume = {29}, number = {5}, pages = {1246-1250}, doi = {10.1177/10781552221147507}, pmid = {36572997}, issn = {1477-092X}, mesh = {Humans ; Female ; Middle Aged ; *Tamoxifen/adverse effects ; Antineoplastic Agents, Hormonal/adverse effects ; *Breast Neoplasms/pathology ; Arthralgia/chemically induced ; }, abstract = {INTRODUCTION: Tamoxifen is widely used for the treatment of hormone-responsive breast cancer. In this article, we report a case of a patient who developed hand deformities following long-term administration of tamoxifen.

CASE REPORT: A 57-year-old woman, followed for invasive ductal carcinoma of the left breast under tamoxifen for 7 years, presenting joint pain with deformities in her fingers.

MANAGEMENT & OUTCOME: Following the appearance of the adverse effect, tamoxifen was stopped. A series of biologic and radiologic analysis were performed in order to explain the appearance of this event. A substitution treatment was discussed and a rheumatologist's opinion was requested.

DISCUSSION: Tamoxifen appears to be associated with the development of inflammatory osteoarthritis resembling rheumatoid arthritis. Possible mechanisms of such an effect are discussed.}, } @article {pmid36568215, year = {2022}, author = {Xu, ML and Zeng, SE and Li, F and Cui, XW and Liu, GF}, title = {Preoperative prediction of lymphovascular invasion in patients with T1 breast invasive ductal carcinoma based on radiomics nomogram using grayscale ultrasound.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {1071677}, pmid = {36568215}, issn = {2234-943X}, abstract = {PURPOSE: The aim of this study was to develop a radiomics nomogram based on grayscale ultrasound (US) for preoperatively predicting Lymphovascular invasion (LVI) in patients with pathologically confirmed T1 (pT1) breast invasive ductal carcinoma (IDC).

METHODS: One hundred and ninety-two patients with pT1 IDC between September 2020 and August 2022 were analyzed retrospectively. Study population was randomly divided in a 7: 3 ratio into a training dataset of 134 patients (37 patients with LVI-positive) and a validation dataset of 58 patients (19 patients with LVI-positive). Clinical information and conventional US (CUS) features (called clinic_CUS features) were recorded and evaluated to predict LVI. In the training dataset, independent predictors of clinic_CUS features were obtained by univariate and multivariate logistic regression analyses and incorporated into a clinic_CUS prediction model. In addition, radiomics features were extracted from the grayscale US images, and the radiomics score (Radscore) was constructed after radiomics feature selection. Subsequent multivariate logistic regression analysis was also performed for Radscore and the independent predictors of clinic_CUS features, and a radiomics nomogram was developed. The performance of the nomogram model was evaluated via its discrimination, calibration, and clinical usefulness.

RESULTS: The US reported axillary lymph node metastasis (LNM) (US_LNM) status and tumor margin were determined as independent risk factors, which were combined for the construction of clinic_CUS prediction model for LVI in pT1 IDC. Moreover, tumor margin, US_LNM status and Radscore were independent predictors, incorporated as the radiomics nomogram model, which achieved a superior discrimination to the clinic_CUS model in the training dataset (AUC: 0.849 vs. 0.747; P < 0.001) and validation dataset (AUC: 0.854 vs. 0.713; P = 0.001). Calibration curve for the radiomic nomogram showed good concordance between predicted and actual probability. Furthermore, decision curve analysis (DCA) confirmed that the radiomics nomogram had higher clinical net benefit than the clinic_CUS model.

CONCLUSION: The US-based radiomics nomogram, incorporating tumor margin, US_LNM status and Radscore, showed a satisfactory preoperative prediction of LVI in pT1 IDC patients.}, } @article {pmid36563298, year = {2023}, author = {Braun, A and Reddy, S and Cheng, L and Gattuso, P and Yan, L}, title = {Clinicopathologic Review of Metastatic Breast Cancer to the Gynecologic Tract.}, journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists}, volume = {42}, number = {4}, pages = {414-420}, doi = {10.1097/PGP.0000000000000920}, pmid = {36563298}, issn = {1538-7151}, mesh = {Female ; Humans ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/pathology ; *Genital Neoplasms, Female/secondary ; *Krukenberg Tumor ; *Ovarian Neoplasms ; }, abstract = {Metastatic spread is the single most significant predictor of poor survival in breast cancer. Some of the most common metastatic sites are the bones, lungs, liver, brain, and peritoneal cavity. Clinically metastatic breast cancer to the gynecologic tract is usually asymptomatic and diagnosed as an incidental finding during a histologic examination of gynecologic specimens resected for other reasons. Cases of metastatic breast cancer to gynecologic organs diagnosed from August 1995 to January 2021 were retrieved from our institution's pathology databases, and their clinicopathologic features were reviewed. The most common site of metastasis was the ovary which was involved in about 79% (22 of 28 cases) of metastases to the gynecologic tract. Clinically, only 8 cases (36%) presented with ovarian mass detected in imaging studies and the rest of the cases were all incidental findings. Among ovarian metastasis, 59% of cases were invasive lobular carcinoma and 41% were invasive ductal carcinoma. In 5 cases, metastatic breast cancer was found in the endometrium, including 2 cases with endometrial metastasis only and 3 cases with multiple gynecologic organs involved. Metastatic breast cancer rarely involved the lower gynecologic tract, with only 7% vaginal metastasis and 4% found in the vulva. The absolute majority of metastatic breast cancer outside of the ovaries were lobular carcinoma (88%). Most of the metastatic breast carcinomas were positive for estrogen receptor on immunohistochemistry (27 of 28 cases, 96%). Her-2/neu immunostaining was positive in 4 cases only (14%). Metastatic breast cancer needs to be distinguished from gynecologic primary neoplasms and metastatic tumors from adjacent urinary and GI tracts. A careful review of the patient's history and adequate immunohistochemistry panel are helpful to render the diagnosis.}, } @article {pmid36551567, year = {2022}, author = {Lin, SE and Chang, WW and Hsiao, PK and Hsieh, MC and Chen, WY and Fang, CL and Tsai, CC}, title = {Feasibility of Breast Cancer Metastasis Assessment of Ex Vivo Sentinel Lymph Nodes through a p-H&E Optical Coherence Microscopic Imaging System.}, journal = {Cancers}, volume = {14}, number = {24}, pages = {}, pmid = {36551567}, issn = {2072-6694}, support = {CMRPVVL0151//Chang Gung Medical Foundation/ ; }, abstract = {Frozen-sectioned hematoxylin-eosin (H&E) image evaluation is the current method for intraoperative breast cancer metastasis assessment through ex vivo sentinel lymph nodes (SLNs). After frozen sectioning, the sliced fatty region of the frozen-sectioned specimen is easily dropped because of different freezing points for fatty tissues and other tissues. Optical-sectioned H&E images provide a nondestructive method for obtaining the insight en face image near the attached surface of the dissected specimen, preventing the freezing problem of fatty tissue. Specimens from 29 patients at Wanfang Hospital were collected after excision and were analyzed at the pathology laboratory, and a fluorescence-in-built optical coherence microscopic imaging system (OCMIS) was then used to visualize the pseudo-H&E (p-H&E) images of the SLNs for intraoperative breast cancer metastasis assessment, and the specificity, sensitivity, and accuracy were 100%, 88.9%, and 98.8% (n = 83), respectively. Compared with gold-standard paraffin-sectioned H&E images, the specificity, sensitivity, and accuracy obtained with the frozen-sectioned H&E images (n = 85) of the specimens were the same as those obtained with the p-H&E images (n = 95). Thus, OCMIS is a useful noninvasive image-assisted tool for breast cancer metastasis assessment based on SLN images.}, } @article {pmid36548300, year = {2022}, author = {Shapiro-Kulnane, L and Selengut, M and Salz, HK}, title = {Safeguarding Drosophila female germ cell identity depends on an H3K9me3 mini domain guided by a ZAD zinc finger protein.}, journal = {PLoS genetics}, volume = {18}, number = {12}, pages = {e1010568}, pmid = {36548300}, issn = {1553-7404}, support = {R01 GM129478/GM/NIGMS NIH HHS/United States ; S10 OD016164/OD/NIH HHS/United States ; }, mesh = {Animals ; Male ; *Drosophila/metabolism ; Drosophila melanogaster/genetics/metabolism ; *Drosophila Proteins/genetics/metabolism ; Germ Cells/metabolism ; Homeodomain Proteins/metabolism ; Zinc Fingers/genetics ; Female ; }, abstract = {H3K9me3-based gene silencing is a conserved strategy for securing cell fate, but the mechanisms controlling lineage-specific installation of this epigenetic mark remain unclear. In Drosophila, H3K9 methylation plays an essential role in securing female germ cell fate by silencing lineage inappropriate phf7 transcription. Thus, phf7 regulation in the female germline provides a powerful system to dissect the molecular mechanism underlying H3K9me3 deposition onto protein coding genes. Here we used genetic studies to identify the essential cis-regulatory elements, finding that the sequences required for H3K9me3 deposition are conserved across Drosophila species. Transposable elements are also silenced by an H3K9me3-mediated mechanism. But our finding that phf7 regulation does not require the dedicated piRNA pathway components, piwi, aub, rhino, panx, and nxf2, indicates that the mechanisms of H3K9me3 recruitment are distinct. Lastly, we discovered that an uncharacterized member of the zinc finger associated domain (ZAD) containing C2H2 zinc finger protein family, IDENTITY CRISIS (IDC; CG4936), is necessary for H3K9me3 deposition onto phf7. Loss of idc in germ cells interferes with phf7 transcriptional regulation and H3K9me3 deposition, resulting in ectopic PHF7 protein expression. IDC's role is likely to be direct, as it localizes to a conserved domain within the phf7 gene. Collectively, our findings support a model in which IDC guides sequence-specific establishment of an H3K9me3 mini domain, thereby preventing accidental female-to-male programming.}, } @article {pmid36542569, year = {2022}, author = {Pratt, D and Sunassee, A}, title = {Syringomatous Adenoma of the Nipple with Associated Invasive Carcinoma: A Case Report.}, journal = {South Dakota medicine : the journal of the South Dakota State Medical Association}, volume = {75}, number = {7}, pages = {302-303}, pmid = {36542569}, issn = {0038-3317}, mesh = {Female ; Humans ; Adult ; Nipples/pathology ; *Syringoma/diagnosis/surgery/pathology ; *Adenoma/diagnosis/surgery ; *Adenocarcinoma/pathology ; *Sweat Gland Neoplasms/diagnosis/surgery/pathology ; *Breast Neoplasms/diagnosis/surgery/pathology ; }, abstract = {Syringomatous adenoma of the nipple is a rare benign infiltrative neoplasm that was first described in 1983. At the time of this writing, a literature search revealed no cases of syringomatous adenoma of the nipple in association with invasive carcinoma of the breast. We report a case of syringomatous adenoma of the nipple in a 40-year old female who also had bilateral invasive ductal carcinoma and ductal carcinoma in situ of the breasts. Syringomatous adenomas of the nipple have been postulated to originate from eccrine structures of the nipple due to their microscopic similarity to other tumors of eccrine origin, such as syringomatous carcinoma. However, their exact origin is uncertain. Despite their benign behavior, they usually demonstrate an infiltrative and expansile proliferation into adjacent nipple and breast tissue. They have been confused with tubular carcinoma and low-grade adenosquamous carcinoma of the breast, both clinically and histologically. Complete excision is the therapy of choice, and only incompletely excised lesions have shown recurrence. We present this case to raise awareness that syringomatous adenoma of the nipple may present in patients with a simultaneous invasive carcinoma of the breast.}, } @article {pmid36539444, year = {2022}, author = {Mouabbi, JA and Raghavendra, AS and Bassett, RL and Hassan, A and Tripathy, D and Layman, RM}, title = {Histology-based survival outcomes in hormone receptor-positive metastatic breast cancer treated with targeted therapies.}, journal = {NPJ breast cancer}, volume = {8}, number = {1}, pages = {131}, pmid = {36539444}, issn = {2374-4677}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, abstract = {The addition of targeted therapies (TT) to endocrine therapy (ET) has improved the outcomes of patients with HR-positive, HER2-negative metastatic breast cancer (mBC). However, it is unknown whether patients with invasive lobular carcinoma (ILC) or mixed invasive ductal and lobular carcinoma (mixed) histologies experience the same magnitude of benefit from this therapy as those with invasive ductal carcinoma (IDC). We aim to determine whether patients with IDC, ILC, and mixed HR+/HER2- mBC derive similar benefit from the addition of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is), mammalian target of rapamycin inhibitor (mTORi), and phosphoinositide 3-kinase inhibitor (PI3Ki) to ET in HR+/HER2- mBC. We conducted an observational, population-based investigation using data from the MD Anderson prospectively collected database. We conducted a histology-based analysis of progression-free survival (PFS) and overall survival (OS) durations in 3784 patients with HR+/HER2- mBC who were treated with TT plus ET between January 1, 2010, and December 31, 2021. Out of the 3784 patients, 2975 were included in the final analysis. Of these, 2249 received CDK4/6is (81% IDC, 15% ILC, and 4% mixed), 1027 received everolimus (82% IDC, 14% ILC, and 4% mixed) and 49 received alpelisib (81% IDC and 19% ILC). The addition of targeted therapy to ET did not result in statistically significant differences in PFS or OS duration among patients with IDC, ILC, and mixed HR+/HER2- mBC. We concluded that for patients with HR+/HER2- mBC, the addition of TT to ET leads to a similar magnitude of benefit, irrespective of histology.}, } @article {pmid36539250, year = {2022}, author = {Sugihara, M and Nakao, M and Maejima, T and Kinoshita, R and Hayashi, S and Hirata, Y and Arakawa, S and Kuriyama, M and Muramatsu, H}, title = {[A Case of Second Primary Small Cell Lung Carcinoma after Radiotherapy for Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {49}, number = {12}, pages = {1361-1364}, pmid = {36539250}, issn = {0385-0684}, mesh = {Female ; Humans ; Aged ; *Breast Neoplasms/radiotherapy/surgery/pathology ; *Small Cell Lung Carcinoma ; Mastectomy ; *Lung Neoplasms/surgery ; Lung/pathology ; }, abstract = {We report the case of a 72-year-old woman who underwent partial mastectomy due to left breast cancer(invasive ductal carcinoma)in March 20XX-4. This was followed by radiotherapy(50 Gy/25 Fr)and hormone therapy. In July 20XX, she was referred to our department because a chest computed tomography(CT)scan performed at the postoperative follow-up revealed a band-like consolidation adjacent to the pleura in the lingular segment, with enlarged ipsilateral hilar and mediastinal lymph nodes. CT-guided lung tumor biopsy was performed, and she was diagnosed with limited-stage small cell lung cancer. Chemotherapy with carboplatin, etoposide, and atezolizumab was initiated. Radiotherapy was not performed due to the overlap between the distribution of the lung tumor and the postoperative irradiation field of breast cancer. Due to the difference in the histopathological findings of the first and second primary tumors, and the location of the tumor in the postoperative irradiation field, the second cancer was considered to be radiation-induced cancer despite the short latency period.}, } @article {pmid36527274, year = {2022}, author = {Ansari, N and Nisar, MI and Khalid, F and Mehmood, U and Usmani, AA and Shaheen, F and Hotwani, A and Begum, K and Barkat, A and Yoshida, S and Manu, AA and Sazawal, S and Baqui, AH and Bahl, R and Jehan, F}, title = {Prevalence and risk factors of Severe Acute Respiratory Syndrome Coronavirus 2 infection in women and children in peri-urban communities in Pakistan: A prospective cohort study.}, journal = {Journal of global health}, volume = {12}, number = {}, pages = {05055}, pmid = {36527274}, issn = {2047-2986}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Child ; Female ; Humans ; Child, Preschool ; *COVID-19/epidemiology ; Seroepidemiologic Studies ; Prevalence ; Pakistan/epidemiology ; Prospective Studies ; Antibodies, Viral ; Risk Factors ; }, abstract = {BACKGROUND: Population-based seroepidemiological surveys provide accurate estimates of disease burden. We compare the COVID-19 prevalence estimates from two serial serological surveys and the associated risk factors among women and children in a peri-urban area of Karachi, Pakistan.

METHODS: The AMANHI-COVID-19 study enrolled women and children between November 2020 and March 2021. Blood samples were collected from March to June 2021 (baseline) and September to December 2021 (follow-up) to test for anti-SARS-CoV-2 antibodies using ROCHE Elecsys®. Participants were visited or called weekly during the study for recording symptoms of COVID-19. We report the proportion of participants with anti-SARS-CoV-2 antibodies and symptoms in each survey and describe infection risk factors using step-wise binomial regression analysis.

RESULTS: The adjusted seroprevalence among women was 45.3% (95% confidence interval (CI) = 42.6-47.9) and 82.3% (95% CI = 79.9-84.4) at baseline and follow-up survey, respectively. Among children, it was 18.4% (95% CI = 16.1-20.7) and 57.4% (95% CI = 54.3-60.3) at baseline and follow-up, respectively. Of the women who were previously seronegative, 404 (74.4%) tested positive at the follow-up survey, as did 365 (50.4%) previously seronegative children. There was a high proportion of asymptomatic infection. At baseline, being poorest and lacking access to safe drinking water lowered the risk of infection for both women (risk ratio (RR) = 0.8, 95% CI = 0.7-0.9 and RR = 1.2, 95% CI = 1.1-1.4, respectively) and children (RR = 0.7, 95% CI = 0.5-1.0 and RR = 1.4, 95% CI = 1.0-1.8, respectively). At the follow-up survey, the risk of infection was lower for underweight women and children (RR = 0.4, 95% CI = 0.3-0.7 and RR = 0.7, 95% CI = 0.5-0.8, respectively) and for women in the 30-39 years age group and children who were 24-36 months of age (RR = 0.6, 95% CI = 0.4-0.9 and RR = 0.7, 95% CI = 0.5-0.9, respectively). In both surveys, paternal employment was an important predictor of seropositivity among children (RR = 0.7, 95% CI = 0.6-0.9 and RR = 0.8, 95% CI = 0.7-1.0, respectively).

CONCLUSION: There was a high rate of seroconversion among women and children. Infection was generally mild. Parental education plays an important role in protection of children from COVID-19.}, } @article {pmid36525512, year = {2023}, author = {Wagner, R and Heni, M and Kantartzis, K and Sandforth, A and Machann, J and Schick, F and Peter, A and Fritsche, L and Szendrödi, J and Pfeiffer, AFH and Schürmann, A and Blüher, M and Hauner, H and Seissler, J and Bornstein, S and Roden, M and Stefan, N and Birkenfeld, AL and White, MF and Häring, HU and Fritsche, A}, title = {Lower Hepatic Fat Is Associated With Improved Insulin Secretion in a High-Risk Prediabetes Subphenotype During Lifestyle Intervention.}, journal = {Diabetes}, volume = {72}, number = {3}, pages = {362-366}, pmid = {36525512}, issn = {1939-327X}, support = {R01 AG067913/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Prediabetic State/metabolism ; Insulin Secretion ; Blood Glucose/metabolism ; Liver/metabolism ; *Insulin Resistance ; Life Style ; Insulin/metabolism ; }, abstract = {The objective of this work was to investigate whether impaired insulin secretion can be restored by lifestyle intervention in specific subphenotypes of prediabetes. We assigned 1,045 participants from the Prediabetes Lifestyle Intervention Study (PLIS) to six recently established prediabetes clusters. Insulin secretion was assessed by a C-peptide-based index derived from oral glucose tolerance tests and modeled from three time points during a 1-year intervention. We also analyzed the change of glycemia, insulin sensitivity, and liver fat. All prediabetes high-risk clusters (cluster 3, 5, and 6) had improved glycemic traits during the lifestyle intervention, whereas insulin secretion only increased in clusters 3 and 5 (P < 0.001); however, high liver fat in cluster 5 was associated with a failure to improve insulin secretion (Pinteraction < 0.001). Thus, interventions to reduce liver fat have the potential to improve insulin secretion in a defined subgroup of prediabetes.}, } @article {pmid36519609, year = {2023}, author = {Yuce, E and Karakullukcu, S and Bulbul, H and Alandag, C and Saygin, I and Kavgaci, H}, title = {The effect of the change in hemoglobin-albumin-lymphocyte-platelet scores occurring with neoadjuvant chemotherapy on clinical and pathological responses in breast cancer.}, journal = {Bratislavske lekarske listy}, volume = {124}, number = {1}, pages = {59-63}, doi = {10.4149/BLL_2023_009}, pmid = {36519609}, issn = {0006-9248}, mesh = {Female ; Humans ; Albumins/therapeutic use ; *Breast Neoplasms/drug therapy/pathology ; Hemoglobins ; Ki-67 Antigen ; Lymphocytes ; *Neoadjuvant Therapy ; Prognosis ; Retrospective Studies ; Adult ; Middle Aged ; }, abstract = {INTRODUCTION: Breast-cancer is a common-cause of death in women.(1) We investigated the effects of before/after-NACT on hemoglobin-albumin-lymphocyte-platelet (HALP) scores and of changes therein on clinical/pathological-responses.

MATERIALS AND METHODS: One-hundred-twenty-seven breast-cancer-patients receiving-NACT between December 2009 - January 2019 were investigated retrospectively.

RESULTS: The mean - age was 50.3±12.3 (min 27 - max 79), and 125 patients (98.4 %) were women. Fifty-four (42.5 %) were premenopausal and 71 (55.9 %) postmenopausal. Invasive-ductal-carcinoma was present in 111 patients (92.5 %). Eighty patients (70.2 %) were ≤ T2 and 34 (29.8 %) > T2. Lymph-node-status was positive in 99 patients (83.2 %) and negative in 20 (16.8 %). Ki-67 was ≤ 10 % in 22 (28.9 %), 11-20 % in 23 (30.3 %), and > 20 % in 31 (40.8 %). Complete clinical response was observed in 27 (21.3 %), partial-response in 76 (59.8 %), stable-disease in 21 (16.5 %), and progressive-disease in 3 patients (2.4 %). The objective-response-rate (ORR) was 103 (81.1 %). Pathological-complete-response (pCR) was observed in 24 patients (18.9 %). ORR was higher in Ki-67 > 20 % compared to ≤ 10 % and 10-20 % (90.3 % vs 59.0 % / 78.3 %, respectively, p: 0.027), but no difference occurred in pCR. Neutrophil-lymphocyte-ratio (NLR), platelet-lymphocyte-ratio (PLR), prognostic-nutritional-index (PNI), and HALP were measured before/after NACT. Associations with ORR and pCR were investigated via changes in these with NACT (excepting-PNI), but no-significant results emerged.

CONCLUSIONS: Higher ORR occurred post-NACT in patients with Ki-67 >20 %, while NLR, PLR, PNI, and HALP before/after-NACT and post-NACT-changes (excepting-PNI) had no-effect on ORR/pCR (Tab. 5, Ref. 21). Text in PDF www.elis.sk Keywords: breast cancer, objective response rate (ORR), pathological complete response (pCR), hemoglobin-albumin-lymphocyte-platelet (HALP) score.}, } @article {pmid36510982, year = {2022}, author = {Azmat, H and Faridi, J and Habib, HM and Bugti, UJ and Sheikh, AK and Riaz, SK}, title = {Correlation of B-cell lymphoma 2 immunoexpression in invasive carcinoma of breast, no special type with hormone receptor status, proliferation index, and molecular subtypes.}, journal = {Journal of cancer research and therapeutics}, volume = {18}, number = {Supplement}, pages = {S313-S319}, doi = {10.4103/jcrt.JCRT_735_20}, pmid = {36510982}, issn = {1998-4138}, mesh = {Humans ; Female ; Erb-b2 Receptor Tyrosine Kinases/genetics/metabolism ; Ki-67 Antigen/genetics/metabolism ; Receptors, Progesterone/metabolism ; Receptors, Estrogen/metabolism ; *Carcinoma/pathology ; *Breast Neoplasms/pathology ; Prognosis ; Hormones ; Cell Proliferation/genetics ; Proto-Oncogene Proteins c-bcl-2 ; Biomarkers, Tumor/metabolism ; }, abstract = {BACKGROUND: B-cell lymphoma 2 is involved in various cancers including breast carcinoma. Its expression in breast cancer has been associated with good prognostic factors such as hormone receptor expression, low Ki-67, low grade, and earlier stage. It is also considered to be an independent prognostic factor for luminal and triple-negative tumors.

OBJECTIVE: We aimed to determine the expression of B-cell lymphoma 2 (BCL2) in different molecular subtypes of invasive ductal carcinoma of breast and its association with prognostic indicators.

MATERIALS AND METHODS: Fifty samples of invasive carcinoma of breast, no special type (NST), were categorized into molecular subtypes according to immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki-67 and then evaluated for BCL2 expression. The expression of BCL2 was correlated with ER, PR, HER2, and Ki-67 and compared between luminal and nonluminal subtypes.

RESULTS: The BCL2 expression was seen in 68% of the cases with a significant association with ER, PR, and luminal subtypes. No significant association of BCL2 expression was seen with grade, HER2 and Ki-67 status of the tumor, or age group of the patients. BCL2 expression is significantly associated with ER, PR, and luminal subtypes in breast cancer.

CONCLUSION: BCL2 is a marker of good prognosis in invasive carcinoma of breast, NST.}, } @article {pmid36507575, year = {2023}, author = {McLamore, Q and Syropoulos, S and Leidner, B and Hirschberger, G and van Bezouw, MJ and Rovenpor, D and Paladino, MP and Baumert, A and Bilewicz, M and Bilgen, A and Chatard, A and Chekroun, P and Chinchilla, J and Choi, HS and Euh, H and Gomez, A and Kardos, P and Khoo, YH and Li, M and Légal, JB and Loughnan, S and Mari, S and Tan-Mansukhani, R and Muldoon, O and Noor, M and Petrović, N and Selvanathan, HP and Uluğ, ÖM and Wohl, MJ and Yeung, WLV and Young, K and Zein, RA}, title = {The distinct associations of ingroup attachment and glorification with responses to the coronavirus pandemic: Evidence from a multilevel investigation in 21 countries.}, journal = {The British journal of social psychology}, volume = {62}, number = {2}, pages = {992-1012}, doi = {10.1111/bjso.12614}, pmid = {36507575}, issn = {2044-8309}, mesh = {Humans ; *Pandemics/prevention & control ; *COVID-19 ; Communicable Disease Control ; Government ; Hygiene ; }, abstract = {While public health crises such as the coronavirus pandemic transcend national borders, practical efforts to combat them are often instantiated at the national level. Thus, national group identities may play key roles in shaping compliance with and support for preventative measures (e.g., hygiene and lockdowns). Using data from 25,159 participants across representative samples from 21 nations, we investigated how different modalities of ingroup identification (attachment and glorification) are linked with reactions to the coronavirus pandemic (compliance and support for lockdown restrictions). We also examined the extent to which the associations of attachment and glorification with responses to the coronavirus pandemic are mediated through trust in information about the coronavirus pandemic from scientific and government sources. Multilevel models suggested that attachment, but not glorification, was associated with increased trust in science and compliance with federal COVID-19 guidelines. However, while both attachment and glorification were associated with trust in government and support for lockdown restrictions, glorification was more strongly associated with trust in government information than attachment. These results suggest that both attachment and glorification can be useful for promoting public health, although glorification's role, while potentially stronger, is restricted to pathways through trust in government information.}, } @article {pmid36505983, year = {2022}, author = {Gupta, NK and Gaur, S and Pal, DK}, title = {Role of videourodynamics in the identification of causes of lower urinary tract symptoms and low uroflow in young men.}, journal = {Urology annals}, volume = {14}, number = {4}, pages = {332-335}, pmid = {36505983}, issn = {0974-7796}, abstract = {INTRODUCTION: The etiology of lower urinary tract symptoms (LUTS) is multifactorial with causes attributed either to the dysfunction of the bladder or its outlet. Although the etiologies are well studied in aged men, very limited research trials are available in young men with LUTS. Most of the time young men presenting with chronic irritative or obstructive symptoms are labeled with chronic prostatitis or prostatodynia and are treated empirically. In this study using videourodynamics, we prospectively investigated the etiologies of LUTS and low uroflow in young men.

MATERIALS AND METHODS: Fifty male patients, 18-50 years of age attending the urology outpatient department at a tertiary care center from January 2021 to December 2021 with symptoms suggestive of chronic LUTS and low uroflow (maximum urinary flow rate [Qmax] <15 ml/s at a voided volume >150 ml) were included in the study and underwent multichannel videourodynamic study (VUDS). Clinical characteristics and urodynamic results in different diagnostic groups were tabulated and analyzed. The P ≤ 0.05 was considered statistically significant.

RESULTS: Out of 50 enrolled patients, primary bladder neck obstruction was seen in 21 patients (42%), dysfunctional voiding in 14 (28%), impaired detrusor contractility (IDC) in 9 (18%), and benign prostatic obstruction (BPO) was noted in 6 patients (12%). The mean age and size of the prostate of patients with BPO were greater than those in the remaining groups and patients with IDC had lower Qmax and Pdet at Qmax than those in the remaining patients.

CONCLUSION: Chronic LUTS in young men has a variety of underlying etiologies and VUDS in this population is helpful in attaining an accurate diagnosis and thus may guide toward efficient management.}, } @article {pmid36504399, year = {2023}, author = {Fuchs, H and Padilla-Cabal, F and Oborn, BM and Georg, D}, title = {Commissioning a beam line for MR-guided particle therapy assisted by in silico methods.}, journal = {Medical physics}, volume = {50}, number = {2}, pages = {1019-1028}, doi = {10.1002/mp.16143}, pmid = {36504399}, issn = {2473-4209}, mesh = {*Protons ; *Proton Therapy/methods ; Computer Simulation ; Magnetic Resonance Imaging/methods ; Monte Carlo Method ; Water ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; }, abstract = {BACKGROUND: Radiation therapy is continuously moving towards more precise dose delivery. The combination of online MR imaging and particle therapy, for example, radiation therapy using protons or carbon ions, could enable the next level of precision in radiotherapy. In particle therapy, research towards a combination of MR and particle therapy is well underway, but still far from clinical systems. The combination of high magnetic fields with particle therapy delivery poses several challenges for treatment planning, treatment workflow, dose delivery, and dosimetry.

PURPOSE: To present a workflow for commissioning of a light ion beam line with an integrated dipole magnet to perform MR-guided particle therapy (MRgPT) research, producing not only basic beam data but also magnetic field maps for accurate dose calculation. Accurate dose calculation in magnetic field environments requires high-quality magnetic field maps to compensate for magnetic-field-dependent trajectory changes and dose perturbations.

METHODS: The research beam line at MedAustron was coupled with a resistive dipole magnet positioned at the isocenter. Beam data were measured for proton and carbon ions with and without an applied magnetic field of 1 T. Laterally integrated depth-dose curves (IDC) as well as beam profiles were measured in water while beam trajectories were measured in air. Based on manufacturer data, an in silico model of the magnet was created, allowing to extract high-quality 3D magnetic field data. An existing GATE/Geant4 Monte Carlo (MC) model of the beam line was extended with the generated magnetic field data and benchmarked against experimental data.

RESULTS: A 3D magnetic field volume covering fringe fields until 50 mT was found to be sufficient for an accurate beam trajectory modeling. The effect on particle range retraction was found to be 2.3 and 0.3 mm for protons and carbon ions, respectively. Measured lateral beam offsets in water agreed within 0.4 and -0.5 mm with MC simulations for protons and carbon ions, respectively. Experimentally determined in-air beam trajectories agreed within 0.4 mm in the homogeneous magnetic field area.

CONCLUSION: The presented approach based on in silico modeling and measurements allows to commission a beam line for MRgPT while providing benchmarking data for the magnetic field modeling, required for state-of-the art dose calculation methods.}, } @article {pmid36504339, year = {2022}, author = {Ambrose, JM and Veeraraghavan, VP and Vennila, R and Rupert, S and Sathyanesan, J and Meenakshisundaram, R and Selvaraj, S and Malayaperumal, S and Kullappan, M and Dorairaj, S and Gujarathi, JR and Gandhamaneni, SH and Surapaneni, KM}, title = {Comparison of mammosphere formation from stem-like cells of normal breast, malignant primary breast tumors, and MCF-7 cell line.}, journal = {Journal of the Egyptian National Cancer Institute}, volume = {34}, number = {1}, pages = {51}, pmid = {36504339}, issn = {2589-0409}, support = {F1-17.1/2013-14/MANF-2013-14-CHR-TAM-25064//University Grants Commission/ ; }, mesh = {Humans ; Female ; MCF-7 Cells ; *Breast ; *Breast Neoplasms ; Neoplastic Stem Cells ; }, abstract = {BACKGROUND: Mammosphere formation assay has become a versatile tool to quantify the activity of putative breast cancer stem cells in non-adherent in vitro cultures. However, optimizing the suspension culture system is crucial to establish mammosphere cultures from primary breast tumors.

METHODS: This study aimed at determining the self-renewal and sphere-forming potential of breast cancer stem-like cells derived from human primary invasive ductal carcinoma and normal breast tissue samples, and MCF-7 breast cancer cell line using an optimal suspension culture system. Mammosphere-forming efficiency of the mammospheres generated from the tissue samples and cell line were compared. We evaluated the expression of CD44[+]/CD24[-]/[low] and CD49f[+]/EpCAM[-]/[low] phenotypes in the stem-like cells by flow cytometry. CK-18, CK-19, α-SMA, and EpCAM marker expression was assessed using immunohistochemical staining.

RESULTS: Breast epithelial cells isolated from the three samples formed two-dimensional spheroids in suspension cultures. Interestingly, mammospheres formed from patient-derived primary breast tumors were enriched in breast cancer stem-like cells with the phenotype CD44[+]/CD24[-]/[low] and exhibited a relatively more number of large spheres when compared to the normal breast stem cells. MCF-7-derived SCs were more aggressive and resulted in the formation of a significantly higher number of spheroids. The expression of CK-18/CK-19 and α-SMA/EpCAM proteins was confirmed in breast cancer tissues.

CONCLUSIONS: Thus, the use of primary tumor specimens and breast cancer cell lines as suitable models for elucidating the breast cancer stem cell activity was validated using mammosphere culture system.}, } @article {pmid36501121, year = {2022}, author = {Leikin-Frenkel, A and Schnaider Beeri, M and Cooper, I}, title = {How Alpha Linolenic Acid May Sustain Blood-Brain Barrier Integrity and Boost Brain Resilience against Alzheimer's Disease.}, journal = {Nutrients}, volume = {14}, number = {23}, pages = {}, pmid = {36501121}, issn = {2072-6643}, mesh = {Humans ; *Alzheimer Disease/drug therapy ; Blood-Brain Barrier/metabolism ; alpha-Linolenic Acid/metabolism ; Brain/metabolism ; Apolipoprotein E4/genetics/metabolism ; }, abstract = {Cognitive decline, the primary clinical phenotype of Alzheimer's disease (AD), is currently attributed mainly to amyloid and tau protein deposits. However, a growing body of evidence is converging on brain lipids, and blood-brain barrier (BBB) dysfunction, as crucial players involved in AD development. The critical role of lipids metabolism in the brain and its vascular barrier, and its constant modifications particularly throughout AD development, warrants investigation of brain lipid metabolism as a high value therapeutic target. Yet, there is limited knowledge on the biochemical and structural roles of lipids in BBB functionality in AD. Within this framework, we hypothesize that the ApoE4 genotype, strongly linked to AD risk and progression, may be related to altered fatty acids composition in the BBB. Interestingly, alpha linolenic acid (ALA), the precursor of the majoritarian brain component docosahexaenoic acid (DHA), emerges as a potential novel brain savior, acting via BBB functional improvements, and this may be primarily relevant to ApoE4 carriers.}, } @article {pmid36482277, year = {2023}, author = {Udayasiri, RI and Luo, T and Gorringe, KL and Fox, SB}, title = {Identifying recurrences and metastasis after ductal carcinoma in situ (DCIS) of the breast.}, journal = {Histopathology}, volume = {82}, number = {1}, pages = {106-118}, pmid = {36482277}, issn = {1365-2559}, support = {GNT2002944//Cancer Australia/ ; IIRS-18-051//National Breast Cancer Foundation/ ; GNT1193630//National Health and Medical Research Council/ ; //Peter MacCallum Cancer Foundation/ ; }, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating ; Tumor Microenvironment ; }, abstract = {Ductal carcinoma in situ (DCIS) of the breast is a non-invasive tumour that has the potential to progress to invasive ductal carcinoma (IDC). Thus, it represents a treatment dilemma: alone it does not present a risk to life, however, left untreated it may progress to a life-threatening condition. Current clinico-pathological features cannot accurately predict which patients with DCIS have invasive potential, and therefore clinicians are unable to quantify the risk of progression for an individual patient. This leads to many women being over-treated, while others may not receive sufficient treatment to prevent invasive recurrence. A better understanding of the molecular features of DCIS, both tumour-intrinsic and the microenvironment, could offer the ability to better predict which women need aggressive treatment, and which can avoid therapies carrying significant side-effects and such as radiotherapy. In this review, we summarise the current knowledge of DCIS, and consider future research directions.}, } @article {pmid36481204, year = {2023}, author = {Chen, J and Yang, Y and Luo, B and Wen, Y and Chen, Q and Ma, R and Huang, Z and Zhu, H and Li, Y and Chen, Y and Qian, D}, title = {Further predictive value of lymphovascular invasion explored via supervised deep learning for lymph node metastases in breast cancer.}, journal = {Human pathology}, volume = {131}, number = {}, pages = {26-37}, doi = {10.1016/j.humpath.2022.11.007}, pmid = {36481204}, issn = {1532-8392}, mesh = {Humans ; Female ; Lymphatic Metastasis/pathology ; *Breast Neoplasms/pathology ; *Deep Learning ; Breast ; Prognosis ; *Lymphoma/pathology ; Lymph Nodes/pathology ; Retrospective Studies ; }, abstract = {Lymphovascular invasion, specifically lymph-blood vessel invasion (LBVI), is a risk factor for metastases in breast invasive ductal carcinoma (IDC) and is routinely screened using hematoxylin-eosin histopathological images. However, routine reports only describe whether LBVI is present and does not provide other potential prognostic information of LBVI. This study aims to evaluate the clinical significance of LBVI in 685 IDC cases and explore the added predictive value of LBVI on lymph node metastases (LNM) via supervised deep learning (DL), an expert-experience embedded knowledge transfer learning (EEKT) model in 40 LBVI-positive cases signed by the routine report. Multivariate logistic regression and propensity score matching analysis demonstrated that LBVI (OR 4.203, 95% CI 2.809-6.290, P < 0.001) was a significant risk factor for LNM. Then, the EEKT model trained on 5780 image patches automatically segmented LBVI with a patch-wise Dice similarity coefficient of 0.930 in the test set and output counts, location, and morphometric features of the LBVIs. Some morphometric features were beneficial for further stratification within the 40 LBVI-positive cases. The results showed that LBVI in cases with LNM had a higher short-to-long side ratio of the minimum rectangle (MR) (0.686 vs. 0.480, P = 0.001), LBVI-to-MR area ratio (0.774 vs. 0.702, P = 0.002), and solidity (0.983 vs. 0.934, P = 0.029) compared to LBVI in cases without LNM. The results highlight the potential of DL to assist pathologists in quantifying LBVI and, more importantly, in exploring added prognostic information from LBVI.}, } @article {pmid36479602, year = {2022}, author = {Lee, HJ and Kang, SW and Lee, JE and Jeong, WG and Lee, JS and Park, MH and Lim, HS}, title = {Malignant Apocrine Lesions of the Breast: Multimodality Imaging Findings and Biologic Features.}, journal = {Journal of breast cancer}, volume = {25}, number = {6}, pages = {513-521}, pmid = {36479602}, issn = {1738-6756}, abstract = {The apocrine morphology of the breast is observed in a broad pathological spectrum, ranging from benign cysts to invasive carcinomas. However, the number of clinical research investigating malignant apocrine lesions is limited. This study retrospectively reviewed the data of patients with malignant apocrine lesions admitted in a tertiary center between January 2004 and December 2021, based on the radiology-pathology correlation and the recent advances in their status to enhance the therapeutic implications of androgen receptor (AR). Among the 37 patients with lesions, 27 (73.0%) had triple-negative subtypes with predominant AR expression. The radiological features of malignant apocrine lesions did not differ from those of typical invasive ductal carcinoma or ductal carcinoma in situ. This study demonstrated that knowledge on the imaging features of malignant apocrine lesions and their histological basis could enhance the adoption of new targeted therapies in patients with this particular type of breast cancer.}, } @article {pmid36478904, year = {2023}, author = {Wu, D and Yu, J and Guo, L and Wei, X and Tian, Z and Duan, X}, title = {Analysis of primary synchronous breast invasive ductal carcinoma and lung adenocarcinoma with next-generation sequencing: A case report.}, journal = {Oncology letters}, volume = {25}, number = {1}, pages = {18}, pmid = {36478904}, issn = {1792-1082}, abstract = {Multiple primary cancers (MPCs) have an increasing incidence rate due to the detection of early stages of cancer and the development of effective therapeutic strategies. MPCs are less common compared with metachronous cancers. Therefore, distinguishing synchronous primary tumors from metastasis and developing an individualized treatment strategy can be challenging. In the present study, the case of a 70-year-old female who was referred to The First Hospital of Jilin University (Changchun, China) with an enlarged left cervical lymph node and no other clinical manifestations is reported. Radiography revealed distinct lesions in the left breast, left cervical lymph node and bilateral lungs. Subsequently, a biopsy was performed in all three lesions and then each specimen was subjected to immunohistochemistry, fluorescence in situ hybridization, amplification refractory mutation system-PCR and next-generation sequencing (NGS). Disease-related enrichment of lymph node mutant genes and Gene Ontology Biological Process enrichment of breast, as well as lung, mutant genes were performed using the Database for Annotation, Visualization and Integrated Discovery. Based on the molecular assessment, the patient was finally diagnosed with breast invasive ductal carcinoma, primary lung adenocarcinoma and cervical lymph node metastatic lung adenocarcinoma. Since primary synchronous breast and lung cancer (SBLC) is rare, a molecular assessment, particularly using NGS, could provide important information for both the diagnosis and treatment of SBLC.}, } @article {pmid36473870, year = {2022}, author = {Sandbank, J and Bataillon, G and Nudelman, A and Krasnitsky, I and Mikulinsky, R and Bien, L and Thibault, L and Albrecht Shach, A and Sebag, G and Clark, DP and Laifenfeld, D and Schnitt, SJ and Linhart, C and Vecsler, M and Vincent-Salomon, A}, title = {Validation and real-world clinical application of an artificial intelligence algorithm for breast cancer detection in biopsies.}, journal = {NPJ breast cancer}, volume = {8}, number = {1}, pages = {129}, pmid = {36473870}, issn = {2374-4677}, abstract = {Breast cancer is the most common malignant disease worldwide, with over 2.26 million new cases in 2020. Its diagnosis is determined by a histological review of breast biopsy specimens, which can be labor-intensive, subjective, and error-prone. Artificial Intelligence (AI)-based tools can support cancer detection and classification in breast biopsies ensuring rapid, accurate, and objective diagnosis. We present here the development, external clinical validation, and deployment in routine use of an AI-based quality control solution for breast biopsy review. The underlying AI algorithm is trained to identify 51 different types of clinical and morphological features, and it achieves very high accuracy in a large, multi-site validation study. Specifically, the area under the receiver operating characteristic curves (AUC) for the detection of invasive carcinoma and of ductal carcinoma in situ (DCIS) are 0.99 (specificity and sensitivity of 93.57 and 95.51%, respectively) and 0.98 (specificity and sensitivity of 93.79 and 93.20% respectively), respectively. The AI algorithm differentiates well between subtypes of invasive and different grades of in situ carcinomas with an AUC of 0.97 for invasive ductal carcinoma (IDC) vs. invasive lobular carcinoma (ILC) and AUC of 0.92 for DCIS high grade vs. low grade/atypical ductal hyperplasia, respectively, as well as accurately identifies stromal tumor-infiltrating lymphocytes (TILs) with an AUC of 0.965. Deployment of this AI solution as a real-time quality control solution in clinical routine leads to the identification of cancers initially missed by the reviewing pathologist, demonstrating both clinical utility and accuracy in real-world clinical application.}, } @article {pmid36472800, year = {2023}, author = {Chang, YS and Tu, SJ and Chen, HD and Hsu, MH and Chen, YC and Chao, DS and Chung, CC and Chou, YP and Chang, CM and Lee, YT and Yen, JC and Jeng, LB and Chang, JG}, title = {Integrated genomic analyses of hepatocellular carcinoma.}, journal = {Hepatology international}, volume = {17}, number = {1}, pages = {97-111}, pmid = {36472800}, issn = {1936-0541}, support = {DMR-111-135//China Medical University Hospital/ ; MOST-109-2320-B-039-052//Ministry of Science and Technology (TW)/ ; MOST-110-2321-B-039-002//Ministry of Science and Technology (TW)/ ; }, mesh = {Humans ; *Carcinoma, Hepatocellular/genetics/pathology ; *Liver Neoplasms/genetics/pathology ; Mutation ; Genomics ; Gene Expression Profiling ; Aldehyde Dehydrogenase, Mitochondrial/genetics ; }, abstract = {BACKGROUND: Genomic alterations play important roles in the development of cancer. We explored the impact of protein-coding genes and transcriptomic changes on clinical and molecular alterations in Taiwanese hepatocellular carcinoma (HCC) patients.

METHODS: We analyzed 147 whole-exome sequencing and 100 RNA sequencing datasets of HCC and compared them with The Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma cohort and develop a panel of 81 apoptosis-related genes for molecular classification.

RESULTS: TERT (50%), TP53 (25%), CTNNB1 (14%), ARID1A (12%), and KMT2C (11%) were the most common genetic alterations of cancer-related genes. ALDH2 and KMT2C mutated at much higher frequencies in our cohort than in TCGA, whereas CTNNB1 was found only in 14% of our Taiwanese patients. A high germline mutation rate of ALDH2 in the APOBEC mutational signature and herb drug-related aristolochic acid-associated signature was also observed. Groups A and B of HCC were identified when we used apoptosis-related genes for molecular classification. The latter group, which had poorer survival outcomes, had significantly more aDC, CD4+ Tem, macrophages M2, NKT, plasma cells, and Th1 cells, and less CD4+ memory T cells, CD8+ Tcm, cDC, iDC, and Th2 cells, as well as more inter-chromosome fusion genes. Metatranscriptomic analysis revealed 54 cases of HBV infection. Moreover, we found that the main target gene of HBV integration is ALB.

CONCLUSIONS: Unique genomic alterations were observed in our Taiwanese HCC patients. Molecular classification using apoptosis-related genes could lead to new therapeutic approaches for HCC.}, } @article {pmid36472710, year = {2023}, author = {Tohi, Y and Ishikawa, R and Kato, T and Miyakawa, J and Matsumoto, R and Mori, K and Mitsuzuka, K and Inokuchi, J and Matsumura, M and Shiga, K and Naito, H and Kohjimoto, Y and Kawamura, N and Inoue, M and Kinoshita, H and Hashimoto, K and Goto, K and Haba, R and Kakehi, Y and Sugimoto, M}, title = {Clinical outcomes of intraductal carcinoma or cribriform in radical prostatectomy specimens of men opting for active surveillance: data from the PRIAS-JAPAN study.}, journal = {International journal of clinical oncology}, volume = {28}, number = {2}, pages = {299-305}, pmid = {36472710}, issn = {1437-7772}, mesh = {Male ; Humans ; Prostate/pathology/surgery ; *Prostatic Neoplasms/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Prostate-Specific Antigen ; Magnetic Resonance Imaging ; Japan ; Prospective Studies ; Watchful Waiting ; Prostatectomy ; Neoplasm Grading ; }, abstract = {BACKGROUND: Among early stage prostate cancer patients, intraductal carcinoma of the prostate (IDC-P) and invasive cribriform are key prognostic factors; however, their presence and clinical significance following active surveillance (AS) are unknown. In men who opted for AS, we aimed to examine the presence and impact of IDC-P or cribriform, utilizing radical prostatectomy (RP) specimens.

METHODS: We re-reviewed 137 RP specimens available in the PRIAS-JAPAN prospective cohort between January 2010 and September 2020. We assessed the presence of IDC-P or cribriform, and compared the patients' characteristics and prostate-specific antigen (PSA) recurrence-free survival after RP between groups with and without IDC-P or cribriform. In addition, we examined the predictive factors associated with IDC-P or cribriform.

RESULTS: The percentage of patients with IDC-P or cribriform presence was 34.3% (47 patients). IDC-P or cribriform pattern was more abundant in the higher Gleason grade group in RP specimens (P < 0.001). The rates of PSA recurrence-free survival were significantly lower in the IDC-P or cribriform groups than in those without them (log rank P = 0.0211). There was no association between IDC-P or cribriform on RP with the Prostate Imaging-Reporting and Data System (PI-RADS) 4,5 score on magnetic resonance imaging (MRI) before RP even with adjustments for other covariates (OR, 1.43; 95% confidence interval [CI] 0.511-3.980, P = 0.497).

CONCLUSIONS: IDC-P or cribriform comprised approximately one-third of all RP specimens in men who underwent RP following AS, confirming their prognostic significance.}, } @article {pmid36472640, year = {2023}, author = {Maalmi, H and Strom, A and Petrera, A and Hauck, SM and Strassburger, K and Kuss, O and Zaharia, OP and Bönhof, GJ and Rathmann, W and Trenkamp, S and Burkart, V and Szendroedi, J and Ziegler, D and Roden, M and Herder, C and , }, title = {Serum neurofilament light chain: a novel biomarker for early diabetic sensorimotor polyneuropathy.}, journal = {Diabetologia}, volume = {66}, number = {3}, pages = {579-589}, pmid = {36472640}, issn = {1432-0428}, mesh = {Adult ; Humans ; Biomarkers ; Cross-Sectional Studies ; *Diabetes Mellitus, Type 2 ; *Diabetic Neuropathies/diagnosis ; Intermediate Filaments ; *Polyneuropathies/diagnosis/complications ; Neurofilament Proteins ; }, abstract = {AIMS/HYPOTHESIS: No established blood-based biomarker exists to monitor diabetic sensorimotor polyneuropathy (DSPN) and evaluate treatment response. The neurofilament light chain (NFL), a blood biomarker of neuroaxonal damage in several neurodegenerative diseases, represents a potential biomarker for DSPN. We hypothesised that higher serum NFL levels are associated with prevalent DSPN and nerve dysfunction in individuals recently diagnosed with diabetes.

METHODS: This cross-sectional study included 423 adults with type 1 and type 2 diabetes and known diabetes duration of less than 1 year from the prospective observational German Diabetes Study cohort. NFL was measured in serum samples of fasting participants in a multiplex approach using proximity extension assay technology. DSPN was assessed by neurological examination, nerve conduction studies and quantitative sensory testing. Associations of serum NFL with DSPN (defined according to the Toronto Consensus criteria) were estimated using Poisson regression, while multivariable linear and quantile regression models were used to assess associations with nerve function measures. In exploratory analyses, other biomarkers in the multiplex panel were also analysed similarly to NFL.

RESULTS: DSPN was found in 16% of the study sample. Serum NFL levels increased with age. After adjustment for age, sex, waist circumference, height, HbA1c, known diabetes duration, diabetes type, cholesterol, eGFR, hypertension, CVD, use of lipid-lowering drugs and use of non-steroidal anti-inflammatory drugs, higher serum NFL levels were associated with DSPN (RR [95% CI] per 1-normalised protein expression increase, 1.92 [1.50, 2.45], p<0.0001), slower motor (all p<0.0001) and sensory (all p≤0.03) nerve conduction velocities, lower sural sensory nerve action potential (p=0.0004) and higher thermal detection threshold to warm stimuli (p=0.023 and p=0.004 for hand and foot, respectively). There was no evidence for associations between other neurological biomarkers and DSPN or nerve function measures.

CONCLUSIONS/INTERPRETATION: Our findings in individuals recently diagnosed with diabetes provide new evidence associating higher serum NFL levels with DSPN and peripheral nerve dysfunction. The present study advocates NFL as a potential biomarker for DSPN.}, } @article {pmid36472055, year = {2022}, author = {Ortiz-Rey, JA and Bellas-Pereira, A and San Miguel-Fraile, P and Morellón-Baquera, R and Domínguez-Arístegui, P and González-Carreró Fojón, J}, title = {Intraductal Carcinoma of the Prostate without High-Grade Invasive Adenocarcinoma: Report of Two Cases and Review of the Literature.}, journal = {Archivos espanoles de urologia}, volume = {75}, number = {9}, pages = {738-745}, doi = {10.56434/j.arch.esp.urol.20227509.108}, pmid = {36472055}, issn = {0004-0614}, mesh = {Male ; Humans ; Aged ; Prostate/pathology ; *Prostatic Intraepithelial Neoplasia/genetics/pathology/surgery ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/surgery ; Prostatectomy ; Neoplasm Grading ; *Prostatic Neoplasms/pathology ; *Adenocarcinoma/surgery ; }, abstract = {OBJECTIVES: Intraductal carcinoma of the prostate (IDC-P) is usually associated with high grade, aggresive acinar adenocarcinomas. IDC-P is supposed to result from the spread of the adenocarcinoma along the prostatic ducts. IDC-P rarely occurs without invasive carcinoma or with a coexistent low grade adenocarcinoma.

MATERIAL AND METHODS: We report two patients, 66 and 75 year-old, who presented IDC-P and low-grade acinar adenocarcinoma foci in their radical prostatectomy surgical specimens.

RESULTS: Acinar adenocarcinomas were grade group 1, PTEN+, pT2. In the first case, the invasive adenocarcinoma was adjacent but nor intermingled with the IDC-P, and a discordance in the immunophenotype between them was outstanding (positivity for ERG in the acinar carcinoma being negative in the IDC-P). In the second case, the foci of adenocarcinoma were distant from the IDC-P. The first patient had not biochemical recurrence after a 34 month follow-up period.

CONCLUSIONS: This kind of cases supports the existence of an infrequent subtype of IDC-P that could be considered as an in situ neoplasia.}, } @article {pmid36469156, year = {2023}, author = {Gao, SL and Wang, DY and Wang, X and Zhang, B and Du, F and Ju, J and Yue, J and Kang, YK and Wang, X and Xu, BH and Yuan, P}, title = {Prognostic factors and adjuvant systemic therapy for patients with HER2-positive T1N0 breast cancer: evidence from a real-world study with long-term follow-up.}, journal = {Breast cancer research and treatment}, volume = {197}, number = {3}, pages = {569-582}, pmid = {36469156}, issn = {1573-7217}, support = {No. 81672634//National Natural Science Foundation of China/ ; No. 82172650//National Natural Science Foundation of China/ ; }, mesh = {Female ; Humans ; Adjuvants, Immunologic/therapeutic use ; Anthracyclines/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; *Breast Neoplasms/pathology ; Chemotherapy, Adjuvant/adverse effects ; Disease-Free Survival ; Follow-Up Studies ; Prognosis ; Erb-b2 Receptor Tyrosine Kinases ; Trastuzumab ; }, abstract = {PURPOSE: The optimal adjuvant systemic treatment and potential prognostic factors for patients with T1N0 HER2-positive breast cancer are still unclear. We conducted a real-world study in this relatively low-risk population to identify the clinical-pathological factors of potential prognostic value and to compare the efficacy of different adjuvant strategies.

METHODS: We included patients with HER2-positive T1N0 breast cancer of infiltrating ductal carcinoma (IDC) histology treated at the Cancer Hospital, Chinese Academy of Medical Sciences from April 2010 to April 2017. We performed Cox multivariate analysis to identify the potential prognostic factors for invasive disease-free survival (IDFS). We also compared survival outcomes of (1) patients treated with adjuvant chemotherapy alone, or chemotherapy plus trastuzumab, or observation; (2) patients receiving adjuvant anthracycline-based and non-anthracycline regimens, both combined with trastuzumab. Inverse probability of treatment weighting (IPTW) propensity score was used to reduce selection bias.

RESULTS: Overall, 692 consecutive patients were included, with a median follow-up of 78.0 months for IDFS. Age ≤ 40, T1c, ER + PR + , and adjuvant trastuzumab were identified as independent prognostic factors. For adjuvant treatment, compared with observation and chemotherapy alone, chemotherapy plus trastuzumab could significantly benefit patients (HR = 2.70, P = 0.034; HR = 3.95, P < 0.001). Meanwhile, compared with observation, chemotherapy alone did not significantly benefit patients (HR = 1.37, P = 0.424). For the comparison of anthracycline-based versus non-anthracycline regimens when combined with trastuzumab, patients in both groups had similar IDFS (HR = 1.74, P = 0.242).

CONCLUSIONS: HER2-positive T1N0 IDC patients could benefit from adjuvant chemotherapy plus trastuzumab. Age ≤ 40, T1c, ER + PR + , and adjuvant trastuzumab are independent prognostic factors for this population.}, } @article {pmid36468069, year = {2022}, author = {Amboni, M and Ricciardi, C and Adamo, S and Nicolai, E and Volzone, A and Erro, R and Cuoco, S and Cesarelli, G and Basso, L and D'Addio, G and Salvatore, M and Pace, L and Barone, P}, title = {Machine learning can predict mild cognitive impairment in Parkinson's disease.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {1010147}, pmid = {36468069}, issn = {1664-2295}, abstract = {BACKGROUND: Clinical markers of cognitive decline in Parkinson's disease (PD) encompass several mental non-motor symptoms such as hallucinations, apathy, anxiety, and depression. Furthermore, freezing of gait (FOG) and specific gait alterations have been associated with cognitive dysfunction in PD. Finally, although low cerebrospinal fluid levels of amyloid-β42 have been found to predict cognitive decline in PD, hitherto PET imaging of amyloid-β (Aβ) failed to consistently demonstrate the association between Aβ plaques deposition and mild cognitive impairment in PD (PD-MCI).

AIM: Finding significant features associated with PD-MCI through a machine learning approach.

PATIENTS AND METHODS: Patients were assessed with an extensive clinical and neuropsychological examination. Clinical evaluation included the assessment of mental non-motor symptoms and FOG using the specific items of the MDS-UPDRS I and II. Based on the neuropsychological examination, patients were classified as subjects without and with MCI (noPD-MCI, PD-MCI). All patients were evaluated using a motion analysis system. A subgroup of PD patients also underwent amyloid PET imaging. PD-MCI and noPD-MCI subjects were compared with a univariate statistical analysis on demographic data, clinical features, gait analysis variables, and amyloid PET data. Then, machine learning analysis was performed two times: Model 1 was implemented with age, clinical variables (hallucinations/psychosis, depression, anxiety, apathy, sleep problems, FOG), and gait features, while Model 2, including only the subgroup performing PET, was implemented with PET variables combined with the top five features of the former model.

RESULTS: Seventy-five PD patients were enrolled (33 PD-MCI and 42 noPD-MCI). PD-MCI vs. noPD-MCI resulted in older and showed worse gait patterns, mainly characterized by increased dynamic instability and reduced step length; when comparing amyloid PET data, the two groups did not differ. Regarding the machine learning analyses, evaluation metrics were satisfactory for Model 1 overcoming 80% for accuracy and specificity, whereas they were disappointing for Model 2.

CONCLUSIONS: This study demonstrates that machine learning implemented with specific clinical features and gait variables exhibits high accuracy in predicting PD-MCI, whereas amyloid PET imaging is not able to increase prediction. Additionally, our results prompt that a data mining approach on certain gait parameters might represent a reliable surrogate biomarker of PD-MCI.}, } @article {pmid36465358, year = {2022}, author = {Li, ZX and Chen, JX and Zheng, ZJ and Cai, WJ and Yang, XB and Huang, YY and Gong, Y and Xu, F and Chen, YS and Lin, L}, title = {TGF-β1 promotes human breast cancer angiogenesis and malignant behavior by regulating endothelial-mesenchymal transition.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {1051148}, pmid = {36465358}, issn = {2234-943X}, abstract = {BACKGROUND: Endothelial-mesenchymal transition (EndMT) is an important process of angiogenesis, which plays a significant role in in tumor invasion and metastasis, while its regulatory mechanisms in breast cancer remain to be fully elucidated. We previously demonstrated that tumor-associated macrophages (TAMs) can induce EndMT in endothelial cells by secreting CCL18 through the activation of the TGF-β and Notch signaling pathways in breast cancer. This study was designed to study the role of EndMT in breast cancer angiogenesis and progression in order to explore the underlying mechanism.

METHODS: Immunohistochemistry (IHC) was used to evaluate the expression of microvascular density (MVD) and EndMT markers in breast cancer. TGF-β1 was used to induce EndMT models of differentiated-endothelial breast cancer stem-like cells (BCSLCs). In vitro cell migration, proliferation and matrigel tube-formation assays, as well as in vivo nude mouse tumor-bearing model and nude mouse dorsal skinfold window chamber (DSWC) model, were utilized to investigate the effects in order to explore the mechanism of EndMT induced by TGF-β1 on breast cancer progression.

RESULTS: In this study, we demonstrated that the EndMT markers were positively associated with MVD indicating unfavorable prognosis of invasive ductal carcinoma (IDC) patients. Functionally, TGF-β1 promoted migration, proliferation and angiogenesis of differentiated-endothelial BCSLCs by inducing EndMT in vitro and promoted tumor growth and angiogenesis in vivo. Mechanically, we revealed TGF-β1 induced EndMT by activation of TGF-β and Notch signaling pathways with increase of p-Smad2/3 and Notch1 expression. Moreover, we found Snail and Slug were key factors of TGF-β and Notch signaling pathways.

CONCLUSION: Our findings elucidated the mechanism of TGF-β1 in the promotion of angiogenesis and progression by EndMT in breast cancer.}, } @article {pmid36459596, year = {2024}, author = {Birnbaum, GE and Bachar, T and Levy, GF and Zholtack, K and Reis, HT}, title = {Put Me in Your Shoes: Does Perspective-Taking Inoculate Against the Appeal of Alternative Partners?.}, journal = {Journal of sex research}, volume = {61}, number = {6}, pages = {936-945}, doi = {10.1080/00224499.2022.2150998}, pmid = {36459596}, issn = {1559-8519}, mesh = {Humans ; Male ; Female ; Adult ; *Sexual Partners/psychology ; Young Adult ; *Sexual Behavior/psychology ; *Interpersonal Relations ; }, abstract = {People commit to monogamous relationships with the intent of maintaining sexual exclusivity but often fail to do so. Existing research has focused on individual and relationship characteristics that render relationships more vulnerable to infidelity, paying less attention to strategies that decrease the likelihood of straying. Three experiments investigated the impact of one strategy that might encourage people to enact relationship-protective responses toward alternative partners, perspective-taking. In all studies, participants either adopted the perspective of their partner or not and then evaluated, encountered, or thought about attractive strangers, in Studies 1-3, respectively. Participants' pro-relationship orientation and reactions during these experiences (interest in alternative and current partners, commitment to current relationships, and fantasmatic themes) were recorded. Results showed that perspective-taking decreased sexual and romantic interest in alternatives, while increasing commitment and desire for current partners. These findings suggest that partner perspective-taking discourages engagement in behaviors that may hurt partners and damage the relationship with them.}, } @article {pmid36452681, year = {2022}, author = {Devi, A and Narwal, A and Kamboj, M and Gupta, M and Pandiar, D and Gupta, A}, title = {Low Grade Intraductal Carcinoma of Palate: An Extremely Rare Entity with Review of Literature.}, journal = {Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India}, volume = {74}, number = {Suppl 2}, pages = {2222-2227}, pmid = {36452681}, issn = {2231-3796}, abstract = {Low-grade intraductal carcinoma (LG-IDC) is the new World Health Organization designation for tumors previously called "low-grade cribriform cystadenocarcinoma" and "low-grade salivary duct carcinoma". LG-IDC is a rare low grade malignant salivary gland neoplasm. A 56-year old woman presented with a painless swelling on the right posterior part of palate of 2 months duration. Radiographic examination revealed heterogenously enhancing soft tissue mass on right side of palate. A provisional diagnosis of pleomorphic adenoma was executed and local excision was done. The tumor had a typical feature of intraductal growth pattern composed of low grade ductal epithelial cells with cribriform and micropapillary patterns forming true "Roman bridges". Immunohistochemically myoepithelial cells displayed p63 around all tumor islands. The case was diagnosed as LG-IDC. LG-IDC is an extremely rare entity and awareness of this entity is important to avoid erroneous diagnosis and inappropriate treatment.}, } @article {pmid36451999, year = {2022}, author = {Göker, M and Denys, H and van de Vijver, K and Braems, G}, title = {Genomic assays for lobular breast carcinoma.}, journal = {Journal of clinical and translational research}, volume = {8}, number = {6}, pages = {523-531}, pmid = {36451999}, issn = {2424-810X}, abstract = {BACKGROUND: One of the current challenges in breast cancer is the appropriate treatment of invasive lobular breast cancer (ILC) and defining the high-risk group within ILC. The biological character of ILC typically translates to a good prognosis, however, several studies have indicated that the long-term prognosis is worse than for patients diagnosed with the more commonly invasive ductal carcinoma. Many genomic tests are now available to determine whether those patients are at high risk (HR) and enable tailored treatment. Unfortunately, most of the studies in which these genomic tests have been evaluated entail retrospective analysis of a prospective trial.

AIM: This review focuses on the validation of the available genomic assays based on trials performed in ILC patients, where in some instances, the various subtypes of ILC (classical, pleomorphic, and non-classic type) were taken into account.

RESULTS: Using Oncotype DX in retrospective studies, only 1.3%-8% of ILC tumors were categorized as HR tumors. For MammaPrint, 24% of patients were classified as HR, which was associated with poor outcome. In a recent sub-analysis of the MINDACT study comprising 487 ILC patients, 16.2% were high genomic risk. EndoPredict, Prosigna Breast Cancer Prognostic Gene Signature Assay, and the Breast Cancer Index have been validated in patients receiving only endocrine treatment.

CONCLUSION: Although ILC accounts for the second most common breast cancer subtype in women, none of these tests encompass tumor morphology in their algorithms. Prospective studies on ILC with genomic assays are warranted given the various subtypes of and treatment options for this underestimated, but frequently occurring cancer.

RELEVANCE FOR PATIENTS: Genomic assays can be employed in ILC patients to predict the risk of recurrence and identify those patients who might benefit from chemotherapy in addition to their standard treatment regimen.}, } @article {pmid36447634, year = {2023}, author = {Imai, J and Hanamura, T and Kawanishi, A and Ueda, T and Mishima, Y and Ito, A and Shirataki, Y and Morimachi, M and Kodama, T and Sato, H and Kaneko, M and Sano, M and Teramura, E and Monma, M and Tsuda, S and Tsuruya, K and Mizukami, H and Arase, Y and Fujisawa, M and Miyahara, S and Nakamura, N and Suzuki, T and Matsushima, M and Suzuki, H and Takashimizu, S and Kagawa, T and Nishizaki, Y}, title = {A case of breast cancer with extensive colon metastasis.}, journal = {DEN open}, volume = {3}, number = {1}, pages = {e189}, pmid = {36447634}, issn = {2692-4609}, abstract = {Breast cancer is one of the most common malignancies in women worldwide. Although most breast cancers are curable, in cases of metastasis, many are often found in the lungs, bones, liver, and central nervous system; however, metastasis to the gastrointestinal tract is rare. Invasive lobular carcinoma, which represents only 5%-10% of breast cancers, has a higher risk of metastasis to the gastrointestinal tract than invasive ductal carcinoma. Here, we report a rare case of gastrointestinal metastasis of invasive lobular carcinoma that spread extensively to the colonic mucosa. Given the improved survival rates of breast cancer patients with current treatments, many rarer metastatic diseases, including gastrointestinal metastases, are likely to be increased in the future.}, } @article {pmid36444584, year = {2022}, author = {Shahi, V and Agarwal, P and Qayoom, S and Kumar, V and Tewari, S and Raghuvanshi, S and Singh, US and Goel, MM}, title = {Detection of Epstein Barr Nuclear Antigen-1 (EBNA-1), Early Antigen 1F, 2R (EA-1F, EA- 2R) along with Epstein-Barr virus Latent Membrane Protein 1 (LMP1) in Breast Cancer of Northern India: An Interim Analysis.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {23}, number = {11}, pages = {3717-3723}, pmid = {36444584}, issn = {2476-762X}, mesh = {Humans ; Female ; *Breast Neoplasms ; Herpesvirus 4, Human/genetics ; *Epstein-Barr Virus Infections/complications ; Reproducibility of Results ; Epstein-Barr Virus Nuclear Antigens ; India/epidemiology ; *Carcinoma, Intraductal, Noninfiltrating ; *Carcinoma, Ductal ; Viral Matrix Proteins ; }, abstract = {INTRODUCTION: Worldwide, breast cancer (BC) is a prominent cause of death, with a disproportionately high incidence in developed countries. Epstein-Barr virus (EBV) infection has been reported in up to 90% of the world's population. Although the exact link of EBV infection and breast carcinoma is not yet determined. The present study was carried out to assess the pathological correlation of EBV infection and BC in women from Northern India.

METHODOLOGY: In this prospective observational study, 130 patients with histologically proven breast carcinoma were included. After detailed histology, the paraffin block with infiltrative tumor was selected for molecular analysis and further immunohistochemistry (IHC)- EBV PCR and Epstein-Barr virus latent membrane protein 1 (LMP1) IHC.

RESULTS: Most of the patients were diagnosed with Infiltrating Ductal Carcinoma not otherwise specified (IDC-NOS), followed by Infiltrating Ductal Carcinoma + Ductal Carcinoma in situ (IDC + DCIS). The total of 25 tissues of breast carcinoma had positive EBV PCR results (19.23%). The co-relation between the molecular and immunohistochemical results was significant in 11/25 cases that showed immunoexpression for LMP1 by IHC. Sensitivity of 44% and specificity of 100% were observed for LMP1 IHC, having a PPV value of 100% and an NPV of 88%. No significant correlation was observed between age, tumor subtype, grade, stage with respect to EBV infection; however, there was a significant association with nodal metastasis with extra nodal extension in tumors that had EBV infection.

CONCLUSION: The present study establishes an association between LMP1 and patients with EBV positive breast cancer. The authors suggest that additional multicentric studies be conducted to strengthen the reliability and generalizability of the observations of the current study.}, } @article {pmid36443093, year = {2022}, author = {Burkoň, P and Selingerová, I and Slavik, M and Holánek, M and Vrzal, M and Kazda, T and Hůlková, V and Blažková, M and Poláchová, K and Šlampa, P}, title = {Adjuvant accelerated partial-breast irradiation of early-stage breast cancer using stereotactic approach - methodology, technical challenges and early results of prospective randomized trial.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {35}, number = {5}, pages = {379-391}, doi = {10.48095/ccko2022379}, pmid = {36443093}, issn = {1802-5307}, mesh = {Humans ; Aged ; Middle Aged ; Female ; *Breast Neoplasms/radiotherapy/surgery ; Prospective Studies ; Mastectomy ; Adjuvants, Immunologic ; Radiotherapy, Adjuvant ; }, abstract = {BACKGROUND: The adjuvant radiotherapy (RT) of the early-stage breast cancer patients as local treatment aims to eliminate potential microscopic residual disease in the surgery bed or satellites in its neighborhood. Based on published studies, accelerated partial breast irradiation (APBI) is recommended for strictly selected patients. The aim of this single-institution prospective randomized study was to compare the targeted APBI delivered by stereotactic approach with the currently more commonly used accelerated whole breast irradiation with the boost to the tumor bed in terms of feasibility, safety, tolerance, and cosmetic effects.

MATERIALS AND METHODS: Early-stage breast cancer patients after partial mastectomy were screened for eligibility. The inclusion criteria were age > 50 years, non-lobular carcinoma histology, size 2cm, negative margins 2mm, L0, ER-positive, BRCA negative. Enrolled patients were equally randomized into two arms according to radiotherapeutic regiment - external APBI (5× 6 Gy) and accelerated whole breast irradiation with the boost (15× 2,67 Gy + 5× 2 Gy). These preliminary results of the ongoing study evaluated the first 57 from 84 planned patients.

RESULTS: The median age was 65 years. The tumors were of grade 1 in 60 % of patients, the median size of 9mm and 70 % were classified as invasive ductal carcinoma. Statistical significant differences between the groups in baseline characteristics were not observed. A total of 29 patients was enrolled in the APBI group by the end of 2020. All enrolled patients were evaluated one month after RT. A total of 40 (70,2 %) a 33 (58 %) had examinations 3 and 6 months after RT, respectively. Toxicity evaluation showed statistically significantly fewer acute adverse events in the APBI group in terms of skin erythema, desquamation, skin tenderness, dryness, edema, pigmentation, breast pain and fatigue. Late toxicity evaluated in 3 and 6 months after RT was significantly higher in the control group. The cosmetic effect (independently evaluated by a physician, nurse and patient) was more favorable to the APBI group.

CONCLUSION: The technique using the principles of targeted radiotherapy turned out to be a less toxic and easier feasible approach for adjuvant radiation of early-stage breast cancer patients. Consequently, the presented study increases the level of evidence for RT-indicated patients to the establishment of external APBI into daily clinical practice.}, } @article {pmid36441068, year = {2023}, author = {Pahouja, G and Patel, HD and Desai, S and Rac, G and Cheng, T and Okabe, Y and Gorbonos, A and Quek, ML and Flanigan, RC and Picken, MM and Gupta, GN}, title = {The rising incidence of ductal adenocarcinoma and intraductal carcinoma of the prostate: Diagnostic accuracy of biopsy, MRI-visibility, and outcomes.}, journal = {Urologic oncology}, volume = {41}, number = {1}, pages = {48.e11-48.e18}, doi = {10.1016/j.urolonc.2022.09.025}, pmid = {36441068}, issn = {1873-2496}, mesh = {Male ; Humans ; Prostate/diagnostic imaging/surgery ; *Carcinoma, Intraductal, Noninfiltrating ; Magnetic Resonance Imaging ; Incidence ; Retrospective Studies ; *Prostatic Neoplasms/diagnostic imaging/surgery ; }, abstract = {INTRODUCTION: Ductal adenocarcinoma (DA) and intraductal carcinoma (IDC) of the prostate are associated with higher stage disease at radical prostatectomy (RP). We evaluated diagnostic accuracy of biopsy, MRI-visibility, and outcomes for patients undergoing RP with DA/IDC histology compared to pure acinar adenocarcinoma (AA) of the prostate.

MATERIALS AND METHODS: A retrospective cohort study of men receiving RP between 2014 and 2021 revealing AA, DA, or IDC on final pathology was conducted. Multivariable logistic regression and Cox proportional hazards regression models were employed.

RESULTS: A total of 609 patients were included with 103 found to have DA/IDC. Patients with DA/IDC were older and had higher PSA, biopsy grade group (GG), RP GG, and other pathologic findings (extraprostatic extension, lymphovascular invasion, perineural invasion, pN stage) compared to AA patients (all P < 0.05). On multivariable analysis, higher age, RP GG, and pT3a were associated with DA/IDC on RP (all P < 0.05). Sensitivity and specificity of biopsy compared to RP for diagnosis of DA/IDC was 29.1% (16.7% DA, 27.8% IDC) and 96.6% (99.3% DA, 96.6% IDC), respectively. In a subset of 281 men receiving MRI, PI-RADS distribution was similar for patients with DA/IDC vs. AA (90.7% vs. 80.7% with PI-RADS 4-5 lesions, P = 0.23) with slightly higher biopsy sensitivity (41.9%). DA/IDC was associated with worse BCR (HR = 1.77, P = 0.02) but not biopsy DA/IDC (P = 0.90).

CONCLUSIONS: Sensitivity of prostate biopsy was low for detection of DA/IDC histology at RP. Patients with DA/IDC histology had unfavorable pathologic features at RP and worse BCR. Of patients with DA/IDC at RP, 90.7% were categorized as PI-RADS 4 to 5 on preoperative MRI.}, } @article {pmid36434575, year = {2022}, author = {Gupta, RB and Dang, H and Albreiki, D and Dollin, ML and Weston, B and Gottlieb, CC}, title = {Acute annular outer retinopathy preceded by invasive ductal breast carcinoma: a case report.}, journal = {BMC ophthalmology}, volume = {22}, number = {1}, pages = {452}, pmid = {36434575}, issn = {1471-2415}, mesh = {Humans ; Female ; Fluorescein Angiography/methods ; *Retinal Diseases/complications/diagnosis ; Tomography, Optical Coherence/methods ; Vision Disorders ; Acute Disease ; Atrophy ; *Breast Neoplasms/complications/diagnosis ; }, abstract = {BACKGROUND: Acute annular outer retinopathy (AAOR) is an uncommon disease. To date, there are few documented cases in the literature. Our case report is the first to describe a case of acute annular outer retinopathy in a patient with invasive ductal breast carcinoma.

CASE PRESENTATION: The patient presented with photopsias and visual loss approximately 3 weeks prior to a diagnosis of invasive ductal breast carcinoma. We have documented the outer annular white ring seen in the acute phase of this disease and correlate it anatomically with Spectral-domain optical coherence tomography (SD-OCT) imaging. We identified RPE atrophy with nodular hyperreflectivity and loss of ellipsoid layer within the white annular ring with corresponding visual field loss. Fundus autofluorescence correlated with structural alterations seen on SD-OCT and showed both presumed active hyperautofluorescent zones with patchy hypoautofluorescent zones of atrophy and a classic annular hyperautofluorescent border. This case provides additional information about the natural history of this rare entity and its prognosis and varied presentation.

CONCLUSIONS: The authors report a single case of acute annular outer retinopathy in a patient with invasive ductal breast carcinoma with the corresponding SD-OCT, fundus autofluorescence and visual field findings, during the acute phase of the disease. These findings provide new insight into the characteristic features, etiology and progression of this rare disease.}, } @article {pmid36433714, year = {2023}, author = {Xie, T and Jiang, T and Zhao, Q and Fu, C and Nickel, MD and Peng, W and Gu, Y}, title = {Model-Free and Model-based Parameters Derived From CAIPIRINHA-Dixon-TWIST-VIBE DCE-MRI: Associations With Prognostic Factors and Molecular Subtypes of Invasive Ductal Breast Cancer.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {58}, number = {1}, pages = {81-92}, doi = {10.1002/jmri.28533}, pmid = {36433714}, issn = {1522-2586}, support = {SHDC2020CR2008A//Clinical Research Plan of Shanghai Hospital Development Center/ ; 61731008//National Natural Science Foundation of China/ ; 82071878//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Middle Aged ; Female ; *Breast Neoplasms/diagnostic imaging/pathology ; Prognosis ; Prospective Studies ; Contrast Media ; Magnetic Resonance Imaging ; Retrospective Studies ; }, abstract = {BACKGROUND: CAIPIRINHA-Dixon-TWIST-VIBE (CDTV) dynamic contrast-enhanced MRI (DCE-MRI) can be used to characterize breast cancer. However, the influence of the clinicopathologic factors and molecular subtypes of invasive breast carcinoma (IDC) on the model-free and model-based parameters has not been investigated.

PURPOSE: To compare model-free and model-based parameters of CDTV DCE-MRI with both clinicopathologic factors and molecular subtypes of IDC.

STUDY TYPE: Prospective.

POPULATION: A total of 152 patients (mean age, 52 years) with IDC including 42 luminal A, 64 luminal B, 22 human epidermal growth factor receptor-2 (HER2) positive, and 24 triple-negative subtypes.

FIELD STRENGTH/SEQUENCE: A 3 T; turbo-FLASH, Dixon VIBE, and CDTV.

ASSESSMENT: Model-free parameters (initial enhancement rate [IER] and maximum slope [MS]) were estimated from the time-intensity curve. The mean, minimum, maximum, and range between the minimum and maximum values of inline model-based parameters (K[trans] , kep , and ve) were measured to assess intratumoral heterogeneity of IDC lesions.

STATISTICAL TESTS: Student's t tests, Mann-Whitney U tests, Kruskal-Wallis tests, post hoc Steel-Dwass tests, and receiver operating characteristic (ROC) curves. P < 0.05 was considered significant.

RESULTS: No significant differences in IER and MS values were seen among the clinicopathologic factors and molecular subtypes (Bonferroni-corrected P = 0.011-0.862, P = 0.145-0.601, respectively). The minimum kep values in HER2-positive IDC were significantly lower than those in HER2-negative IDC. The mean and range kep values were independent predictors for distinguishing the high (grade 3) and low (grade 1 or 2) nuclear grade groups according to multivariable analyses. The post hoc test showed that the kep minimum and kep range values were significantly different between luminal A and HER2-positive tumor subtypes, yielding an area-under-the-curve of 0.820.

DATA CONCLUSION: Compared with the model-free parameters, inline kep related model-based parameters on CDTV DCE-MRI can be applied as a feasible tool to differentiate luminal A from HER2-positive breast cancers.

EVIDENCE LEVEL: 2.

TECHNICAL EFFICACY: Stage 2.}, } @article {pmid36431454, year = {2022}, author = {Cansever Mutlu, E and Kaya, M and Küçük, I and Ben-Nissan, B and Stamboulis, A}, title = {Exosome Structures Supported by Machine Learning Can Be Used as a Promising Diagnostic Tool.}, journal = {Materials (Basel, Switzerland)}, volume = {15}, number = {22}, pages = {}, pmid = {36431454}, issn = {1996-1944}, support = {University of Birmingham, College of Engineering and Physical Science//University of Birmingham, College of Engineering and Physical Science/ ; }, abstract = {Principal component analysis (PCA) as a machine-learning technique could serve in disease diagnosis and prognosis by evaluating the dynamic morphological features of exosomes via Cryo-TEM-imaging. This hypothesis was investigated after the crude isolation of similarly featured exosomes derived from the extracellular vehicles (EVs) of immature dendritic cells (IDCs) JAWSII. It is possible to identify functional molecular groups by FTIR, but the unique physical and morphological characteristics of exosomes can only be revealed by specialized imaging techniques such as cryo-TEM. On the other hand, PCA has the ability to examine the morphological features of each of these IDC-derived exosomes by considering software parameters such as various membrane projections and differences in Gaussians, Hessian, hue, and class to assess the 3D orientation, shape, size, and brightness of the isolated IDC-derived exosome structures. In addition, Brownian motions from nanoparticle tracking analysis of EV IDC-derived exosomes were also compared with EV IDC-derived exosome images collected by scanning electron microscopy and confocal microscopy. Sodium-Dodecyl-Sulphate-Polyacrylamide-Gel-Electrophoresis (SDS-PAGE) was performed to separate the protein content of the crude isolates showing that no considerable protein contamination occurred during the crude isolation technique of IDC-derived-exosomes. This is an important finding because no additional purification of these exosomes is required, making PCA analysis both valuable and novel.}, } @article {pmid36430783, year = {2022}, author = {Swindell, WR and Bojanowski, K and Chaudhuri, RK}, title = {Isosorbide Fatty Acid Diesters Have Synergistic Anti-Inflammatory Effects in Cytokine-Induced Tissue Culture Models of Atopic Dermatitis.}, journal = {International journal of molecular sciences}, volume = {23}, number = {22}, pages = {}, pmid = {36430783}, issn = {1422-0067}, support = {N/A//Sytheon/ ; }, mesh = {Humans ; *Dermatitis, Atopic/drug therapy ; Cytokines ; Fatty Acids ; Isosorbide ; Tumor Necrosis Factor-alpha/pharmacology ; Plant Oils ; Oleic Acid ; }, abstract = {Atopic dermatitis (AD) is a chronic disease in which epidermal barrier disruption triggers Th2-mediated eruption of eczematous lesions. Topical emollients are a cornerstone of chronic management. This study evaluated efficacy of two plant-derived oil derivatives, isosorbide di-(linoleate/oleate) (IDL) and isosorbide dicaprylate (IDC), using AD-like tissue culture models. Treatment of reconstituted human epidermis with cytokine cocktail (IL-4 + IL-13 + TNF-α + IL-31) compromised the epidermal barrier, but this was prevented by co-treatment with IDL and IDC. Cytokine stimulation also dysregulated expression of keratinocyte (KC) differentiation genes whereas treatment with IDC or IDL + IDC up-regulated genes associated with early (but not late) KC differentiation. Although neither IDL nor IDC inhibited Th2 cytokine responses, both compounds repressed TNF-α-induced genes and IDL + IDC led to synergistic down-regulation of inflammatory (IL1B, ITGA5) and neurogenic pruritus (TRPA1) mediators. Treatment of cytokine-stimulated skin explants with IDC decreased lactate dehydrogenase (LDH) secretion by more than 50% (more than observed with cyclosporine) and in vitro LDH activity was inhibited by IDL and IDC. These results demonstrate anti-inflammatory mechanisms of isosorbide fatty acid diesters in AD-like skin models. Our findings highlight the multifunctional potential of plant oil derivatives as topical ingredients and support studies of IDL and IDC as therapeutic candidates.}, } @article {pmid36428573, year = {2022}, author = {Gulde, S and Foscarini, A and April-Monn, SL and Genio, E and Marangelo, A and Satam, S and Helbling, D and Falconi, M and Toledo, RA and Schrader, J and Perren, A and Marinoni, I and Pellegata, NS}, title = {Combined Targeting of Pathogenetic Mechanisms in Pancreatic Neuroendocrine Tumors Elicits Synergistic Antitumor Effects.}, journal = {Cancers}, volume = {14}, number = {22}, pages = {}, pmid = {36428573}, issn = {2072-6694}, support = {314061271-TRR 205-B11//Deutsche Forschungsgemeinschaft/ ; 70113629//German Cancer Aid/ ; 2017.073.2 and 2017.012.1//Wilhelm Sander Stiftung/ ; KFS-4227-08-2017//Swiss Cancer Research Foundation/ ; }, abstract = {Pancreatic neuroendocrine neoplasms (PanNENs) are the second most common malignancy of the pancreas. Surgery remains the only curative treatment for localized disease. For patients with inoperable advanced or metastatic disease, few targeted therapies are available, but their efficacy is unpredictable and variable. Exploiting prior knowledge on pathogenetic processes involved in PanNEN tumorigenesis, we tested buparlisib (PI3K inhibitor) and ribociclib (CDK4/6 inhibitor), as single agents or in combination, in different preclinical models. First, we used cell lines representative of well-differentiated (INS-1E, NT-3) and poorly differentiated (BON-1) PanNENs. The combination of buparlisib with ribociclib reduced the proliferation of 2D and 3D spheroid cultures more potently than the individual drugs. Buparlisib, but not ribociclib, induced apoptosis. The anti-proliferative activity of the drugs correlated with downstream target inhibition at mRNA and protein levels. We then tested the drugs on primary islet microtissues from a genetic PanNET animal model (Men1-defective mice) and from wild-type mice: the drug combination was effective against the former without altering islet cell physiology. Finally, we treated PanNET patient-derived islet-like 3D tumoroids: the combination of buparlisib with ribociclib was effective in three out of four samples. Combined targeting of PI3K and CDK4/6 is a promising strategy for PanNENs spanning various molecular and histo-pathological features.}, } @article {pmid36420892, year = {2023}, author = {Naito, Y and Kato, M and Kawanishi, H and Yamamoto, A and Sakamoto, F and Hirabayashi, H and Kobayashi, M and Matsukawa, Y and Kimura, T and Araki, H and Nishikimi, T and Kondo, A and Yoshino, Y and Hashimoto, Y and Nakano, Y and Tsuzuki, T}, title = {Clinical utility of intraductal carcinoma of the prostate in treatment selection for metastatic hormone-sensitive prostate cancer.}, journal = {The Prostate}, volume = {83}, number = {4}, pages = {307-315}, doi = {10.1002/pros.24462}, pmid = {36420892}, issn = {1097-0045}, mesh = {Male ; Humans ; *Prostatic Neoplasms/pathology ; Prostate/pathology ; Androgen Antagonists/therapeutic use ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Retrospective Studies ; Hormones/therapeutic use ; }, abstract = {BACKGROUND: In recent years, the usefulness of androgen receptor axis-targeted agents (ARATs) such as abiraterone, enzalutamide, and apalutamide for the upfront treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has been demonstrated. However, it remains unclear which patients would truly benefit from these treatments. Furthermore, intraductal carcinoma of the prostate (IDC-P) is a known poor prognostic factor in patients with prostate cancer. We investigated the association between the presence of IDC-P and response to therapy in patients with mHSPC.

METHODS: This retrospective analysis included 318 patients with mHSPC who received treatment at Nagoya University and its 12 affiliated institutions between 2014 and 2021. Their biopsy specimens were evaluated for the presence of IDC-P. The patients were classified according to their first-line treatment into the ARAT (n = 100, receiving a combination of androgen-deprivation therapy [ADT] and ARAT) or conventional therapy (n = 218, receiving ADT with or without standard antiandrogen agents) group. We compared the overall survival (OS) and second progression-free survival (PFS2) between the ARAT and conventional groups according to the presence of IDC-P to evaluate whether presence of IDC-P predicts the response to each treatment. PFS2 was defined as the period from mHSPC diagnosis to disease progression on second-line treatment or death. Propensity score matching with one-to-one nearest-neighbor matching was used to minimize the potential effects of selection bias and confounding factors. The clinicopathological variables of the patients were well-balanced after propensity score matching.

RESULTS: Most patients in the ARAT (79%) and conventional therapy (71%) groups were ICD-P positive. In the propensity score-matched cohort, the OS and PFS2 of IDC-P-positive patients were significantly longer in the ARAT group than in the conventional group (OS: hazard ratio [HR], 0.36; p = 0.047; PFS2: HR, 0.30; p < 0.001). In contrast, no difference in OS and PFS2 was observed between the ARAT and conventional groups in IDC-P-negative patients (OS: HR, 1.09; p = 0.920; PFS2: HR, 0.40; p = 0.264).

CONCLUSIONS: The findings highlight a high prevalence of IDC-P among patients with mHSPC and suggest that IDC-P positivity may be a reliable indicator that ARAT should be implemented as first-line treatment.}, } @article {pmid36420590, year = {2023}, author = {Roberts, AC and Lunt, LG and Coogan, AC and Madrigrano, A}, title = {The Role of Radiation Therapy in Locally Advanced Breast Cancer in a Patient With Li-Fraumeni Syndrome.}, journal = {The American surgeon}, volume = {89}, number = {11}, pages = {4958-4960}, doi = {10.1177/00031348221135780}, pmid = {36420590}, issn = {1555-9823}, mesh = {Female ; Humans ; Adult ; *Li-Fraumeni Syndrome/complications/surgery ; *Breast Neoplasms/radiotherapy/surgery/pathology ; *Neoplasms, Radiation-Induced/etiology/surgery ; Mastectomy/adverse effects ; }, abstract = {Li-Fraumeni syndrome (LFS) is associated with many different cancers, including early onset breast cancer. Due to an increased risk of radiation-induced malignancy, radiation therapy is often avoided in this patient population. This case study evaluates a 38-year-old female with a history of juvenile granulosa cell tumor of the ovary and malignant phyllodes tumor of right breast, who subsequently developed bilateral invasive ductal carcinoma and was treated with bilateral mastectomies. Studies show that in a high-risk patient, post-mastectomy radiation therapy (PMRT) should not be ruled out due to a history of LFS, as the benefit of PMRT may outweigh the risk of a radiation-induced malignancy.}, } @article {pmid36419161, year = {2022}, author = {Philippson, C and Larsen, S and Simon, S and Vandekerkhove, C and De Caluwe, A and Van Gestel, D and Chintinne, M and Veys, I and De Neubourg, F and Noterman, D and Roman, M and Nogaret, JM and Desmet, A}, title = {Intraoperative electron radiotherapy in early invasive ductal breast cancer: 6-year median follow-up results of a prospective monocentric registry.}, journal = {Breast cancer research : BCR}, volume = {24}, number = {1}, pages = {83}, pmid = {36419161}, issn = {1465-542X}, mesh = {Humans ; Female ; *Mastectomy, Segmental ; Electrons ; *Breast Neoplasms/radiotherapy/surgery/pathology ; Prospective Studies ; Follow-Up Studies ; Neoplasm Recurrence, Local/radiotherapy ; Registries ; }, abstract = {BACKGROUND: Intraoperative electron radiotherapy (IOERT) can be used to treat early breast cancer during the conservative surgery thus enabling shorter overall treatment times and reduced irradiation of organs at risk. We report on our first 996 patients enrolled prospectively in a registry trial.

METHODS: At Jules Bordet Institute, from February 2010 onwards, patients underwent partial IOERT of the breast. Women with unifocal invasive ductal carcinoma, aged 40 years or older, with a clinical tumour size ≤ 20 mm and tumour-free sentinel lymph node (on frozen section and immunohistochemical analysis). A 21 Gy dose was prescribed on the 90% isodose line in the tumour bed with the energy of 6 to 12 MeV (Mobetron®-IntraOp Medical).

RESULTS: Thirty-seven ipsilateral tumour relapses occurred. Sixteen of those were in the same breast quadrant. Sixty patients died, and among those, 12 deaths were due to breast cancer. With 71.9 months of median follow-up, the 5-year Kaplan-Meier estimate of local recurrence was 2.7%.

CONCLUSIONS: The rate of breast cancer local recurrence after IOERT is low and comparable to published results for IORT and APBI. IOERT is highly operator-dependent, and appropriate applicator sizing according to tumour size is critical. When used in a selected patient population, IOERT achieves a good balance between tumour control and late radiotherapy-mediated toxicity morbidity and mortality thanks to insignificant irradiation of organs at risk.}, } @article {pmid36414494, year = {2023}, author = {Zhang, C and Liang, Z and Feng, Y and Xiong, Y and Manwa, C and Zhou, Q}, title = {Risk Factors for Lymphovascular Invasion in Invasive Ductal Carcinoma Based on Clinical and Preoperative Breast MRI Features: a Retrospective Study.}, journal = {Academic radiology}, volume = {30}, number = {8}, pages = {1620-1627}, doi = {10.1016/j.acra.2022.10.029}, pmid = {36414494}, issn = {1878-4046}, mesh = {Humans ; Retrospective Studies ; Lymphatic Metastasis ; *Magnetic Resonance Imaging ; Risk Factors ; *Carcinoma, Ductal ; }, abstract = {RATIONALE AND OBJECTIVES: Lymphovascular invasion (LVI) plays an important role in the prediction of metastasis and prognosis in breast cancer (BC) patients. The present study assessed correlations between preoperative breast MRI, clinical features, and LVI in patients with invasive ductal carcinoma (IDC) and identified risk factors based on these correlation factors.

MATERIALS AND METHODS: Patients confirmed with IDC between 01/2012 and 12/2021 were retrospectively reviewed at our hospital. A total of 5 clinical and 14 MRI features to characterize tumours were extracted. LVI evaluated in hematoxylin and eosin sections. T-test and chi-square tests were used to compare the differences in clinical and MRI features between the LVI positive and negative groups. The associations between individual features and LVI were analysed by univariable logistic regression analysis, and risk factors for LVI were identified by multivariable logistic regression analysis based on these correlation factors.

RESULTS: This study included 353 patients with IDC, including 130 with positive LVI. Age, CEA, CA-153, amount of fibroglandular tissue (FGT), background parenchymal enhancement, tumour size, shape, skin thickening, nipple retraction, adjacent vessel sign, and axillary lymph node (ALN) size in the LVI positive group were significantly different from the LVI negative group (all p<0.05). Multivariate logistic regression analysis revealed that age (odds ratio OR = 1.030), CA-153 (OR = 1.018), heterogeneous FGT (OR = 2.484), shape (OR = 2.157), and ALN size (OR = 1.051) were risk factors for LVI (all p<0.05).

CONCLUSION: Preoperative breast MRI and clinical features correlated with LVI, age, CA-153, heterogeneous FGT, shape, and ALN size are risk factors for LVI in patients with IDC.}, } @article {pmid36412445, year = {2022}, author = {Karaman, H and Senel, F and Tasdemir, A and Özer, I and Dogan, M}, title = {A single centre experience in Turkey for comparison between core needle biopsy and surgical specimen evaluation results for HER2, SISH, estrogen receptors and progesterone receptors in breast cancer patients.}, journal = {Journal of cancer research and therapeutics}, volume = {18}, number = {6}, pages = {1789-1795}, doi = {10.4103/jcrt.JCRT_601_20}, pmid = {36412445}, issn = {1998-4138}, mesh = {Female ; Humans ; Biopsy, Large-Core Needle ; *Breast Neoplasms/diagnosis ; *Carcinoma ; In Situ Hybridization ; Receptors, Estrogen ; Receptors, Progesterone ; Retrospective Studies ; Silver ; Turkey ; Erb-b2 Receptor Tyrosine Kinases ; }, abstract = {BACKGROUND: Breast carcinoma diagnosis can be made with core-needle biopsy (CNB), but there are controversies regarding the evaluation of hormone receptor (HR) status in needle biopsy specimens. When preoperative neoadjuvant therapy is required in breast cancer cases, the CNB specimen should be evaluated to decide on the treatment.

OBJECTIVES: In this study, we aimed to compare the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and silver in situ hybridization (SISH) results of the CNB specimens and surgical specimens (SS) of our breast carcinoma cases.

MATERIALS AND METHODS: This retrospective study included cases diagnosed with breast cancer in our center for approximately 1 year between 2017 and 2018. About 97 cases with both CNB specimens and SS were included in the study. Data such as the ER, PR, HER2, and SISH evaluation results in CNB and SS, age distribution and histopathological type, metastatic lymph nodes, lymphovascular invasion, tumor size, and grade of the tumor were recorded. The data were analyzed using SPSS 22.0 (Statistical Package for the Social Sciences, Armonk, NY, USA) software.

RESULTS: All of the cases were female and 70.1% of them were aged over 45. About 27.8% of the cases were aged 31-45 years, and 2.1% were aged under 30. When evaluated according to the histopathological type of the tumor, 71.1% of cases were invasive ductal carcinoma (IDC), 8.2% were invasive lobular carcinoma (ILC), 6.2% were IDC + ILC, 11.3% were another carcinoma, and 3.1% were in situ carcinoma. 12.4% of the cases were Grade I, 43.3% were Grade II, and 20.6% were Grade III. 43.3% of our cases' tumor size were ≤2 cm and 56.7% >2 cm. 50 (51.5%) of these cases had no lymph node metastasis. It was found out that 36 (37.1%) of the cases had 1-4 metastatic lymph nodes and 11 (11.3%) of them had 5 and more metastatic lymph nodes. It was found out that 44 (45.4.%) of the cases had no lymphovascular invasion and 53 (54.6%) of them had a lymphovascular invasion. When HR statuses in CNB and SS were compared, ER was found to have a sensitivity of 96.1% and a specificity of 100%. PR was found to have a sensitivity of 94.2% and a specificity of 66.7%. HER2 was found to have a sensitivity of 100% and a specificity of 73.4%.

CONCLUSION: ER evaluation results are reliable in deciding on needle biopsy material. PR may show the heterogeneous distribution in HER2 tumor. Thus, if PR and HER2 results in needle biopsy material are negative, assessments should be repeated in SS.}, } @article {pmid36412439, year = {2022}, author = {Abbas, Z and Nouroz, F and Ejaz, S}, title = {Exceptional behavior of breast cancer-associated type 1 gene in breast invasive carcinoma.}, journal = {Journal of cancer research and therapeutics}, volume = {18}, number = {6}, pages = {1743-1753}, doi = {10.4103/jcrt.JCRT_1310_20}, pmid = {36412439}, issn = {1998-4138}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Genes, BRCA1 ; BRCA1 Protein/genetics ; *Carcinoma/genetics ; *Antineoplastic Agents ; }, abstract = {BACKGROUND: Cellular expression level of Breast Cancer-Associated Type 1 (BRCA1) encoded protein is the sign of genome integrity, stability, and surveillance. BRCA1 after sensing DNA damage activates repairing system and if mutated leaves genomic lesions unrepaired and triggers transformation of normal breast cells into cancerous ones.

AIMS OF STUDY: We conducted in silico study to have a holistic view of BRCA1's correlation with multiple variables of breast invasive carcinoma.

MATERIALS AND METHODS: We used user-friendly online GeneCardsSuite pathway-level enrichment analysis, UALCAN portal differential expression analysis, cBioPortal cancer genome platform for mutatome map construction, and cancer cell lines encyclopedia genomics of drug sensitivity toolkit to understand correlation of BRCA1 expression with the effectiveness of anti-cancer drugs.

RESULTS: Contrary to general behavior of a tumor suppressor gene our study revealed BRCA1 overexpression under all circumstances. This novel finding needs to be explored further to understand functional impact of BRCA1 overexpression on the expression of many genes which are transcriptionally regulated by BRCA1 and promotion of tumriogenesis.

CONCLUSION: Our study highlights the potential role of BRCA1-regulated genes in oncogenesis and recommends use of BRCA1-linked genes as future therapeutic targets for effective disease management.}, } @article {pmid36411355, year = {2022}, author = {Kalyan, VSRK and Meena, S and Karthikeyan, S and Jawahar, D}, title = {Isolation, screening, characterization, and optimization of bacteria isolated from calcareous soils for siderophore production.}, journal = {Archives of microbiology}, volume = {204}, number = {12}, pages = {721}, pmid = {36411355}, issn = {1432-072X}, support = {E28ACC//Science and Engineering Research Board/ ; }, mesh = {*Siderophores ; *Soil ; India ; Bacteria/genetics ; Iron Chelating Agents ; }, abstract = {The most effective agricultural practice to prevent iron deficiency in calcareous soils is fertilizing with synthetic chelates. These compounds are non-biodegradable, and persistent in the environment; hence, there is a risk of leaching metals into the soil horizon. To tackle iron deficiency-induced chlorosis (IDC) in crops grown on calcareous soils, environmentally friendly solutions are needed rather than chemical application as it affects the soil health further. Hence, the present work focused on isolating and screening calcareous soil-specific bacteria capable of producing iron-chelating siderophores. Siderophore-producing bacteria (SPB) was isolated from the groundnut (Arachis hypogea L.) rhizosphere region, collected from Coimbatore district, Tamil Nadu, of which 17 bacterial isolates were positive for siderophore production assayed by chrome azurol sulphonate. The performance of SPB isolates was compared for siderophore kinetics, level of siderophore production, type of siderophore produced and iron-chelating capacity under 15 mM KHCO3. Four best performing isolates were screened, with average siderophores yield ranging ∼60-80% under pH 8, with sucrose as carbon source and NH2SO4 as nitrogen source at 37 °C. The four efficient SPB were molecularly identified as B. licheniformis, B. subtilis, B. licheniformis, and O. grignonense based on 16S rDNA sequencing. The simultaneous inhibition method showed T.viride has the highest antagonistic effect against S.rolfsii, and M.phaseolina with a reduction of mycelial growth by 69.3 and 65.1%, respectively, compared to control. Our results indicate that the optimized conditions enhanced siderophores chelation by suppressing the stem and root rot fungi, which could help in a cost-effective and environmentally friendly manner.}, } @article {pmid36406197, year = {2022}, author = {Albores-Mendez, EM and Casanas-Pimentel, RG and Reyes-Chacon, IR and Maldonado Cubas, J and Lopez-Cruz, J and Rincon-Huerta, JA and Camacho-Ibarra, A and San Martin-Martinez, E}, title = {Cancer Progression Is not Different in Mice of Different Gender Inoculated With Cells of the Triple-Negative 4T1 Breast Cancer Model.}, journal = {World journal of oncology}, volume = {13}, number = {5}, pages = {249-258}, pmid = {36406197}, issn = {1920-454X}, abstract = {BACKGROUND: Breast cancer in men is a rare and poorly studied disease, and its treatment is based on women breast cancer studies. However, clinical outcome is not the same in men and women. Basic studies and clinical trials in animal models provide detailed information on cancer, origin, development, cell signaling pathways, sites of metastasis, and target molecules. It is necessary to explore the biology of breast cancer in male animal models that allow observing their similarity.

METHODS: The triple-negative 4T1 breast cancer model was developed in both male and female mice and studied weekly during 4 weeks. For that, twenty 8-week-old female and male BALB/c mice were used. Sixteen mice (eight males and eight females) were inoculated into the second left thoracic mammary pad with 20,000 4T1 cells, resuspended in 20 µL phosphate-buffered saline (PBS). All samples were processed for immunodetection, characterized histopathologically and immunohistochemically.

RESULTS: In this work, we describe the development of a triple-negative 4T1 breast cancer model in male BALB/c mice. Breast tumors were characterized histopathologically at different time points and corresponded to a moderately differentiated invasive ductal carcinoma, estrogen receptor ER-/progesterone receptor PR-/human epidermal growth factor receptor 2 HER2-/Ki67+, with histological grade II (moderately differentiated; a solid mass with occasional duct formation and moderate to severe nuclear pleomorphism), infiltrating the adipose and muscular tissue, and metastasis to lungs. From the results, we did not observe differences in the time of tumor development, necrosis, color change of tumor tissue, and lung metastasis between male and female mice. Even though we did not find histological differences, response to treatment and molecular signaling may be different.

CONCLUSIONS: The histogenesis of male breast tumors was similar to that of female BALB/c mice. The histological and immunohistochemical characteristics of male tumors also match the features reported for stage IV human breast cancer of men and women. The murine male breast cancer model described here can be a significant tool to explore the molecular mechanisms involved in male breast cancer tumorigenesis and metastasis and may bring new approaches for clinical treatment of triple-negative breast cancer in men.}, } @article {pmid36399606, year = {2023}, author = {Gao, G and Epstein, JI}, title = {High-Grade Desmoplastic Foamy Gland Prostatic Adenocarcinoma.}, journal = {Archives of pathology & laboratory medicine}, volume = {147}, number = {9}, pages = {1039-1049}, doi = {10.5858/arpa.2022-0165-OA}, pmid = {36399606}, issn = {1543-2165}, mesh = {Male ; Humans ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Prostate/surgery/pathology ; *Prostatic Neoplasms/pathology ; *Adenocarcinoma/pathology ; Prostatectomy ; Biopsy, Needle ; }, abstract = {CONTEXT.—: It is important to recognize high-grade foamy gland prostatic adenocarcinoma with desmoplastic stroma given its aggressive clinical course with frequent metastases and death.

OBJECTIVE.—: To review the morphology, immunohistochemistry, and prognosis for this rare subtype of prostate adenocarcinoma.

DESIGN.—: Twenty-four cases received for consultation from 2010 to 2021 were analyzed including needle biopsy (n = 21), transurethral resection (n = 2), and a cystoprostatectomy (n = 1).

RESULTS.—: Patients ranged in age from 40 to 89 years (mean, 67 years). On average, 8 cores per case were involved (mean 67% core involvement). Extraprostatic extension and seminal vesicle invasion were observed in 6 of 21 (29%) and 3 of 21 (14%) needle biopsy cases, respectively. Twenty of the 24 cases (83%) were Grade Group (GG) 5 with 4 of 24 (17%) being GG4. Tumor necrosis as a component of Gleason pattern 5 was observed in 21 of 24 cases (88%). Associated intraductal adenocarcinoma (IDC) was observed in 22 of 24 cases (92%), with 4 of 24 cases (17%) demonstrating extensive IDC. Diagnostic challenges were as follows: (1) sparse isolated cancer glands embedded in the dense desmoplastic stroma; (2) fragmented glands; and (3) aberrant staining for high-molecular-weight cytokeratin in a nonbasal cell pattern in all cases. PTEN loss was observed in 9 cases, and p53 nuclear accumulation was observed in 8 cases. Three patients were lost to follow-up. Overall, of the 16 patients with meaningful follow-up, 12 (75%) either had metastases or died from prostate cancer.

CONCLUSIONS.—: High-grade desmoplastic foamy gland adenocarcinoma is difficult to diagnose and grade and has a poor prognosis.}, } @article {pmid36398701, year = {2023}, author = {Kant, V}, title = {'The spirit is willing, but the flesh is weak?': systemic unknown-knowns for ergonomics in India.}, journal = {Ergonomics}, volume = {66}, number = {9}, pages = {1382-1397}, doi = {10.1080/00140139.2022.2149851}, pmid = {36398701}, issn = {1366-5847}, abstract = {While the worldwide ergonomics community increases its sophistication in solving global problems, specific systemic challenges still plague Indians in urban mega-cities such as Mumbai. This paper aims to highlight the gaps using the knowns-unknowns framework, which exists in the Indian ergonomics community's capability to address such systemic challenges. Within this framework, the epistemological category of 'unknown-knowns' is explicated further using a case study of urban accidental deaths and injuries in Mumbai, India. These systemic casualties are essential to note because they are not only hidden from public awareness but can be avoided by proper ergonomics interventions. The article concludes with four main directions for the Indian ergonomics community in solving systemic problems in terms of, (a) capacity-building, (b) advocacy; (c) developing all realms of ergonomics with particular emphasis on complex systems; (d) developing India-centric pathways for ergonomics as a discipline. Practitioner's summary: This paper aims to highlight gaps in the academic Indian ergonomics community's capacity to solve public systemic problems. An India-centric way forward for awareness, engagement, and academic capacity building is suggested to develop a comprehensive national ergonomics mission.}, } @article {pmid36396676, year = {2022}, author = {Contrepois, K and Chen, S and Ghaemi, MS and Wong, RJ and Jehan, F and Sazawal, S and Baqui, AH and Stringer, JSA and Rahman, A and Nisar, MI and Dhingra, U and Khanam, R and Ilyas, M and Dutta, A and Mehmood, U and Deb, S and Hotwani, A and Ali, SM and Rahman, S and Nizar, A and Ame, SM and Muhammad, S and Chauhan, A and Khan, W and Raqib, R and Das, S and Ahmed, S and Hasan, T and Khalid, J and Juma, MH and Chowdhury, NH and Kabir, F and Aftab, F and Quaiyum, A and Manu, A and Yoshida, S and Bahl, R and Pervin, J and Price, JT and Rahman, M and Kasaro, MP and Litch, JA and Musonda, P and Vwalika, B and Shaw, G and Stevenson, DK and Aghaeepour, N and Snyder, MP}, title = {Author Correction: Prediction of gestational age using urinary metabolites in term and preterm pregnancies.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {19753}, doi = {10.1038/s41598-022-23715-7}, pmid = {36396676}, issn = {2045-2322}, support = {001/WHO_/World Health Organization/International ; }, } @article {pmid36395590, year = {2022}, author = {Lin, Z and He, Y and Qiu, C and Yu, Q and Huang, H and Yiwen Zhang, and Li, W and Qiu, T and Xiaoping Li, }, title = {A multi-omics signature to predict the prognosis of invasive ductal carcinoma of the breast.}, journal = {Computers in biology and medicine}, volume = {151}, number = {Pt A}, pages = {106291}, doi = {10.1016/j.compbiomed.2022.106291}, pmid = {36395590}, issn = {1879-0534}, mesh = {Humans ; *Breast ; Area Under Curve ; ROC Curve ; Risk Factors ; *Carcinoma, Ductal ; }, abstract = {BACKGROUND: Precisely evaluating the prognosis of invasive ductal carcinoma (IDC) of the breast is challenging as most prognostic signatures use single-omics data based on gene or clinical information.

METHODS: Whole-slide images (WSIs), transcriptome, and clinical data of breast IDC were collected from the Cancer Genome Atlas Database. The cancer-associated fibroblast (CAF) gene sets were downloaded from the Molecular Signatures Database. The WSI feature was extracted by artificial feature engineering. The CAF prognostic genes were determined by the Gene Set Enrichment Analysis, the Wilcoxon test, and univariate Cox regression. The IDC patients were divided into the training and test sets. The prognostic signatures based on WSIs, IDC-CAFs, bi-omics, and tri-omics were constructed using multivariate Cox regression. The samples were divided into low- and high-risk groups according to the median risk score. The Kaplan-Meier survival and receiver operating characteristic curves were applied to validate the prediction performance of the four signatures.

RESULTS: In total, 508 IDC patients with complete data were included. The area under the curve (AUC) of single-omics signature based on WSI characteristics and CAFs was 0.765 and 0.775, whereas the AUC of bi-omics was 0.823. The tri-omics signature based on WSIs, CAFs, and lymph node status demonstrated the best predictive value with an AUC of 0.897.

CONCLUSION: The multi-omics signature based on WSIs, CAFs, and clinical characteristics showed excellent prediction ability in breast IDC patients, whose risk factors can also provide a valuable diagnostic reference for the clinical course.}, } @article {pmid36394689, year = {2023}, author = {Mamtani, A and Grabenstetter, A and Sevilimedu, V and Morrow, M and Gemignani, ML}, title = {Do non-classic invasive lobular carcinomas derive a benefit from neoadjuvant chemotherapy?.}, journal = {Breast cancer research and treatment}, volume = {197}, number = {2}, pages = {417-423}, pmid = {36394689}, issn = {1573-7217}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P30CA008748//NIH/NCI Cancer Center Support Grant/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Lobular/pathology ; *Carcinoma, Ductal, Breast/pathology ; Neoadjuvant Therapy ; Breast/pathology ; }, abstract = {PURPOSE: Invasive lobular breast cancers (ILCs) respond poorly to neoadjuvant chemotherapy (NAC). The degree of benefit of NAC among non-classic ILC (NC-ILC) variants compared with classic ILCs (C-ILCs) is unknown.

METHODS: Consecutive patients with Stage I-III ILC treated from 2003 to 2019 with NAC and surgery were identified, and grouped as C-ILC or NC-ILC as per the original surgical pathology report, with pathologist (A.G.) review performed if original categorization was unclear. A subset of similarly treated invasive ductal cancers (IDCs) was identified for comparison. Clinicopathologic characteristics and pathologic complete response (pCR) rates were evaluated.

RESULTS: Of 145 patients with ILC, 101 (70%) were C-ILC and 44 (30%) were NC-ILC (IDC cohort: 1157 patients). ILC patients were older, more often cT3/T4 and cN2/N3, and less often high-grade compared to IDC patients. Those with NC-ILC were less often ER+/HER2- (55% versus 93%), and more often HER2 + (25% versus 7%) and TN (21% versus 0%, all p < 0.001). Breast pCR was more common among NC-ILC, but most frequent in IDC. Nodal pCR rates were also lowest among C-ILC patients, but similar among NC-ILC and IDC patients. On multivariable analysis, C-ILC (OR 0.09) and LVI (OR 0.51) were predictive of lack of breast pCR; non-ER+/HER2- subtypes and breast pCR were predictive of nodal pCR. When our analysis was repeated with patients stratified by receptor subtype, histology was not independently predictive of either breast or nodal pCR.

CONCLUSION: NC-ILC patients were significantly more likely to achieve breast and nodal pCR compared with C-ILC patients, but when stratified by subtype, histology was not independently predictive of breast or nodal pCR.}, } @article {pmid36382077, year = {2022}, author = {Srinivasan, S and Patel, S and Khade, A and Bedi, G and Mohite, J and Sen, A and Poovaiah, R}, title = {Efficacy of a novel augmentative and alternative communication system in promoting requesting skills in young children with Autism Spectrum Disorder in India: A pilot study.}, journal = {Autism & developmental language impairments}, volume = {7}, number = {}, pages = {23969415221120749}, pmid = {36382077}, issn = {2396-9415}, abstract = {Background & aims: The study assessed the efficacy of a novel, child-friendly, socio-culturally sensitive, icon-based Augmentative and Alternative Communication (AAC) system called Jellow Communicator, in teaching requesting skills to young children with Autism Spectrum Disorder (ASD) in a special school in Mumbai, India. Jellow is a comprehensive AAC system with a lexicon and pictorial library designed using a participatory, user-centric design process. The content of Jellow has been developed bearing in mind the socio-cultural and linguistic diversity of India. Jellow is available in low-tech (flashcards, booklet) and high-tech (Android and iOS app and desktop application) versions. Methods: The quasi-experimental longitudinal study involved seventeen 3.5-12-year-old children with ASD with communication challenges. Children were taught to use the Jellow AAC system to request for preferred items, as part of their regular speech therapy sessions. Each child received one-on-one training sessions with a licensed speech therapist twice a week over a 3-month duration, with each session lasting around 20-30 min. A systematic training protocol adapted from the original Picture Exchange Communication System (PECS) was developed to train children to use the Jellow system, progressing from flashcards to the app version of Jellow. Behavioral training strategies such as modeling, least-to-most prompting, differential reinforcement, and behavior chain interruption were used to facilitate requesting behaviors. The speech therapist assessed children's developmental level across multiple domains at pretest and posttest. We coded 3 videos per child, i.e., one early, one mid, and one late training session each, to assess changes in children's stage of communication, spontaneous requesting abilities, level of attention during training trials, and average time to completion for requesting trials. In addition, caregivers filled out questionnaires to assess training-related changes in children's adaptive functioning levels as well as the psychosocial impact of the Jellow AAC system on children's quality of life. Results: Children significantly improved their stage of communication, and a majority of children transitioned from flashcards to using the Jellow app to request for preferred items. Children also increased the proportion of spontaneous requests over the course of training. Caregivers reported a positive perceived psychosocial impact of the Jellow AAC system on their child's self-esteem, adaptability, and competence. Conclusions: The findings from our pilot study support the use of the novel, socio-culturally adapted, Jellow Communicator AAC system for teaching requesting skills to young children with ASD who use multiple communication modalities. Future studies should replicate our findings with a larger group of participants using a randomized controlled trial design. Implications: This is the first experimental study to systematically assess the effects of an indigenously-developed comprehensive AAC system adapted to the sociocultural and linguistic landscape of India. Our study results provide support for the use of the cost-effective Jellow Communicator AAC system in facilitating requesting skills in children with ASD who use multiple communication modalities. Clinicians can use low-tech and high-tech versions of Jellow to promote communication skills in children with ASD.}, } @article {pmid36378000, year = {2022}, author = {Almehmadi, M and Salih, MM and Shafie, A and Alsharif, A and Alsiwiehr, N and El-Askary, A and Alzahrani, K and Al-Hazmi, A and Aljuaid, A and Abdulazziz, O and Almalki, AA and Allahyani, M and Eed, E and Alharbi, AM and Halawi, M and Allam, HH and Abutawil, H and Alosimi, E and Gharib, AF}, title = {Seroprevalence of IgM and IgG Against SARS-CoV-2 after Two Doses of Pfizer-BioNTech COVID-19 Vaccine in Women with Breast Cancer.}, journal = {Clinical laboratory}, volume = {68}, number = {11}, pages = {}, doi = {10.7754/Clin.Lab.2022.220316}, pmid = {36378000}, issn = {1433-6510}, mesh = {Humans ; Female ; Middle Aged ; SARS-CoV-2 ; Immunoglobulin M ; Seroepidemiologic Studies ; *COVID-19/epidemiology/prevention & control ; BNT162 Vaccine ; *Breast Neoplasms ; COVID-19 Vaccines ; Antibodies, Viral ; Immunoglobulin G ; *Carcinoma, Ductal ; }, abstract = {BACKGROUND: This study evaluates the seroprevalence of immunoglobulin M (IgM) and G (IgG) antibodies against SARS-CoV-2 after two doses of Pfizer-BioNTech COVID-19 vaccination from women with breast cancer in Jazan city Kingdom of Saudi Arabia, antibody detections were performed one month and three months after the administration of the second dose.

METHODS: Overall, 103 breast cancer patients were included. Individuals who had had two doses of Pfizer-BioNTech vaccine, patients who were earlier diagnosed with COVID-19 infection, had not finalized immunization plan, or who received the second dose recently were excluded from the study. The antibodies detection test was run according to the manufacturer's directions of Viva Diag™ SARS-CoV-2 IgM/IgG Rapid Test (COVID-19 IgM/IgG Rapid Test).

RESULTS: This study included 62 (60.2%) and 41 (39.8%) patients with invasive ductal carcinoma and invasive lobular carcinoma, respectively. The age, median and interquartile range (IQR) was 54.0 (26) years. Regarding reactivity of antibodies, after one month IgM antibody showed 64 (62.1%) positive and 39 (37.9%) negative while IgG antibody showed positive results in all patients. After three months IgM antibody showed 44 (42.7%) positive and 59 (57.3%) negative, while IgG showed 87 (84.5%) positive and 16 (15.5%) negative. There were significant differences in the IgM and IgG seropositivity. There were 19.3% patients with ductal carcinoma who were positive and then turned negative versus 17.7% who were positive and then turned negative, respectively (p < 0.001). There were significant differences in IgM antibody positivity among different age groups.

CONCLUSIONS: Our results recommend the importance of screening for an antibody response for breast cancer patient after immunization in order to reveal persons who need early and late extra enhancing vaccine dose. Upcoming studies recommended to estimate different methods that raise cancer patients' immune response.}, } @article {pmid36376280, year = {2022}, author = {Haythorne, E and Lloyd, M and Walsby-Tickle, J and Tarasov, AI and Sandbrink, J and Portillo, I and Exposito, RT and Sachse, G and Cyranka, M and Rohm, M and Rorsman, P and McCullagh, J and Ashcroft, FM}, title = {Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6754}, pmid = {36376280}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/V011979/1/MRC_/Medical Research Council/United Kingdom ; BB/R017220/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/T002107/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Glucose/metabolism ; Glycolysis/physiology ; Insulin/metabolism ; *Hyperglycemia/metabolism ; Pyruvic Acid/metabolism ; *Islets of Langerhans/metabolism ; *Diabetes Mellitus/metabolism ; }, abstract = {Chronic hyperglycaemia causes a dramatic decrease in mitochondrial metabolism and insulin content in pancreatic β-cells. This underlies the progressive decline in β-cell function in diabetes. However, the molecular mechanisms by which hyperglycaemia produces these effects remain unresolved. Using isolated islets and INS-1 cells, we show here that one or more glycolytic metabolites downstream of phosphofructokinase and upstream of GAPDH mediates the effects of chronic hyperglycemia. This metabolite stimulates marked upregulation of mTORC1 and concomitant downregulation of AMPK. Increased mTORC1 activity causes inhibition of pyruvate dehydrogenase which reduces pyruvate entry into the tricarboxylic acid cycle and partially accounts for the hyperglycaemia-induced reduction in oxidative phosphorylation and insulin secretion. In addition, hyperglycaemia (or diabetes) dramatically inhibits GAPDH activity, thereby impairing glucose metabolism. Our data also reveal that restricting glucose metabolism during hyperglycaemia prevents these changes and thus may be of therapeutic benefit. In summary, we have identified a pathway by which chronic hyperglycaemia reduces β-cell function.}, } @article {pmid36375403, year = {2023}, author = {Baré, J and Gheddou, A and Kalinowski, MB}, title = {Overview of temporary radioxenon background measurement campaigns conducted for the CTBTO between 2008 and 2018.}, journal = {Journal of environmental radioactivity}, volume = {257}, number = {}, pages = {107053}, doi = {10.1016/j.jenvrad.2022.107053}, pmid = {36375403}, issn = {1879-1700}, mesh = {Xenon Radioisotopes/analysis ; *Air Pollutants, Radioactive/analysis ; *Radiation Monitoring/methods ; International Cooperation ; Nuclear Reactors ; }, abstract = {The Comprehensive Nuclear-Test-Ban Treaty (CTBT) specifies that an overall network of at least 40 International Monitoring System (IMS) stations should monitor the presence of radioxenon in the atmosphere upon its entry into force. The measurement of radioxenon concentrations in the air is one of the major techniques to detect underground nuclear explosions. It is, together with radionuclide particulate monitoring, the only component of the network able to confirm whether an event originates from a nuclear test, leaving the final proof to on-site inspection. Correct and accurate interpretation of radioxenon detections by State Signatories is a key parameter of the verification regime of the Preparatory Commission for the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO). In this context, the discrimination between the highly variable radioxenon background generated by normal operations of nuclear facilities and CTBT-relevant events is a challenging, but critical, task. To this end, the radioxenon background that can be expected at IMS noble gas systems must be sufficiently characterized and understood. All activities conducted to study the global radioxenon background are focused on the calibration and performance of the verification system as described in the Treaty. The unique CTBTO noble gas system network is designed to optimally covering the globe. By the end of 2019, 31 systems were put in operation, 25 of which being already certified. It took two decades from the first experimental setup of noble gas system in the field to reach this stage of maturity. In the meantime, it was an urgent need to gain empirical evidence of atmospheric radioxenon concentrations with the full spectrum of characteristics that IMS noble gas systems may be observing. This experience was significantly advanced through temporary measurement campaigns. Their objective was to gain the additional necessary knowledge for a correct understanding and categorization of radioxenon detections. The site selection for these campaigns put emphasis on regions with low coverage by the initially few experimental noble gas systems at IMS locations or where potential interferences with normal background might be observed. Short-term measurements were first initiated in 2008. Sites of potential interest were identified, and campaigns up to few weeks were performed. Based on the findings of these short campaigns, transportable systems were procured by the CTBTO. Longer temporary measurement campaigns were started afterwards and operated by local hosts in different regions of the globe. Site selections were based on purely scientific criteria. Objectives of the measurement campaigns were continually reassessed, and projects were designed to meet the scientific needs for radioxenon background understanding as required for nuclear explosion monitoring. As of today, several thousands of samples have been collected and measured. Spectra of temporary measurement campaigns were (and are still) analysed in the International Data Centre (IDC). As they are not part of the CTBT monitoring system, no IDC product is generated. Analysis results are stored in a non-operational database of the CTBTO and made available, together with raw data, to authorized users of States Signatories through a Secure Web Portal (SWP) and to scientific institutions for approved research projects through a virtual Data Exploitation Centre (vDEC) after signing a cost-free confidentiality agreement (https://www.ctbto.org/specials/vdec). This paper aims at providing an overview of the temporary measurement campaigns conducted by the CTBTO since the very first field measurements. It lays out scientific results in a systematic approach. This overview demonstrates the asset of radioxenon background measurement data that have been collected with a wide variety of characteristics that may be observed at IMS stations. It bears a tremendous opportunity for development, enhancement and validation of methodologies for CTBT monitoring. In 2018, a campaign started in Japan with transportable noble gas systems in the vicinity of the IMS station RN38 in Takasaki. It will be described separately once the measurements are completed.}, } @article {pmid36374375, year = {2023}, author = {Li, J and Sun, B and Li, Y and Li, S and Wang, J and Zhu, Y and Lu, H}, title = {Correlation analysis between shear-wave elastography and pathological profiles in breast cancer.}, journal = {Breast cancer research and treatment}, volume = {197}, number = {2}, pages = {269-276}, pmid = {36374375}, issn = {1573-7217}, support = {82172025//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/surgery/pathology ; *Elasticity Imaging Techniques ; Multivariate Analysis ; Ultrasonography, Mammary ; }, abstract = {PURPOSE: To explore the correlation between shear-wave elastography (SWE) parameters and pathological profiles of invasive breast cancer.

METHODS: A total of 197 invasive breast cancers undergoing preoperative SWE and primary surgical treatment were included. Maximum elastic modulus (Emax), mean elastic modulus (Emean), and elastic modulus standard deviation (Esd) were calculated by SWE. Pathological profile was gold standard according to postoperative pathology. The relationship between SWE parameters and pathological factors were analyzed using univariate and multivariate analysis.

RESULTS: In univariate analysis, large cancers showed significantly higher Emax, Emean and Esd (all P < 0.001). Emax and Esd in the group of histological grade III were higher than those in the group of grade I (both P < 0.05). Invasive lobular carcinomas (ILC) showed higher Emean than invasive ductal carcinoma (IDC) (P < 0.001). Lymphovascular invasion (LVI) group showed higher Emax values than negative group (P < 0.05). Emax, Emean and Esd of the Ki-67 positive group presented higher values than negative group (all P < 0.05). Androgen receptor (AR) positive lesions had lower Esd than AR negative lesions (P < 0.05). In multivariate analysis, invasive size independently influenced Emax (P < 0.001). Invasive size and pathological type both independently influenced Emean (both P < 0.001). Invasive size and AR status were both independently influenced Esd (both P < 0.05).

CONCLUSION: SWE parameters correlated with pathological profiles of invasive breast cancer.In particular, AR positive group showed significantly low Esd than negative group.}, } @article {pmid36372577, year = {2023}, author = {Di Lena, É and Antoun, A and Hopkins, B and Barone, N and Do, U and Meterissian, S}, title = {Sentinel lymph node biopsy in women over 70: Evaluation of rates of axillary staging and impact on adjuvant therapy in elderly women.}, journal = {Surgery}, volume = {173}, number = {3}, pages = {603-611}, doi = {10.1016/j.surg.2022.09.016}, pmid = {36372577}, issn = {1532-7361}, mesh = {Female ; Humans ; Aged ; Sentinel Lymph Node Biopsy ; Lymph Node Excision ; Retrospective Studies ; *Breast Neoplasms/surgery/pathology ; Mastectomy ; Axilla/pathology ; Neoplasm Staging ; *Sentinel Lymph Node/pathology ; }, abstract = {BACKGROUND: The 2016 Society of Surgical Oncology Choosing Wisely guidelines recommended against routine sentinel lymph node biopsy in women ≥70 years old with favorable, early-stage breast cancer, as sentinel lymph node biopsy does not decrease recurrence or mortality in these patients. This study's objective was to evaluate the use of sentinel lymph node biopsy and its effect on management in elderly patients.

METHODS: A retrospective analysis of female patients ≥70 years old with stage I-II, clinically node-negative, hormone-receptor positive, HER2-negative disease undergoing upfront breast cancer surgery between 2017 and 2019. Primary outcome was rate of sentinel lymph node biopsy. Secondary outcome was effect of sentinel lymph node biopsy on adjuvant therapy.

RESULTS: In total, 142 patients were included. Median age was 76 (interquartile range 73-81), and 71.8% underwent lumpectomy. On final pathology, 57.7% had invasive ductal carcinoma, and median tumor size was 15 mm (interquartile range 10-24.3). A total of 118 patients (83.1%) underwent sentinel lymph node biopsy; of these, 27 (22.9%) were positive for N1mi (7 patients) or N1a disease (20 patients). On multivariate regression analysis, patients undergoing sentinel lymph node biopsy were more likely to be younger (odds ratio 0.87, 95% confidence interval 0.78-0.95). The major risk factor for sentinel lymph node biopsy positivity was lymphovascular invasion (odds ratio 13.4, 95% confidence interval 4.57-40.1). Patients with sentinel lymph node biopsy positivity were more likely to receive local adjuvant radiation therapy (odds ratio 4.66, 95% confidence interval 1.49-16.8) and tended to receive more adjuvant regional radiation therapy (75.0% if sentinel lymph node biopsy positive compared with 15.3% if sentinel lymph node biopsy negative, P < .001).

CONCLUSION: Despite the 2016 Choosing Wisely guidelines, more than 80% of patients ≥70 years old underwent sentinel lymph node biopsy at our institution. If sentinel lymph node biopsy was positive, this is associated with over 4-fold higher rates of adjuvant radiation therapy.}, } @article {pmid36369328, year = {2022}, author = {Yang, Y and Gao, D and Xie, X and Qin, J and Li, J and Lin, H and Yan, D and Deng, K}, title = {DeepIDC: A Prediction Framework of Injectable Drug Combination Based on Heterogeneous Information and Deep Learning.}, journal = {Clinical pharmacokinetics}, volume = {61}, number = {12}, pages = {1749-1759}, pmid = {36369328}, issn = {1179-1926}, support = {82130112//the National Natural Science Foundation of China/ ; DFL20190702//the Beijing Excellent Talent Project/ ; }, mesh = {Humans ; *Deep Learning ; Drug Combinations ; Algorithms ; Machine Learning ; Drug Interactions ; }, abstract = {BACKGROUND AND OBJECTIVE: In clinical practice, injectable drug combination (IDC) usually provides good therapeutic effects for patients. Numerous clinical studies have directly indicated that inappropriate IDC generates adverse drug events (ADEs). The clinical application of injections is increasing, and many injections lack relevant combination information. It is still a significant need for experienced clinical pharmacists to participate in evidence-based drug decision making, monitor medication safety, and manage drug interactions. Meanwhile, a large number of injection pairs and dosage combinations limit exhaustive screening. Here, we present a prediction framework, called DeepIDC, that can expediently screen the feasibility of IDCs using heterogeneous information with deep learning. This is the first specific prediction framework to identify IDCs.

METHODS: Since the interaction between the injected drugs may occur in the direct physical and chemical reactions at the time of mixing or may be the indirect interaction of their drug targets and pathways, we used molecular fingerprints, drug-target associations, and drug-pathway associations to convert injections into a string of digital vectors. Then, based on these injection vectors, we combined a bidirectional long short-term memory and a feed-forward neural network to build a prediction model for accurate and instructive prediction of IDC.

RESULTS: In three realistic evaluation scenarios, DeepIDC has achieved ideal prediction results. Furthermore, compared with the other five machine-learning methods, the proposed predictor is more efficient and robust. Among the top 30 potential IDCs of each IDC class predicted by DeepIDC, we found that 9 cases were experimentally verified in the literature or available on Drug.com.

CONCLUSION: The information we extracted in vivo and in vitro can effectively characterize injectable drugs. DeepIDC developed based on deep learning algorithm provides a valuable unified framework for new IDC discovery, which can make up for the lack of IDC information and predict potential IDC events.}, } @article {pmid36365810, year = {2022}, author = {Malik, MS and Zulfiqar, MH and Khan, MA and Mehmood, MQ and Massoud, Y}, title = {Facile Pressure-Sensitive Capacitive Touch Keypad for a Green Intelligent Human-Machine Interface.}, journal = {Sensors (Basel, Switzerland)}, volume = {22}, number = {21}, pages = {}, pmid = {36365810}, issn = {1424-8220}, support = {ITL//King Abdullah University of Science and Technology/ ; }, mesh = {Humans ; *Touch ; Electrodes ; Electronics ; *Graphite ; Plastics ; }, abstract = {There is a great demand for human-machine interfaces (HMIs) in emerging electronics applications. However, commercially available plastic-based HMIs are primarily rigid, application-specific, and hard to recycle and dispose of due to their non-biodegradability. This results in electronic and plastic waste, potentially damaging the environment by ending up in landfills and water resources. This work presents a green, capacitive pressure-sensitive (CPS), touch sensor-based keypad as a disposable, wireless, and intelligent HMI to mitigate these problems. The CPS touch keypads were fabricated through a facile green fabrication process by direct writing of graphite-on-paper, using readily available materials such as paper and pencils, etc. The interdigitated capacitive (IDC) touch sensors were optimized by analyzing the number of electrode fingers, dimensions, and spacing between the electrode fingers. The CPS touch keypad was customized to wirelessly control a robotic arm's movements based on the touch input. A low-pressure touch allows slow-speed robotic arm movement for precision movements, and a high-pressure touch allows high-speed robotic arm movement to cover the large movements quickly. The green CPS touch keypad, as a disposable wireless HMI, has the potential to enforce a circular economy by mitigating electronic and plastic waste, which supports the vision of a sustainable and green world.}, } @article {pmid36357456, year = {2022}, author = {Voon, W and Hum, YC and Tee, YK and Yap, WS and Salim, MIM and Tan, TS and Mokayed, H and Lai, KW}, title = {Performance analysis of seven Convolutional Neural Networks (CNNs) with transfer learning for Invasive Ductal Carcinoma (IDC) grading in breast histopathological images.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {19200}, pmid = {36357456}, issn = {2045-2322}, support = {IPSR/RMC/UTARRF/2022-C1/H02//UTAR Research Fund (UTARRF)/ ; FRGS/1/2019/ICT04/UTAR/02/1//Fundamental Research Grant Scheme/ ; }, mesh = {Humans ; *Neural Networks, Computer ; Publications ; Machine Learning ; *Carcinoma, Ductal ; }, abstract = {Computer-aided Invasive Ductal Carcinoma (IDC) grading classification systems based on deep learning have shown that deep learning may achieve reliable accuracy in IDC grade classification using histopathology images. However, there is a dearth of comprehensive performance comparisons of Convolutional Neural Network (CNN) designs on IDC in the literature. As such, we would like to conduct a comparison analysis of the performance of seven selected CNN models: EfficientNetB0, EfficientNetV2B0, EfficientNetV2B0-21k, ResNetV1-50, ResNetV2-50, MobileNetV1, and MobileNetV2 with transfer learning. To implement each pre-trained CNN architecture, we deployed the corresponded feature vector available from the TensorFlowHub, integrating it with dropout and dense layers to form a complete CNN model. Our findings indicated that the EfficientNetV2B0-21k (0.72B Floating-Point Operations and 7.1 M parameters) outperformed other CNN models in the IDC grading task. Nevertheless, we discovered that practically all selected CNN models perform well in the IDC grading task, with an average balanced accuracy of 0.936 ± 0.0189 on the cross-validation set and 0.9308 ± 0.0211on the test set.}, } @article {pmid36357366, year = {2022}, author = {Willemsen, N and Kotschi, S and Bartelt, A}, title = {Fire up the pyre: inosine thermogenic signaling for obesity therapy.}, journal = {Signal transduction and targeted therapy}, volume = {7}, number = {1}, pages = {375}, pmid = {36357366}, issn = {2059-3635}, support = {PROTEOFIT/ERC_/European Research Council/International ; }, mesh = {Humans ; *Bacterial Proteins ; *Signal Transduction ; Inosine ; Obesity/genetics ; }, } @article {pmid36353989, year = {2023}, author = {Vos, DY and Wijers, M and Smit, M and Huijkman, N and Kloosterhuis, NJ and Wolters, JC and Tissink, JJ and Pronk, ACM and Kooijman, S and Rensen, PCN and Kuivenhoven, JA and van de Sluis, B}, title = {Cargo-Specific Role for Retriever Subunit VPS26C in Hepatocyte Lipoprotein Receptor Recycling to Control Postprandial Triglyceride-Rich Lipoproteins.}, journal = {Arteriosclerosis, thrombosis, and vascular biology}, volume = {43}, number = {1}, pages = {e29-e45}, doi = {10.1161/ATVBAHA.122.318169}, pmid = {36353989}, issn = {1524-4636}, mesh = {Animals ; Humans ; Mice ; Hepatocytes/metabolism ; Lipoproteins/metabolism ; *Low Density Lipoprotein Receptor-Related Protein-1/genetics ; Mice, Knockout ; *Proprotein Convertase 9/genetics/metabolism ; Receptors, LDL ; Triglycerides/metabolism ; Vesicular Transport Proteins ; }, abstract = {BACKGROUND: The copper metabolism MURR1 domains/coiled-coil domain containing 22/coiled-coil domain containing 93 (CCC) complex is required for the transport of low-density lipoprotein receptor (LDLR) and LRP1 (LDLR-related protein 1) from endosomes to the cell surface of hepatocytes. Impaired functioning of hepatocytic CCC causes hypercholesterolemia in mice, dogs, and humans. Retriever, a protein complex consisting of subunits VPS26C, VPS35L, and VPS29, is associated with CCC, but its role in endosomal lipoprotein receptor transport is unclear. We here investigated the contribution of retriever to hepatocytic lipoprotein receptor recycling and plasma lipids regulation.

METHODS: Using somatic CRISPR/Cas9 gene editing, we generated liver-specific VPS35L or VPS26C-deficient mice. We determined total and surface levels of LDLR and LRP1 and plasma lipids. In addition, we studied the protein levels and composition of CCC and retriever.

RESULTS: Hepatocyte VPS35L deficiency reduced VPS26C levels but had minimal impact on CCC composition. VPS35L deletion decreased hepatocytic surface expression of LDLR and LRP1, accompanied by a 21% increase in plasma cholesterol levels. Hepatic VPS26C ablation affected neither levels of VPS35L and CCC subunits, nor plasma lipid concentrations. However, VPS26C deficiency increased hepatic LDLR protein levels by 2-fold, probably compensating for reduced LRP1 functioning, as we showed in VPS26C-deficient hepatoma cells. Upon PCSK9 (proprotein convertase subtilisin/kexin type 9)-mediated LDLR elimination, VPS26C ablation delayed postprandial triglyceride clearance and increased plasma triglyceride levels by 26%.

CONCLUSIONS: Our study suggests that VPS35L is shared between retriever and CCC to facilitate LDLR and LRP1 transport from endosomes to the cell surface. Conversely, retriever subunit VPS26C selectively transports LRP1, but not LDLR, and thereby may control hepatic uptake of postprandial triglyceride-rich lipoprotein remnants.}, } @article {pmid36350000, year = {2022}, author = {Chen, W and Wang, G and Zhang, G}, title = {Insights into the transition of ductal carcinoma in situ to invasive ductal carcinoma: morphology, molecular portraits, and the tumor microenvironment.}, journal = {Cancer biology & medicine}, volume = {19}, number = {10}, pages = {1487-1495}, pmid = {36350000}, issn = {2095-3941}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Tumor Microenvironment/genetics ; *Carcinoma, Ductal, Breast/pathology ; Biomarkers, Tumor ; *Breast Neoplasms/genetics ; }, } @article {pmid36347469, year = {2022}, author = {Forster, C and Prax, K and Jaensch, P and Müller, S and Hepp, T and Schlager, H and Friedland, K and Zerth, J}, title = {[The Economic Evaluation of the GLICEMIA 2.0 Study as an Example of a Complex Intervention].}, journal = {Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany))}, volume = {84}, number = {12}, pages = {1165-1173}, pmid = {36347469}, issn = {1439-4421}, mesh = {Humans ; Cost-Benefit Analysis ; *Diabetes Mellitus, Type 2/therapy ; Germany ; Research Design ; }, abstract = {BACKGROUND: A piggyback approach was used to evaluate the cost-effectiveness of the prevention program delivered at the point of care pharmacy in the GLICEMIA 2.0 study that sought to guide participants in the intervention group to improved glycemic control in type 2 diabetes with sustained incentivization of lifestyle changes, therapeutic compliance, and adherence. The control group received passive medication management and monitoring.

METHODS: Primary endpoint of the GLICEMIA 2.0 study was the stabilization of HbA1c values. For health economic evaluation, incremental differences in output changes were examined, defined as the difference in the distribution of the HbA1c values between both groups over time. Direct program costs and anticipated indirect costs of service utilization were used as cost parameters. A net monetary benefit approach was used to validate cost-effectiveness thresholds via the formation of ICER values.

RESULTS: The intervention group had significantly higher reductions in HbA1c-values. Risk stratification of initial HbA1c showed (short-term) cost effectiveness for initially higher HbA1c values. Due to the limited study period, no long-term differences in medical resource utilization could be assessed.

CONCLUSION: The GLICEMIA program indicates considerable effectiveness potentials, especially for high-risk patients. The study design seems to have assisted the intervention group's adherence in contrast to the control group. Detailed impacts within the complex intervention could not be validated due to restrictions of the study design as a complex intervention. Overall, statements about effect sustainability and further utilization rates progressions are limited due to a lack of follow-up.}, } @article {pmid36344177, year = {2022}, author = {Cai, Q and Shah, RB}, title = {Cribriform Lesions of the Prostate Gland.}, journal = {Surgical pathology clinics}, volume = {15}, number = {4}, pages = {591-608}, doi = {10.1016/j.path.2022.07.001}, pmid = {36344177}, issn = {1875-9157}, mesh = {Male ; Humans ; Prostate/pathology ; *Prostatic Intraepithelial Neoplasia/pathology ; *Prostatic Neoplasms/diagnosis/pathology ; *Precancerous Conditions/pathology ; Diagnosis, Differential ; }, abstract = {"Cribriform lesions of the prostate represent an important and often diagnostically challenging spectrum of prostate pathology. These lesions range from normal anatomical variation, benign proliferative lesions, premalignant, suspicious to frankly malignant and biologically aggressive entities. The concept of cribriform prostate adenocarcinoma (CrP4) and intraductal carcinoma of the prostate (IDC-P), in particular, has evolved significantly in recent years with a growing body of evidence suggesting that the presence of these morphologies is important for clinical decision-making in prostate cancer management. Therefore, accurate recognition and reporting of CrP4 and IDC-P architecture are especially important. This review discusses a contemporary diagnostic approach to cribriform lesions of the prostate with a focus on their key morphologic features, differential diagnosis, underlying molecular alterations, clinical significance, and reporting recommendations."}, } @article {pmid36340971, year = {2022}, author = {Shir-Raz, Y and Elisha, E and Martin, B and Ronel, N and Guetzkow, J}, title = {Censorship and Suppression of Covid-19 Heterodoxy: Tactics and Counter-Tactics.}, journal = {Minerva}, volume = {}, number = {}, pages = {1-27}, pmid = {36340971}, issn = {0026-4695}, abstract = {The emergence of COVID-19 has led to numerous controversies over COVID-related knowledge and policy. To counter the perceived threat from doctors and scientists who challenge the official position of governmental and intergovernmental health authorities, some supporters of this orthodoxy have moved to censor those who promote dissenting views. The aim of the present study is to explore the experiences and responses of highly accomplished doctors and research scientists from different countries who have been targets of suppression and/or censorship following their publications and statements in relation to COVID-19 that challenge official views. Our findings point to the central role played by media organizations, and especially by information technology companies, in attempting to stifle debate over COVID-19 policy and measures. In the effort to silence alternative voices, widespread use was made not only of censorship, but of tactics of suppression that damaged the reputations and careers of dissenting doctors and scientists, regardless of their academic or medical status and regardless of their stature prior to expressing a contrary position. In place of open and fair discussion, censorship and suppression of scientific dissent has deleterious and far-reaching implications for medicine, science, and public health.}, } @article {pmid36339683, year = {2022}, author = {Wang, X and Xue, Y}, title = {Analysis of Prognostic Factors and Construction of Prognostic Models for Invasive Micropapillary Carcinoma of the Breast.}, journal = {Computational and mathematical methods in medicine}, volume = {2022}, number = {}, pages = {1072218}, pmid = {36339683}, issn = {1748-6718}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/pathology ; Prognosis ; Retrospective Studies ; *Carcinoma, Papillary/therapy ; *Breast Neoplasms/diagnosis ; }, abstract = {OBJECTIVE: To compare and analyze the clinical characteristics of invasive micropapillary carcinoma (IMPC) of the breast (IMPC-B) and invasive ductal carcinoma (IDC) of the breast (IDC-B) and establish a prognostic model of IMPC-B.

METHODS: We retrospectively analyzed data for patients diagnosed with breast cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018 and screened 581 patients with IMPC and 1325 patients with IDC. We compared age, race, laterality, tumor site, histological grade, type of surgery, radiation, chemotherapy, whether the first primary tumor, T stage, N stage, M stage, and molecular type between IMPC-B and IDC-B and draw survival curves of IMPC-B and IDC-B. The relationship between clinical factors and prognosis was investigated by univariate analysis using the Log-rank test and multivariate analysis of the Cox proportional hazards regression model. A risk scoring model was constructed based on independent risk factors to distinguish high-risk and low-risk patients; in addition, a nomogram was created to predict patient survival.

RESULTS: There were differences between the two groups in the age of onset, race, tumor site, histological grade, type of surgery, N stage, and molecular type (p < 0.05). Overall survival was decreased in IMPC-B compared with IDC-B (p < 0.05). The prognosis of IMPC-B was significantly correlated with histological grade, whether the first primary tumor, type of surgery, radiotherapy, chemotherapy, T stage, and N stage. Based on the relationship between the above factors and overall survival prognosis, the risk score model we constructed can effectively distinguish high-risk and low-risk patients (p < 0.05). The established nomogram had better performance in predicting survival in patients with IMPC-B (C - index = 0.78).

CONCLUSION: IMPC-B has a worse prognosis than IDC-B, with earlier age of onset, higher histological grade, and later N stage, and luminal breast cancer is the main type. The nomogram can well predict the prognosis of patients with IMPC-B, which has a high clinical reference value and provides a scientific basis for clinical treatment.}, } @article {pmid36338724, year = {2022}, author = {Zhao, YY and Xiang, QM and Chen, JL and Zhang, L and Zheng, WL and Ke, D and Shi, RS and Yang, KW}, title = {SLC25A25-AS1 over-expression could be predicted the dismal prognosis and was related to the immune microenvironment in prostate cancer.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {990247}, pmid = {36338724}, issn = {2234-943X}, abstract = {It has been established that long-chain coding RNA (lncRNA) SLC25A25-AS1 is associated with cancer progression. However, the roles and mechanisms of SLC25A25-AS1 in prostate cancer (PC) have not been reported in the literature. The present study explored the relationship between SLC25A25-AS1 expression and PC progression via comprehensive analysis. The pan-cancer expression of SLC25A25-AS1 was identified using data from The Cancer Genome Atlas (TCGA) database and tissue specimens from our hospital. The expression levels of SLC25A25-AS1 in various subgroups based on the clinical features were identified. The prognostic value of SLC25A25-AS1 and SLC25A25-AS1 co-expressed lncRNAs in PC patients was assessed by survival analysis and ROC analysis, and prognosis-related risk models of SLC25A25-AS1 were constructed. The relationship between SLC25A25-AS1 and the PC immune microenvironment was investigated using correlation analysis. SLC25A25-AS1 expression in PC was significantly increased and correlated with the T stage, clinical stage, Gleason score (GS), and dismal prognosis. SLC25A25-AS1 overexpression exhibited good performance in evaluating the prognosis of PC patients. The area under the curves (AUCs) of the 1-, 3-, and 5-year overall survival (OS) for SLC25A25-AS1 was 1, 0.876, and 0.749. Moreover, the AUCs for the 1-, 3-, and 5-year progress free interval (PFI) for SLC25A25-AS1 were 0.731, 0.701, and 0.718. SLC25A25-AS1 overexpression correlated with the infiltration of CD8 T cells, interstitial dendritic cells (IDC), macrophages and other cells. AC020558.2, ZNF32-AS2, AP4B1-AS1, AL355488.1, AC109460.3, SNHG1, C3orf35, LMNTD2-AS1, and AL365330.1 were significantly associated with SLC25A25-AS1 expression, and short OS and PFI in PC patients. The risk models of the SLC25A25-AS1-related lncRNAs were associated with a dismal prognosis in PC. Overall, SLC25A25-AS1 expression was increased in PC and related to the prognosis and PC immune microenvironment. The risk model of SLC25A25-AS1 have huge prospect for application as prognostic tools in PC.}, } @article {pmid36335424, year = {2022}, author = {Mekheal, E and Kania, BE and Kumari, P and Kumar, V and Maroules, M}, title = {Gynecomastia and Malignancy: A Case of Male Invasive Ductal Breast Carcinoma Treated with Neoadjuvant Chemotherapy.}, journal = {The American journal of case reports}, volume = {23}, number = {}, pages = {e937370}, pmid = {36335424}, issn = {1941-5923}, mesh = {Humans ; Male ; Female ; Neoadjuvant Therapy ; *Breast Neoplasms/pathology ; Receptors, Progesterone/therapeutic use ; Erb-b2 Receptor Tyrosine Kinases ; Receptors, Estrogen/therapeutic use ; Mastectomy ; *Breast Neoplasms, Male/surgery ; *Gynecomastia/etiology/drug therapy/surgery ; Estrogens/therapeutic use ; *Carcinoma, Ductal/drug therapy/surgery ; *Carcinoma, Ductal, Breast/therapy/drug therapy ; Chemotherapy, Adjuvant ; }, abstract = {BACKGROUND Male breast cancer represents a rare malignancy with identifiable risk factors, including genetics, radiation exposure, liver dysfunction, and concomitant diagnosis of Klinefelter syndrome. Gynecomastia can commonly present in these patients, and despite increased estrogen levels in adipose breast tissue, gynecomastia has not been proven to be a significant risk factor for carcinoma development. Male patients with new-onset breast masses are recommended to undergo diagnostic mammograms and breast ultrasound for further evaluation. Those diagnosed with breast cancer most commonly have invasive ductal carcinoma of the breast, and over half of these patients are found to have estrogen and progesterone receptor (ER/PR) positivity. CASE REPORT In this case report, we present a Black man with gynecomastia and an areolar lesion for a 6-month duration following a traumatic event. He was initially referred to the surgical team for further evaluation, and subsequent imaging and biopsy data revealed ER/PR-positive invasive ductal carcinoma. Multidisciplinary discussions were held, and the patient was arranged to begin neoadjuvant treatment with doxorubicin hydrochloride and cyclophosphamide, followed by treatment with paclitaxel (AC-T) chemotherapy, followed by bilateral mastectomy and adjuvant hormonal therapy. CONCLUSIONS The treatment of male breast cancer has remained relatively like that of female breast cancer, which may be due to the limited data in the treatment of male breast cancer. Thus far, studies involving neoadjuvant chemotherapy of female patients have demonstrated promising responses to expand surgical options for patients and possibly decrease the rates of recurrence. Additional studies are warranted to discern optimal therapy for the male patient population.}, } @article {pmid36332363, year = {2022}, author = {Davis, AA and Gerratana, L and Clifton, K and Medford, AJ and Velimirovic, M and Hensing, WL and Bucheit, L and Shah, AN and D'Amico, P and Reduzzi, C and Zhang, Q and Dai, CS and Denault, EN and Bagegni, NA and Opyrchal, M and Ademuyiwa, FO and Bose, R and Gradishar, WJ and Behdad, A and Ma, CX and Bardia, A and Cristofanilli, M}, title = {Circulating tumour DNA characterisation of invasive lobular carcinoma in patients with metastatic breast cancer.}, journal = {EBioMedicine}, volume = {86}, number = {}, pages = {104316}, pmid = {36332363}, issn = {2352-3964}, support = {UL1 TR001422/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/genetics/metabolism/pathology ; *Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; *Circulating Tumor DNA/genetics ; Retrospective Studies ; DNA Copy Number Variations ; Phosphatidylinositol 3-Kinases/genetics ; }, abstract = {BACKGROUND: Limited data exist to characterise molecular differences in circulating tumour DNA (ctDNA) for patients with invasive lobular carcinoma (ILC). We analysed metastatic breast cancer patients with ctDNA testing to assess genomic differences among patients with ILC, invasive ductal carcinoma (IDC), and mixed histology.

METHODS: We retrospectively analysed 980 clinically annotated patients (121 ILC, 792 IDC, and 67 mixed histology) from three academic centers with ctDNA evaluation by Guardant360™. Single nucleotide variations (SNVs), copy number variations (CNVs), and oncogenic pathways were compared across histologies.

FINDINGS: ILC was significantly associated with HR+ HER2 negative and HER2 low. SNVs were higher in patients with ILC compared to IDC or mixed histology (Mann Whitney U test, P < 0.05). In multivariable analysis, HR+ HER2 negative ILC was significantly associated with mutations in CDH1 (odds ratio (OR) 9.4, [95% CI 3.3-27.2]), ERBB2 (OR 3.6, [95% confidence interval (CI) 1.6-8.2]), and PTEN (OR 2.5, [95% CI 1.05-5.8]) genes. CDH1 mutations were not present in the mixed histology cohort. Mutations in the PI3K pathway genes (OR 1.76 95% CI [1.18-2.64]) were more common in patients with ILC. In an independent cohort of nearly 7000 metastatic breast cancer patients, CDH1 was significantly co-mutated with targetable alterations (PIK3CA, ERBB2) and mutations associated with endocrine resistance (ARID1A, NF1, RB1, ESR1, FGFR2) (Benjamini-Hochberg Procedure, all q < 0.05).

INTERPRETATION: Evaluation of ctDNA revealed differences in pathogenic alterations and oncogenic pathways across breast cancer histologies with implications for histologic classification and precision medicine treatment.

FUNDING: Lynn Sage Cancer Research Foundation, OncoSET Precision Medicine Program, and UL1TR001422.}, } @article {pmid36328867, year = {2023}, author = {Cha, Y and Lee, S}, title = {Endoscopy-assisted latissimus dorsi muscle flap harvesting technique for immediate breast reconstruction.}, journal = {Annales de chirurgie plastique et esthetique}, volume = {68}, number = {4}, pages = {308-314}, doi = {10.1016/j.anplas.2022.09.004}, pmid = {36328867}, issn = {1768-319X}, mesh = {Humans ; Female ; Adult ; Middle Aged ; *Breast Neoplasms/surgery/pathology ; Mastectomy/methods ; *Superficial Back Muscles/surgery ; Cicatrix/surgery ; *Mammaplasty/methods ; Endoscopy/methods ; Postoperative Complications/surgery ; Retrospective Studies ; }, abstract = {BACKGROUND: The purpose of this study is to investigate the usefulness of endoscopy-assisted latissimus dorsi muscle flap (LDMF) harvesting in immediate breast reconstruction following partial mastectomy.

MATERIALS AND METHODS: From November 2016 to December 2019, sixteen female breast cancer patients who underwent immediate breast reconstruction following partial mastectomy underwent LDMF harvesting with endoscopic assistance. This surgical technique was carried out with only one subaxillary skin incision without leaving a scar on the back. Patients' demographic characteristics, histopathologic factors, operative data, postoperative complications, and oncologic safety were collected through electronic chart review.

RESULTS: In sixteen patients, LDMFs were harvested successfully using an endoscopy-assisted technique without conversion to an open technique. The mean age of the patients was 48.0±8.0 years, and the mean body mass index was 24.4±3.9kg/m[2]. The most common histologic subtype was invasive ductal carcinoma, with a mean tumor size of 3.2±2.3cm. In terms of LDMF harvesting time, it took 168.4±44.0minutes. The most common postoperative complication, donor site seroma (75%), was managed non-surgically during the outpatient visit. In terms of cosmetic aspects, we've seen a high level of patient satisfaction, especially with scarring.

CONCLUSIONS: Endoscopy-assisted LDMF harvesting technique is safe and useful for breast reconstruction after partial mastectomy. Compared to the conventional open technique, this method does not leave a long scar on the donor site. As a result, it leads to better cosmetic outcomes and improves patient satisfaction.}, } @article {pmid36320968, year = {2022}, author = {Rathod, GB and Desai, KN and Shrivastava, A and Maru, AM}, title = {Correlation of Tumor Budding With Known Clinicopathological, Histomorphological and Hormonal Receptor Status in Patients With Invasive Breast Carcinoma.}, journal = {Cureus}, volume = {14}, number = {9}, pages = {e29637}, pmid = {36320968}, issn = {2168-8184}, abstract = {Introduction: Tumor blossoming may be a predictive indicator for a variety of cancers. At the invasive origin of the tumor, cells get detached from the original tumor mass. Aims & objectives: Studying breast cancer tumor budding, as well as its link to other prognostic indicators, such as clinicopathological features and hormone receptor status, will be the focus of this study. Materials & methods: Over six years, 110 cases of invasive breast cancer were examined. Ten high-power fields were used to analyze H&E-stained slices for tumor sprouting. It was determined that the tumor buds were divided into low and high grades. Tumor budding and other prognostic factors were compared using the chi-square test. It was considered significant if the p-value was less than or equal to 0.05. Results: There were 110 cases of invasive ductal carcinoma, which accounts for more than half of the total cases (88.18%). A total of 144 tumors were present, of which 74 displayed strong budding and 36 displayed poor budding. A correlation between tumor budding and tumor size, lymph node metastasis, and tumor stage is statistically significant (P = 0.0099). Conclusion: Tumor budding in breast cancer is an easily visible in microscopy, novel prognostic indicator. A new prognostic element may be added to the reporting process.}, } @article {pmid36319039, year = {2022}, author = {Khan, AM and Arjyal, L and Shamaileh, L and Simon, M}, title = {Gemcitabine-induced digital ischaemia in a patient with metastatic breast cancer.}, journal = {BMJ case reports}, volume = {15}, number = {11}, pages = {}, pmid = {36319039}, issn = {1757-790X}, mesh = {Female ; Humans ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; Deoxycytidine ; Ischemia ; Middle Aged ; Gemcitabine ; }, abstract = {A woman in her 50s with HER2 (human epidermal growth factor receptor 2) positive, estrogen/progesterone receptor negative, metastatic invasive ductal carcinoma of the breast, presented with acral cyanosis and severe throbbing pain after recent administration of gemcitabine. She was treated with aspirin, heparin, amlodipine, topical nitroglycerin and analgesics. Gemcitabine was discontinued permanently. She had a gradual recovery except for a small necrotic area over the right 4th digit. However, surgical intervention was avoided.}, } @article {pmid36309875, year = {2022}, author = {Chen, K and Chen, X and Su, Y}, title = {Is conservative treatment a good choice for pediatric intervertebral disc calcification in children?.}, journal = {European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society}, volume = {31}, number = {12}, pages = {3324-3329}, pmid = {36309875}, issn = {1432-0932}, mesh = {Humans ; Male ; Female ; Child ; Child, Preschool ; Conservative Treatment ; *Intervertebral Disc Degeneration/diagnostic imaging/therapy/complications ; *Ossification of Posterior Longitudinal Ligament/complications ; Longitudinal Ligaments ; *Calcinosis/diagnostic imaging/therapy/complications ; Magnetic Resonance Imaging ; *Intervertebral Disc/diagnostic imaging/pathology ; *Intervertebral Disc Displacement/complications ; }, abstract = {PURPOSE: Paediatric intervertebral disc calcification (PIDC) is a rare disease, and its aetiology remains unknown. This study aimed to analyse the characteristics and clinical outcomes of patients with PIDC.

METHODS: After applying the exclusion and inclusion criteria, 159 children diagnosed with PIDC were analysed at our hospital between January 2010 and November 2020. Patients' demographic and clinical data were collected, such as sex, pain, duration time, physical examination, white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and radiography, computed tomography, and magnetic resonance imaging findings. Patients were followed up for at least 6 months, and radiography or symptoms were evaluated. Fisher's exact test or χ[2]-test was used for statistical analyses.

RESULTS: One hundred and fifty-nine patients were ultimately followed up with for about 12.5 ± 5.8 months. There were 103 male and 56 female, with an average age of 6.08 ± 2.62 years (2 months to 12 years). A total of 109 patients had only one PIDC, 29 patients had two PIDCs, and 21 patients had multiple PIDCs. Thirty patients were found incidentally and were asymptomatic. A total of 106 patients had neck torticollis. Sixteen patients had IDC herniations, fifteen patients had posterior longitudinal ligament calcification, two patients had anterior longitudinal ligament calcification, and 17 patients had herniation of the vertebral canal. All patients underwent conservative treatment, and none underwent surgery. All patients' symptoms resolved after either collar fixation or neck traction.

CONCLUSION: PIDC can be treated conservatively, even when accompanied by herniation, longitudinal ligament calcification, or clinical neck symptoms.

LEVEL OF EVIDENCE: IV.}, } @article {pmid36309195, year = {2022}, author = {Lin, CW and Chiang, MH and Tam, KW}, title = {Treatment of Mammary Paget Disease: A systematic review and meta-analysis of real-world data.}, journal = {International journal of surgery (London, England)}, volume = {107}, number = {}, pages = {106964}, doi = {10.1016/j.ijsu.2022.106964}, pmid = {36309195}, issn = {1743-9159}, mesh = {Humans ; Female ; *Paget's Disease, Mammary/surgery ; Mastectomy ; *Breast Neoplasms/surgery ; Sentinel Lymph Node Biopsy ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; }, abstract = {BACKGROUND: Because the lesions of mammary Paget disease (MPD) are often limited to the nipple-areolar complex, the extension of optimal tumor excision is inconclusive. Moreover, the risk of potential tumor upstaging is unknown; therefore, the application of sentinel lymph node biopsy (SLNB) is required for analysis. We systematically reviewed the real-world data to evaluate the optimal treatment and potential predictors of poorer prognosis for MPD.

METHODS: The PubMed, Embase, and Cochrane Library databases were searched for relevant studies. Clinical studies were included if they evaluated the outcome of positive rates of SLNB, prognostic risk factors of MPD, and survival outcomes of treatments of interest for MPD, including mastectomy, breast-conserving surgery (BCS) with radiotherapy, and BCS alone.

RESULTS: A total of 38 studies with 24,062 patients were retrieved. Compared with BCS alone (21.2%), mastectomy (5.9%; P < 0.001) and BCS with radiotherapy (8; P = 0.001) had significantly lower local recurrence rates. Patients with palpable tumors (30.2%) had significantly worse prognoses than those with impalpable (3.4%) tumors in metastasis (P < 0.001), and significantly higher local recurrence rates were observed in patients with underlying invasive carcinoma (6.7%) than those with noninvasive carcinoma (4.5%; P = 0.032). The positive rate of SLNB was 17% (95% CI: 0.115-0.226).

CONCLUSION: Except for MPD alone, BCS alone is not recommended for treating MPD with invasive ductal carcinoma and MPD with ductal carcinoma in situ. Moreover, a palpable mass, underlying invasive carcinoma, and positive lymph node status may lead to a poorer prognosis, which may be taken into consideration for the application of SLNB.}, } @article {pmid36308374, year = {2022}, author = {Gautam, P and Feroz, Z and Tiwari, S and Vijayraghavalu, S and Shukla, GC and Kumar, M}, title = {Investigating the Role of Glutathione S- Transferase Genes, Histopathological and Molecular Subtypes, Gene-Gene Interaction and Its Susceptibility to Breast Carcinoma in Ethnic North- Indian Population.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {23}, number = {10}, pages = {3481-3490}, pmid = {36308374}, issn = {2476-762X}, support = {R15 CA252997/CA/NCI NIH HHS/United States ; }, mesh = {Female ; Humans ; *Breast Neoplasms/epidemiology/genetics ; Case-Control Studies ; *Genetic Predisposition to Disease ; Genotype ; Glutathione ; Glutathione S-Transferase pi/genetics ; Glutathione Transferase/genetics ; Risk Factors ; }, abstract = {BACKGROUND: Breast Cancer (BC) is a genetically and clinically heterogeneous disease including complex interactions between gene-gene and gene-environment components. This study aimed, to explore whether the Glutathione S- transferase (GSTs) gene polymorphism has role in BC susceptibility. We further evaluated the frequency of four subtypes of BC based on molecular classification followed by microscopic histological analysis to study the grades of invasive ductal carcinoma (IDC).

MATERIALS AND METHOD: Polymorphism in GST genes in North-Indian BC patients was assessed by multiplex-PCR and PCR-RFLP methods. 105 BC patients and 145 healthy controls were enrolled for this study. Data was analyzed by calculating the odds ratio (OR) and 95% CI from logistic regression analyses.

RESULTS: Our findings revealed that GSTM1 null genotype (OR = 2.231; 95% CI = 1.332-3.737; p-value= 0.002) is significantly associated to BC risk in ethnic North- Indian population. However, the risk for BC susceptibility in North-Indians does not appear to be associated with GSTT1 null genotype. The GSTP1 (Val/Val) genotype (OR=1.545; CI=0.663-3.605; p-value= 0.314) was also found to be susceptible for BC risk. Combination of three high risk GST genotypes association exhibiting gene-gene interaction further confirmed the increased risk to BC in this region.

CONCLUSIONS: The results of present study indicated that polymorphism in GSTM1 and rs1695 of GSTP1 genes may influence BC development among North-Indian women. Thus, the screening of GSTM1 and GSTP1 gene should be recommended for the earlier investigation for BC as a precautionary measure.}, } @article {pmid36303871, year = {2022}, author = {Al-Saoudi, E and Christensen, MMB and Nawroth, P and Fleming, T and Hommel, EE and Jørgensen, ME and Fleischer, J and Hansen, CS}, title = {Advanced glycation end-products are associated with diabetic neuropathy in young adults with type 1 diabetes.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {891442}, pmid = {36303871}, issn = {1664-2392}, mesh = {Young Adult ; Humans ; *Diabetic Neuropathies/complications ; *Diabetes Mellitus, Type 1/complications ; Cross-Sectional Studies ; *Diabetes Mellitus, Type 2/complications ; Lipids ; }, abstract = {AIMS/HYPOTHESIS: Advanced glycation end-products (AGEs) may contribute to the development of diabetic neuropathy. In young adults with type 1 diabetes, we aimed to investigate the association between AGEs and cardiovascular autonomic neuropathy (CAN) and distal symmetric polyneuropathy (DSPN).

METHODS: This cross-sectional study comprised 151 young adults. CAN was assessed by cardiovascular autonomic reflex tests; lying-to-standing test, deep breathing test (E/I), Valsalva manoeuvre, and heart rate variability indices; and the mean square of the sum of the squares of differences between consecutive R-R intervals and standard deviation of normal-to-normal intervals (SDNN), high- (HF) and low-frequency (LF) power, total frequency power, and the LF/HF ratio. DSPN was assessed by light touch, pain and vibration perception threshold (VPT), neuropathy questionnaires, and objective measures. AGEs were analysed in four groups using z-scores adjusted for relevant confounders and multiple testing: i) "glycolytic dysfunction", ii) "lipid peroxidation", iii) "oxidative stress", and iv) "glucotoxicity".

RESULTS: A higher z-score of "glycolytic dysfunction" was associated with higher VPT (4.14% (95% CI 1.31; 7.04), p = 0.004) and E/I (0.03% (95% CI 0.01; 0.05), p = 0.005), "lipid peroxidation" was associated with higher LF/HF ratio (37.72% (95% CI 1.12; 87.57), p = 0.044), and "glucotoxicity" was associated with lower SDNN (-4.20% (95% CI -8.1416; -0.0896), p = 0.047). No significance remained after adjustment for multiple testing.

CONCLUSIONS/INTERPRETATIONS: In young adults with type 1 diabetes, increased levels of AGEs involving different metabolic pathways were associated with several measures of CAN and DSPN, suggesting that AGEs may play a diverse role in the pathogeneses of diabetic neuropathy.}, } @article {pmid36299777, year = {2022}, author = {Bealy, MA and Abugooda, AA and Ahmed, RME and Khalil, NAR and Elasbali, AM and Mohamed, GEY and Eltom, FM and Ahmed, H}, title = {Patterns of Immunohistochemical Expression of P53, BCL2, PTEN, and HER2/neu Tumor Markers in Specific Breast Cancer Lesions.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2022}, number = {}, pages = {2026284}, pmid = {36299777}, issn = {1741-427X}, abstract = {OBJECTIVE: This study aimed to associate the expression of P53, BCL2, PTEN, and HER2/neu tumor markers in specific breast cancer lesions.

METHODS: This study analyzed the immunohistochemical expression of P53, BCL2, PTEN, and HER2/neu tumor markers for 306 patients who presented with lesions. Tissue blocks and patients' identification data were retrieved from the department of pathology, AL Madinah Almonwarah hospital, Al Madinah, UAE.

RESULTS: Of the 306 patients, 104 had benign lesions and 202 had malignancy (including 194 females and 6 males). Most females were presented with invasive ductal carcinoma (IDC), followed by infiltrating ductal carcinoma, and invasive lobular carcinoma (ILC), representing 70%, 23.2%, and 3.7%, respectively. Positive P53, BCL2, PTEN, and HER2 were identified in 20.8%, 11.9%, 91%, and 18.3%, respectively.

CONCLUSION: : The expression of P53, BCL2, PTEN, and HER2/neu tumor markers among Saudi patients with breast cancer is relatively similar in many parts of the world.}, } @article {pmid36296007, year = {2022}, author = {Hu, W and Wu, B and Srivastava, SK and Ay, SU}, title = {Comparative Study and Simulation of Capacitive Sensors in Microfluidic Channels for Sensitive Red Blood Cell Detection.}, journal = {Micromachines}, volume = {13}, number = {10}, pages = {}, pmid = {36296007}, issn = {2072-666X}, abstract = {Microfluidics provides an indispensable platform for combining analytical operations such as sample preparation, mixing, separation/enrichment, and detection onto a single compact platform, defined as a lab-on-a-chip (LOC) device with applicability in biomedical and life science applications. Due to its ease of integration, 1D interdigital capacitive (IDC) sensors have been used in microfluidic platforms to detect particles of interest. This paper presents a comparative study on the use of capacitive sensors for microfluidic devices to detect bioparticles, more specifically red blood cells (RBCs). The detection sensitivities of 1D, 2D, and 3D capacitive sensors were determined by simulation using COMSOL Multiphysics[®] v5.5. A water-filled 25 μm × 25 μm PDMS microfluidic channel was used with different sizes (5-10 μm) of red blood cells passing across the capacitive sensor regions. The conformal mapping was used for translating the 1D IDC sensor dimensions into equivalent 2D/3D parallel plate capacitance (PPC) sensor dimensions, creating similar absolute sensor capacitance. The detection sensitivity of each capacitive sensor is determined, and a new 3D PPC sensor structure was proposed to improve the sensitivity for high-resolution RBC detection in microfluidic channels. Proposed 2D and 3D sensors provide a 3× to 20× improvement in sensitivity compared to the standard 1D IDC structures, achieving a 100 aF capacitance difference when a healthy RBC passes in the structure.}, } @article {pmid36291370, year = {2022}, author = {Riskin, Y and Riskin, A and Zaitoon, H and Habib, C and Blanche, E and Gover, A and Mintz, A}, title = {The Effects of Rudeness on NICU Medical Teams Studied by a New Tool for the Assessment of Decision-Making Group Dynamics.}, journal = {Children (Basel, Switzerland)}, volume = {9}, number = {10}, pages = {}, pmid = {36291370}, issn = {2227-9067}, abstract = {BACKGROUND: Group decision-making can be placed on a continuum of group dynamics, between Groupthink and Polythink.

OBJECTIVE: To present a new assessment tool for the characterization of medical teams' decision-making group dynamics, and test it to study the effects of exposure to rudeness on various types of group dynamics.

METHODS: Three judges who watched videotapes of critical care simulations evaluated 24 neonatal intensive care unit teams' decision-making processes. Teams were rated using the new assessment tool, especially designed for this quantitative study, based on items adapted from symptoms of Polythink and Groupthink.

RESULTS: Measures of reliability, inter-rater agreement and internal consistency, were reasonably good. Confirmatory factor analysis refined the tool and verified that the symptoms in each category (Polythink or Groupthink) of the refined 14 items' assessment tool were indeed measures of the construct. The average General Score was in the range of the balanced dynamic on the continuum, and without tendency towards one of the extremities (Groupthink or Polythink). No significant effect of exposure to rudeness on group dynamics was found.

CONCLUSIONS: This is a first attempt at using quantitative methods to evaluate decision-making group dynamics in medicine, by adapting symptoms of Groupthink and Polythink as items in a structured assessment tool. It suggests a new approach to understanding decision-making processes of medical teams. The assessment tool seems to be a promising, feasible and reasonably reliable research tool to be further studied in medicine and other disciplines engaged in decision-making.}, } @article {pmid36289427, year = {2022}, author = {Xu, R and Yang, TX and Fang, KW and Wang, G and Li, P}, title = {Efficacy, according to urodynamics, of OnabotulinumtoxinA compared with antimuscarinic drugs, for neurogenic detrusor overactivity: a systematic review and network meta-analysis.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {17905}, pmid = {36289427}, issn = {2045-2322}, mesh = {Humans ; *Botulinum Toxins, Type A ; Urodynamics ; Muscarinic Antagonists/therapeutic use/pharmacology ; *Urinary Bladder, Neurogenic/drug therapy ; Solifenacin Succinate/pharmacology/therapeutic use ; Tolterodine Tartrate/pharmacology ; Bayes Theorem ; Treatment Outcome ; *Urinary Bladder, Overactive/drug therapy ; }, abstract = {To summarize the differences in urodynamic outcomes between oral antimuscarinic drugs and OnabotulinumtoxinA, and finding a therapy that maintains good urodynamics in neurogenic detrusor overactivity (NDO). We conducted a literature search of EMBASE and PubMed, with the language limited to English. In the analysis, all of the published randomized trials of OnabotulinumtoxinA or antimuscarinic drugs used to treat NDO were found and the results were finally obtained through Bayesian model analysis. A total of 12 RCTs and 2208 patients were included. OnabotulinumtoxinA 300U was superior to other drugs in terms of MCC, volume at IDC, and Pdetmax endpoints. OnabotulinumtoxinA 200U was more effective on the urodynamic endpoint of BC than other drugs or doses of OnabotulinumtoxinA. According to the MCC urodynamic results, oxybutynin, solifenacin 10 mg, and tolterodine 4 mg also had positive effects. OnabotulinumtoxinA 300U, 200U and 100U were better in improving the urodynamic results of NDO, and the current evidence also shows that selective injection of onabotulinumtoxinA can effectively improve the urodynamic results.}, } @article {pmid36288886, year = {2022}, author = {Takahashi, E and Imai, K and Fukuyama, M and Terata, K and Nanjo, H and Ishiyama, K and Hiroshima, Y and Yatsuyanagi, M and Kudo, C and Morishita, A and Wakita, A and Takashima, S and Sato, Y and Nomura, K and Minamiya, Y}, title = {Changes in Serum Trace Element Concentrations Before and After Surgery in Resectable Breast Cancer.}, journal = {Anticancer research}, volume = {42}, number = {11}, pages = {5323-5334}, doi = {10.21873/anticanres.16039}, pmid = {36288886}, issn = {1791-7530}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; *Breast Neoplasms/surgery/pathology ; *Carcinoma, Ductal, Breast/surgery/pathology ; Mastectomy ; *Trace Elements ; Vanadium ; Copper ; Boron ; *Selenium ; Titanium ; Reproducibility of Results ; Retrospective Studies ; Biomarkers ; Chromium ; Zinc ; }, abstract = {BACKGROUND/AIM: Minerals and trace elements (TEs) play vital roles in normal biological functions and in all cancers. Breast carcinoma is the most commonly occurring cancer in women. The aim of this study was to evaluate changes in TE levels before and after breast cancer surgery and the clinical utility and reliability of TE levels assayed using inductively coupled plasma mass spectrometry (ICP-MS).

PATIENTS AND METHODS: Thirteen patients with ductal carcinoma in situ (DCIS) and 34 with invasive ductal carcinoma (IDC) treated with planned surgery were enrolled between August 2017 and February 2019. Blood samples were collected before and the day after resection of the primary tumor. All enrolled patients received mastectomy or quadrantectomy and axillary lymph node dissection/biopsy. Serum TE concentrations were determined using ICP-MS.

RESULTS: Changes in boron, titanium, vanadium, chromium, copper, zinc, and selenium levels from before to after surgery differed between IDC and DCIS patients. Boron and copper levels before surgery and changes in titanium, vanadium, and chromium before and after surgery are potential predictors distinguishing DCIS from IDC. Subset analysis showed that chromium is a potential biomarker for luminal subtype, while titanium and chromium are potential biomarkers for pathological staging.

CONCLUSION: Changes in serum TEs before and after surgery may help with diagnosis and staging of breast cancer and in establishing TE supplementation protocols.}, } @article {pmid36284635, year = {2022}, author = {Zhang, H and Yuan, J and Xiang, Y and Liu, Y}, title = {Comprehensive Analysis of NPSR1-AS1 as a Novel Diagnostic and Prognostic Biomarker Involved in Immune Infiltrates in Lung Adenocarcinoma.}, journal = {Journal of oncology}, volume = {2022}, number = {}, pages = {2099327}, pmid = {36284635}, issn = {1687-8450}, abstract = {The incidence of lung adenocarcinoma (LUAD), the most common subtype of lung cancer, continues to make lung cancer the largest cause of cancer-related deaths worldwide. Long noncoding RNAs (lncRNAs) have been shown to have a significant role in both the onset and progression of lung cancer. In this study, we aimed to investigate the clinical significance and underlying mechanism of lncRNA NPSR1-AS1 (NPSR1-AS1) in LUAD. First, we performed an analysis on TCGA and identified 229 differentially expressed lncRNAs (DELs) (including 216 upregulated lncRNAs and 13 downregulated lncRNAs). Then, we carried out a screening of the lncRNAs associated with survival, and a total of 382 survival-related lncRNAs were found. 15 survival-related DELs were identified. Among them, our attention focused on NPSR1-AS1. We found that the expression of NPSR1-AS1 was much higher in LUAD specimens compared to nontumor tissues. According to the results of the ROC assays, high NPSR1-AS1 expression had an AUC value of 0.904 for LUAD, with a 95% confidence interval ranging from 0.881 to 0.927. The expression of NPSR1-AS1 was shown to be significantly elevated in a wide variety of cancers, according to the findings of a pancancer investigation. Functional enrichment analysis confirmed that NPSR1-AS1 was involved in LUAD progression via regulating several tumor-related pathways. Patients with high levels of NPSR1-AS1 expression were shown to have a shorter disease-specific survival (DSS) or overall survival (OS) than those with low levels of NPSR1-AS1 expression, according to the findings of a clinical investigation. It was determined by multivariate analysis that NPSR1-AS1 expressions served as an independent prognostic factor for the overall survival of LUAD patients. The results of immune cell infiltration revealed that the expressions of NPSR1-AS1 were negatively associated with CD8 T cells, pDC, cytotoxic cells, mast cells, iDC, neutrophils, NK CD56dim cells, DC, Th17 cells, Tgd, and macrophages, while they were positively associated with NK CD56bright cells and B cells. Overall, our findings revealed that NPSR1-AS1 could serve as a potential biomarker to assess the clinical outcome and immune infiltration level in LUAD.}, } @article {pmid36283996, year = {2024}, author = {Sanderson, C and Verdellen, C and Debes, N and Tárnok, Z and van de Griendt, J and Zimmerman-Brenner, S and Murphy, T}, title = {Addressing co-occurring conditions in behavioural therapy for tic disorders: a review and guideline.}, journal = {European child & adolescent psychiatry}, volume = {33}, number = {7}, pages = {2111-2127}, pmid = {36283996}, issn = {1435-165X}, mesh = {Humans ; *Tic Disorders/therapy ; *Behavior Therapy/methods ; *Comorbidity ; Child ; Attention Deficit Disorder with Hyperactivity/therapy/complications ; Autism Spectrum Disorder/therapy/complications ; Obsessive-Compulsive Disorder/therapy ; Practice Guidelines as Topic ; Adult ; Tourette Syndrome/therapy ; Adolescent ; }, abstract = {Co-occurring psychiatric conditions are very common in tic disorders and Tourette syndrome. These additional symptoms are often detrimental to quality of life and may impact upon the implementation and efficacy of evidence-based behavioural therapies (BT) for tics. Combining a review of the available literature, relevant theory, and expert clinical practice, we present a guideline for implementing behavioural and psychosocial interventions when common comorbidities are present. These include attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, disruptive behaviour, autism spectrum disorder (ASD) and depression. Practical recommendations are provided for assessment, formulation and management of specific and multiple comorbidities in BT for both children and adults. Despite comorbidities being common in tic disorders, few studies have comprehensively addressed how they may influence the efficacy or implementation of existing therapies or how such treatments may need to be modified or sequenced. We outline recommendations for future research, including randomised control trials of BT for those with specific or multiple comorbidities, as well as adequately powered sub-group analyses within larger scale trials or naturalistic study designs. Transdiagnostic models of psychiatric disorders and treatment, including modular cross-diagnostic therapies, which recognise the dimensionality of psychiatric disorders are also highlighted as an important focus in treatment development in tic disorders.}, } @article {pmid36283257, year = {2022}, author = {Öztürk, Ç and Aşkan, G and Öztürk, SD and Okcu, O and Şen, B and Bedir, R}, title = {Does the number of cell forming tumor budding alter the prognostic value in invasive ductal carcinoma of breast?.}, journal = {Pathology, research and practice}, volume = {240}, number = {}, pages = {154157}, doi = {10.1016/j.prp.2022.154157}, pmid = {36283257}, issn = {1618-0631}, mesh = {Humans ; Female ; Prognosis ; Lymphatic Metastasis/pathology ; *Breast Neoplasms/pathology ; Lymph Nodes/pathology ; *Carcinoma, Ductal/pathology ; *Carcinoma, Ductal, Breast/pathology ; Retrospective Studies ; }, abstract = {BACKGROUND AND OBJECTIVE: The most commonly used definition for tumor budding (TB) is a single or a cell cluster of tumor cells up to 4 cells. However, there are different opinions regarding the number of cell (NOC) forming TB. It has been proven that TB is associated with poor prognostic factors in most tumors. The current study, it was aimed to investigate the prognostic value of NOC forming TB in invasive ductal carcinoma of the breast.

MATERIALS AND METHODS: 326 cases with the diagnosis of invasive ductal carcinoma were examined. The NOC forming TB was counted from hematoxylin and eosin stained slide under X200 magnification for each case, and scoring five different TB as 1, ≤ 2, ≤ 3, ≤ 4, ≤ 5, respectively. Receiver operating characteristic (ROC) analysis based on survival was performed for each TB value separately, and the cut-off was determined.

RESULTS: All TB values were associated with poor outcome (p < 0.001), presence of distant metastasis (p < 0.001), high Ki67 proliferation index (p < 0.05), advanced stage (p < 0.05), presence of lymphovascular invasion (p < 0.001), and metastatic axillary lymph node (p < 0.001). According to ROC analysis performed to compare the predictiveness of survival, the area under the curve was similar for all TB values.

CONCLUSION: TB was associated with poor prognostic parameters, and the prognostic value of TB was not affected by NOC forming TB. The NOC up to 4 cells which have been accepted for colon carcinomas, could also provide practicality in breast carcinomas.}, } @article {pmid36282904, year = {2022}, author = {Cao, S and Qiu, Y and Unarta, IC and Goonetilleke, EC and Huang, X}, title = {The Ion-Dipole Correction of the 3DRISM Solvation Model to Accurately Compute Water Distributions around Negatively Charged Biomolecules.}, journal = {The journal of physical chemistry. B}, volume = {126}, number = {43}, pages = {8632-8645}, doi = {10.1021/acs.jpcb.2c04431}, pmid = {36282904}, issn = {1520-5207}, mesh = {*Water/chemistry ; Thermodynamics ; Solvents/chemistry ; Solutions/chemistry ; *Nucleotides ; }, abstract = {The 3D reference interaction site model (3DRISM) provides an efficient grid-based solvation model to compute the structural and thermodynamic properties of biomolecules in aqueous solutions. However, it remains challenging for existing 3DRISM methods to correctly predict water distributions around negatively charged solute molecules. In this paper, we first show that this challenge is mainly due to the orientation of water molecules in the first solvation shell of the negatively charged solute molecules. To properly consider this orientational preference, position-dependent two-body intramolecular correlations of solvent need to be included in the 3DRISM theory, but direct evaluations of these position-dependent two-body intramolecular correlations remain numerically intractable. To address this challenge, we introduce the Ion-Dipole Correction (IDC) to the 3DRISM theory, in which we incorporate the orientation preference of water molecules via an additional solute-solvent interaction term (i.e., the ion-dipole interaction) while keeping the formulism of the 3DRISM equation unchanged. We prove that this newly introduced IDC term is equivalent to an effective direct correlation function which can effectively consider the orientation effect that arises from position dependent two-body correlations. We first quantitatively validate our 3DRISM-IDC theory combined with the PSE3 closure on Cl[-], [ClO][-] (a two-site anion), and [NO2][-] (a three-site anion). For all three anions, we show that our 3DRISM-IDC theory significantly outperforms the 3DRISM theory in accurately predicting the solvation structures in comparison to MD simulations, including RDFs and 3D water distributions. Furthermore, we have also demonstrated that the 3DRISM-IDC can improve the accuracy of hydration free-energy calculation for Cl[-]. We further demonstrate that our 3DRISM-IDC theory yields significant improvements over the 3DRISM theory when applied to compute the solvation structures for various negatively charged solute molecules, including adenosine triphosphate (ATP), a short peptide containing 19 residues, a DNA hairpin containing 24 nucleotides, and a riboswitch RNA molecule with 77 nucleotides. We expect that our 3DRISM-IDC-PSE3 solvation model holds great promise to be widely applied to study solvation properties for nucleic acids and other biomolecules containing negatively charged functional groups.}, } @article {pmid36281523, year = {2023}, author = {Chen, MY and Zarrin-Khameh, N and Xu, Y}, title = {Fine needle aspiration of pancreatic lesions focusing on secondary tumors with emphasis of metastatic breast cancer: A clinicopathological study with follow-up.}, journal = {Cancer medicine}, volume = {12}, number = {5}, pages = {5485-5493}, pmid = {36281523}, issn = {2045-7634}, mesh = {Humans ; Female ; Biopsy, Fine-Needle ; *Breast Neoplasms/pathology ; Retrospective Studies ; Follow-Up Studies ; Pancreas/pathology ; *Pancreatic Neoplasms/diagnosis/pathology ; *Carcinoma, Squamous Cell/pathology ; *Carcinoma, Renal Cell/pathology ; *Kidney Neoplasms/pathology ; }, abstract = {BACKGROUND: The data on metastatic tumors to the pancreas diagnosed by fine needle aspiration (FNA) biopsy is limited. We report our experience of FNA of primary and secondary pancreatic tumors emphasizing metastatic breast cancer in the pancreas.

METHOD: Total 274 cases of pancreatic FNA in 10 years were retrospectively reviewed. Literature review of metastatic breast cancers to the pancreas was performed.

RESULTS: Out of the 274 cases, 7 (7/274, 2.6%) cases were non-diagnostic, 46 (46/274, 16.8%) cases were negative for malignancy, and 40 (40/274, 14.6%) cases were under the category of atypical cells. There were 133 (133/274, 48.5%) cases diagnosed as positive for malignancy, 20 (20/274, 7.3%) suspicious for malignancy, and 28 (28/274, 10.2%) cases in the category of neoplastic: other. The most common neoplasm diagnosed was ductal adenocarcinoma (114/274, 41.6%; 114/133, 85.7% in positive for malignancy category). Ten cases (10/274, 3.7%) were diagnosed as metastatic neoplasms to the pancreas, including four breast infiltrating ductal carcinomas (IDC), one endocervical adenocarcinoma, one anal/rectal squamous cell carcinoma, one renal cell carcinoma, one hepatocellular carcinoma, one seminoma and one lung adenocarcinoma. We summarized the biomarkers of the four metastatic breast cancers and conducted literature review on biomarkers of metastatic breast cancers to the pancreas.

CONCLUSIONS: Upon analyzing FNAs of primary and secondary tumors in the pancreas, we have found breast carcinoma is the most common secondary pancreatic neoplasm in our patient population. Triple negative breast ductal carcinoma is the most common tumor among the metastasis of breast carcinomas to the pancreas. To the best of our knowledge, this study is the first report with a literature review focusing on biomarkers of metastatic breast cancer to the pancreas.}, } @article {pmid36276283, year = {2022}, author = {Shen, N and Zhu, S and Zhang, Z and Yong, X}, title = {High Expression of COL10A1 Is an Independent Predictive Poor Prognostic Biomarker and Associated with Immune Infiltration in Advanced Gastric Cancer Microenvironment.}, journal = {Journal of oncology}, volume = {2022}, number = {}, pages = {1463316}, pmid = {36276283}, issn = {1687-8450}, abstract = {Medical technology has become more and more sophisticated recently, which, however, fails to contribute to a better prognosis for patients suffering advanced gastric cancer (GC). Hence, new biomarkers specific to GC diagnosis and prognosis shall be identified urgently. This study screened differentially expressed genes (DEGs) between 375 GC samples and 32 paracancer tissue samples from TCGA datasets. The expression of Collagen type X alpha 1 (COL10A1) in GC was analyzed. The chi-square test assisted in analyzing the relevance of COL10A1 to the clinicopathologic characteristics. The Kaplan-Meier method helped to assess the survival curves and log-rank tests assisted in the examination of the differences. The Cox proportional hazard regression model served for analyzing the risk factors for GC. Then, we developed a nomogram that contained the COL10A1 expression and clinical information. Finally, how COL10A1 expression was associated with the immune infiltration was also evaluated. In this study, 7179 upregulated and 3771 downregulated genes were identified. Among them, COL10A1 expression was distinctly increased in GC specimens compared with nontumor specimens. High COL10A1 expression exhibited an obvious relation to tumor T and pathologic stage. ROC assays confirmed the diagnostic value of COL10A1 expression in screening GC samples from normal samples. Survival data displayed that patients with high COL10A1 expression exhibited a shorter OS and DSS than those with low COL10A1 expression. We obtained a predictive nomogram, which could better predict the COL10A1 expression by virtue of discrimination and calibration. The prognostic value of COL10A1 expression was further confirmed in GSE84426 datasets. Immune assays revealed that COL10A1 expression was associated with tumor-filtrating immune cells, like CD8 T cells, cytotoxic cells, DC, eosinophils, iDC, macrophages, mast cells, NK CD56dim cells, NK cells, pDC, T helper cells, Tem, Th1 cells, Th17 cells, and Treg. Overall, we firstly proved that COL10A1 may be a novel and valuable prognostic and diagnostic factor for GC patients. In addition, COL10A1 has potential to be an immune indicator in GC.}, } @article {pmid36276118, year = {2022}, author = {Wang, Z and Fan, G and Zhu, H and Yu, L and She, D and Wei, Y and Huang, J and Li, T and Zhan, S and Zhou, S and Zhu, Y and Wang, Y and Chen, X and Zhao, J and Zhou, G}, title = {PLOD2 high expression associates with immune infiltration and facilitates cancer progression in osteosarcoma.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {980390}, pmid = {36276118}, issn = {2234-943X}, abstract = {BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumors in children and adolescents. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) is a key gene in mediating the formation of the stabilized collagen cross-link, playing an important role in the progression of cancer. However, the interaction between OS and PLOD2 has not been clarified so far.

METHODS: The target gene PLOD2 was screened through our own RNA-seq results and other two RNA-seq results from GEO database. The expression of PLOD2 in OS was detected by RT-qPCR, Western blot and immunohistochemistry. Functional experiments were performed to investigate the role of PLOD2 in OS cell invasion, migration and angiogenesis in vitro. An OS lung metastasis model was established to investigate the function of PLOD2 in OS metastasis and angiogenesis in vivo. The role of PLOD2 in immune infiltration in OS was explored by KEGG/GO analysis and immune infiltration analysis with TARGET, TCGA and TIMER.

RESULTS: PLOD2 was high-expressed in OS, which was related to poor prognosis of OS patients. PLOD2 promoted OS cell migration, invasion and angiogenesis in vitro and aggravated OS metastasis and angiogenesis in vivo. Bioinformatic analysis showed that PLOD2 played an important role in immune cell infiltration in OS, including CD8 positive T cells, macrophages M0 cells, DC cells, endothelial cells, iDC cells, ly endothelial cells, MEP cells, mv endothelial cells, native B cells, smooth muscle cells and Th1 cells. Immunohistochemical results showed that the expression of CD4 and CD8A was negatively correlated with the expression of PLOD2 in OS.

CONCLUSION: PLOD2 was high-expressed in OS and promoted OS migration, invasion and angiogenesis in vitro and facilitated OS metastasis and angiogenesis in vivo. PLOD2 was associated with immune cell infiltration in OS, which could be a promising target to treat OS patients with metastasis and utilized to guide clinical immunotherapy in the future.}, } @article {pmid36275485, year = {2022}, author = {Rehman, B and Mumtaz, A and Sajjad, B and Urooj, N and Khan, SM and Zahid, MT and Mannan, H and Chaudhary, MZ and Khan, A and Parvaiz, MA}, title = {Papillary Carcinoma of Breast: Clinicopathological Characteristics, Management, and Survival.}, journal = {International journal of breast cancer}, volume = {2022}, number = {}, pages = {5427837}, pmid = {36275485}, issn = {2090-3170}, abstract = {OBJECTIVE: To study clinicopathological features, treatment strategies, and prognosis of papillary carcinoma of breast. Material and Methods. Data from 58 patients were retrospectively reviewed from January 2010 to December 2016. Four types of papillary carcinoma (on final resected specimen) were included, i.e., invasive papillary carcinoma (IPC), intracystic (encapsulated) papillary carcinoma (EPC), solid papillary carcinoma (SPC), and papillary DCIS (ductal carcinoma in situ). Various features of the four types were observed and compared.

RESULTS: Of the 58 patients, 8 were males (13.7%). The mean age at presentation was 61 years; the mean tumor size was 33 mm. The frequency of each histological type was as follows: IPC (n = 22/38%), EPC (n = 22/38%), SPC (n = 12/20.6%), and papillary DCIS (n = 2/3.4%). Only two patients were ER negative (both IPC). HER-2 Neu was positive in 3 patients only, out of which 2 died of progressive disease (one EPC and one IPC). LN metastasis was present in 3 (5%) patients (one in each of 1st three types) and only one died of bone metastasis that was also Her-2Neu positive. All patients underwent upfront surgery except two patients who had synchronous IDC on the contralateral side. Breast conservation surgery (BCS) was performed in 34 (58.6%) and mastectomy in 22 (37.9%) patients. 13 patients did not undergo invasive axillary staging; the rest of 43 (74%) patients did (32 sentinel biopsy and 11 axillary dissection). Chemotherapy was given to 18 patients (31%), mostly to IPC (n = 12). Only 2 patients had bone metastasis (one was IPC and one EPC). Cancer-related death was observed in 3 patients. For all groups combined, 5-year OS was 98% and DFS was 92%.

CONCLUSION: Overall, papillary carcinoma of the breast has an excellent prognosis, even though less intense treatment modalities were used. It is still difficult to define the optimum management and avoid overtreatment, given the limited data in the literature.}, } @article {pmid36273358, year = {2022}, author = {Aihara, T and Kumamaru, H and Ishitobi, M and Miyashita, M and Miyata, H and Tamura, K and Yoshida, M and Ogo, E and Nagahashi, M and Asaga, S and Kojima, Y and Kadoya, T and Aogi, K and Niikura, N and Iijima, K and Hayashi, N and Kubo, M and Yamamoto, Y and Takeuchi, Y and Imoto, S and Jinno, H}, title = {Prognosis and effectiveness of chemotherapy for medullary breast carcinoma.}, journal = {Breast cancer research and treatment}, volume = {196}, number = {3}, pages = {635-645}, pmid = {36273358}, issn = {1573-7217}, mesh = {Humans ; Female ; Erb-b2 Receptor Tyrosine Kinases ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/drug therapy/pathology ; Prognosis ; Chemotherapy, Adjuvant ; }, abstract = {PURPOSE: We aimed to determine the prognosis and potential benefit of postoperative chemotherapy according to subtype of medullary breast carcinoma (MedBC), a very rare invasive breast cancer.

METHODS: A cohort of 1518 female patients with unilateral MedBC and 284,544 invasive ductal carcinoma (IDC) cases were enrolled from the Japanese Breast Cancer Registry. Prognosis of MedBC was compared to IDC among patients with estrogen receptor (ER)-negative and HER2-negative subtype (553 exact-matched patients) and ER-positive and HER2-negative subtype (163 MedBC and 489 IDC patients via Cox regression). Disease free-survival (DFS) and overall survival (OS) were compared between propensity score-matched adjuvant chemotherapy users and non-users with ER-negative and HER2-negative MedBC.

RESULTS: Among ER-negative and HER2-negative subtype patients, DFS (hazard ratio (HR) 0.45; 95% confidence interval (95% CI), 0.30-0.68; log-rank P < 0.001) and OS (HR 0.51; 95% CI 0.32-0.83; log-rank P = 0.004) were significantly better in MedBC than IDC. Patients treated with postoperative chemotherapy showed better DFS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) and OS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) compared to those without. For the ER-positive and HER2-negative subtype, the point estimate for HR for DFS was 0.60 (95% CI 0.24-1.22) while that for OS was 0.98 (95% CI 0.46-1.84) for MedBC.

CONCLUSION: In ER-negative and HER2-negative MedBC, the risk of recurrence and death was significantly lower than that of IDC, about half. Postoperative chemotherapy reduced recurrence and mortality. ER-positive and HER2-negative MedBC may have a lower risk of recurrence compared to IDC.}, } @article {pmid36270911, year = {2023}, author = {Cheng, L and Tariq, H and Yan, L and Reddy, SB and Gattuso, P}, title = {Fine-needle aspiration of intramammary lymph nodes: a clinical, radiographic, and cytologic review.}, journal = {Journal of the American Society of Cytopathology}, volume = {12}, number = {1}, pages = {41-47}, doi = {10.1016/j.jasc.2022.09.004}, pmid = {36270911}, issn = {2213-2945}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology ; Biopsy, Fine-Needle ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Retrospective Studies ; *Fibroadenoma/diagnostic imaging/pathology ; *Breast Neoplasms/diagnostic imaging/pathology ; Lymph Nodes/diagnostic imaging/pathology ; }, abstract = {INTRODUCTION: Recognizing and sampling intramammary lymph nodes (IMLNs) is important in the clinical management of patients with breast carcinomas. We undertook a retrospective study to evaluate the clinical utility of fine-needle aspiration (FNA) in assessing IMLNs.

MATERIALS AND METHODS: Our pathology database was searched for all IMLN FNA cytology cases from January 2005 to December 2021. The cytologic findings, radiographic features, and clinical data were reviewed.

RESULTS: A total of 149 cases were identified. Eighteen of 149 (12%) patients had synchronous breast tumors, including 13 invasive ductal carcinomas (IDCs), 1 ductal carcinoma in situ (DCIS), and 4 fibroadenomas. Among patients with synchronous IDCs, FNA of IMLNs was positive for metastatic carcinoma in 4 of 13 (30.7%) cases. The 4 patients with positive IMLNs all received mastectomies. Fifteen of 149 (10.7%) patients had a prior history of breast tumors, including 9 IDCs, 4 DCISs, 1 lobular carcinoma in situ (LCIS), and 1 fibroadenoma. Two of 149 (1.3%) patients had a prior history of lymphoma. In the patients with prior history of IDC, DCIS, LCIS, lymphomas and fibroadenomas, IMLN FNAs were all negative for malignancy. Two of 149 cases (1.3%) showed granulomatous lymphadenitis. The remaining 112 cases had negative IMLN FNAs and no significant clinical or pathological findings.

CONCLUSIONS: Our study showed that IMLNs are commonly associated with synchronous/metachronous breast tumors (33 of 149, 22.1%). The incidence of positive IMLN FNA in patients with synchronous invasive breast carcinoma was 30.7% (4 of 13). FNA of IMLNs in conjunction with clinical presentation and radiologic findings allows triage of patients for appropriate clinical management and avoids additional unnecessary surgical procedures.}, } @article {pmid36269831, year = {2022}, author = {Demir, S and Wolff, G and Wieder, A and Maida, A and Bühler, L and Brune, M and Hautzinger, O and Feuchtinger, A and Poth, T and Szendroedi, J and Herzig, S and Ekim Üstünel, B}, title = {TSC22D4 interacts with Akt1 to regulate glucose metabolism.}, journal = {Science advances}, volume = {8}, number = {42}, pages = {eabo5555}, pmid = {36269831}, issn = {2375-2548}, mesh = {Animals ; Mice ; Glucose/metabolism ; Insulin/metabolism ; *Insulin Resistance ; Phosphatidylinositol 3-Kinases/metabolism ; *Proto-Oncogene Proteins c-akt/metabolism ; Transcription Factors ; Transforming Growth Factor beta1 ; }, abstract = {Maladaptive insulin signaling is a key feature in the pathogenesis of severe metabolic disorders, including obesity and diabetes. Enhancing insulin sensitivity represents a major goal in the treatment of patients affected by diabetes. Here, we identify transforming growth factor-β1 stimulated clone 22 D4 (TSC22D4) as a novel interaction partner for protein kinase B/Akt1, a critical mediator of insulin/phosphatidylinositol 3-kinase signaling pathway. While energy deprivation and oxidative stress promote the TSC22D4-Akt1 interaction, refeeding mice or exposing cells to glucose and insulin impairs this interaction, which relies on an intrinsically disordered region (D2 domain) within TSC22D4. Functionally, the interaction with TSC22D4 reduces basal phosphorylation of Akt and its downstream targets during starvation, thereby promoting insulin sensitivity. Genetic, liver-specific reconstitution experiments in mice demonstrate that the interaction between TSC22D4 and Akt1 improves glucose handling and insulin sensitivity. Overall, our findings postulate a model whereby TSC22D4 acts as an environmental sensor and interacts with Akt1 to regulate insulin signaling and glucose metabolism.}, } @article {pmid36259855, year = {2022}, author = {Peach, A and Blaise, B and Parker, J and Larson, R}, title = {Noninflammatory presentation of cutaneous breast cancer: a retrospective case series at a single academic institution with review of the literature.}, journal = {Dermatology online journal}, volume = {28}, number = {4}, pages = {}, doi = {10.5070/D328458515}, pmid = {36259855}, issn = {1087-2108}, mesh = {Humans ; Male ; Female ; *Breast Neoplasms/pathology ; Retrospective Studies ; *Skin Neoplasms/diagnosis/pathology ; *Melanoma/pathology ; Hormones ; }, abstract = {Breast cancer with skin involvement is an uncommon clinical presentation of this malignancy. Breast cancer overall has a relatively high mortality rate and wide variety of presentations, making skin involvement by breast cancer a necessary consideration in the differential diagnosis for many types of breast lesions. A retrospective review of our own small academic dermatology outpatient clinic, between August 2006 and January 2020, found four cases of noninflammatory breast cancer with skin involvement diagnosed through biopsy by our dermatologists. This review was approved by the local Institutional Review Board. Of the four patients identified, three were female and one was male. One patient had prior history of invasive ductal carcinoma in remission before recurrence was diagnosed. Another patient had a history of melanoma in situ before diagnosis with breast cancer. Patients were treated with various combinations of surgery, radiation, and hormone therapy. These four cases are presented here in detail, which emphasize the role of the dermatologist in recognizing various cutaneous manifestations of noninflammatory breast cancer in order to make a timely diagnosis.}, } @article {pmid36258934, year = {2022}, author = {Salehiazar, S and Huang, H and Aghighi, M and Venegas, R}, title = {Lymphoepithelioma-Like Carcinoma of the Breast: A Case Report of a Rare Type of Invasive Carcinoma.}, journal = {Cureus}, volume = {14}, number = {9}, pages = {e29231}, pmid = {36258934}, issn = {2168-8184}, abstract = {Lymphoepithelioma carcinoma (LELC) is an extremely rare type of mammary cancer. Based on the histology, it can be misdiagnosed with inflammatory lesions like mastitis and medullary carcinoma or other hematopoietic neoplasms like lymphoma in the breast. Since LELC has a good response to chemotherapy with a good prognosis, t is prognostically important to recognize LELC. We report a rare case of LELC in a 51-year-old pre-menopausal female with a left breast mass, diagnosed with invasive ductal carcinoma (IDC), LELC type, treated with mastectomy, followed by adjuvant chemotherapy and radiotherapy, with a disease-free interval of 10 months. Herein, we present the case with its clinical presentation, radiologic imaging, histopathological features, and immunohistochemistry (IHC) findings. The rarity of this type of breast tumor warrants studying the behavior of these uncommon tumors to avoid misdiagnosis and establish well-defined criteria for diagnosis.}, } @article {pmid36257189, year = {2022}, author = {Metz, L and Bowyer, T and Burnett, J and Dion, M and Eslinger, P and Friese, J and Doll, C and McIntyre, J and Schrom, B}, title = {Source Term Analysis of Xenon (STAX): An effort focused on differentiating man-made isotope production from nuclear explosions via stack monitoring.}, journal = {Journal of environmental radioactivity}, volume = {255}, number = {}, pages = {107037}, doi = {10.1016/j.jenvrad.2022.107037}, pmid = {36257189}, issn = {1879-1700}, mesh = {Humans ; Xenon/analysis ; Xenon Radioisotopes/analysis ; *Radiation Monitoring/methods ; Explosions ; *Air Pollutants, Radioactive/analysis ; Isotopes/analysis ; }, abstract = {An overview of the hardware and software developed for the Source Term Analysis of Xenon (STAX) project is presented which includes the data collection from two stack monitoring systems installed at medical isotope production facilities, infrastructure to transfer data to a central repository, and methods for sharing data from the repository with users. STAX is an experiment to collect radioxenon emission data from industrial nuclear facilities with the goal of developing a better understanding of the global radioxenon background and the effect industrial radioxenon releases have on nuclear explosion monitoring. A final goal of this work is to utilize collected data along with atmospheric transport modeling to calculate the contribution of a peak or set of peaks detected by the International Monitoring System (IMS) to provide desired discriminating information to the International Data Centre (IDC) and National Data Centers (NDCs). Types of data received from the STAX equipment are shown and collected data was used for a case study to predict radioxenon concentrations at two IMS stations closest to the Institute for RadioElements (IRE) in Belgium. The initial evaluation of results indicate that the data is very valuable to the nuclear explosion monitoring community.}, } @article {pmid36249638, year = {2022}, author = {Adam, R and Herman, M and Hodges, L and Duong, TQ and Fineberg, S and Roknsharifi, S}, title = {Invasive Lobular Cancer Arising in a Surgical Scar From Lumpectomy for a Previous Invasive Ductal Cancer of the Breast.}, journal = {Cureus}, volume = {14}, number = {9}, pages = {e29054}, pmid = {36249638}, issn = {2168-8184}, abstract = {We describe a case of pathology-proven invasive lobular breast cancer (ILC) arising in a scar over 15 years after lumpectomy for previous invasive ductal carcinoma (IDC). The tumor was detected on screening mammography as a new focal asymmetry at the scar site and confirmed at diagnostic mammography. Ultrasound demonstrated an irregular, shadowing, hypoechoic mass at the scar site. Ultrasound-guided biopsy revealed poorly differentiated invasive lobular carcinoma. MRI and CT showed an irregular mass with pectoralis muscle invasion. Multimodality imaging findings are described. This is the first case to our knowledge reporting multimodality imaging findings of a breast cancer developing at the site of a surgical scar that is histologically different from the originally resected cancer.}, } @article {pmid36249118, year = {2022}, author = {Sabour Takanlou, L and Cecener, G and Sabour Takanlou, M and Ozturk Nazlioglu, H and Tezcan Unlu, H and Isik, O and Egeli, U and Tunca, B and Cubukcu, E and Tolunay, S and Gokgoz, MS}, title = {Correlation between Ubiquitin E3 Ligases (SIAHs) and Heat Shock Protein 90 in Breast Cancer Patients.}, journal = {Iranian journal of public health}, volume = {51}, number = {8}, pages = {1836-1846}, pmid = {36249118}, issn = {2251-6093}, abstract = {BACKGROUND: Breast cancer is a heterogeneous disease and differences in the expression levels of the ER, PR, and HER2 the triplet of established biomarkers used for clinical decision-making have been reported among breast cancer patients. Furthermore, resistance to anti-estrogen and anti-HER2 therapies emerges in a considerable rate of breast cancer patients, and novel drug therapies are required. Several anomalous signaling pathways have been known in breast cancer have been known; heat shock protein 90 (HSP90) is one of the most plenty proteins in breast cells. The family of ubiquitin ligases such as SIAH1 and SIAH2 is known to specifically target misfolded proteins to the proteasome; also, they have been illustrated to play a role in RAS signaling and as an essential downstream signaling component required for EGFR/HER2 in breast cancer.

METHODS: The expression of SIAH2, HSP90, and HER2 was assessed by quantitative Real-Time PCR in 85 invasive ductal carcinoma breast tumor samples at Uludag University Hospital in Turkey during the years 2018-2019, and its association with the clinicopathologic variables of patients was evaluated.

RESULTS: HSP90, SIAH1, and SIAH2 were significantly (P=0.0271, P=0.022, and P=0.0311) upregulated tumor tissue of patients with breast cancer. Moreover, this study observed a significant association between the high expression of SIAH2/HSP90 with ER status, high expression of HSP90 with Recurrence/Metastasis, and high expression of SIAH2 with Ki-67 proliferation index.

CONCLUSION: The HSP90 and SIAH2 expressions play a significant role in breast cancer development by combining the experimental and clinical data obtained from the literature.}, } @article {pmid36248759, year = {2022}, author = {Zengel, B and Çavdar, D and Özdemir, Ö and Taşlı, F and Karataş, M and Şimşek, C and Uslu, A}, title = {Gastrointestinal Tract Metastases of Invasive Lobular Carcinoma of the Breast: An Immunohistochemical Survey Algorithm.}, journal = {European journal of breast health}, volume = {18}, number = {4}, pages = {375-380}, pmid = {36248759}, issn = {2587-0831}, abstract = {Invasive lobular carcinoma (ILC) accounts for almost 15% of all breast carcinomas. The potential of ILC to metastasize to the gastointestinal system is significantly greater than that of invasive ductal carcinoma. Gastric metastasis occurred in the ninth year of the follow-up in a patient who was operated on the right breast due to ILC. The patient was investigated for simultaneous masses in the stomach and colon, and a random mass was found in her right breast.}, } @article {pmid36248758, year = {2022}, author = {Kelten Talu, C and Yeni Erdem, B and Arslan, E and Nazli, MA and Cakir, Y and Can Trabulus, D}, title = {The Clinicopathologic Features of 22 Cases With Primary Invasive Papillary Carcinoma of the Breast Identified in 1153 Cases With Invasive Breast Carcinoma: Single-Center Experience.}, journal = {European journal of breast health}, volume = {18}, number = {4}, pages = {360-370}, pmid = {36248758}, issn = {2587-0831}, abstract = {OBJECTIVE: Invasive papillary carcinoma (IPC) of the breast is an uncommon histologic subtype with limited data in the literature. The aim of this study was to increase the evidence base by presenting clinicopathological findings of cases diagnosed as IPC.

MATERIALS AND METHODS: Hematoxylin and eosin sections and immunostaining of surgical excision specimens diagnosed as invasive breast carcinoma were re-evaluated, retrospectively.

RESULTS: IPC was detected in 22 cases (1.9%), of which 7 (0.6%) had pure and 15 (1.3%) had mixed morphology. Histologic types accompanying IPC were: Invasive ductal carcinoma (IDC) (15/15); invasive micropapillary carcinoma (3/15); and pleomorphic lobular carcinoma (1/15). Patient ages ranged between 36 and 89 (median 56.5) and the tumor size from 8 to 70 mm (median 19 mm). The histologic grade was 3 in five cases, 2 in 13, and 1 in four cases. The nuclear grade was 3 in 10 cases and 2 in 12. The values of positivity for estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, and Ki-67 index indicated Luminal B phenotype in 16 (72.7%), triple-negative in 5 (22.7%), and Luminal A in 1 case (4.6%). Ductal carcinoma in situ was noted in 19 cases (86.4%).

CONCLUSION: IPC was mostly detected as an accompanying carcinoma to IDC at postmenopausal ages and was mostly Luminal B phenotype with intermediate-to-high grade features.}, } @article {pmid36246806, year = {2022}, author = {Ren, Y and Zhang, J and Zhang, JD and Xu, JZ}, title = {Efficacy of digital breast tomosynthesis combined with magnetic resonance imaging in the diagnosis of early breast cancer.}, journal = {World journal of clinical cases}, volume = {10}, number = {28}, pages = {10042-10052}, pmid = {36246806}, issn = {2307-8960}, abstract = {BACKGROUND: The incidence and mortality rate of breast cancer in China rank 120[th] and 163[rd], worldwide, respectively. The incidence of breast cancer is on the rise; the risk increases with age but is slightly reduced after menopause. Early screening, diagnosis, and timely determination of the best treatment plan can ensure clinical efficacy and prognosis.

AIM: To evaluate the clinical value of magnetic resonance imaging (MRI) combined with digital breast tomosynthesis (DBT) in diagnosing early breast cancer and the effect of breast-conserving surgery by arc incision.

METHODS: This study was divided into two parts. Firstly, 110 patients with early breast cancer confirmed by pathological examination and 110 with benign breast diseases diagnosed simultaneously in Changzhi People's Hospital of Shanxi Province and Shanxi Dayi Hospital from May 2019 to September 2020 were included in the breast cancer group and the benign group, respectively. Both groups underwent DBT and MRI examination, and the pathological results were used as the gold standard to evaluate the effectiveness of the combined application of DBT and MRI in the diagnosis of early breast cancer. Secondly, according to the operation method, 110 patients with breast cancer were divided into either a breast-conserving group (69 patients) or a modified radical mastectomy group (41 patients). The surgical effect, cosmetic effect, and quality of life of the two groups were compared.

RESULTS: Among the 110 cases of breast cancer, 66 were of invasive ductal carcinoma (60.00%), and 22 were of ductal carcinoma in situ (20.00%). Among the 110 cases of benign breast tumors, 55 were of breast fibromas (50.00%), and 27 were of breast adenosis (24.55%). The sensitivity, specificity, and area under the curve (AUC) of DBT in the differential diagnosis of benign and malignant breast tumors were 73.64%, 84.55%, and 0.791, respectively. The sensitivity, specificity, and AUC of MRI in the differential diagnosis of benign and malignant breast tumors were 84.55%, 85.45%, and 0.850, respectively. The sensitivity, specificity, and AUC of DBT combined with MRI in the differential diagnosis of benign and malignant breast tumors were 97.27%, 93.64%, and 0.955, respectively. The blood loss, operation time and hospitalization time of the breast-conserving group were significantly lower than those of the modified radical treatment group, and the difference was statistically significant (P < 0.05). After 3 mo of observation, the breast cosmetic effect of the breast-conserving group was better than that of the modified radical group, and the difference was statistically significant (P < 0.05). Before surgery, the quality-of-life scores of the breast-conserving and modified radical mastectomy groups did not differ (P > 0.05). Three months after surgery, the quality-of-life scores in both groups were higher than those before surgery (P < 0.05), and the quality-of-life score of the breast-conserving group was higher than that of the modified radical group (P < 0.05). In the observation of tumor recurrence rate two years after the operation, four patients in the breast-conserving group and one in the modified radical treatment group had a postoperative recurrence. There was no significant difference in the recurrence rate between the two groups (χ [2] = 0.668, P = 0.414 > 0.05).

CONCLUSION: MRI combined with DBT in diagnosing early breast cancer can significantly improve the diagnostic efficacy compared with the two alone. Breast-conserving surgery leads to better cosmetic breast effects and reduces the impact of surgery on postoperative quality of life.}, } @article {pmid36246597, year = {2022}, author = {Zhao, Z and Jiang, N and Zhang, Y and Bai, Y and Liu, T and Li, T and Guo, H and Yang, R}, title = {Analysis and identification of the necroptosis landscape on therapy and prognosis in bladder cancer.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {919829}, pmid = {36246597}, issn = {1664-8021}, abstract = {Bladder cancer (BLCA) is one of the most common malignant tumors of the urinary system, but the current therapeutic strategy based on chemotherapy and immune checkpoint inhibitor (ICI) therapy cannot meet the treatment needs, mainly owing to the endogenous or acquired apoptotic resistance of cancer cells. Targeting necroptosis provides a novel strategy for chemotherapy and targeted drugs and improves the efficacy of ICIs because of strong immunogenicity of necroptosis. Therefore, we systemically analyzed the necroptosis landscape on therapy and prognosis in BLCA. We first divided BLCA patients from The Cancer Genome Atlas (TCGA) database into two necroptosis-related clusters (C1 and C2). Necroptosis C2 showed a significantly better prognosis than C1, and the differential genes of C2 and C1 were mainly related to the immune response according to GO and KEGG analyses. Next, we constructed a novel necroptosis-related gene (NRG) signature consisting of SIRT6, FASN, GNLY, FNDC4, SRC, ANXA1, AIM2, and IKBKB to predict the survival of TCGA-BLCA cohort, and the accuracy of the NRG score was also verified by external datasets. In addition, a nomogram combining NRG score and several clinicopathological features was established to more accurately and conveniently predict the BLCA patient's survival. We also found that the NRG score was significantly related to the infiltration levels of CD8 T cells, NK cells, and iDC cells, the gene expression of CTLA4, PD-1, TIGIT, and LAG3 of TME, and the sensitivity to chemotherapy and targeted agents in BLCA patients. In conclusion, the NRG score has an excellent performance in evaluating the prognosis, clinicopathologic features, tumor microenvironment (TME), and therapeutic sensitivity of BLCA patients, which could be utilized as a guide for chemotherapy, ICI therapy, and combination therapy.}, } @article {pmid36245246, year = {2022}, author = {Blawski, R and Toska, E}, title = {A Unique FOXA1-Associated Chromatin State Dictates Therapeutic Resistance in Lobular Breast Cancer.}, journal = {Cancer research}, volume = {82}, number = {20}, pages = {3668-3670}, pmid = {36245246}, issn = {1538-7445}, support = {K22 CA245487/CA/NCI NIH HHS/United States ; P30 CA006973/CA/NCI NIH HHS/United States ; R21 CA252530/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/drug therapy/genetics/metabolism ; Chromatin/genetics ; Drug Resistance, Neoplasm/genetics ; Female ; Hepatocyte Nuclear Factor 3-alpha/genetics ; Humans ; Receptors, Estrogen/genetics/metabolism ; Retrospective Studies ; Tamoxifen/pharmacology/therapeutic use ; }, abstract = {Invasive lobular carcinomas (ILC) are the second most common histologic subtype of breast cancer, accounting for up to 15% of cases. ILC is estrogen receptor (ER) positive, yet its biology is distinct from invasive ductal carcinomas (IDC), and retrospective analyses have indicated a poorer outcome with endocrine therapy. In this issue of Cancer Research, Nardone and colleagues investigated the mechanisms of this differential therapy response in ILC, which cannot be solely explained by the genetic profile of these tumors. The authors conducted a thorough examination of the epigenome of ILC compared with IDC in clinical and preclinical models and revealed an alternative chromatin accessibility state in ILC driven by the pioneer factor FOXA1. FOXA1 regulates its own expression in a feed-forward mechanism by binding to an ILC-unique FOXA1 enhancer site. This results in a FOXA1-ER axis that promotes the transcription of genes associated with tumor progression and tamoxifen resistance. Targeting the FOXA1 enhancer region blocks this transcriptional program and inhibits ILC proliferation. These results shed light on a new epigenetic mechanism driving ILC tumor progression and treatment resistance, which may have profound therapeutic implications. See related article by Nardone et al., p. 3673.}, } @article {pmid36243006, year = {2022}, author = {Sekar, R and Motzler, K and Kwon, Y and Novikoff, A and Jülg, J and Najafi, B and Wang, S and Warnke, AL and Seitz, S and Hass, D and Gancheva, S and Kahl, S and Yang, B and Finan, B and Schwarz, K and Okun, JG and Roden, M and Blüher, M and Müller, TD and Krahmer, N and Behrends, C and Plettenburg, O and Miaczynska, M and Herzig, S and Zeigerer, A}, title = {Vps37a regulates hepatic glucose production by controlling glucagon receptor localization to endosomes.}, journal = {Cell metabolism}, volume = {34}, number = {11}, pages = {1824-1842.e9}, doi = {10.1016/j.cmet.2022.09.022}, pmid = {36243006}, issn = {1932-7420}, mesh = {Animals ; Mice ; *Diabetes Mellitus, Type 2/metabolism ; Endosomes/metabolism ; Glucagon/metabolism ; Glucose/metabolism ; Lipids ; Liver/metabolism ; Mammals/metabolism ; Mice, Inbred C57BL ; *Receptors, Glucagon/metabolism ; Endosomal Sorting Complexes Required for Transport/metabolism ; }, abstract = {During mammalian energy homeostasis, the glucagon receptor (Gcgr) plays a key role in regulating both glucose and lipid metabolisms. However, the mechanisms by which these distinct signaling arms are differentially regulated remain poorly understood. Using a Cy5-glucagon agonist, we show that the endosomal protein Vps37a uncouples glucose production from lipid usage downstream of Gcgr signaling by altering intracellular receptor localization. Hepatocyte-specific knockdown of Vps37a causes an accumulation of Gcgr in endosomes, resulting in overactivation of the cAMP/PKA/p-Creb signaling pathway to gluconeogenesis without affecting β-oxidation. Shifting the receptor back to the plasma membrane rescues the differential signaling and highlights the importance of the spatiotemporal localization of Gcgr for its metabolic effects. Importantly, since Vps37a knockdown in animals fed with a high-fat diet leads to hyperglycemia, although its overexpression reduces blood glucose levels, these data reveal a contribution of endosomal signaling to metabolic diseases that could be exploited for treatments of type 2 diabetes.}, } @article {pmid36240525, year = {2022}, author = {Sandor, MF and Schwalbach, B and Hofmann, V and Istrate, SE and Schuller, Z and Ionescu, E and Heimann, S and Ragazzi, M and Lux, MP}, title = {Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscope for intraoperative margin assessment - POLARHIS study.}, journal = {Breast (Edinburgh, Scotland)}, volume = {66}, number = {}, pages = {118-125}, pmid = {36240525}, issn = {1532-3080}, mesh = {Female ; Humans ; *Breast Neoplasms/diagnostic imaging/surgery/pathology ; *Carcinoma, Ductal, Breast/diagnostic imaging/surgery/pathology ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/surgery/pathology ; Lasers ; Margins of Excision ; Mastectomy, Segmental/methods ; Neoplasm Recurrence, Local/pathology ; Prospective Studies ; Reoperation ; Retrospective Studies ; }, abstract = {INTRODUCTION: Breast-conserving surgery (BCS) in case of breast cancer and/or in-situ-carcinoma lesions (DCIS) intends to completely remove breast cancer while saving healthy tissue as much as possible to achieve better aesthetic and psychological outcomes for the patient. Such modality should result in postoperative tumor-free margins of the surgical resection in order to carry on with the next therapeutical steps of the patient care. However, 10-40% of patients undergo more than one procedure to achieve acceptable cancer-negative margins. A 2nd operation or further operation (re-operation) has physical, psychological, and economic consequences. It also delays the administration of adjuvant therapy, and has been associated with an elevated risk of local and distant disease relapse. In addition, a high re-operation rate can have significant economic effects - both for the service provider and for the payer. A more efficient intraoperative assessment of the margin may address these issues. Recently, a large field-of-view confocal laser scanning microscope designed to allow real-time intraoperative margin assessment has arrived on the market - the Histolog Scanner. In this paper, we present the first evaluation of lumpectomy margins assessment with this new device.

MATERIALS AND METHODS: 40 consecutive patients undergoing BCS with invasive and/or DCIS were included. The whole surface of the surgical specimens was imaged right after the operation using the Histolog Scanner (HLS). The assessment of all the specimen margins was performed intraoperatively according to the standard-of-care of the center which consists of combined ultrasound (IOUS) and/or conventional specimen radiography (CSR), and gross surgical inspection. Margin assessment on HLS images was blindly performed after the surgery by 5 surgeons and one pathologist. The capabilities to correctly determine margin status in HLS images was compared to the final histopathological assessment. Furthermore, the potential reduction of positive-margin and re-operation rates by utilization of the HLS were extrapolated.

RESULTS: The study population included 7/40 patients with DCIS (17.5%), 17/40 patients with DCIS and invasive ductal cancer (IDC NST) (42.5%), 10/40 patients with IDC NST (25%), 4/40 with invasive lobular cancer (ILC) (10%), and 1/40 patients with a mix of IDC NST, DCIS, and ILC. Clinical routine resulted in 13 patients with positive margins identified by final histopathological assessment, resulting in 12 re-operations (30% re-operation rate). Amongst these 12 patients, 10 had DCIS components involved in their margin, confirming the importance of improving the detection accuracy of this specific lesion. Surgeons, who were given a short familiarization on HLS images, and a pathologist were able to detect positive margins in 4/12 and 7/12 patients (33% and 58%), respectively, that were missed by the intraoperative standard of care. In addition, a retrospective analysis of the HLS images revealed that cancer lesions can be identified in 9/12 (75%) patients with positive margins.

CONCLUSION: The present study presents that breast cancer can be detected by surgeons and pathologists in HLS images of lumpectomy margins leading to a potential reduction of 30% and 75% of the re-operations. The Histolog Scanner is easily inserted into the clinical workflow and has the potential to improve the intraoperative standard-of-care for the assessment of breast conserving treatments. In addition, it has the potential to increase oncological safety and cosmetics by avoiding subsequent resections and can also have a significant positive economic effect for service providers and cost bearers. The data presented in this study will have to be further confirmed in a prospective phase-III-trial.}, } @article {pmid36239760, year = {2022}, author = {Oesterreich, S and Nasrazadani, A and Zou, J and Carleton, N and Onger, T and Wright, MD and Li, Y and Demanelis, K and Ramaswamy, B and Tseng, G and Lee, AV and Williams, N and Kruse, M}, title = {Clinicopathological Features and Outcomes Comparing Patients With Invasive Ductal and Lobular Breast Cancer.}, journal = {Journal of the National Cancer Institute}, volume = {114}, number = {11}, pages = {1511-1522}, pmid = {36239760}, issn = {1460-2105}, support = {NCI P30CA047904/NH/NIH HHS/United States ; NCI P30CA016058/CA/NCI NIH HHS/United States ; F30 CA264963/CA/NCI NIH HHS/United States ; P30 CA016058/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; /KOMEN/Susan G. Komen/United States ; }, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/drug therapy ; *Breast Neoplasms/drug therapy ; Receptors, Estrogen ; Retrospective Studies ; *Carcinoma, Lobular/diagnosis ; }, abstract = {BACKGROUND: There is increasing interest in better understanding the biology and clinical presentation of invasive lobular cancer (ILC), which is the most common special histological subtype of breast cancer. Limited large contemporary data sets are available allowing comparison of clinicopathologic features between ILC and invasive ductal cancer (IDC).

METHODS: The Great Lakes Breast Cancer Consortium was formed to compare clinical behavior of ILC (n = 3617) and IDC (n = 30 045) from 33 662 patients treated between 1990 and 2017 at 3 large clinical centers. We used Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching to evaluate treatment differences and outcomes. All statistical testing used 2-sided P values.

RESULTS: Compared with IDC, patients with ILC were more frequently diagnosed at later stages and with more lymph node involvement (corrected P < .001). Estrogen receptor-positive ILCs were of lower grade (grade 1 and 2: 90% in ILC vs 72% in IDC) but larger in size (T3 and 4: 14.3% in ILC vs 3.4% in IDC) (corrected P < .001), and since 1990, the mean ILC size detected at diagnosis increased yearly. Patients with estrogen receptor (ER)-positive ILC underwent statistically significantly more mastectomies compared with ER-positive IDC (57% vs 46%). Using Kaplan-Meier analysis, patients with ER-positive ILC had statistically significantly worse disease-free survival and overall survival than ER-positive IDC although 6 times more IDCs were classified as high risk by OncotypeDx Breast Recurrence Score assay.

CONCLUSIONS: This large, retrospective, collaborative analysis with 3 clinical centers identified meaningful differences in clinicopathological features between ILC and IDC, providing further evidence that these are 2 different entities requiring different clinical management.}, } @article {pmid36238916, year = {2022}, author = {Kim, YJ and Jung, HK and Kim, W}, title = {An Unusual Presentation of Extensive Ductal Carcinoma in Situ Accompanying Invasive Ductal Carcinoma on MRI: A Case Report.}, journal = {Journal of the Korean Society of Radiology}, volume = {83}, number = {4}, pages = {898-903}, pmid = {36238916}, issn = {2951-0805}, abstract = {The incidence of ductal carcinoma in situ has increased with the rise in screening mammography; currently, ductal carcinoma in situ constitutes 20%-25% of all breast cancers, and up to half of them may become invasive. Its early detection is critical in improving the cure rate. Moreover, MRI has higher sensitivity for its detection than mammography. Herein, we report an unusual case of ductal carcinoma in situ presenting as a continuous, serpentine, linear enhancement with regional distribution on MRI.}, } @article {pmid36238494, year = {2022}, author = {Zhao, W and Wu, T and Zhan, J and Dong, Z}, title = {Identification of the Immune Status of Hypertrophic Cardiomyopathy by Integrated Analysis of Bulk- and Single-Cell RNA Sequencing Data.}, journal = {Computational and mathematical methods in medicine}, volume = {2022}, number = {}, pages = {7153491}, pmid = {36238494}, issn = {1748-6718}, mesh = {Animals ; Biomarkers ; *Cardiomyopathy, Hypertrophic/genetics/metabolism ; Gene Regulatory Networks ; Mice ; *MicroRNAs ; Sequence Analysis, RNA ; }, abstract = {OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiomyopathy and immune infiltration is considered an indispensable factor involved in its pathogenesis. In this study, we attempted to combine bulk sequencing and single-cell sequencing to map the immune infiltration-related genes in hypertrophic cardiomyopathy.

METHODS: The GSE36961, GSE160997, and GSE122930 datasets were obtained from the Gene Expression Omnibus database. The compositional patterns of the 18 types of immune cell fraction and pathway enrichment score in control and HCM patients were estimated based on the GSE36961 cohort using xCell algorithm. The Weighted Gene Coexpression Network Analysis (WGCNA) was performed to identify genes associated with immune infiltration for hypertrophic cardiomyopathy. The area under the curve (AUC) value was obtained and used to evaluate the discriminatory ability of common immune-related DEGs. "NetworkAnalyst" platform was used to identify TF-gene and TF-miRNA interaction with identified common genes. Heat map was used to determine the association between common DEGs and various immune cells.

RESULTS: Immune infiltration analysis by the xCell algorithm showed a higher level of CD8+ naive T cells, CD8+ T cells, as well as a lower level of activated dendritic cells (aDC), dendritic cells (DC), immature dendritic cells (iDC), conventional dendritic cells (cDC), macrophages, M1 macrophages, monocytes, and NKT cell in HCM compared with the control group in GSE36961 dataset. aDC, macrophages, and M1 macrophages were the top three discriminators between HCM and control groups with the area under the curve (AUC) of 0.907, 0.867, and 0.941. WGCNA analysis showed that 1258 immune-related genes were included in four different modules. Of these modules, the turquoise module showed a pivotal correlation with HCM. 13 common immune-related DEGs were found by intersecting common DEGs in GSE36961 and GSE160997 datasets with genes from the genes in turquoise module. 5 hub immune-related genes (S100A9, TYROBP, FCER1G, CD14, and S100A8) were identified by protein interaction network. Through analysis of single-cell sequencing data, S100a9, TYROBP, FCER1G, and S100a8 were mainly expressed by infiltrated M1 proinflammatory cells, especially Ccr2-M1 proinflammatory macrophage cells in the heart immune microenvironment while Cd14 was expressed by infiltrated M1 proinflammatory macrophage cells and M2 macrophages in transverse aortic constriction (TAC) mice at 1 week. Higher M2 macrophage and M1 proinflammatory macrophage infiltration as well as lower Ccr2-M1 proinflammatory macrophage and dendritic cells were shown in TAC 1week mice compared with sham mice.

CONCLUSIONS: There was a difference in immune infiltration between HCM patients and normal groups. aDC, macrophages, and M1 macrophages were the top three discriminator immune cell subsets between HCM and control groups. S100A9, TYROBP, FCER1G, CD14, and S100A8 were identified as potential biomarkers to discriminate HCM from the control group. S100a9, TYROBP, FCER1G, and S100a8 were mainly expressed by infiltrated M1 proinflammatory cells, especially Ccr2-M1 proinflammatory cells in the heart immune microenvironment while Cd14 was expressed by M2 macrophages in transverse aortic constriction (TAC) mice at 1 week.}, } @article {pmid36237742, year = {2022}, author = {Makaranka, S and Frixou, M and Mustafa, A and Husain, E}, title = {Cutaneous Sebaceous Carcinoma Presenting as a Large Fungating Breast Tumour in Synchronicity With Primary Carcinomata of the Breasts.}, journal = {Cureus}, volume = {14}, number = {9}, pages = {e28896}, pmid = {36237742}, issn = {2168-8184}, abstract = {Sebaceous carcinomas are rare malignant tumours which arise from sebaceous glands. They are subclassified into ocular and extraocular subtypes and most commonly occur in the head and neck region. Tumours below the neck occur infrequently, and most commonly resemble benign skin lesions such as pyogenic granulomata and molluscum contagiosum, or malignant skin tumours like basal and squamous cell carcinomas (SCCs). We report a case of an 86-year-old lady presenting with a fungating breast tumour which began as a "mole" and exhibited insidious growth over five years to reach a maximum size of 10 cm. An excision biopsy was performed by the breast surgery team and histopathological analysis revealed a sebaceous carcinoma arising from the skin adnexa. On subsequent follow up, the patient was found to have a 19 mm mass in the left breast and a 20 mm mass in the right breast, which was P5 and P3 on clinical palpation, respectively. Core biopsies of left and right breast lesions showed invasive lobular carcinoma and invasive ductal carcinoma with lobular features respectively; the patient was started on primary letrozole treatment. The patient also went on to have a 2 cm wide local excision of the sebaceous carcinoma scar which was excised down to the pectoralis fascia. This is a unique presentation of a sebaceous gland carcinoma presenting as a fungating breast tumour. These tumours have a high metastatic potential and local recurrence rate, and can co-exist with primary carcinoma of the breast.}, } @article {pmid36237483, year = {2022}, author = {Alsumai, TS and Alhazzaa, N and Alshamrani, A and Assiri, S and Alhefdhi, A}, title = {Factors Predicting Positive Sentinel Lymph Node Biopsy in Clinically Node-Negative Breast Cancer.}, journal = {Breast cancer (Dove Medical Press)}, volume = {14}, number = {}, pages = {323-334}, pmid = {36237483}, issn = {1179-1314}, abstract = {PURPOSE: Sentinel lymph node (SLN) biopsy (SLNB) is the standard tool to stage the axilla of breast cancer patients. This study aimed to identify the predictors of positive SLNB in patients with clinically node-negative breast cancer.

PATIENTS AND METHODS: A retrospective, single-institution cohort of patients with early-stage breast cancer without clinically identifiable axillary lymphadenopathy was chosen from January 2010 to December 2018. Logistic regression was used to identify possible predictors of positive SLNB.

RESULTS: Four hundred and seventy patients were identified; their mean age was 50±11 years. Most patients had the following characteristics: invasive ductal carcinoma (n=382, 81.3%), unilateral tumor (n=461, 98.1%), unifocal disease (n=351, 74.7%), intermediate grade (n=276, 59.0%), and estrogen and progesterone receptor positivity with human epidermal growth factor receptor 2 negativity (n=305, 64.9%). The mean size of the breast mass was 2.3±1.5 cm. SLNB was positive in 128 (27.2%) cases. The mean number of SLNs was 2±1.2. Axillary lymph node dissection was performed in 109 patients. The mean number of lymph nodes removed was 15±6. In 66 (60.6%) of the 109 patients with metastatic axillary nodes, only the SLNs were found to be positive. The number of SLNs, tumor size, tumor grade, receptor status, prominent axillary lymph nodes, and lymphovascular invasion predicted positive SLNB (P = 0.01, 0.03, 0.03, and 0.04 and <0.001 and <0.001, respectively).

CONCLUSION: Our results suggest that a number of histopathological and radiological characteristics of breast cancer can predict SLNB positivity in clinically node-negative breast cancer patients.}, } @article {pmid36230503, year = {2022}, author = {Chang, YS and Chou, YP and Chung, CC and Lee, YT and Yen, JC and Jeng, LB and Chang, JG}, title = {Molecular Classification of Hepatocellular Carcinoma Using Wnt-Hippo Signaling Pathway-Related Genes.}, journal = {Cancers}, volume = {14}, number = {19}, pages = {}, pmid = {36230503}, issn = {2072-6694}, support = {DMR-111-131//China Medical University Hospital/ ; MOST-109-2320-B-039-052 and MOST-110-2321-B-039-002//Ministry of Science and Technology of Taiwan/ ; }, abstract = {In Taiwan, a combination of hepatitis B and C infection, economic boom-related food and alcohol overconsumption, and Chinese medicine prescriptions has led to a high rate of hepatocellular carcinoma (HCC). However, the causative factors and underlying tumor biology for this unique HCC environment have not been identified. Wnt and Hippo signaling pathways play an important regulatory role in HCC development, and their functions are generally considered as positive and negative regulators of cell proliferation, respectively. In this study, we characterized the molecular features of HCC using a newly developed classification system based on the expression of the Wnt-Hippo signaling pathway-related genes. RNA sequencing (RNA-Seq) was performed on liver tumor tissues from 100 patients with liver cancer. RNA-Seq data for 272 previously characterized Wnt-Hippo signaling pathway-related genes were used for hierarchical clustering. We analyzed the data in terms of prognostic value, transcriptome features, immune infiltration, and clinical characteristics, and compared the resulting subclasses with previously published classifications. Four subclasses of HCC (HCCW1-4) were identified. Subclass HCCW1 displayed the highest PCDHB4 expression. Subclass HCCW2 displayed lower Edmondson-Steiner grades (I and II) and CTNNB1 mutation frequencies. Subclass HCCW3 was associated with a good prognosis, the highest PCDHGB7 expression, high CD8+ naïve T cells abundance, and relatively low TP53 mutation rates. Subclass HCCW4 was associated with a poor prognosis, the highest PCDHB2 and PCDHB6 expression, a relatively high abundance of Th1 cells, NKT and class-switched memory B cells, relatively low enrichment of cDC, iDC, and CD4+ memory T cells, and high Edmondson-Steiner grades (III and IV). We also identified Wnt-Hippo signaling pathway-related genes that may influence immune cell infiltration. We developed a panel of 272 Wnt-Hippo signaling pathway-related genes to classify HCC into four groups based on Taiwanese HCC and The Cancer Genome Atlas Liver Hepatocellular Carcinoma datasets. This novel molecular classification system may aid the treatment of HCC.}, } @article {pmid36229464, year = {2022}, author = {Wong, HY and Sheng, Q and Hesterberg, AB and Croessmann, S and Rios, BL and Giri, K and Jackson, J and Miranda, AX and Watkins, E and Schaffer, KR and Donahue, M and Winkler, E and Penson, DF and Smith, JA and Herrell, SD and Luckenbaugh, AN and Barocas, DA and Kim, YJ and Graves, D and Giannico, GA and Rathmell, JC and Park, BH and Gordetsky, JB and Hurley, PJ}, title = {Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6036}, pmid = {36229464}, issn = {2041-1723}, support = {S10 OD023475/OD/NIH HHS/United States ; R01 CA194024/CA/NCI NIH HHS/United States ; R01 CA211695/CA/NCI NIH HHS/United States ; S10 OD016355/OD/NIH HHS/United States ; T32 CA009582/CA/NCI NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; P30 CA068485/CA/NCI NIH HHS/United States ; T32 CA009592/CA/NCI NIH HHS/United States ; R01 CA214494/CA/NCI NIH HHS/United States ; R01 CA218526/CA/NCI NIH HHS/United States ; R01 CA217987/CA/NCI NIH HHS/United States ; }, mesh = {Apolipoproteins E ; *Carcinoma, Intraductal, Noninfiltrating/genetics ; Extracellular Matrix Proteins ; Humans ; Ligands ; Male ; Neoplasm Grading ; *Prostatic Neoplasms/pathology ; RNA ; Receptors, Antigen, T-Cell ; Single-Cell Analysis ; Tumor Microenvironment/genetics ; }, abstract = {Cribriform prostate cancer, found in both invasive cribriform carcinoma (ICC) and intraductal carcinoma (IDC), is an aggressive histological subtype that is associated with progression to lethal disease. To delineate the molecular and cellular underpinnings of ICC/IDC aggressiveness, this study examines paired ICC/IDC and benign prostate surgical samples by single-cell RNA-sequencing, TCR sequencing, and histology. ICC/IDC cancer cells express genes associated with metastasis and targets with potential for therapeutic intervention. Pathway analyses and ligand/receptor status model cellular interactions among ICC/IDC and the tumor microenvironment (TME) including JAG1/NOTCH. The ICC/IDC TME is hallmarked by increased angiogenesis and immunosuppressive fibroblasts (CTHRC1[+]ASPN[+]FAP[+]ENG[+]) along with fewer T cells, elevated T cell dysfunction, and increased C1QB[+]TREM2[+]APOE[+]-M2 macrophages. These findings support that cancer cell intrinsic pathways and a complex immunosuppressive TME contribute to the aggressive phenotype of ICC/IDC. These data highlight potential therapeutic opportunities to restore immune signaling in patients with ICC/IDC that may afford better outcomes.}, } @article {pmid36223973, year = {2022}, author = {Singh, N and Singh, R and Decker, B and Robins, D and Vidal, G}, title = {Metastatic triple negative breast cancer with NTRK gene fusion on tissue but not on ctDNA molecular profile.}, journal = {BMJ case reports}, volume = {15}, number = {10}, pages = {}, pmid = {36223973}, issn = {1757-790X}, mesh = {*Breast Neoplasms/genetics/pathology ; Carcinoma ; *Circulating Tumor DNA/genetics ; Female ; Gene Fusion ; Humans ; Oncogene Proteins, Fusion/genetics ; Protein Kinase Inhibitors ; *Triple Negative Breast Neoplasms/drug therapy/genetics ; }, abstract = {A woman presented to medical oncology with almost 4 years of untreated, slowly progressing, triple negative metastatic breast cancer to the lung. About 15 years prior, she was diagnosed with invasive ductal carcinoma of the right breast with ipsilateral chest wall recurrence 6 years later. Comprehensive molecular profiling of a metastatic lesion detected a hotspot ETV6-NTRK3 fusion, which was not present on circulating tumour DNA or molecular profile performed 4 years prior. A second look pathological examination demonstrated tumour characteristics consistent with secretory breast carcinoma. Identification of ETV6--NKRT3 fusion allowed for treatment with larotrectinib, a tyrosine kinase inhibitor specifically indicated for secretory breast carcinoma. After 3 months, she experienced a partial response.}, } @article {pmid36220898, year = {2022}, author = {Batashvili, M and Sheaffer, R and Katz, M and Doron, Y and Kempler, N and Levy, DA}, title = {Behavioural reconsolidation interference not observed in a within-subjects design.}, journal = {NPJ science of learning}, volume = {7}, number = {1}, pages = {26}, pmid = {36220898}, issn = {2056-7936}, abstract = {Studies of reconsolidation interference posit that reactivation of a previously consolidated memory via a reminder brings it into an active, labile state, leaving it open for potential manipulation. If interfered with, this may disrupt the original memory trace. While evidence for pharmacological reconsolidation interference is widespread, it remains unclear whether behavioural interference using the presentation of competing information can engender it, especially in declarative memory. Almost all previous studies in this area have employed between-subjects designs, in which there are potential confounds, such as different retrieval strategies for the multiple conditions. In the current studies, within-subjects paradigms were applied to test the effects of reconsolidation interference on associative recognition and free recall. In Experiment 1, participants engaged in pair-associate learning of unrelated object pictures on Day 1, and after a reminder, interference, reminder + interference, or no manipulation (control) on Day 2, were tested on associative recognition of these pairs on Day 3. In Experiments 2 and 3, memoranda were short stories studied on Day 1. On Day 2, stories were assigned to either control, reminder, interference by alternative stories, or reminder + interference conditions. On Day 3 participants recalled the Day 1 stories, and answered yes/no recognition questions. Reminders improved subsequent memory, while interference was effective in reducing retrieval in differing degrees across the experiments. Importantly, the reminder + interference condition was no more effective in impairing retrieval than the interference-alone condition, contrary to the prediction of the behavioural reconsolidation-interference approach.}, } @article {pmid36216835, year = {2022}, author = {Tzachor, A and Richards, CE and Jeen, S}, title = {Transforming agrifood production systems and supply chains with digital twins.}, journal = {NPJ science of food}, volume = {6}, number = {1}, pages = {47}, pmid = {36216835}, issn = {2396-8370}, abstract = {Digital twins can transform agricultural production systems and supply chains, curbing greenhouse gas emissions, food waste and malnutrition. However, the potential of these advanced virtualization technologies is yet to be realized. Here, we consider the promise of digital twins across six typical agrifood supply chain steps and emphasize key implementation barriers.}, } @article {pmid36214134, year = {2022}, author = {Zweck, E and Scheiber, D and Schultheiss, HP and Kuss, O and Kelm, M and Roden, M and Westenfeld, R and Szendroedi, J}, title = {Impaired Myocardial Mitochondrial Respiration in Humans With Prediabetes: A Footprint of Prediabetic Cardiomyopathy.}, journal = {Circulation}, volume = {146}, number = {15}, pages = {1189-1191}, doi = {10.1161/CIRCULATIONAHA.122.058995}, pmid = {36214134}, issn = {1524-4539}, mesh = {Blood Glucose ; *Cardiomyopathies ; *Diabetes Mellitus, Type 2 ; Humans ; Mitochondria, Heart ; Myocardium ; *Prediabetic State ; Respiration ; }, } @article {pmid36213813, year = {2022}, author = {Akpoghor, OD and Eghonghon, AR and Osime, OC}, title = {Pattern of Emergency Presentation of Patients with Breast Cancer at the University of Benin Teaching Hospital.}, journal = {Journal of the West African College of Surgeons}, volume = {12}, number = {2}, pages = {70-74}, pmid = {36213813}, issn = {2276-6944}, abstract = {BACKGROUND: Breast cancer is the most common malignancy affecting women in Nigeria. Presentation is usually elective. However, some patients present as an emergency with complications of the disease and its treatment. This study aimed to capture the features of this population of patients with breast cancer presenting as an emergency.

MATERIALS AND METHODS: The study was a prospective cross-sectional study conducted between March 2021 and February 2022. All the patients with histologically diagnosed breast cancer presenting as an emergency were recruited into the study. Relevant information was retrieved and analysed.

RESULTS: Over the study period, 34 patients were recruited. They were all females and ages ranged between 27 and 74 years of age (mean: 45.56 ± 11.71 years), and the highest incidence was in the fifth decade of life. The first symptom in all patients was a breast lump, and the duration of disease ranged between 3 and 84 months (mean: 29.21 ± 22.38 months). The right breast was most commonly involved, and invasive ductal carcinoma (no specific type) was the commonest histologic type in 88.24% of cases. Over half of the patients seen had received no treatment after establishing the diagnosis of breast cancer. For those who received treatment, radiotherapy was the least accessed form of treatment. The most common symptoms were difficulty breathing and jaundice (29.41% each), and metastatic disease was the most common diagnosis. The duration of admission ranged between 1 and 35 days, and a mortality rate of 45.45% was recorded.

CONCLUSION: The most common indication for emergency presentation in patients with breast cancer was metastatic disease.}, } @article {pmid36213589, year = {2022}, author = {Paulson, MR and Maita, K and Avila, FR and Torres-Guzman, RA and Garcia, JP and Eldaly, A and Forte, AJ and Maniaci, MJ}, title = {Colectomy Complicated by High-Output Ileostomy Managed in a Virtual Hybrid Hospital-at-Home Program.}, journal = {Case reports in surgery}, volume = {2022}, number = {}, pages = {3177934}, pmid = {36213589}, issn = {2090-6900}, abstract = {Chronically ill patients with superimposed acute illness requiring hospitalization are more likely to develop an extended length of stay, hospital-acquired infections, and adverse events throughout their hospitalization. An excellent alternative to managing this population of patients in the traditional bricks-and-mortal (BAM) hospital is the hospital-at-home (HaH) model. The Advanced Care at Home (ACH) program is Mayo Clinic's HaH model that provides acute and postacute care to high-acuity patients in their homes rather than in the traditional hospital and skilled nursing facility. We report a case of postoperative care through the ACH program of a patient suffering from short gut syndrome, high-output ileostomy, and severe protein-calorie malnutrition in the setting of previously diagnosed triple-negative invasive ductal carcinoma (IDC) of the right breast complicated by lung and brain metastasis. The patient had multiple complications that required repeated scare escalations directed by a multidisciplinary virtual care. Despite these complications, the ACH model of care was able to keep the patient in the home setting the majority of the time, limiting BAM hospital days, and eliminating the need to use the emergency department for acute escalation for 3 months. The patient was able to recover during this time period and proceed to successful take-down of the ileostomy. This case highlights the benefits of the ACH program by offering high-acuity hospital-level care to severely ill patients in the comfort of their homes. Highly qualified providers paired with curated technology in the home allowed for prompt identification of patient decompensation and timely initiation of treatment while avoiding institutionalization.}, } @article {pmid36210658, year = {2022}, author = {Erdogan, O and Parlakgumus, A and Tas, ZA and Yener, K and Turan, U}, title = {Invasive and Non-invasive Ductal Carcinoma within Malignant Phyllodes Tumour with Axillary Lymph Node Metastases.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {32}, number = {8}, pages = {S92-S94}, doi = {10.29271/jcpsp.2022.Supp2.S92}, pmid = {36210658}, issn = {1681-7168}, mesh = {Axilla/pathology ; *Breast Neoplasms/pathology/surgery ; *Carcinoma, Ductal/pathology/surgery ; *Carcinoma, Ductal, Breast/pathology/surgery ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/pathology ; Lymphatic Metastasis/pathology ; Mastectomy ; *Phyllodes Tumor/pathology/surgery ; }, abstract = {Phyllodes tumours are uncommon breast neoplasms constituting 1-2% of breast malignancies. Metastasis is usually haematogenous, and axillary lymph node dissection is not routinely performed. A phyllodes tumour with concomitant invasive ductal carcinoma (IDC) is even rarer. When IDCor ductal carcinoma in-situ (DCIS) is detected, the management of the condition changes completely. We report a case of a 22-year female presenting with a mass in the right breast and palpable axillary lymph nodes. The pathological examination demonstrated a malignant phyllodes tumour with concomitant IDC and DCIS. The patient elected to have modified radical mastectomy, and the pathological examination showed metastasis in the axillary lymph nodes. The patient was administered appropriate therapy. At the last visit, she did not have the clinical signs of disease. This is the first youngest case of axillary lymph node metastases with both DCIS and IDC on pathological examination in malignant phyllodes tumour. Key Words: Malignant phyllodes, Invasive ductal carcinoma, Ductal carcinoma in-situ, Lymph node metastasis.}, } @article {pmid36208091, year = {2023}, author = {Lu, X and Ying, Y and Zhang, W and Li, R and Zhang, J}, title = {High MutS homolog 2 expression predicts poor prognosis and is related to immune infiltration in endometrial carcinoma.}, journal = {Cell biology international}, volume = {47}, number = {1}, pages = {201-215}, doi = {10.1002/cbin.11925}, pmid = {36208091}, issn = {1095-8355}, support = {182102410095//Science and Technology Department of Henan Province/ ; 212102310466//Science and Technology Department of Henan Province/ ; 2019GGJS004//Education Department of Henan Province/ ; LHGJ20220473//Health Commission of Henan Province/ ; SBGJ202002119//Health Commission of Henan Province/ ; }, mesh = {Female ; Humans ; *Endometrial Neoplasms/diagnosis/pathology ; *MutS Homolog 2 Protein/genetics/metabolism ; Promoter Regions, Genetic ; *Biomarkers, Tumor/genetics/metabolism ; }, abstract = {Several studies have shown that MutS homolog 2 (MSH2) is highly expressed in many cancer tissues. Transcriptome expression data were collected from the Cancer Genome Atlas (TCGA) database. We analyzed the expression of MSH2 in normal and tumor tissues, the relationship between MSH2 expression and various prognostic factors, and the relationship between MSH2 expression and overall survival, disease specific survival, and progression free interval. We also examined MSH2 promoter methylation between endometrial cancer and normal endometrial tissues, and identified the prognostic value of MSH2 methylation in endometrial cancer. MSH2 was highly expressed in endometrial cancer tumor tissues compared with normal tissues. High MSH2 expression might be an independent prognostic factor for OS, DSS, and PFI. Further, high MSH2 expression was correlated with age and histological type, but not with BMI, clinical stage, tumor invasion, or other clinical features. MSH2 promoter methylation in endometrial cancer was significantly lower than in normal tissues. Additionally, MSH2 levels, OS, DSS, and PFI were associated with BMI, age, tumor invasion, and histological type. ssGSEA showed that MSH2 expression was positively correlated with the infiltration of Th2 cells, Tcm cells, T helper cells, and Tgd cells, whereas it was negatively correlated with NK CD56 bright cells, pDC cells, iDC cells, cytotoxic cells, and neutrophils. Increased MSH2 expression and reduced MSH2 methylation in endometrial cancer predicts poor prognosis. MSH2 may be used as a biomarker for the diagnosis and prognosis of endometrial cancer and as an immunotherapy target.}, } @article {pmid36206823, year = {2022}, author = {Maggi, G and Di Meglio, D and Vitale, C and Amboni, M and Obeso, I and Santangelo, G}, title = {The impact of executive dysfunctions on Theory of Mind abilities in Parkinson's disease.}, journal = {Neuropsychologia}, volume = {176}, number = {}, pages = {108389}, doi = {10.1016/j.neuropsychologia.2022.108389}, pmid = {36206823}, issn = {1873-3514}, mesh = {Humans ; *Theory of Mind/physiology ; *Parkinson Disease/complications/psychology ; Neuropsychological Tests ; Executive Function/physiology ; *Cognitive Dysfunction ; }, abstract = {Theory of Mind (ToM) is the ability to infer and reason about others' mental states, a process impaired by Parkinson's disease (PD). ToM performance in PD seems to be strongly related to executive functioning but the exact nature of this relationship is still unclear. We aim to investigate the direct impact of several executive dysfunctions on ToM deficits (Affective and Cognitive ToM) in PD patients. Sixty-eight PD patients underwent neuropsychological tests evaluating executive control such as inhibition, cognitive flexibility, processing speed or working memory and Cognitive and Affective ToM. We divided participants into two groups based on their performance on executive tests: PD patients with poor executive functioning (PD-EF-) and those with preserved executive functioning (PD-EF+). To explore the direct impact of executive subdomains on ToM abilities, two mediation models were executed in the whole sample. We found that PD patients with poor executive functioning reported poorer scores on Affective and Cognitive ToM tasks than PD patients with preserved executive functions, controlling for age and education. Moreover, parallel mediation models, conducted in the whole sample, indicated that performance on phonological fluency mediated the relationships between educational level and both Affective and Cognitive ToM, controlling the effect of other executive tests. These findings further support the idea that executive functions are crucial in ToM processes. Particularly, phonological fluency, whose execution requires both verbal abilities and cognitive flexibility, mediated ToM performance controlling the effect of other executive functions. The identification of neuropsychological processes underpinning ToM abilities might represent a plausible target for cognitive training to strengthen ToM abilities in PD.}, } @article {pmid36203455, year = {2022}, author = {Zheng, Y and Bai, L and Sun, J and Zhu, L and Huang, R and Duan, S and Dong, F and Tang, Z and Li, Y}, title = {Diagnostic value of radiomics model based on gray-scale and contrast-enhanced ultrasound for inflammatory mass stage periductal mastitis/duct ectasia.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {981106}, pmid = {36203455}, issn = {2234-943X}, abstract = {OBJECTIVE: The present study aimed to investigate the clinical application value of the radiomics model based on gray-scale ultrasound (GSUS) and contrast-enhanced ultrasound (CEUS) images in the differentiation of inflammatory mass stage periductal mastitis/duct ectasia (IMSPDM/DE) and invasive ductal carcinoma (IDC).

METHODS: In this retrospective study, 254 patients (IMSPDM/DE: 129; IDC:125) were enrolled between January 2018 and December 2020 as a training cohort to develop the classification models. The radiomics features were extracted from the GSUS and CEUS images. The least absolute shrinkage and selection operator (LASSO) regression model was employed to select the corresponding features. Based on these selected features, logistic regression analysis was used to aid the construction of these three radiomics signatures (GSUS, CEUS and GSCEUS radiomics signature). In addition, 80 patients (IMSPDM/DE:40; IDC:40) were recruited between January 2021 and November 2021 and were used as the validation cohort. The best radiomics signature was selected. Based on the clinical parameters and the radiomics signature, a classification model was built. Finally, the classification model was assessed using nomogram and decision curve analyses.

RESULTS: Three radiomics signatures were able to differentiate IMSPDM/DE from IDC. The GSCEUS radiomics signature outperformed the other two radiomics signatures and the AUC, sensitivity, specificity, and accuracy were estimated to be 0.876, 0.756, 0.804, and 0.798 in the training cohort and 0.796, 0.675, 0.838 and 0.763 in the validation cohort, respectively. The lower patient age (p<0.001), higher neutrophil count (p<0.001), lack of pausimenia (p=0.023) and GSCEUS radiomics features (p<0.001) were independent risk factors of IMSPDM/DE. The classification model that included the clinical factors and the GSCEUS radiomics signature outperformed the GSCEUS radiomics signature alone (the AUC values of the training and validation cohorts were 0.962 and 0.891, respectively). The nomogram was applied to the validation cohort, reaching optimal discrimination, with an AUC value of 0.891, a sensitivity of 0.888, and a specificity of 0.750.

CONCLUSIONS: The present study combined the clinical parameters with the GSCEUS radiomics signature and developed a nomogram. This GSCEUS radiomics-based classification model could be used to differentiate IMSPDM/DE from IDC in a non-invasive manner.}, } @article {pmid36202832, year = {2022}, author = {Shawi, RE and Kilanava, K and Sakr, S}, title = {An interpretable semi-supervised framework for patch-based classification of breast cancer.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {16734}, pmid = {36202832}, issn = {2045-2322}, mesh = {*Breast Neoplasms/diagnosis/pathology ; Cohort Studies ; Female ; Humans ; Neural Networks, Computer ; New Jersey ; Supervised Machine Learning ; }, abstract = {Developing effective invasive Ductal Carcinoma (IDC) detection methods remains a challenging problem for breast cancer diagnosis. Recently, there has been notable success in utilizing deep neural networks in various application domains; however, it is well-known that deep neural networks require a large amount of labelled training data to achieve high accuracy. Such amounts of manually labelled data are time-consuming and expensive, especially when domain expertise is required. To this end, we present a novel semi-supervised learning framework for IDC detection using small amounts of labelled training examples to take advantage of cheap available unlabeled data. To gain trust in the prediction of the framework, we explain the prediction globally. Our proposed framework consists of five main stages: data augmentation, feature selection, dividing co-training data labelling, deep neural network modelling, and the interpretability of neural network prediction. The data cohort used in this study contains digitized BCa histopathology slides from 162 women with IDC at the Hospital of the University of Pennsylvania and the Cancer Institute of New Jersey. To evaluate the effectiveness of the deep neural network model used by the proposed approach, we compare it to different state-of-the-art network architectures; AlexNet and a shallow VGG network trained only on the labelled data. The results show that the deep neural network used in our proposed approach outperforms the state-of-the-art techniques achieving balanced accuracy of 0.73 and F-measure of 0.843. In addition, we compare the performance of the proposed semi-supervised approach to state-of-the-art semi-supervised DCGAN technique and self-learning technique. The experimental evaluation shows that our framework outperforms both semi-supervised techniques and detects IDC with an accuracy of 85.75%, a balanced accuracy of 0.865, and an F-measure of 0.773 using only 10% labelled instances from the training dataset while the rest of the training dataset is treated as unlabeled.}, } @article {pmid36196411, year = {2022}, author = {Giap, F and O'steen, L and Liu, IC and Spiguel, LE and Shaw, CM and Morris, CG and Mailhot Vega, RB and Lightsey, JL and Bradley, JA and Mendenhall, NP and Okunieff, PG and Lockney, NA}, title = {Intraoperative radiation therapy for early-stage breast cancer: a single-institution experience.}, journal = {Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology}, volume = {27}, number = {4}, pages = {666-676}, pmid = {36196411}, issn = {1507-1367}, abstract = {BACKGROUND: To assess outcomes and toxicity after low-energy intraoperative radiotherapy (IORT) for early-stage breast cancer (ESBC).

MATERIALS AND METHODS: We reviewed patients with unilateral ESBC treated with breast-conserving surgery and 50-kV IORT at our institution. Patients were prescribed 20 Gy to the surface of the spherical applicator, fitted to the surgical cavity during surgery. Patients who did not meet institutional guidelines for IORT alone on final pathology were recommended adjuvant treatment, including additional surgery and/or external-beam radiation therapy (EBRT). We analyzed ipsilateral breast tumor recurrence, overall survival, recurrence-free survival and toxicity.

RESULTS: Among 201 patients (median follow-up, 5.1 years; median age, 67 years), 88% were Her2 negative and ER positive and/or PR positive, 98% had invasive ductal carcinoma, 87% had grade 1 or 2, and 95% had clinical T1 disease. Most had pathological stage T1 (93%) N0 (95%) disease. Mean IORT applicator dose at 1-cm depth was 6.3 Gy. Post-IORT treatment included additional surgery, 10%; EBRT, 11%; adjuvant chemotherapy, 9%; and adjuvant hormonal therapy, 74%. Median total EBRT dose was 42.4 (range, 40.05-63) Gy and median dose per fraction was 2.65 Gy. At 5 years, the cumulative incidence of ipsilateral breast tumor recurrence was 2.7%, the overall survival rate was 95% with no breast cancer-related deaths, and the recurrence-free survival rate was 96%. For patients who were deemed unsuitable for postoperative IORT alone and did not receive recommended risk-adapted EBRT, the IBTR rate was 4.7% versus 1.7% (p = 0.23) for patients who were either suitable for IORT alone or unsuitable and received adjuvant EBRT. Cosmetic toxicity data was available for 83%, with 7% experiencing grade 3 breast toxicity and no grade 4-5 toxicity.

CONCLUSIONS: IORT for select patients with ESBC results in acceptable outcomes in regard to ipsilateral breast tumor recurrence and toxicity.}, } @article {pmid36196281, year = {2022}, author = {Culbert, M and Shock, L and Fabricius, MM and Nelson, N}, title = {Reverse Abdominoplasty for Reconstruction Following Oncologic Resection of Extensive Breast Disease.}, journal = {Cureus}, volume = {14}, number = {9}, pages = {e28664}, pmid = {36196281}, issn = {2168-8184}, abstract = {We present two cases of patients with extensive breast disease who underwent a reverse abdominoplasty for closure following resection: one of Paget's disease extending beyond the breast borders and another of a locally recurrent triple-negative invasive ductal carcinoma following mastectomy in a patient who previously had an ipsilateral thoracotomy. The reverse abdominoplasty flap is a reconstructive option not readily considered for closure following mastectomy. However, we believe that the reverse abdominoplasty flap should be considered when evaluating patients for anterior chest wall reconstruction because it is a simple and versatile coverage option.}, } @article {pmid36192585, year = {2022}, author = {Arakawa, T and Miyake, H and Nagai, H and Yoshioka, Y and Shibata, K and Takahashi, D and Yuasa, N and Sumi, H and Yoshikawa, K and Kiriyama, A and Fujino, M}, title = {Non-tumor forming and diffusely spreading invasive pancreatic cancer.}, journal = {Clinical journal of gastroenterology}, volume = {15}, number = {6}, pages = {1185-1192}, pmid = {36192585}, issn = {1865-7265}, mesh = {Male ; Humans ; Aged ; *Carcinoma, Pancreatic Ductal/diagnostic imaging/surgery ; *Pancreatic Intraductal Neoplasms/pathology ; *Pancreatic Neoplasms/diagnostic imaging/surgery ; Pancreatectomy ; Pancreatic Ducts/diagnostic imaging/pathology ; }, abstract = {A 78-year-old man presented to our hospital with loss of appetite and epigastric discomfort. Computed tomography (CT) revealed dilation of the main pancreatic duct and three cystic lesions in the pancreatic neck, body, and tail. Endoscopic ultrasonography showed a mural nodule > 5 mm enhanced with Sonazoid in a cyst. Therefore, the patient was diagnosed with intra-ductal papillary mucinous neoplasm (IPMN) and underwent distal pancreatectomy. Macroscopic examination of the cut surface of the resected specimen showed no solid tumors in the pancreatic parenchyma. The histopathological diagnosis of the cysts was IPMN with low-grade dysplasia. Ten months after surgery, the serum carbohydrate antigen 19-9 level was elevated, and CT showed multiple peritoneal and pulmonary nodules, suggesting peritoneal dissemination and lung metastases. Since recurrence of pancreatic cancer was suspected, repeat histopathological examination of the resected specimen was performed, revealing small clusters of atypical epithelial cells diffusely spreading in the pancreatic tissue. The diagnosis was changed to invasive ductal carcinoma (pT2N1bM0, stage IIB). Invasive pancreatic cancer that does not form a solid mass, and shows diffuse spreading with small clusters is extremely rare. Imaging diagnosis and histopathological examination should be carefully performed in such cases.}, } @article {pmid36190529, year = {2022}, author = {van der Slot, MA and Seyrek, N and Kweldam, CF and den Bakker, MA and Busstra, MB and Gan, M and Klaver, S and Rietbergen, JBW and van Leenders, GJLH}, title = {Percentage Gleason pattern 4 and PI-RADS score predict upgrading in biopsy Grade Group 2 prostate cancer patients without cribriform pattern.}, journal = {World journal of urology}, volume = {40}, number = {11}, pages = {2723-2729}, pmid = {36190529}, issn = {1433-8726}, mesh = {Male ; Humans ; *Prostatic Neoplasms/surgery/pathology ; Magnetic Resonance Imaging ; Neoplasm Grading ; Prostate/pathology ; Prostatectomy ; Biopsy ; }, abstract = {PURPOSE: To identify parameters to predict upgrading in biopsy Grade Group (GG) 2 prostate cancer patients without cribriform and intraductal carcinoma (CR/IDC) on biopsy.

METHODS: Preoperative biopsies from 657 men undergoing radical prostatectomy (RP) for prostate cancer were reviewed for GG, presence of CR/IDC, percentage Gleason pattern 4, and tumor length. In men with biopsy GG2 without CR/IDC (n = 196), clinicopathologic features were compared between those with GG1 or GG2 without CR/IDC on RP (GG ≤ 2-) and those with GG2 with CR/IDC or any GG > 2 (GG ≥ 2+). Logistic regression analysis was used to predict upgrading in the biopsy cohort.

RESULTS: In total 283 men had biopsy GG2 of whom 87 (30.7%) had CR/IDC and 196 (69.3%) did not. CR/IDC status in matched biopsy and RP specimens was concordant in 179 (63.3%) and discordant in 79 (27.9%) cases (sensitivity 45.1%; specificity 92.6%). Of 196 biopsy GG2 men without CR/IDC, 106 (54.1%) had GG ≥ 2+ on RP. Multivariable logistic regression analysis showed that age [odds ratio (OR): 1.85, 95% confidence interval (CI)1.09-3.20; p = 0.025], percentage Gleason pattern 4 (OR 1.54, 95% CI 1.17-2.07; p = 0.003), PI-RADS 5 lesion (OR 2.17, 95% CI 1.03-4.70; p = 0.045) and clinical stage T3 (OR 3.60; 95% CI 1.08-14.50; p = 0.049) were independent parameters to predict upgrading to GG ≥  2+ on RP in these men.

CONCLUSIONS: Age, clinical stage T3, percentage Gleason pattern 4 and presence of PI-RADS 5 lesions are independent predictors for upgrading in men with biopsy GG2 without CR/IDC. These findings allow for improved clinical decision-making on surveillance eligibility in intermediate-risk prostate cancer patients.}, } @article {pmid36189356, year = {2022}, author = {Saeed, U and Piracha, ZZ and Uppal, SR and Waheed, Y and Uppal, R}, title = {SARS-CoV-2 induced hepatic injuries and liver complications.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {726263}, pmid = {36189356}, issn = {2235-2988}, mesh = {Aged ; *COVID-19/complications ; *Carcinoma, Hepatocellular ; *Gastrointestinal Diseases ; Humans ; Liver/pathology ; *Liver Neoplasms/pathology ; Pandemics ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is resilient, highly pathogenic, and rapidly transmissible. COVID-19 patients have been reported to have underlying chronic liver abnormalities linked to hepatic dysfunction.

DISCUSSION: Viral RNAs are detectable in fecal samples by RT-PCR even after negative respiratory samples, which suggests that SARS-CoV-2 can affect the gastrointestinal tract and the liver. The case fatality rates are higher among the elderly and those with underlying comorbidities such as hypertension, diabetes, liver abnormality, and heart disease. There is insufficient research on signaling pathways. Identification of molecular mechanisms involved in SARS-CoV-2-induced damages to hepatocytes is challenging. Herein, we demonstrated the multifactorial effects of SARS-CoV-2 on liver injury such as psychological stress, immunopathogenesis, systemic inflammation, ischemia and hypoxia, drug toxicity, antibody-dependent enhancement (ADE) of infection, and several others which can significantly damage the liver.

CONCLUSION: During the COVID-19 pandemic, it is necessary for clinicians across the globe to pay attention to SARS-CoV-2-mediated liver injury to manage the rising burden of hepatocellular carcinoma. To face the challenges during the resumption of clinical services for patients with pre-existing liver abnormalities and HCC, the impact of SARS-CoV-2 on hepatocytes should be investigated both in vitro and in vivo.}, } @article {pmid36182676, year = {2023}, author = {Sogunro, OA and Maini, M and Deldar, R and Maini, AS and Greige, N and Greenwalt, I and Wehner, P and De La Cruz, L and Son, JD}, title = {Prognostic Predictors of Mortality in Male Breast Cancer: Outcomes in an Urban Population.}, journal = {The Journal of surgical research}, volume = {281}, number = {}, pages = {192-199}, doi = {10.1016/j.jss.2022.08.035}, pmid = {36182676}, issn = {1095-8673}, mesh = {Humans ; Male ; Female ; *Breast Neoplasms, Male/pathology ; Prognosis ; Retrospective Studies ; Urban Population ; *Atrial Fibrillation ; *Breast Neoplasms ; *Kidney Failure, Chronic ; }, abstract = {INTRODUCTION: Male breast cancer (MBC) accounts for 0.5% to 1% of all breast cancers diagnosed annually. The purpose of this study is to evaluate prognostic factors in MBC.

METHODS: We performed a retrospective chart review of patients with MBC between 2010 and 2021. Demographics, comorbidities, cancer characteristics, recurrence, and mortality were collected. Cox proportional hazards regression model was used to determine prognostic factors. A Kaplan-Meier curve was used to plot survival probabilities.

RESULTS: A total of 47 male patients were identified. The mean age at presentation was 64.1 y. Twenty eight (59.6%) patients were African American and 14 patients (29.8%) were Caucasian. Most patients had invasive ductal carcinoma (89.4%) and presented with T1 or T2 tumors (40.4% and 38.3%, respectively). Three patients (6.4%) had a recurrence and eight patients (17%) died. Using mortality as an end point, age (≥ 76.1 y) indicated a hazard ratio (HR) of 1.13 (P = 0.004), diabetes mellitus (HR = 5.45, P = 0.023), atrial fibrillation (HR = 8.0, P = 0.009), end-stage renal disease (HR 6.47, P = 0.023), Eastern Cooperative Oncology Group performance status of 3 (HR = 7.92, P = 0.024), poorly differentiated grade (HR = 7.21, P = 0.033), and metastatic disease (HR = 30.94, P = 0.015) had an increased risk of mortality. Overall survival at 3 y was 79.2%.

CONCLUSIONS: Advanced age, diabetes mellitus, atrial fibrillation, end-stage renal disease, Eastern Cooperative Oncology Group score of 3, poorly differentiated tumors, and metastatic disease are unfavorable prognostic factors in MBC. Compared to female breast cancer, MBC showed poorer overall survival.}, } @article {pmid36178915, year = {2022}, author = {Mussa, FM and Massawe, HP and Bhalloo, H and Moledina, S and Assenga, E}, title = {Magnitude and associated factors of anti-retroviral therapy adherence among children attending HIV care and treatment clinics in Dar es Salaam, Tanzania.}, journal = {PloS one}, volume = {17}, number = {9}, pages = {e0275420}, pmid = {36178915}, issn = {1932-6203}, mesh = {Child ; Cross-Sectional Studies ; *HIV Infections/complications/drug therapy/epidemiology ; Humans ; Odds Ratio ; Surveys and Questionnaires ; Tanzania/epidemiology ; }, abstract = {INTRODUCTION: The HIV pandemic continues to contribute significantly towards childhood mortality and morbidity. The up-scaling of the Anti-retroviral therapy (ART) access has seen more children surviving and sanctions great effort be made on ensuring adherence. Adherence is a dynamic process that changes over time and is determined by variable factors. This necessitates the urgency to conduct studies to determine the potential factors affecting adherence in our setting and therefore achieve the 90-90-90 goal of sustainable viral suppression.

OBJECTIVES: To assess the magnitude and associated factors of ART adherence among children (1-14 years) attending HIV care and treatment clinics during the months of July to November 2018 in Dar es Salaam.

METHODS: A cross-sectional clinic-based study, conducted in three selected HIV care and treatment clinics in urban Dar es Salaam; Muhimbili National Hospital (MNH), Temeke Regional Referral Hospital (TRRH), Infectious Disease Centre- DarDar Paediatric Program (IDC-DPP) HIV clinics during the months of July to November 2018. HIV-infected children aged 1-14 years who had been on treatment for at least six months were consecutively enrolled until the sample size was achieved. A structured questionnaire was used for data collection. Four-day self-report, one-month self-recall report and missed clinic appointments were used to assess adherence. Frequencies and percentages were used to describe categorical data. The odds ratio was used to analyse the possible factors affecting ART adherence Logistic regression models were used to determine the factors associated with ART adherence. Analysis was conducted using SPSS version 20.0 and p-value <0.05 were considered statistically significant.

RESULTS: 333 participants were recruited. The overall good adherence (≥95%) was approximated to be 60% (CI-54.3-65.1) when subjected to all three measures. On multivariable logistic regression, factors associated with higher odds of poor adherence were found to be caregivers aged 17-25 years [AOR = 3.5, 95%CI-(1.5-8.4)], children having an inter-current illness [AOR = 10.8, 95%CI-(2.3-50.4)], disbelief in ART effectiveness [AOR = 5.495; 95%CI-(1.669-18.182)] and advanced clinical stage [AOR = 1.972; 95% CI-(1.119-3.484)]. The major reasons reported by caregivers for missing medications included forgetfulness (41%), high pill burden (21%), busy schedule (11%) and long waiting hours at the clinic (9%).

In the urban setting of Dar es Salaam, ART adherence among children was found to be relatively low when combined adherence measures were used. Factors associated with poor ART adherence found were younger aged caregivers, and child intercurrent illness, while factors conferring good adherence were belief in ART effectiveness and lower HIV clinical stage. More attention and support should be given to younger aged caregivers, children with concomitant illness and advanced HIV clinical stages. Educating caregivers on ART effectiveness may also aid in improving adherence.}, } @article {pmid36176414, year = {2022}, author = {Kawaguchi, S and Tamura, N and Tanaka, K and Kobayashi, Y and Sato, J and Kinowaki, K and Shiiba, M and Ishihara, M and Kawabata, H}, title = {Clinical prediction model based on 18F-FDG PET/CT plus contrast-enhanced MRI for axillary lymph node macrometastasis.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {989650}, pmid = {36176414}, issn = {2234-943X}, abstract = {PURPOSE: Positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) are useful for detecting axillary lymph node (ALN) metastasis in invasive ductal breast cancer (IDC); however, there is limited clinical evidence to demonstrate the effectiveness of the combination of PET/CT plus MRI. Further axillary surgery is not recommended against ALN micrometastasis (lesion ≤2 mm) seen in sentinel lymph nodes, especially for patients who received proper adjuvant therapy. We aimed to evaluate the efficacy of a prediction model based on PET/CT plus MRI for ALN macrometastasis (lesion >2 mm) and explore the possibility of risk stratification of patients using the preoperative PET/CT plus MRI and biopsy findings.

MATERIALS AND METHODS: We retrospectively investigated 361 female patients (370 axillae; mean age, 56 years ± 12 [standard deviation]) who underwent surgery for primary IDC at a single center between April 2017 and March 2020. We constructed a prediction model with logistic regression. Patients were divided into low-risk and high-risk groups using a simple integer risk score, and the false negative rate for ALN macrometastasis was calculated to assess the validity. Internal validation was also achieved using a 5-fold cross-validation.

RESULTS: The PET/CT plus MRI model included five predictor variables: maximum standardized uptake value of primary tumor and ALN, primary tumor size, ALN cortical thickness, and histological grade. In the derivation (296 axillae) and validation (74 axillae) cohorts, 54% and 61% of patients, respectively, were classified as low-risk, with a false-negative rate of 11%. Five-fold cross-validation yielded an accuracy of 0.875.

CONCLUSIONS: Our findings demonstrate the validity of the PET/CT plus MRI prediction model for ALN macrometastases. This model may aid the preoperative identification of low-risk patients for ALN macrometastasis and provide helpful information for PET/MRI interpretation.}, } @article {pmid36175695, year = {2022}, author = {Silva, FHS and Underwood, A and Almeida, CP and Ribeiro, TS and Souza-Fagundes, EM and Martins, AS and Eliezeck, M and Guatimosim, S and Andrade, LO and Rezende, L and Gomes, HW and Oliveira, CA and Rodrigues, RC and Borges, IT and Cassali, GD and Ferreira, E and Del Puerto, HL}, title = {Transcription factor SOX3 upregulated pro-apoptotic genes expression in human breast cancer.}, journal = {Medical oncology (Northwood, London, England)}, volume = {39}, number = {12}, pages = {212}, pmid = {36175695}, issn = {1559-131X}, support = {05/20160//PRPq UFMG/ ; }, mesh = {*Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/genetics ; Caspase 3 ; Female ; Fluorescein-5-isothiocyanate ; Humans ; RNA, Messenger ; SOXB1 Transcription Factors ; Tumor Suppressor Proteins ; Up-Regulation ; bcl-2-Associated X Protein ; }, abstract = {BACKGROUND: Sex-determining region Y-box 3 (SOX3) protein, a SOX transcriptions factors group, has been identified as a key regulator in several diseases, including cancer. Downregulation of transcriptions factors in invasive ductal carcinoma (IDC) can interfere in neoplasia development, increasing its aggressiveness. We investigated SOX3 protein expression and its correlation with apoptosis in the MDA-MB-231 cell line, as SOX3 and Pro-Caspase-3 immunoexpression in paraffin-embedded invasive ductal carcinoma tissue samples from patients (n = 27). Breast cancer cell line MDA-MD-231 transfected with pEF1-SOX3 + and pEF1-Empty vector followed by cytotoxicity assay (MTT), Annexin-V FITC PI for apoptosis percentage assessment by flow cytometry, qPCR for apoptotic-related gene expression, immunofluorescence, and immunohistochemistry to SOX3 immunolocalization in culture cells, and paraffin-embedded invasive ductal carcinoma tissue samples.

RESULTS: Apoptotic rate was higher in cells transfected with pEF1-SOX3 + (56%) than controls (10%). MDA-MB-231 transfected with pEF1-SOX3 + presented upregulation of pro-apoptotic mRNA from CASP3, CASP8, CASP9, and BAX genes, contrasting with downregulation antiapoptotic mRNA from BCL2, compared to non-transfected cells and cells transfected with pEF1-empty vector (p < 0.005). SOX3 protein nuclear expression was detected in 14% (4/27 cases) of ductal carcinoma cases, and pro-Caspase-3 expression was positive in 50% of the cases.

CONCLUSION: Data suggest that SOX3 transcription factor upregulates apoptosis in breast cancer cell line MDA-MB-231, and has a down nuclear expression in ductal carcinoma cases, and need to be investigated as a tumor suppressor protein, and its loss of expression and non-nuclear action turn the cells resistant to apoptosis. Further studies are necessary to understand how SOX3 protein regulates the promoter regions of genes involved in apoptosis.}, } @article {pmid36172685, year = {2022}, author = {Alinezhadi, M and Makvandi, M and Kaydani, GA and Jazayeri, SN and Charostad, J and Talaeizadeh, AT and Angali, KA}, title = {Detection of High-Risk Human Papillomavirus DNA in Invasive Ductal Carcinoma Specimens.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {23}, number = {9}, pages = {3201-3207}, pmid = {36172685}, issn = {2476-762X}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Alphapapillomavirus/genetics ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal ; Case-Control Studies ; DNA ; DNA, Viral/genetics ; Female ; *Fibroadenoma/genetics ; Formaldehyde ; Humans ; Middle Aged ; Papillomaviridae/genetics ; *Papillomavirus Infections ; Paraffin Embedding ; Young Adult ; }, abstract = {BACKGROUND: According to several studies, there is an association between human papillomavirus (HPV) and breast cancer. Therefore, detection and genotyping of HPV seem important. The present study aimed to investigate the presence of HPV DNA in breast tissues by analyzing the L1 gene.

MATERIALS AND METHODS: This case-control study was conducted on 63 formalin-fixed paraffin-embedded (FFPE) tissues of invasive ductal carcinoma (IDC) as the case group and 32 FFPE tissues of fibroadenoma as the control group. HPV DNA was detected using the polymerase chain reaction assay. Positive samples were then subjected to genotyping. All statistical analyses were performed in SPSS version 22.0.

RESULTS: The patients' age ranged from 15 to 92 years, with a mean age of 43.54±16.36 years. HPV DNA was detected in 17/95 (17.89%) samples, including 9/32 (28.12%) fibroadenoma samples and 8/63 (12.69%) IDC samples. No significant difference was observed regarding the presence of HPV DNA between the IDC and fibroadenoma tissues (P=0.08). However, a significant difference was found in the detection of high-risk HPV (HR-HPV) between the case and control groups (P=0.03). In the case group, 87.5% of the detected viruses (7/8 samples) were HR-HPV, while in the control group, 22.22% of positive samples (2/9 samples) were HR-HPV (P=0.03). Based on the results, HR-HPV and low-risk HPV genotypes were detected in 53% (9/17) and 47% (8/17) of positive samples, respectively.

CONCLUSION: In this study, 12.69% of IDC samples were positive for HPV genomes, and HR-HPV was detected in 87.5% of these samples. The present results suggest the important role of HR-HPV in the development of breast cancer.}, } @article {pmid36172329, year = {2022}, author = {Zangouri, V and Niazkar, HR and Nasrollahi, H and Homapour, F and Ranjbar, A and Seyyedi, MS}, title = {Benign or premalignant? Idiopathic granulomatous mastitis later diagnosed as ductal carcinoma breast cancer: Case report and review of literature.}, journal = {Clinical case reports}, volume = {10}, number = {9}, pages = {e6323}, pmid = {36172329}, issn = {2050-0904}, abstract = {Idiopathic granulomatous mastitis (IGM) is a rare benign infectious disease of the breast, commonly presenting with a unilateral breast mass. Since GM's clinical presentation and imaging can be very similar to breast cancer, diagnosing GM can be challenging. So far, various reports have demonstrated the probable correlation and co-occurrence of granulomatous mastitis and breast cancer. This report presents a 38-year-old female with invasive ductal carcinoma, previously diagnosed as IGM.}, } @article {pmid36171873, year = {2022}, author = {Levy, DA}, title = {Optimizing the social utility of judicial punishment: An evolutionary biology and neuroscience perspective.}, journal = {Frontiers in human neuroscience}, volume = {16}, number = {}, pages = {967090}, pmid = {36171873}, issn = {1662-5161}, abstract = {Punishment as a response to impairment of individual or group welfare may be found not only among humans but also among a wide range of social animals. In some cases, acts of punishment serve to increase social cooperation among conspecifics. Such phenomena motivate the search for the biological foundations of punishment among humans. Of special interest are cases of pro-social punishment of individuals harming others. Behavioral studies have shown that in economic games people punish exploiters even at a cost to their own welfare. Additionally, neuroimaging studies have reported activity during the planning of such punishment in brain areas involved in the anticipation of reward. Such findings hint that there is an evolutionarily honed basic drive to punish social offenders. I argue that the transfer of punishment authority from the individual to the group requires that social offenders be punished as a public good, even if such punishment is not effective as retribution or deterrent. Furthermore, the social need for punishment of offenders has implications for alternatives to incarceration, publicity of punishment, and judicial structure.}, } @article {pmid36168611, year = {2022}, author = {Martin, TA and Choudhry, S and Holton, LH and Mylander, WC and Tafra, L and Liang, W and Jackson, RS}, title = {Outcomes of Margin Reexcision after Oncoplastic Breast Reduction.}, journal = {Plastic and reconstructive surgery. Global open}, volume = {10}, number = {9}, pages = {e4509}, pmid = {36168611}, issn = {2169-7574}, abstract = {UNLABELLED: Tissue rearrangement after an oncoplastic breast reduction may complicate identification of margins during reexcision. Little is known about outcomes of reoperation in this setting.

METHODS: This is a single-institution, retrospective analysis of outcomes of margin reexcisions after lumpectomy with concurrent oncoplastic Wise-pattern reduction from 2015 to 2020. Outcomes assessed were the rate of successful breast conservation, in-breast recurrence, wound issues or complications, effect on cosmesis, and delay to onset of adjuvant therapy.

RESULTS: From 2015 to 2020, 649 patients underwent lumpectomy with oncoplastic Wise-pattern reduction. Forty-seven patients (7.2%) had greater than or equal to one positive margin(s); of these, 28 went directly to mastectomy, and 19 underwent margin reexcision. Residual disease was found in seven of 19 patients (37%) at reexcision. The rate of successful breast-conserving therapy was 95% with a mean follow-up of 31 months. There was one (5%) in-breast recurrence (invasive ductal carcinoma [IDC] occurring 30 months after the original operation); this patient had a mastectomy for treatment of her recurrence. The overall complication rate was 37%. Radiation was administered to 18 patients (95%), and two patients (11%) had delay of radiation past 6 weeks due to wound complications. Of the 14 patients with photographs available, 12 of 14 patients (86%) were blindly assessed to have equivalent or better cosmesis after margin reexcision (versus initial lumpectomy).

CONCLUSION: Margin reexcision after oncoplastic breast reduction with Wise-pattern is feasible and effective, and can be done without compromising the initial cosmetic results.}, } @article {pmid36168441, year = {2022}, author = {Wenger, D and Kurumety, S and Aydi, ZB}, title = {A case report: invasive ductal carcinoma in mosaic Li-Fraumeni syndrome.}, journal = {Journal of surgical case reports}, volume = {2022}, number = {9}, pages = {rjac408}, pmid = {36168441}, issn = {2042-8812}, abstract = {Li-Fraumeni syndrome (LFS) is a rare autosomal dominant condition caused by pathogenic variants in the TP53 tumor suppressor gene and characterized by a high lifetime risk of various cancers with a very early age of onset. We are presenting a 41-year-old woman with right invasive ductal cancer and no family history of cancers, diagnosed with mosaic LFS confirmed with blood and skin punch biopsy samples. She was treated with neoadjuvant chemotherapy, mastectomy and sentinel node biopsy with completion axillary dissection. Adjuvant radiation was not recommended due to increased risk of secondary cancers. She also elected to undergo risk reducing contralateral mastectomy. Further research is warranted to determine the appropriate clinical management and surveillance strategies in patients with mosaic LFS as whether individuals with mosaic LFS have differing cancer risks in comparison to classic germline LFS is unknown.}, } @article {pmid36168301, year = {2022}, author = {Amiri-Dashatan, N and Yekta, RF and Koushki, M and Arefi Oskouie, A and Esfahani, H and Taheri, S and Kazemian, E}, title = {Metabolomic study of serum in patients with invasive ductal breast carcinoma with LC-MS/MS approach.}, journal = {The International journal of biological markers}, volume = {37}, number = {4}, pages = {349-359}, doi = {10.1177/03936155221123343}, pmid = {36168301}, issn = {1724-6008}, mesh = {Humans ; Female ; Chromatography, Liquid/methods ; Tandem Mass Spectrometry/methods ; Metabolomics/methods ; *Breast Neoplasms/pathology ; Case-Control Studies ; *Carcinoma, Ductal, Breast/metabolism ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is the most common type of breast cancer so its early detection can lead to a significant decrease in mortality rate. However, prognostic factors for IDC are not adequate and we need novel markers for the treatment of different individuals. Although positron emission tomography and magnetic resonance imaging techniques are available, they are based on morphological features that do not provide any clue for molecular events accompanying cancer progression. In recent years, "omics" approaches have been extensively developed to propose novel molecular signatures of cancers as putative biomarkers, especially in biofluids. Therefore, a mass spectrometry-based metabolomics investigation was performed to find some putative metabolite markers of IDC and potential metabolites with prognostic value related to the estrogen receptor, progesterone receptor, lymphovascular invasion, and human epidermal growth factor receptor 2.

METHODS: An untargeted metabolomics study of IDC patients was performed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The multivariate principal component analysis by XCMS online built a model that could separate the study groups and define the significantly altered m/z parameters. The most important biological pathways were also identified by pathway enrichment analysis.

RESULTS: The results showed that the significantly altered metabolites in IDC serum samples mostly belonged to amino acids and lipids. The most important involved pathways included arginine and proline metabolism, glycerophospholipid metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis.

CONCLUSIONS: Significantly altered metabolites in IDC serum samples compared to healthy controls could lead to the development of metabolite-based potential biomarkers after confirmation with other methods and in large cohorts.}, } @article {pmid36162357, year = {2022}, author = {Camarneiro, R and Ferreira, Á and Barros, M and Brito E Melo, M}, title = {Occult breast cancer presenting as axillary lymphadenopathy - Case Report.}, journal = {International journal of surgery case reports}, volume = {99}, number = {}, pages = {107677}, pmid = {36162357}, issn = {2210-2612}, abstract = {INTRODUCTION: Occult breast carcinoma (OBC) is a rare entity and therefore generates discussion regarding diagnosis, approach, and prognosis. This article aims to present a case of OBC and reviews some concepts discussed in the literature.

PRESENTATION OF CASE: 43-year-old woman with right axillary adenopathies, without further complaints, whose biopsy shows a lymph node metastasis from invasive ductal carcinoma of the breast. Breast study, breast RMI and FDG-PET did not identify the primary tumour. As decided by a multidisciplinary team, the patient underwent neoadjuvant chemotherapy, axillary surgery, breast radiotherapy and hormone therapy. Four years after surgery, the patient has no evidence of the primary tumour and no axillary recurrence.

DISCUSSION: OBC was described in 1907. Although the best therapeutic approach is widely discussed in the literature, it is consensual that as long as the existence of a primary tumour is excluded by breast MRI, the conservative approach (excision of axillary adenopathy and breast and axillary radiotherapy) is more advocated.

CONCLUSION: Breast cancer must be considered in the differential diagnosis of a patient with axillary lymphadenopathy. The conservative approach of OBC is the preferred since breast MRI does not identify any suspicious lumps.}, } @article {pmid36157240, year = {2022}, author = {Wang, L and Deng, X and Chen, Y and Zhao, Y and Li, Z}, title = {PRR15 Is a Novel Diagnostic and Prognostic Biomarker in Papillary Thyroid Cancer and Modulates the Tumor Microenvironment.}, journal = {Journal of oncology}, volume = {2022}, number = {}, pages = {3290479}, pmid = {36157240}, issn = {1687-8450}, abstract = {Papillary thyroid cancer (PTC), accounting for more than 80 percent of all cases of thyroid cancer, is a form of a cancerous tumor that has a very favorable prognosis. However, patients diagnosed with PTC who are already in an advanced state have a dismal outlook. This study aimed to establish the diagnostic relevance of PRR15 expression in PTC patients as well as its levels in PTC samples and its connection with immune infiltrates. The TCGA and GEO datasets were combed through to obtain information on PTC patients. The "Limma" program was used to screen for differentially expressed mRNAs (DEMs), and the results were displayed using volcano plots and heat maps. The Wilcoxon test was used to examine the level of PRR15 expression in PTC patients in comparison with that of normal tissues. To study the connection between the immune infiltration level and PRR15 expression in PTC, the single-sample sequence set enrichment analysis (ssGSEA) from the R package was utilized. The expression of PRR15 was analyzed with RT-PCR in PTC cells and normal cells. In order to evaluate the diagnostic significance of PRR15 expression, ROC assays were carried out. Experiments using CCK-8 were carried out to investigate the impact that PRR15 knockdown could have on the proliferation of PTC cells. In this study, 17 overlapped DEMs between PTC specimens and normal specimens were identified, including MPPED2, IPCEF1, SLC4A4, PKHD1L1, DIO1, CRABP1, TPO, TFF3, SPX, TCEAL2, ZCCHC12, SYTL5, PRR15, CHI3L1, SERPINA1, GABRB2, and CITED1. Our attention focused on PRR15 which was highly expressed in PTC specimens as compared with nontumor specimens. PRR15 had an AUC value of 0.926 (95% CI 0.902-0.950) for PTC based on TCGA datasets. Pan-cancer assays suggested PRR15 as an oncogenic gene in many types of tumors. Moreover, we found that PRR15 expression was positively correlated with eosinophils, NK cells, NK CD56bright cells, IDC, macrophages, DC, mast cells, and Th1 cells. Further investigations with CCK-8 demonstrated that inhibiting PRR15 resulted in a decrease in the proliferation of PTC cells. Overall, PRR15 was confirmed to be a biomarker for PTC patients and a predictor of response to immunotherapy.}, } @article {pmid36156504, year = {2022}, author = {Gherlone, N and Sowa, P and Osipova, M and Walton, R}, title = {Acellular Dermal Matrix Mimicking a New Retroareolar Mass After Central Pillar Neonipple Reconstruction.}, journal = {Annals of plastic surgery}, volume = {89}, number = {5}, pages = {500-501}, doi = {10.1097/SAP.0000000000003270}, pmid = {36156504}, issn = {1536-3708}, mesh = {Female ; Humans ; Middle Aged ; *Acellular Dermis ; *Breast Neoplasms/surgery ; Mastectomy/methods ; *Mammaplasty/methods ; Nipples/surgery ; *Breast Implants ; *Breast Implantation/methods ; Retrospective Studies ; }, abstract = {Acellular dermal matrix (ADM) is an increasingly popular alloplastic cadaveric dermis used to enhance postmastectomy reconstruction. Acellular dermal matrix can be used as a nipple-shaped cylinder in central pillar nipple reconstruction to help maintain long-term projection. We report a unique presentation of ADM mimicking a retroareolar mass after central pillar neonipple reconstruction. A 49-year-old woman with a history of invasive ductal carcinoma underwent delayed nipple reconstruction after lumpectomy and oncoplastic closure using an inframammary V-Y advancement flap.The nipple reconstruction was performed using pretattoo and articulated tab flaps. A rolled tube of acellular dermal matrix was placed in the central aspect of the neonipple reconstruction for projection. At 4 months postoperative, a screening mammogram and ultrasound noted a new retroareolar mass classified as BIRADS 4 necessitating a breast biopsy. Biopsy revealed portions of fibrous connective tissue consistent with partially incorporated acellular dermal matrix allograft. There was no evidence of malignancy. To mitigate the risk of future radiographic or clinical misinterpretation of ADM in nipple reconstruction, the placement of radiopaque markers such as microclips on the ADM implant could be a useful adjunct. Radiologists and surgeons should include ADM artifact in their differential diagnosis of radiologic imaging when evaluating a new mass in the proximity of prior ADM placement in neonipple reconstruction of the breast.}, } @article {pmid38633394, year = {2022}, author = {Evlice, O and Bektaş, M and Arık, Ö and Acet, A and Marim, F and Kaya, İ and Şener, A and Erarslan, S and Mistanoğlu, D and Ak, Ö}, title = {Antibiotic Use among Patients Hospitalized with COVID-19 and Treated in Three Different Clinics.}, journal = {Infectious diseases & clinical microbiology}, volume = {4}, number = {3}, pages = {199-205}, pmid = {38633394}, issn = {2667-646X}, abstract = {OBJECTIVE: In this study, we aimed to determine and compare the rates of empirical antibiotic use and duration between the chest diseases clinic (CDC), infectious disease clinic (IDC), and internal medicine clinic (IMC) among patients hospitalized because of COVID-19.

METHODS: This cross-sectional study was performed in a single university hospital. The study included all patients aged 18 years and older hospitalized with a PCR-confirmed COVID-19 between May 30, 2021, and August 30, 2021. Clinical and laboratory findings were recorded from the electronic medical records database.

RESULTS: The study included a total of 581 inpatients, of whom 310 (53.4%) were women. Of the 581 patients, 475 (81.8%) were prescribed antibiotics. The rate of antibiotic prescription was 71.6% for IDC, 88.5% for CDC, and 87.4% for IMC. The most commonly used antibiotic was moxifloxacin in all groups. The mean treatment duration was 8.9±6.16 days. The mean duration of antibiotic treatment was 11.1±5.90 days for CDC, 11.3±6.74 days for IMC, and 5.3 days±3.76 for IDC.

CONCLUSION: Patients with COVID-19 who were treated in IDC had a lower rate and shorter duration of antibiotic use compared to the other clinics. However, the rate of antibiotic prescription in all three groups was very high. Therefore, antimicrobial management programs should be meticulously conducted to reduce unnecessary antibiotic use.}, } @article {pmid36151122, year = {2022}, author = {Vitkin, E and Singh, A and Wise, J and Ben-Elazar, S and Yakhini, Z and Golberg, A}, title = {Nondestructive protein sampling with electroporation facilitates profiling of spatial differential protein expression in breast tumors in vivo.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {15835}, pmid = {36151122}, issn = {2045-2322}, mesh = {Animals ; Electroporation ; Mice ; Neoplasm Proteins ; *Neoplasms/pathology ; Precision Medicine ; *Proteomics ; }, abstract = {Excision tissue biopsy, while central to cancer treatment and precision medicine, presents risks to the patient and does not provide a sufficiently broad and faithful representation of the heterogeneity of solid tumors. Here we introduce e-biopsy-a novel concept for molecular profiling of solid tumors using molecular sampling with electroporation. As e-biopsy provides access to the molecular composition of a solid tumor by permeabilization of the cell membrane, it facilitates tumor diagnostics without tissue resection. Furthermore, thanks to its non tissue destructive characteristics, e-biopsy enables probing the solid tumor multiple times in several distinct locations in the same procedure, thereby enabling the spatial profiling of tumor molecular heterogeneity.We demonstrate e-biopsy in vivo, using the 4T1 breast cancer model in mice to assess its performance, as well as the inferred spatial differential protein expression. In particular, we show that proteomic profiles obtained via e-biopsy in vivo distinguish the tumors from healthy breast tissue and reflect spatial tumor differential protein expression. E-biopsy provides a completely new molecular sampling modality for solid tumors molecular cartography, providing information that potentially enables more rapid and sensitive detection at lesser risk, as well as more precise personalized medicine.}, } @article {pmid36143823, year = {2022}, author = {Nanev, V and Naneva, S and Yordanov, A and Strashilov, S and Konsoulova, A and Vasileva-Slaveva, M and Betova, T and Ivanov, I}, title = {Lymphoepithelioma-like Carcinoma of the Breast Synchronous with a High-Grade Invasive Ductal Carcinoma and Ductal Carcinoma in Situ in a Different Quadrant of the Same Breast: A Case Report.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {9}, pages = {}, pmid = {36143823}, issn = {1648-9144}, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal ; *Carcinoma, Intraductal, Noninfiltrating ; *Carcinoma, Squamous Cell/pathology ; Female ; Humans ; Middle Aged ; }, abstract = {Lymphoepithelioma-like breast carcinoma (LELC) is a rare type of malignant breast tumor that is not included in the current edition of the World Health Organization (WHO) classification of breast tumors. Currently, there are no clearly defined therapeutic strategies, and the general information on breast LELC is based on sporadic clinical cases described in the medical literature. We present a clinical case that describes a 49-year-old woman with a tumor formation in the right breast, histologically verified as LELC, together with a non-palpable, synchronous high-grade invasive ductal carcinoma and ductal carcinoma in situ Grade 2 (DCIS G2) in a different quadrant of the same breast. To our knowledge, this is the first case described in the literature that combines a LELC with a synchronous carcinoma in the same breast.}, } @article {pmid36131945, year = {2022}, author = {Ramdass, MJ and Gonzales, J and Maharaj, D and Simeon, D and Barrow, S}, title = {Breast Carcinoma Receptor Expression in a Caribbean Population.}, journal = {Surgery journal (New York, N.Y.)}, volume = {8}, number = {3}, pages = {e262-e265}, pmid = {36131945}, issn = {2378-5128}, abstract = {Trinidad and Tobago are islands in the Southern Caribbean with a unique mix of races within the population consisting of East Indian (EI) (37.6%), Afro-Caribbean (AC) (36.3%), mixed (24.2%), and Caucasian, Chinese, Lebanese, Syrian, Amerindian, and Spanish groups accounting for 1.9%. It makes it suitable for a comparison of breast carcinoma receptor expression within a fixed environment. This study included 257 women with an age range of 28 to 93 years (mean = 57.2, standard deviation = 15.0), peak age group of 51 to 60 consisting of 105 EI, 119 AC, and 33 mixed descent. Invasive ductal carcinoma accounted for 88%, invasive lobular 9.7%, and ductal carcinoma in situ 2.3%. The triple-negative rates were 24.8, 33.6, and 30.3% for EI, AC, and mixed races, respectively, with the Pearson's chi-square test revealing statistical significance for the AC versus EI (p < 0.001); AC versus mixed (p < 0.001); and EI versus mixed (p = 0.014) groups. The overall estrogen (ER), progesterone (PR), and human epidermal growth receptor (HER) expression negative rates were 52, 64, and 79%, respectively. Chi-square test of the following combinations: ER +/PR +/HER + ; ER +/PR +/HER - ; ER -/PR -/HER + ; ER +/PR -/HER + ; ER +/PR -/HER - ; ER -/PR +/HER + ; ER -/PR +/HER- revealed no statistical differences (p = 0.689).}, } @article {pmid36131807, year = {2022}, author = {Sapon-Cousineau, S and Moldoveanu, D and Charpentier, D and Gagnon, A and Patocskai, É}, title = {Locally advanced breast cancer arising in the axilla.}, journal = {Journal of surgical case reports}, volume = {2022}, number = {9}, pages = {rjac425}, pmid = {36131807}, issn = {2042-8812}, abstract = {Locally advanced breast cancer arising from ectopic axillary breast tissue is an unusual presentation of this malignancy. The work-up and treatment approach pose some unique challenges. We present the case of a 37-year-old female presenting with a left axillary lesion with skin involvement. Radiological studies and biopsy demonstrated an underlying axillary mass compatible with a triple-positive invasive ductal carcinoma of the breast. Following neoadjuvant therapy, the patient underwent nipple-sparing mastectomy with wide local excision of the involved axillary skin and axillary lymph node dissection. Ectopic locally advanced breast cancer can be treated similarly to its orthotopic counterpart, favoring a neoadjuvant therapy approach followed by surgical excision. Special considerations include the local anatomy of the tumor, the extent of surgery and reconstructive options.}, } @article {pmid36128357, year = {2022}, author = {Miyazaki, Y and Shimizu, J and Kubo, Y and Tabata, N and Aso, T}, title = {Quantitative classification of invasive and noninvasive breast cancer using dynamic magnetic resonance imaging of the mammary gland.}, journal = {Journal of clinical imaging science}, volume = {12}, number = {}, pages = {45}, pmid = {36128357}, issn = {2156-7514}, abstract = {OBJECTIVES: Breast cancers are classified as invasive or noninvasive based on histopathological findings. Although time-intensity curve (TIC) analysis using magnetic resonance imaging (MRI) can differentiate benign from malignant disease, its diagnostic ability to quantitatively distinguish between invasive and noninvasive breast cancers has not been determined. In this study, we evaluated the ability of TIC analysis of dynamic MRI data (MRI-TIC) to distinguish between invasive and noninvasive breast cancers.

MATERIAL AND METHODS: We collected and analyzed data for 429 cases of epithelial invasive and noninvasive breast carcinomas. TIC features were extracted in washout areas suggestive of malignancy.

RESULTS: The graph determining the positive diagnosis rate for invasive and noninvasive cases revealed that the cut-off θi/ni value was 21.6° (invasive: θw > 21.6°, noninvasive: θw ≤ 21.6°). Tissues were classified as invasive or noninvasive using this cut-off value, and each result was compared with the histopathological diagnosis. Using this method, the accuracy of tissue classification by MRI-TIC was 88.6% (380/429), which was higher than that using ultrasound (73.4%, 315/429).

CONCLUSION: MRI-TIC is effective for the classification of invasive vs. noninvasive breast cancer.}, } @article {pmid36120242, year = {2022}, author = {Ali, S and Rathore, Z and Rafique, Z and Chughtai, AS and Atiq, A}, title = {Expression of SOX10 in Triple-Negative Breast Carcinoma in Pakistan.}, journal = {Cureus}, volume = {14}, number = {8}, pages = {e27938}, pmid = {36120242}, issn = {2168-8184}, abstract = {Background The term triple-negative breast cancer (TNBC) refers to a particular class of aggressive, poorly differentiated neoplasms that show the absence of estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER2) antibodies. SOX10 (SRY-related HMG-box 10) is a nuclear transcription factor that is commonly used to identify cancers of neural origin, but it has recently been linked to TNBC. The purpose of this study is to determine SOX10 expression in TNBC, its association with tumor grade for molecular categorization, and to determine the diagnostic significance of SOX10 in TNBC at the metastatic site in the case of an unknown primary. Methodology SOX10 was used to stain a tissue microarray of 100 patients. According to the tumor grade, SOX10 staining was classified as negative (<1%), patchy (1-10%), focal (10-70%), and diffuse (70-100%). SPSS version 22 (IBM Corp., Armonk, NY, USA) software was used to conduct the statistical analysis. Results The expression of SOX10 regarding positivity and intensity was higher in high-grade tumors than in intermediate-grade tumors (p = 0.001 and p = 0.007, respectively). Conclusions SOX10 is a reliable novel marker for the diagnosis of TNBC and has diagnostic utility in the unknown primary at the metastatic site.}, } @article {pmid36110985, year = {2022}, author = {}, title = {Erratum: Skin eruption involving bilateral breasts following radiation therapy for invasive ductal carcinoma of the left breast: Erratum.}, journal = {International journal of women's dermatology}, volume = {8}, number = {3}, pages = {e052}, pmid = {36110985}, issn = {2352-6475}, abstract = {[This corrects the article DOI: 10.1097/JW9.0000000000000016.].}, } @article {pmid36109587, year = {2022}, author = {Sobhani, F and Muralidhar, S and Hamidinekoo, A and Hall, AH and King, LM and Marks, JR and Maley, C and Horlings, HM and Hwang, ES and Yuan, Y}, title = {Spatial interplay of tissue hypoxia and T-cell regulation in ductal carcinoma in situ.}, journal = {NPJ breast cancer}, volume = {8}, number = {1}, pages = {105}, pmid = {36109587}, issn = {2374-4677}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; R01 CA185138/CA/NCI NIH HHS/United States ; U2C CA233254/CA/NCI NIH HHS/United States ; P01 CA091955/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; U01 CA214183/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; }, abstract = {Hypoxia promotes aggressive tumor phenotypes and mediates the recruitment of suppressive T cells in invasive breast carcinomas. We investigated the role of hypoxia in relation to T-cell regulation in ductal carcinoma in situ (DCIS). We designed a deep learning system tailored for the tissue architecture complexity of DCIS, and compared pure DCIS cases with the synchronous DCIS and invasive components within invasive ductal carcinoma cases. Single-cell classification was applied in tandem with a new method for DCIS ductal segmentation in dual-stained CA9 and FOXP3, whole-tumor section digital pathology images. Pure DCIS typically has an intermediate level of colocalization of FOXP3+ and CA9+ cells, but in invasive carcinoma cases, the FOXP3+ (T-regulatory) cells may have relocated from the DCIS and into the invasive parts of the tumor, leading to high levels of colocalization in the invasive parts but low levels in the synchronous DCIS component. This may be due to invasive, hypoxic tumors evolving to recruit T-regulatory cells in order to evade immune predation. Our data support the notion that hypoxia promotes immune tolerance through recruitment of T-regulatory cells, and furthermore indicate a spatial pattern of relocalization of T-regulatory cells from DCIS to hypoxic tumor cells. Spatial colocalization of hypoxic and T-regulatory cells may be a key event and useful marker of DCIS progression.}, } @article {pmid36107313, year = {2022}, author = {Walth-Hummel, AA and Herzig, S and Rohm, M}, title = {Nuclear Receptors in Energy Metabolism.}, journal = {Advances in experimental medicine and biology}, volume = {1390}, number = {}, pages = {61-82}, pmid = {36107313}, issn = {0065-2598}, mesh = {Adipose Tissue/metabolism ; *Diabetes Mellitus, Type 2/genetics/metabolism ; Energy Metabolism/physiology ; Humans ; *Metabolic Diseases/genetics/metabolism ; Receptors, Cytoplasmic and Nuclear/genetics/metabolism ; }, abstract = {Nuclear receptors are master regulators of energy metabolism through the conversion of extracellular signals into gene expression signatures. The function of the respective nuclear receptor is tissue specific, signal and co-factor dependent. While normal nuclear receptor function is central to metabolic physiology, aberrant nuclear receptor signaling is linked to various metabolic diseases such as type 2 diabetes mellitus, obesity, or hepatic steatosis. Thus, the tissue specific manipulation of nuclear receptors is a major field in biomedical research and represents a treatment approach for metabolic syndrome. This chapter focuses on key nuclear receptors involved in regulating the metabolic function of liver, adipose tissue, skeletal muscle, and pancreatic β-cells. It also addresses the importance of nuclear co-factors for fine-tuning of nuclear receptor function. The mode of action, role in energy metabolism, and therapeutic potential of prominent nuclear receptors is outlined.}, } @article {pmid36101863, year = {2022}, author = {Yu, T and Cheng, W and Wang, T and Chen, Z and Ding, Y and Feng, J and Duan, Y and Hu, A and Li, M and Zhang, H and Li, Y and Ma, F and Guo, B}, title = {Survival Outcomes of Breast-Conserving Therapy versus Mastectomy in Early-Stage Breast Cancer, Including Centrally Located Breast Cancer: A SEER-Based Study.}, journal = {The breast journal}, volume = {2022}, number = {}, pages = {5325556}, pmid = {36101863}, issn = {1524-4741}, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Lobular/pathology ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy ; Mastectomy, Segmental ; }, abstract = {PURPOSE: This study aims to analyze the survival outcomes of breast cancer (BC) patients, especially centrally located breast cancer (CLBC) patients undergoing breast-conserving therapy (BCT) or mastectomy.

METHODS: Surveillance, epidemiology, and end results (SEER) data of patients with T1-T2 invasive ductal or lobular breast cancer receiving BCT or mastectomy were reviewed. We used X-tile software to convert continuous variables to categorical variables. Chi-square tests were utilized to compare baseline information. The multivariate logistic regression model was performed to evaluate the relationship between predictive variables and treatment choice. Survival outcomes were visualized by Kaplan-Meier curves and cumulative incidence function curves and compared using multivariate analyses, including the Cox proportional hazards model and competing risks model. Propensity score matching was performed to alleviate the effects of baseline differences on survival outcomes.

RESULT: A total of 180,495 patients were enrolled in this study. The breast preservation rates fluctuated around 60% from 2000 to 2015. Clinical features including invasive ductal carcinoma (IDC), lower histologic grade, smaller tumor size, fewer lymph node metastases, positive ER and PR status, and chemotherapy use were independently correlated with BCT in both BC and CLBC cohorts. In all the classic Cox models and competing risks models, BCT was an independent favorable prognostic factor for BC, including CLBC patients in most subgroups. In addition, despite the low breast-conserving rate compared with tumors located in the other areas, CLBC did not impair the prognosis of BCT patients.

CONCLUSION: BCT is optional and preferable for most early-stage BC, including CLBC patients.}, } @article {pmid36098873, year = {2022}, author = {Hiraoka, E and Masumoto, N and Furukawa, T and Kuraoka, N and Nagamine, I and Kido, A and Sentani, K and Ootagaki, S}, title = {Follicular lymphoma without lymphadenopathy incidentally diagnosed by sentinel lymph node biopsy during breast cancer surgery: a case report.}, journal = {Surgical case reports}, volume = {8}, number = {1}, pages = {167}, pmid = {36098873}, issn = {2198-7793}, abstract = {BACKGROUND: Concurrent breast cancer and malignant lymphoma is a rare phenomenon. This report describes malignant lymphoma that was incidentally diagnosed from a sentinel lymph node biopsy (SLNB) during breast cancer surgery.

CASE PRESENTATION: A 73-year-old woman with a history of ovarian cancer and diabetes presented with right focal asymmetric density on a mammogram acquired during routine breast cancer screening. Ultrasonography (US) and magnetic resonance imaging (MRI) showed a 13.5-mm tumor in the upper lateral region of the right breast. A US-guided Mammotome biopsy revealed invasive ductal carcinoma of the right breast. Preoperative assessments including positron emission tomography-computerized tomography, found no evidence of axillary lymphadenopathy or distant metastasis. Because the breast cancer was stage I, the patient underwent a right mastectomy and a sentinel lymph node biopsy (SLNB) at our hospital. Pathological assessment of the biopsy revealed follicular lymphoma (FL), but no metastatic breast cancer. The patient was referred to hematology to stage the FL. Bone marrow findings were negative and stage I FL was diagnosed. After the mastectomy, she was monitored and given adjuvant therapy with an aromatase inhibitor.

CONCLUSIONS: Follicular lymphoma was incidentally diagnosed from an SLNB obtained to determine the dissemination of early-stage breast cancer. Collaboration with hematologists is important to determine optimal treatment plans for such patients regardless of the rarity of such events.}, } @article {pmid36098816, year = {2023}, author = {Patil, A and Swerdlow, SH and Lossos, IS and Chapman, JR}, title = {Atypical follicular hyperplasia with light chain-restricted germinal centers after COVID-19 booster: a diagnostic pitfall.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {482}, number = {5}, pages = {905-910}, pmid = {36098816}, issn = {1432-2307}, mesh = {Humans ; Female ; COVID-19 Vaccines/adverse effects ; Hyperplasia/pathology ; *COVID-19/pathology ; Neoplasm Recurrence, Local/pathology ; *Precancerous Conditions/pathology ; Germinal Center/pathology ; *Lymphoma, Follicular/pathology ; *Lymphadenopathy/pathology ; *Breast Neoplasms/pathology ; COVID-19 Testing ; Immunization, Secondary ; }, abstract = {There has been a surge in COVID-19 vaccine-associated lymphadenopathy (LAD), including after the booster dose of vaccine. This can create diagnostic dilemmas in oncology patients as the relatively sudden LAD can mimic metastasis or cancer recurrence, at a risk of leading to additional but unnecessary anti-neoplastic therapy. Here we report the histopathologic features in a case of persistent LAD occurring in a patient with history of breast invasive ductal carcinoma which followed a COVID-19 vaccine booster. A needle core and then excisional biopsy showed atypical follicular hyperplasia with features that histologically and phenotypically could mimic follicular lymphoma, but the findings were ultimately interpreted to be reactive in nature and related temporally to COVID-19 vaccine. To our knowledge, this is the first case of an atypical lymphoproliferative lesion with features potentially mimicking lymphoma associated with COVID-19 vaccine.}, } @article {pmid36097900, year = {2022}, author = {Gao, BB and Zheng, Q and Yu, L and Luo, DJ and Nie, X and Xu, X}, title = {[Clinicopathological features and HER2 expression of metaplastic squamous cell carcinoma of the breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {51}, number = {9}, pages = {843-849}, doi = {10.3760/cma.j.cn112151-20220430-00356}, pmid = {36097900}, issn = {0529-5807}, mesh = {*Carcinoma, Ductal ; *Carcinoma, Squamous Cell/pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; }, abstract = {Objective: To investigate the clinicopathological features and HER2 expression of metaplastic squamous cell carcinoma (MSCC) of the breast. Methods: A total of 47 MSCC cases diagnosed in the Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China from January 2010 to December 2021 were reviewed. The clinical information (including the follow-up data of HER2 positive patients) and pathological features were collected and analyzed. Results: All of the patients were female. Among the 47 cases, 25 were pure squamous cell carcinoma (PSCC) and 22 were mixed metaplastic carcinoma with squamous cell component (MMSC). The median age of the patients was 54 years (range, 29-84 years). The maximum diameter of the mass ranged from 0.8 to 10.0 cm, with a mean value of 3.3 cm, 85.7% (24/28) of the cases were smaller than 5 cm, and only 4 cases were larger than or equal to 5 cm. 89.5% of the MMSC presented with a solid mass. Cystic changes were more commonly found in the PSCC group (50%, P<0.05) than the MMSC group. 36.7% (11/30) of the patients had lymph node metastasis at the time of diagnosis. The squamous cell carcinoma component in all cases showed diffuse or patchy expression of p63, p40 and CK5/6. 55.3% (26/47) of the cases showed triple-negative phenotype. Among the 7 HER2-positive patients, 6 were MMSC group, which had a significantly higher rate of HER2-positivity than that in the PSCC group (1 case). In 1 MMSC case, immunohistochemistry showed HER2 2+in the invasive ductal carcinoma component and HER2 negativity (0) in the squamous cell carcinoma component, but HER2 FISH was negative in invasive ductal carcinoma and positive in squamous cell carcinoma component. Six HER2-positive MSCC patients received anti-HER2-targeted therapy, including two patients who received neoadjuvant chemotherapy combined with anti-HER2-targeted therapy before surgery. One patient achieved pathological complete remission, while the other achieved partial remission (the residual tumors were squamous cell carcinoma components). After 9-26 months of follow-up, four patients had no disease progression, two patients developed pulmonary metastases, and one patient showed local recurrence. Conclusions: MSCC is a group of heterogeneous diseases. PSCC and MMSC may be two different entities. Most of the MSCC are triple-negative and HER2 positivity is more commonly seen in MMSC with invasive ductal carcinoma component. Some HER2-positive MSCC patients can achieve complete remission or long-term progression-free survival after receiving anti-HER2 targeted therapy, but the squamous cell carcinoma component may be less sensitive to targeted therapy than the invasive ductal carcinoma component.}, } @article {pmid36097899, year = {2022}, author = {Pan, XY and Wu, JK and Lang, ZQ and Qu, L and Jiang, L}, title = {[The value of immunohistochemical expression of Ki-67 and CD34 in differentiating ductal carcinoma in situ from ductal carcinoma in situ-like invasive breast cancer].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {51}, number = {9}, pages = {838-842}, doi = {10.3760/cma.j.cn112151-20220428-00339}, pmid = {36097899}, issn = {0529-5807}, mesh = {Antigens, CD34 ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Cell Adhesion Molecules ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; *Neuroblastoma ; }, abstract = {Objective: To investigate the expression of Ki-67 and CD34 in the differential diagnosis of ductal carcinoma in situ (DCIS) and DCIS-like invasive breast cancer (DLIBC). Methods: A total of 100 cases of DCIS and 150 cases of DLIBC diagnosed pathologically in Yantai Yuhuangding Hospital from January 2019 to March 2022 were collected. The expression of p63, CK5/6, Ki-67 and CD34 in both groups were detected by immunohistochemical (IHC) staining and evaluated. Results: The 100 cases of DCIS included 11 cases of low-grade DCIS, 28 cases of intermediate-grade DCIS and 61 cases of high-grade DCIS. IHC staining of p63 and CK5/6 showed the myoepithelial cells around cancerous duct were complete or partial absence. Ki-67 expression showed two patterns: high expression in the basal layers and scattered expression within the tumor. Most cases showed mainly high basal expression (77/100, 77%), and the proportion of this pattern was significantly different between low grade and high grade DCIS (P<0.05). All cases showed complete CD34 expression surrounding the cancerous duct with different proportion (vascular necklace) suggested small vessels proliferation. The 150 cases of DLIBC included 142 cases of invasive ductal carcinoma (IDC) (three cases of basal-like breast cancer was included), two cases of secretory carcinoma, three cases of solid papillary carcinoma, two cases of adenoid cystic carcinoma and one case of acinar cell carcinoma. Among 142 cases of IDC, 13 cases were grade Ⅰ, 77 were grade Ⅱ and 52 were grade Ⅲ. IHC staining of p63 showed complete absence of myoepithelium. CK5/6 was negative in most cases and only positively expressed within the tumor in 3 cases of basal-like breast cancer. Ki-67 indicated a scattered expression pattern within the tumor. In most cases, CD34 immunostaining showed scattered positive blood vessels within the tumor while only two cases showed incomplete expression of CD34 around the tumor (2/150, 1.3%). The different expression patterns of Ki-67 and CD34 in DCIS and DLIBC was statistically significant (P<0.05). Conclusions: The different expression patterns of Ki-67 and CD34 are helpful to distinguish DLIBC from DCIS. The appearance of "vascular necklace" with CD34 and the high expression of Ki-67 around the cancerous duct highly support the diagnosis of DCIS, and the scattered expression pattern of CD34 supports DLIBC.}, } @article {pmid36096439, year = {2022}, author = {Li, H and Wang, S and Zeng, Q and Chen, C and Lv, X and Ma, M and Su, H and Ma, B and Chen, C and Fang, J}, title = {Serum Raman spectroscopy combined with multiple classification models for rapid diagnosis of breast cancer.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {40}, number = {}, pages = {103115}, doi = {10.1016/j.pdpdt.2022.103115}, pmid = {36096439}, issn = {1873-1597}, mesh = {Humans ; Female ; Spectrum Analysis, Raman/methods ; *Breast Neoplasms/diagnosis ; Reproducibility of Results ; *Photochemotherapy/methods ; Discriminant Analysis ; Support Vector Machine ; Principal Component Analysis ; Algorithms ; }, abstract = {Breast cancer is a malignant tumor with the highest incidence rate in women. Current diagnostic methods are time-consuming, costly, and dependent on physician experience. In this study, we used serum Raman spectroscopy combined with multiple classification algorithms to implement an auxiliary diagnosis method for breast cancer, which will help in the early diagnosis of breast cancer patients. We analyzed the serum Raman spectra of 171 invasive ductal carcinoma (IDC) and 100 healthy volunteers; The analysis showed differences in nucleic acids, carotenoids, amino acids, and lipid concentrations in their blood. These differences provide a theoretical basis for this experiment. First, we used adaptive iteratively reweighted penalized least squares (airPLS) and Savitzky-Golay (SG) for baseline correction and smoothing denoising to remove the effect of noise on the experiment. Then, the Principal component analysis (PCA) algorithm was used to extract features. Finally, we built four classification models: support vector machine (SVM), decision tree (DT), linear discriminant analysis (LDA), and Neural Network Language Model (NNLM). The LDA, SVM, and NNLM achieve 100% accuracy. As supplementary, we added the classification experiment of the raw data. By comparing the experimental results of the two groups, We concluded that the NNLM was the best model. The results show the reliability of the combination of serum Raman spectroscopy and classification models under large sample conditions.}, } @article {pmid36093543, year = {2022}, author = {Li, C and Qian, B}, title = {Male triple negative axillary accessory breast cancer-a case report.}, journal = {Translational cancer research}, volume = {11}, number = {8}, pages = {2926-2930}, pmid = {36093543}, issn = {2219-6803}, abstract = {BACKGROUND: Breast cancer is the most common malignancy among women worldwide. In men, cases of breast cancer are few and account for less than 1% of all cases of breast cancer. Majority of male breast cancer is hormone receptor-positive. The incidence of male breast cancer derived from axillary accessory breast is very low. Here we report a case of male triple negative axillary accessory breast cancer.

CASE DESCRIPTION: We present a case of male triple negative axillary accessory breast cancer in a 67-year-old man, which progressively increased in size through a period of 1 year. Ultrasound examination showed a 31 mm × 17 mm mass in the right axillary tail region with some accessory breast tissue around. We performed right accessory breast resection and right axillary lymph nodes dissection. Postoperative pathological analysis revealed right accessory breast invasive ductal carcinoma with apocrine metaplasia. The tumor size was 3.5 cm × 3.3 cm. In addition, 5 metastatic lymph nodes were seen in 27 axillary lymph nodes. Immunohistochemistry showed estrogen-receptor (ER) (-), progesterone-receptor (PR) (-), human epidermal growth factor receptor 2 (HER2) (2+). Fluorescence in situ hybridization (FISH) test obtained a negative result. The patient was treated with adjuvant chemotherapy and radiotherapy. Until now, no obvious signs of recurrence or metastasis have been observed during regular follow-ups.

CONCLUSIONS: Male triple negative axillary accessory breast cancer is rare. Treatment of male triple negative axillary accessory breast cancer is similar to that of women. Most patients undergo surgery and adjuvant chemotherapy.}, } @article {pmid36093343, year = {2022}, author = {Choi, JI and Prabhu, K and Hartsell, WF and DeWees, T and Sinesi, C and Vargas, C and Benda, RK and Cahlon, O and Chang, AL}, title = {Outcomes and toxicities after proton partial breast radiotherapy for early stage, hormone receptor positive breast cancer: 3-Year results of a phase II multi-center trial.}, journal = {Clinical and translational radiation oncology}, volume = {37}, number = {}, pages = {71-77}, pmid = {36093343}, issn = {2405-6308}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, abstract = {PURPOSE: Proton therapy (PT) for partial breast irradiation (PBI) in early-stage breast cancer can decrease morbidity versus photon PBI with superior organs-at-risk sparing. We report 3-year outcomes of the first prospective, multicenter, phase II trial of proton PBI.

METHODS AND MATERIALS: This Proton Collaborative Group phase II trial (PCG BRE007-12) recruited women ≥ 50 years with node-negative, estrogen receptor (ER)-positive, ≤3cm, invasive ductal carcinoma (IDC) or ductal carcinoma in situ undergoing breast conserving surgery followed by proton PBI (40 Gy(RBE), 10 daily fractions). Primary endpoint was freedom from ipsilateral breast cancer recurrence. Adverse events were prospectively graded using CTCAEv4.0. Breast Cancer Treatment Outcome Scale (BCTOS) assessed patient-reported quality of life (PRQOL).

RESULTS: Thirty-eight evaluable patients enrolled between 2/2013-11/2016. Median age was 67 years (range 50-79); 55 % had left-sided disease, and median tumor size was 0.9 cm. Treatment was delivered in ≥ 2 fields predominantly with uniform scanning PT (n = 37). At 35-month median follow-up (12-62), all patients were alive, and none had local, regional or distant disease progression. One patient developed an ER-negative contralateral IDC. Seven grade 2 adverse events occurred; no radiotherapy-related grade ≥ 3 toxicities occurred. Changes in BCTOS subdomain mean scores were maximum 0.36, indicating no meaningful change in PRQOL. Median heart volume receiving 5 Gy (V5Gy), lung V20Gy, and lung V10Gy were 0 %, 0 % and 0.19 %, respectively.

CONCLUSION: At 3 years, proton PBI provided 100 % cancer control for early-stage, ER-positive breast cancer. Toxicities are minimal, and PRQOL remains acceptable with continued follow-up. These findings support PT as a safe and effective PBI delivery option.}, } @article {pmid36089720, year = {2022}, author = {Aker, FV and Ekren, E and Dogan, M and Gurleyik, G and Tanrikulu, E and Oven, BB}, title = {Clinicopathological Features and Prognosis of Invasive Micropapillary Carcinoma Compared to Invasive Ductal Carcinoma-NOS: Worse or Better?.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {32}, number = {9}, pages = {1196-1201}, doi = {10.29271/jcpsp.2022.09.1196}, pmid = {36089720}, issn = {1681-7168}, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Papillary/pathology ; Female ; Humans ; Prognosis ; Retrospective Studies ; }, abstract = {OBJECTIVE: To evaluate whether there are differences in invasive micropapillary carcinoma (IMPC) and invasive ductal carcinoma-NOS (IDC-NOS) according to the clinicopathological features and prognosis including molecular subtypes.

STUDY DESIGN: Descriptive study.

PLACE AND DURATION OF STUDY: Department of Pathology, University of Health Sciences, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey, from 2003 to 2016.

METHODOLOGY: Operated breast cancer cases (58 IMPC + 326 IDC-NOS), with long-term follow-up findings (cases followed up until 2020), were reviewed. The cases, whose other component was only IDC-NOS, were included in the mixed IMPC group. The clinical features, including clinical presentation, treatments, and follow-up information were obtained from the patient clinical database. The IMPC cases included in the study were re-examined, and micropapillary tumour components were confirmed based on the criteria set by the World Health Organisation (WHO). The clinicopathological findings, recurrence, and survival data of both groups were compared. In addition, IDC-NOS was divided into the molecular subgroups and compared with IMPC cases in terms of 5-year overall survival (OS).

RESULTS: There was no significant difference between the two groups for the distribution of molecular subtypes. There was a statistically significant difference among the nuclear grade, tumour size, nodal status, lymphovascular, and perineural invasion. In the first 5-year period, the OS rate for IDC-NOS and IMPC was 90.8% and 86.2% (p<0.05). The 5-year OS rate of luminal A, luminal B, HER2, triple negative (TN), and IMPC patients was 97.6%, 91.3%, 90%, 70%, and 86.2%, respectively (p<0.05). The OS rate in patients with TN and IMPC was similar which was found significantly lower than the other groups (luminal A, luminal B, and HER2). The median OS was 51.3 months and 53.9 months for the patients with TN and IMPC, respectively (p<0.001). This difference disappeared in the 10th and 15th years of follow-up.

CONCLUSION: The majority of the deaths in IMPC occurred within the first 5 years. The 5-year OS rates were similar in the TN and IMPC patients. The survival pattern of IMPC is parallel with TN, Therefore, clinical, therapeutic, and prognostic evaluation in IMPC can be done like TN.

KEY WORDS: Invasive ductal carcinoma, Invasive micropapillary carcinoma, Survival.}, } @article {pmid38213652, year = {2023}, author = {Bhatia, JK and Malik, A and Chaudhary, T and Gopal, A and Boruah, D and Singh, B}, title = {Evaluation of Number Density of Tumor-Associated Macrophages by Immunohistochemistry and Semiquantitative Scoring in Invasive Breast Cancer: An Indian Study.}, journal = {Journal of microscopy and ultrastructure}, volume = {11}, number = {4}, pages = {214-219}, pmid = {38213652}, issn = {2213-8803}, abstract = {CONTEXT: Tumor microenvironment is emerging as a critical factor for progression of breast cancer. Tumor-associated macrophages (TAMs) play an important role in promoting tumor growth.

AIM: This study was aimed at correlation of number density (ND) of TAMs with invasive ductal carcinoma (IDC) grading utilizing an image morphometric technique. We also sought to compare the TAMs and ND in the tumoral area and stromal region. We also explored the relationship between the clinical and pathological prognostic parameters.

SUBJECTS AND METHODS: The study included 75 cases of IDC that had undergone modified radical mastectomy. The Institutional Ethics Committee approved the study. Samples were classified as Grade 1, 2, and 3. Cases were graded as per the modified Bloom and Richardson criterion. Mean with standard deviation was calculated for each group. We utilized CD68 and CD163 immunostained sections for determining the ND of TAMs. TAMs were evaluated using computerized digital photomicrograph system with image analyzing software. ND was defined as the number of TAMs in total number of TAMs in five high-power fields/total area of five fields. ND was calculated separately in tumor and tumor stroma (TS). Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2/neu (HER2/neu) were scored in accordance with recommendations. Ki-67 was scored as per the recommended guidelines.

STATISTICAL ANALYSIS USED: Data were tabulated in Microsoft Excel. SPSS version 20.0 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. To determine the relationship between macrophage density and clinicopathologic parameters, we used the independent t-test. To determine the differences in the parameters, analysis of variance (ANOVA) was utilized.

RESULTS: Age of the patients ranged from 34 to 58 years (mean: 55.5). One-way ANOVA between various grades of tumor indicating significant differences in terms of CD68 and CD163 densities in tumor and stroma (P < 0.0001). i.e., significant increased density of CD68 and CD163 was observed in Grade 3 tumor as compared to other two groups. A greater histological grade, ER, PR negative status, and a high Ki-67 index were all associated with TAM ND. There was no relation to HER2/neu status. Result of unpaired t-test indicates increased density in stroma as compared to tumor among various grades of IDC.

CONCLUSIONS: We analyzed images with a software using photographs of the stained slides. This helped in quantitative analysis of TAMs on the CD68 and CD163 stained sections. This approach standardizes and reproducibly counts TAMs per unit area. We found significant difference between the number densities of TAMs in grades of invasive breast carcinoma. There were statistically significant differences in numerical densities of TAMs with ER, PR negativity, and Ki-67. There was no correlation with HER2/neu. Densities of CD68 and CD163 densities are more prevalent in TS as compared to intratumoral region.}, } @article {pmid38603004, year = {2022}, author = {Gruneau Brulin, J and Shaver, PR and Mikulincer, M and Granqvist, P}, title = {Attachment in the time of COVID-19: Insecure attachment orientations are associated with defiance of authorities' guidelines during the pandemic.}, journal = {Journal of social and personal relationships}, volume = {39}, number = {8}, pages = {2528-2548}, pmid = {38603004}, issn = {0265-4075}, abstract = {Previous research has linked people's relational attachment orientations to emotional reactions and coping during crises, and to social trust and trust in societal institutions. The COVID-19 pandemic is a global crisis for which collective efforts, such as social distancing, are necessary to stop the spread of the virus. During previous pandemics, people high in trust have typically adhered to such efforts. In the present study, we investigated whether attachment orientations were related to people's adherence to authorities' guidelines to stop the spread of COVID-19. We also tested whether previous mediational findings-linking attachment-related avoidance to welfare state trust via social trust-would replicate. We used a web-based survey of 620 participants. Our findings showed that attachment-related anxiety was linked to low adherence to social distancing regulations. This finding was especially noteworthy because high attachment-anxious participants also experienced more negative emotions, yet negative emotions were generally linked to high adherence. Thus, people higher in attachment anxiety seem to have more difficulties in avoiding social situations despite heightened risk of catching and spreading the virus. In addition, attachment-related avoidance was negatively related to adherence and to welfare state trust, and its effects on welfare state trust were statistically mediated by low social trust.}, } @article {pmid38751542, year = {2022}, author = {King, CA and Masanam, MK and Maini, AS and Merritt, CM and Fan, KL and Greenwalt, IT}, title = {Reduction in tumor grade and Ki-67 in postmenopausal patient with node-positive invasive ductal carcinoma following combination hormone replacement therapy cessation: a case report.}, journal = {Translational breast cancer research : a journal focusing on translational research in breast cancer}, volume = {3}, number = {}, pages = {29}, pmid = {38751542}, issn = {2218-6778}, abstract = {BACKGROUND: While praised for its benefits in treating symptoms related to menopausal changes, hormone replacement therapy (HRT) has been associated with an increased risk for hormone-dependent cancer development, particularly endometrial and breast. Few studies have elucidated the relationship between HRT cessation and hormone receptor-positive breast cancer proliferation. We report herein, to the best of our knowledge, the first case of 28.6% relative reduction in proliferation index marker Ki-67 in node-positive hormone receptor-positive breast cancer following HRT cessation.

CASE DESCRIPTION: We report an unusual case of a 64-year-old female patient with longstanding HRT for fifteen years who underwent immediate discontinuation after diagnosis of poorly differentiated invasive ductal carcinoma. We observed a reduction in tumor grade from poorly differentiated at time of biopsy to moderately differentiated at time of surgery following cessation of HRT, as well as a reduction in the tumor proliferation index (Ki-67) from 70% to 50%. The patient has remained recurrence-free at the one-year mark postoperatively with continued follow-up.

CONCLUSIONS: This case highlights potential clinical benefits associated with HRT discontinuation in the postmenopausal population with preexisting hormone-dependent cancers with high proliferation index, as well as the usefulness of Ki-67 in measuring response to aromatase inhibition in this subpopulation of patients.

KEYWORDS: Hormone replacement therapy (HRT); breast cancer; tumor grade; Ki-67; case report.}, } @article {pmid38751534, year = {2022}, author = {Bhagat, N and Lautenslager, L and Hadad, I}, title = {A case report of gender-affirming mastectomy in a transgender individual with breast cancer.}, journal = {Translational breast cancer research : a journal focusing on translational research in breast cancer}, volume = {3}, number = {}, pages = {27}, pmid = {38751534}, issn = {2218-6778}, abstract = {BACKGROUND: Gender-affirming mastectomy (GAM), in contrast to simple mastectomy (SM), utilizes preservation of subcutaneous and breast tissue to produce a cosmetically favorable result for transgender patients, however does not remove all future malignancy risk. Here we present a case report of a transmale patient who was evaluated for GAM and subsequently found to have a malignant breast mass, necessitating multi-disciplinary intervention and coordination between breast and plastic surgery teams. This patient's unique and rare presentation with breast cancer prior to GAM emphasized the paucity of previously detailed cases in the literature and demonstrated the likely degree of variability in decision-making for treatment of these patients without universal guidelines for management.

CASE DESCRIPTION: The patient is a 47-year-old African American transgender male who was found to have a 3-cm breast mass on routine pre-operative mammographic screening prior to GAM. Pathology confirmed grade II invasive ductal carcinoma (IDC) and further genetic testing showed the patient was BRCA2 positive. The breast and plastic surgery teams coordinated the GAM to best address the mass while achieving cosmetic goals. This case was complicated by positive nipple margins on intra-operative cold specimen, which necessitated deviation from the initial plan to perform bilateral nipple grafts, and instead utilized excess areolar tissue from the left nipple to reconstruct the contralateral right nipple. Graft survival and overall repair quality at 6 weeks was satisfactory to both patient and provider.

CONCLUSIONS: This case highlights several of the challenges encountered when considering or performing GAMs in transmale patients with underlying breast cancer. Surgical considerations for these patients differ from cisgender individuals undergoing mastectomy for oncologic breast findings. Further research is needed to better determine the ideal operative practice and ideal follow-up screening for these patients.}, } @article {pmid38536377, year = {2022}, author = {Harwood-Gross, A and Weltman, A and Kanat-Maymon, Y and Pat-Horenczyk, R and Brom, D}, title = {Peace of mind: Promoting psychological growth and reducing the suffering of combat veterans.}, journal = {Military psychology : the official journal of the Division of Military Psychology, American Psychological Association}, volume = {34}, number = {6}, pages = {668-678}, pmid = {38536377}, issn = {1532-7876}, abstract = {The Peace of Mind (POM) program was designed to enable combat veterans in Israel to process their combat experience, address difficulties in the transition to civilian life and facilitate psychological growth as a result of their military experience. During the course of the program, 1068 participants were studied at four time points. Post-traumatic symptoms were measured using the PTSD checklist for DSM-5 (PCL-5), and post-traumatic growth (PTG) was measured using the Post Traumatic Growth Inventory (PTGI). Multilevel Modeling (MLM) was used to assess symptom and psychological trajectories for all participants and for those who began with and without PTSD symptoms, respectively. The results demonstrated that those who began the program with elevated PTSD symptoms experienced a significant reduction in PTSD symptoms following the completion of the intensive element of the program. Additionally, all participants demonstrated an increase in PTG following the intensive section of the program and this was maintained throughout follow-up. The findings indicate that the POM program is beneficial in relation to both positive and negative outcomes of traumatic military experiences though it is clear that the transition from combat to civilian life is more complex than the current measures identify and that further research needs to examine the distinct lifestyle and functional changes which occur following the program.}, } @article {pmid37197402, year = {2021}, author = {Bashir, S and Loya, A and Tabish, S and Mushtaq, S and Hassan, U and Hussain, M}, title = {Expression of B-cell Lymphoma 2 in Breast Cancer.}, journal = {Journal of cancer & allied specialties}, volume = {7}, number = {1}, pages = {e369}, pmid = {37197402}, issn = {2411-989X}, abstract = {INTRODUCTION: Immunohistochemical expression of B-cell lymphoma 2 (BCL-2) is seen variably in invasive ductal carcinoma. This study was conducted to determine the frequency of BCL-2 expression in different histologic grades of invasive ductal carcinoma.

MATERIALS AND METHODS: A cross-sectional study was conducted in the Department of Pathology at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Pakistan, on subjects with invasive ductal carcinoma of various histologic grades. Immunohistochemistry was done using the BCL-2 antibody in all cases. The frequency of BCL-2-positive cases in different histologic grades was noted. Post-stratification, the Chi-square test was applied. P ≤ 0.05 was considered statistically significant.

RESULTS: All 52 subjects were female (100%) with a mean age of 47.58 ± 1.43 years. BCL-2 expression was observed in 28 (53.85 %) subjects with breast cancer. Out of 33 participants with Grade III, 13 (39.39 %) participants were positive for BCL- 2 expression. Among 18 subjects with Grade II, 14 (77.78 %) subjects were positive for BCL-2 expression. Reduced frequency of BCL-2 expression was observed with increasing histologic grade (i.e., more in low-grade tumours and less in Grade III), but the difference was statistically not significant.

CONCLUSION: A differential expression of BCL-2 was observed across different grades of invasive ductal carcinoma. However, the difference was not statistically significant.}, } @article {pmid36238077, year = {2021}, author = {Lee, SY and Woo, OH and Shin, HS and Song, SE and Cho, KR and Seo, BK and Hwang, SY}, title = {Assessment of Additional MRI-Detected Breast Lesions Using the Quantitative Analysis of Contrast-Enhanced Ultrasound Scans and Its Comparability with Dynamic Contrast-Enhanced MRI Findings of the Breast.}, journal = {Taehan Yongsang Uihakhoe chi}, volume = {82}, number = {4}, pages = {889-902}, pmid = {36238077}, issn = {2288-2928}, abstract = {PURPOSE: To assess the diagnostic performance of contrast-enhanced ultrasound (CEUS) for additional MR-detected enhancing lesions and to determine whether or not kinetic pattern results comparable to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast can be obtained using the quantitative analysis of CEUS.

MATERIALS AND METHODS: In this single-center prospective study, a total of 71 additional MR-detected breast lesions were included. CEUS examination was performed, and lesions were categorized according to the Breast Imaging-Reporting and Data System (BI-RADS). The sensitivity, specificity, and diagnostic accuracy of CEUS were calculated by comparing the BI-RADS category to the final pathology results. The degree of agreement between CEUS and DCE-MRI kinetic patterns was evaluated using weighted kappa.

RESULTS: On CEUS, 46 lesions were assigned as BI-RADS category 4B, 4C, or 5, while 25 lesions category 3 or 4A. The diagnostic performance of CEUS for enhancing lesions on DCE-MRI was excellent, with 84.9% sensitivity, 94.4% specificity, and 97.8% positive predictive value. A total of 57/71 (80%) lesions had correlating kinetic patterns and showed good agreement (weighted kappa = 0.66) between CEUS and DCE-MRI. Benign lesions showed excellent agreement (weighted kappa = 0.84), and invasive ductal carcinoma (IDC) showed good agreement (weighted kappa = 0.69).

CONCLUSION: The diagnostic performance of CEUS for additional MR-detected breast lesions was excellent. Accurate kinetic pattern assessment, fairly comparable to DCE-MRI, can be obtained for benign and IDC lesions using CEUS.}, } @article {pmid36238057, year = {2021}, author = {Park, HM and Lim, HS and Ki, SY and Lee, HJ and Lee, JS and Park, MH}, title = {[Invasive Ductal Carcinoma Originating from a Borderline Phyllodes Tumor in a Young Female: A Case Report].}, journal = {Taehan Yongsang Uihakhoe chi}, volume = {82}, number = {4}, pages = {971-976}, pmid = {36238057}, issn = {2288-2928}, abstract = {Phyllodes tumors of the breast are relatively rare fibroepithelial tumors that account for less than 1% of primary breast neoplasms. Phyllodes tumors have epithelial and stromal components and they originate from the periductal stroma. They are classified as benign, borderline, or malignant. Carcinomatous differentiation of the epithelial components of phyllodes tumors is rare, and their imaging features have not been accurately described. Herein, we report a rare case of invasive ductal carcinoma originating from a borderline phyllodes tumor in a 21-year-old female with radiologic and pathologic findings.}, } @article {pmid37117717, year = {2021}, author = {Tzachor, A and Richards, CE and Holt, L}, title = {Future foods for risk-resilient diets.}, journal = {Nature food}, volume = {2}, number = {5}, pages = {326-329}, pmid = {37117717}, issn = {2662-1355}, abstract = {Future foods, such as microalgae, mycoprotein and mealworm, have been suggested as nutritious and sustainable dietary options. Here we consider one of the most profound, yet neglected, benefits of future foods farming systems-their potential to provide essential nutrition in the face of systemic disturbances-and discuss major barriers to realizing this prospect.}, } @article {pmid36238736, year = {2021}, author = {Woo, SH and Jung, HK and Kim, W}, title = {Bilateral Breast Cancer in a Patient with Neurofibromatosis Type 1: A Case Report.}, journal = {Taehan Yongsang Uihakhoe chi}, volume = {82}, number = {2}, pages = {417-422}, pmid = {36238736}, issn = {2288-2928}, abstract = {Neurofibromatosis type 1 (NF1) is a rare neuroectodermal disease that is associated with an increased risk of malignancy. Here, we report a rare case of bilateral breast cancer in a 49-year-old woman with NF1 that presented as a microlobulated oval hypoechoic mass and a complex cystic solid mass on sonography. She underwent bilateral mastectomy. The masses were diagnosed as invasive ductal carcinoma, ductal carcinoma in situ, and a malignant peripheral nerve sheath tumor. We describe the imaging findings, including ultrasonography, CT, and [18]F-fluorodeoxyglucose PET.}, } @article {pmid38424859, year = {2020}, author = {Bonnet, SE and Carter, GJ and Berg, WA}, title = {Encapsulated Papillary Carcinoma of the Breast: Imaging Features with Histopathologic Correlation.}, journal = {Journal of breast imaging}, volume = {2}, number = {6}, pages = {590-597}, doi = {10.1093/jbi/wbaa068}, pmid = {38424859}, issn = {2631-6129}, abstract = {Encapsulated papillary carcinoma (EPC) is a rare, clinically indolent breast malignancy most common in postmenopausal women. Absence of myoepithelial cells at the periphery is a characteristic feature. Mammographically, EPC typically presents as a mostly circumscribed, noncalcified, dense mass that can have focally indistinct margins when there is associated frank invasive carcinoma. Ultrasound shows a circumscribed solid or complex cystic and solid mass, and occasional hemorrhage in the cystic component may produce a fluid-debris level; the solid components typically show intense washout enhancement on MRI. Color Doppler may demonstrate a prominent vascular pedicle and blood flow within solid papillary fronds. Encapsulated papillary carcinoma can exist in pure form; however, EPC is often associated with conventional ductal carcinoma in-situ and/or invasive ductal carcinoma, no special type. Adjacent in-situ and invasive disease may be only focally present at the periphery of EPC and potentially unsampled at core-needle biopsy. In order to facilitate diagnosis, the mass wall should be included on core-needle biopsy, which will show absence of myoepithelial markers. Staging and prognosis are determined by any associated frankly invasive component, with usually excellent long-term survival and rare distant metastases.}, } @article {pmid38424856, year = {2020}, author = {Chen, C and Dodelzon, K and Ginter, PS and Drotman, MB and Arleo, EK}, title = {Postoperative Imaging Appearance of an Implantable Three-dimensional Bioabsorbable Tissue Marker After Breast Surgery: Initial Experience at a Single Institution.}, journal = {Journal of breast imaging}, volume = {2}, number = {6}, pages = {561-568}, doi = {10.1093/jbi/wbaa081}, pmid = {38424856}, issn = {2631-6129}, abstract = {OBJECTIVE: Three-dimensional bioabsorbable tissue marker (BTM) placement during breast surgery is performed for the purpose of improved surgical cavity delineation for radiotherapy and improved cosmetic outcome. The purpose of this study is to evaluate the postsurgical imaging findings of BTM.

METHODS: This Institutional Review Board-approved retrospective review included all patients implanted with BTM at breast surgery from January 2017 to September 2018. Demographics, tumor characteristics, imaging, and histologic findings were evaluated. Medical records were reviewed during a three-year period to evaluate for tumor recurrence.

RESULTS: Ninety-seven patients had BTM implanted, of which 76 patients had imaging follow-up of at least 1 year. Of the 76 patients who had mammographic follow-up, 3 (3.9%) developed suspicious microcalcifications requiring biopsy, yielding ductal carcinoma in-situ in 2 patients and benign calcifications in 1 patient. Of 61 patients who had sonographic follow-up, 44 (72.1%) patients had complex fluid collections containing avascular, heterogeneously hyperechoic solid components, which remained stable or decreased in size over time; no recurrent tumors were found in this group. One patient (1.6%) had a vascular solid mass, which yielded recurrent papilloma. Four (6.6%) patients developed irregular hypoechoic masses at the surgical site, one of which corresponded with a developing asymmetry mammographically; biopsy yielded fibromatosis. Tissue sampling of the remaining three cases yielded invasive ductal carcinoma, fat necrosis, and radiation changes, respectively.

CONCLUSION: Accurate identification of the expected postoperative imaging appearance of BTM may prevent unnecessary biopsy. Suspicious findings necessitating biopsy are pleomorphic calcifications, developing asymmetry and vascular and irregular hypoechoic masses.}, } @article {pmid38424901, year = {2020}, author = {Samreen, N and Moy, L and Lee, CS}, title = {Architectural Distortion on Digital Breast Tomosynthesis: Management Algorithm and Pathological Outcome.}, journal = {Journal of breast imaging}, volume = {2}, number = {5}, pages = {424-435}, doi = {10.1093/jbi/wbaa034}, pmid = {38424901}, issn = {2631-6129}, abstract = {Architectural distortion on digital breast tomosynthesis (DBT) can occur due to benign and malignant causes. With DBT, there is an increase in the detection of architectural distortion compared with 2D digital mammography, and the positive predictive value is high enough to justify tissue sampling when imaging findings are confirmed. Workup involves supplemental DBT views and ultrasound, with subsequent image-guided percutaneous biopsy using the modality on which it is best visualized. If architectural distortion is subtle and/or questionable on diagnostic imaging, MRI may be performed for problem solving, with subsequent biopsy of suspicious findings using MRI or DBT guidance, respectively. If no suspicious findings are noted on MRI, a six-month follow-up DBT may be performed. On pathology, malignant cases are noted in 6.8%-50.7% of the cases, most commonly due to invasive ductal carcinoma, followed by invasive lobular carcinoma. Radial scars are the most common benign cause, with stromal fibrosis and sclerosing adenosis being much less common. As there is an increase in the number of benign pathological outcomes for architectural distortion on DBT compared with 2D digital mammography, concordance should be based on the level of suspicion of imaging findings. As discordant cases have upgrade rates of up to 25%, surgical consultation is recommended for discordant radiologic-pathologic findings.}, } @article {pmid36238615, year = {2020}, author = {Lee, DH and Yoon, RG and An, JK and Woo, JJ}, title = {Ultrasonographic Features and the Diagnostic Role of Core Needle Biopsy at Metastatic Breast Cancer in the Thyroid gland: A Case Report.}, journal = {Taehan Yongsang Uihakhoe chi}, volume = {81}, number = {3}, pages = {719-725}, pmid = {36238615}, issn = {2288-2928}, abstract = {Metastases to the thyroid gland have rarely been reported in clinical settings, and the thyroid gland is an uncommon site for breast carcinoma metastasis. We report a case of a 64-year-old breast cancer patient diagnosed with metastatic breast carcinoma in the thyroid gland after performing ultrasonography (US)-guided core needle biopsy (CNB) and subsequent total thyroidectomy. On US, the thyroid lesion appeared to be mildly enlarged with multiple internal hypoechoic lines and a few microcalcifications without mass formation. Under US-guidance, CNB was performed by targeting the area with microcalcifications and subsequently diagnosed as metastatic breast carcinoma. Total thyroidectomy revealed that the patient had metastatic invasive ductal carcinoma of the breast with lymphatic spread involving both lobes and the isthmus of the thyroid gland. Although the thyroid gland is an uncommon metastatic site, the unusual features of thyroid metastasis can be observed on US; thus, US-guided CNB effectively aids the diagnosis of thyroid metastasis.}, } @article {pmid36133137, year = {2019}, author = {Amiri, A and Hastert, F and Stühn, L and Dietz, C}, title = {Structural analysis of healthy and cancerous epithelial-type breast cells by nanomechanical spectroscopy allows us to obtain peculiarities of the skeleton and junctions.}, journal = {Nanoscale advances}, volume = {1}, number = {12}, pages = {4853-4862}, pmid = {36133137}, issn = {2516-0230}, abstract = {The transition of healthy epithelial cells to carcinoma is associated with an alteration in the structure and organization of the cytoskeleton of the cells. A comparison of the mechanical properties of cancerous and healthy cells indicated a higher deformability of the cancer cells based on averaging the mechanical properties of single cells. However, the exact reason for softening of the cancerous cells compared to their counterparts remains unclear. Here, we focused on nanomechanical spectroscopy of healthy and cancerous ductal epithelial-type breast cells by means of atomic force microscopy with high lateral and depth precision. As a result, based on atomic force microscopy measurements formation of significantly fewer microtubules in cancerous cells which was observed in our study is most likely one of the main causes for the overall change in mechanical properties without any phenotypic shift. Strikingly, in a confluent layer of invasive ductal carcinoma cells, we observed the formation of cell-cell junctions that have the potential for signal transduction among neighboring cells such as desmosomes and adherens junctions. This increases the possibility of cancerous cell collaboration in malignancy, infiltration or metastasis phenomena.}, } @article {pmid38424872, year = {2019}, author = {Grimm, LJ and Enslow, M and Ghate, SV}, title = {Solitary, Well-Circumscribed, T2 Hyperintense Masses on MRI Have Very Low Malignancy Rates.}, journal = {Journal of breast imaging}, volume = {1}, number = {1}, pages = {37-42}, doi = {10.1093/jbi/wby014}, pmid = {38424872}, issn = {2631-6129}, abstract = {OBJECTIVE: The purpose of this study was to determine the malignancy rate of solitary MRI masses with benign BI-RADS descriptors.

METHODS: A retrospective review was conducted of all breast MRI reports that described a mass with a final BI-RADS assessment of 3, 4, or 5, from February 1, 2005, through February 28, 2014 (n = 1510). Studies were excluded if the mass was not solitary, did not meet formal criteria for a mass, or had classically suspicious BI-RADS features (e.g., washout kinetics, and spiculated margin). The masses were reviewed by 2 fellowship-trained breast radiologists who reported consensus BI-RADS mass margin, shape, internal-enhancement, and kinetics descriptors. The T2 signal was reported as hyperintense if equal to or greater than the signal intensity of the axillary lymph nodes. Pathology results or 2 years of imaging follow-up were recorded. Comparisons were made between mass descriptors and clinical outcomes.

RESULTS: There were 127 women with 127 masses available for analysis. There were 76 (60%) masses that underwent biopsy for an overall malignancy rate of 4% (5/127): 2 ductal carcinoma in situ (DCIS) and 3 invasive ductal carcinoma. The malignancy rate was 2% (1/59) for T2 hyperintense solitary masses. The malignancy rate was greater than 2% for all of the following BI-RADS descriptors: oval (3%, 3/88), round (5%, 2/39), circumscribed (4%, 5/127), homogeneous (4%, 3/74), and dark internal septations (4%, 2/44).

CONCLUSION: T2 hyperintense solitary masses without associated suspicious features have a low malignancy rate, and they could be considered for a BI-RADS 3 final assessment.}, } @article {pmid36338780, year = {2019}, author = {Lam, JC and Gregson, DB and Robinson, S and Somayaji, R and Welikovitch, L and Conly, JM and Parkins, MD}, title = {Infectious diseases consultation improves key performance metrics in the management of Staphylococcus aureus bacteremia: A multicentre cohort study.}, journal = {Journal of the Association of Medical Microbiology and Infectious Disease Canada = Journal officiel de l'Association pour la microbiologie medicale et l'infectiologie Canada}, volume = {4}, number = {1}, pages = {24-32}, pmid = {36338780}, issn = {2371-0888}, abstract = {BACKGROUND: Staphylococcus aureus bacteremia (SAB) is associated with significant morbidity and mortality. We sought to identify factors associated with infectious diseases consultation (IDC) and understand how IDC associates with SAB patient management and outcomes.

METHODS: A multicentre retrospective study was performed between 2012 and 2014 in a large Canadian Health Zone in order to determine factors associated with IDC and performance of key quality of care determinants in SAB management and clinical outcomes. Factors subject to quality of care determinants were established a priori and studied for associations with IDC and 30-day all-cause mortality using multivariable analysis.

RESULTS: Of 961 SAB episodes experienced by 892 adult patients, 605 episodes received an IDC. Patients receiving IDC were more likely to have prosthetic valves and joints and to have community-acquired and known sources of SAB, but increasing age decreased IDC occurrence. IDC was the strongest independent predictor for quality of care performance metrics, including repeat blood cultures and echocardiography. Mortality at 30 days was 20% in the cohort, and protective factors included IDC, achievement of source control, targeted therapy within 48 hours, and follow-up blood cultures but not the performance of echocardiography.

CONCLUSIONS: There were significant gaps between the treatments and investigations that patients actually received for SAB and what is considered the optimal management of their condition. IDC is associated with improved attainment of targeted SAB quality of care determinants and reduced mortality rates. Based on our findings, we propose a policy of mandatory IDC for all cases of SAB to improve patient management and outcomes.}, } @article {pmid36085291, year = {2022}, author = {Karihtala, P and Porvari, K and Roininen, N and Voutilainen, S and Mattson, J and Heikkilä, P and Haapasaari, KM and Selander, K}, title = {Comparison of the mutational profiles of neuroendocrine breast tumours, invasive ductal carcinomas and pancreatic neuroendocrine carcinomas.}, journal = {Oncogenesis}, volume = {11}, number = {1}, pages = {53}, pmid = {36085291}, issn = {2157-9024}, support = {P30 CA013148/CA/NCI NIH HHS/United States ; }, abstract = {The pathophysiology and the optimal treatment of breast neuroendocrine tumours (NETs) are unknown. We compared the mutational profiles of breast NETs (n = 53) with those of 724 publicly available invasive ductal carcinoma (IDC) and 98 pancreatic NET (PNET) cases. The only significantly different pathogenetic or unknown variant rate between breast NETs and IDCs was detected in the TP53 (11.3% in breast NETs and 41% in IDCs, adjusted p value 0.027) and ADCK2 (9.4% in breast NETs vs. 0.28% in IDCs, adjusted p value 0.045) genes. Between breast NETs and PNETs, different pathogenetic or unknown variant frequencies were detected in 30 genes. For example, MEN1 was mutated in only 6% of breast NETs and 37% in PNETs (adjusted p value 0.00050), and GATA3 pathogenetic or unknown variants were only found in 17.0% of breast NETs and 0% in PNETs (adjusted p value 0.0010). The most commonly affected oncogenic pathways in the breast NET cases were PI3K/Akt/mTOR, NOTCH and RTK-RAS pathways. Breast NETs had typically clock-like mutational signatures and signatures associated with defective DNA mismatch repair in their mutational landscape. Our results suggest that the breast NET mutational profile more closely resembles that of IDCs than that of PNETs. These results also revealed several potentially druggable targets, such as MMRd, in breast NETs. In conclusion, breast NETs are indeed a separate breast cancer entity, but their optimal treatment remains to be elucidated.}, } @article {pmid36084562, year = {2022}, author = {Nguyen, TH and El-Helou, E and Pop, CF and Shall, A and Zaiter, M and Naccour, J and Ho, XD and Nguyen, TTH and Nguyen, TMC and Bui, TT and Nguyen, VC and Hoang, H}, title = {Primary invasive ductal carcinoma of axillary accessory breast.}, journal = {International journal of surgery case reports}, volume = {98}, number = {}, pages = {107597}, pmid = {36084562}, issn = {2210-2612}, abstract = {Primary accessory breast cancer is an extremely rare pathology, representing less than 1 % of all breast cancers, and it is found in more than 90 % of cases in the axilla. The diagnosis of accessory axillary breast cancer (AABC) is often late and at an advanced stage with an average delay of 40.5 months. Histological sampling and immunohistochemical results confirm the diagnosis. Most patients are diagnosed with stage II disease or higher, so it is considered to have a poor prognosis. There is no specific management for AABC; it follows the guidelines for orthotopic pectoral breast cancer. We therefore report the case of a 50-year-old woman diagnosed with grade II invasive ductal carcinoma found in accessory axillary breast, treated by wide local resection and sentinel lymph node dissection.}, } @article {pmid36082773, year = {2023}, author = {Ryder, JH and Van Schooneveld, TC and Lyden, E and El Ramahi, R and Stohs, EJ}, title = {The interplay of infectious diseases consultation and antimicrobial stewardship in candidemia outcomes: A retrospective cohort study from 2016 to 2019.}, journal = {Infection control and hospital epidemiology}, volume = {44}, number = {7}, pages = {1102-1107}, doi = {10.1017/ice.2022.209}, pmid = {36082773}, issn = {1559-6834}, mesh = {Adult ; Humans ; *Candidemia/drug therapy ; Retrospective Studies ; *Antimicrobial Stewardship ; *Communicable Diseases/drug therapy ; Candida ; Referral and Consultation ; Antifungal Agents/therapeutic use ; }, abstract = {OBJECTIVE: To evaluate the need for mandatory infectious diseases consultation (IDC) for candidemia in the setting of antimicrobial stewardship guidance.

DESIGN: Retrospective cohort study from January 2016 to December 2019.

SETTING: Academic quaternary-care referral center.

PATIENTS: All episodes of candidemia in adults (n = 92), excluding concurrent bacterial infection or death or hospice care within 48 hours.

METHODS: Primary outcome was all-cause 30-day mortality. Secondary outcomes included guideline-adherence and treatment choice. Guideline-adherence was assessed with the EQUAL Candida score.

RESULTS: Of 186 episodes of candidemia, 92 episodes in 88 patients were included. Central venous catheters (CVCs) were present in 66 episodes (71.7%) and were the most common infection source (N = 38, 41.3%). The most frequently isolated species was Candida glabrata (40 of 94, 42.6%). IDC was performed in 84 (91.3%) of 92 candidemia episodes. Mortality rates were 20.8% (16 of 77) in the IDC group versus 25% (2 of 8) in the no-IDC group (P = .67). Other comparisons were numerically different but not significant: repeat blood culture (98.8% vs 87.5%; P = .17), echocardiography (70.2% vs 50%; P = .26), CVC removal (91.7% vs 83.3%; P = .45), and initial echinocandin treatment (67.9% vs 50%; P = .44). IDC resulted in more ophthalmology examinations (67.9% vs 12.5%; P = .0035). All patients received antifungal therapy. Antimicrobial stewardship recommendations were performed in 19 episodes (20.7%). The median EQUAL Candida score with CVC was higher with IDC (16 vs 11; P = .001) but not in episodes without CVC (12 vs 11.5; P = .81).

CONCLUSIONS: In the setting of an active antimicrobial stewardship program and high consultation rates, mandatory IDC may not be warranted for candidemia.}, } @article {pmid36082093, year = {2022}, author = {Kimura, A and Yamada, A and Shibata, Y and Inoue, S and Oshi, M and Harada, F and Kadokura, T and Takeuchi, H and Hasegawa, N and Kakuta, Y and Endo, I and Chishima, T}, title = {A case of matrix-producing carcinoma of the breast treated with preoperative chemotherapy.}, journal = {Gland surgery}, volume = {11}, number = {8}, pages = {1424-1430}, pmid = {36082093}, issn = {2227-684X}, abstract = {BACKGROUND: Matrix-producing carcinoma (MPC) is a rare tumor accounting for 0.1% of all breast cancers. Although MPC is usually triple-negative breast cancer, there have been few reports of preoperative chemotherapy for MPC that is considered chemotherapy-resistant. Herein, we report a case of MPC that was successfully treated with preoperative chemotherapy.

CASE DESCRIPTION: The patient was a 47-year-old woman diagnosed with right multiple breast cancer, clinical stage IIA. One of the tumors was identified as MPC and the other was invasive ductal carcinoma. The maximum tumor diameter of MPC was 3.8-cm. On immunohistochemistry, the tumor cells of MPC tested negative for estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). The Ki67 index was 90%. Preoperative chemotherapy was performed. EC (epirubicin 90 mg/m[2] and cyclophosphamide 600 mg/m[2]) was administered every 3 weeks for a total of 4 courses, followed by 12 courses of weekly paclitaxel (80 mg/m[2]). Then, she underwent right skin-sparing mastectomy, sentinel lymph node biopsy, and deep inferior epigastric perforator flap reconstruction. There was no metastasis to the sentinel lymph nodes. Postoperative pathological results showed that the residual tumor of the MPC measured only 0.1 cm. On the other hand, the residual tumor of the invasive ductal carcinoma was 0.7 cm. Endocrine therapy with oral tamoxifen was initiated for the invasive ductal carcinoma. Three years after surgery, no recurrence was observed. It has been reported that prognosis was correlated with residual cancer after preoperative chemotherapy. In addition, preoperative chemotherapy is of high clinical significance for the selection of postoperative treatment.

CONCLUSIONS: Although our case of MPC was successfully treated with preoperative chemotherapy, the standard of care for MPC remains uncertain. Development of a new targeted therapy for MPC is warranted.}, } @article {pmid36077795, year = {2022}, author = {Shu, L and Tong, Y and Li, Z and Chen, X and Shen, K}, title = {Can HER2 1+ Breast Cancer Be Considered as HER2-Low Tumor? A Comparison of Clinicopathological Features, Quantitative HER2 mRNA Levels, and Prognosis among HER2-Negative Breast Cancer.}, journal = {Cancers}, volume = {14}, number = {17}, pages = {}, pmid = {36077795}, issn = {2072-6694}, support = {81772797, 82072937//National Natural Science Foundation of China/ ; 20172007//Shanghai Municipal Education Commission/ ; 21YF1427400//Science and Technology Commission of Shanghai Municipality/ ; }, abstract = {Background: Human epidermal growth factor receptor 2 (HER2)-low tumor is a new entity defined as HER2 immunohistochemistry (IHC) 1+ or 2+/fluorescence in situ hybridization (FISH)-negative. We aimed to evaluate whether HER2 mRNA levels tested by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) could better define HER2-low tumors. Patients and methods: Consecutive breast cancer patients with hormonal receptor-positive, HER2-negative diseases, and HER2 mRNA results were included. Clinicopathologic features, HER2 mRNA expression level, and prognosis were compared among HER2 0, 1+ and 2+/FISH− groups. Concordance of the HER2 category between qRT-PCR and IHC/FISH was analyzed for each group. Results: 2296 patients were included: 368 (16.0%) HER2 0, 911 (39.7%) 1+, and 1017 (44.3%) 2+/FISH− tumors. HER2 1+ cases shared similarities with HER2 0 tumors in terms of clinicopathologic features (all p > 0.05), whereas IHC 2+/FISH− cases were less often non-IDC (p = 0.045), node-negative (p = 0.044), and Ki-67 < 14% (p <0.001). The mRNA expression was similar between HER2 0 and 1+ cases (p = 0.063), and both were lower than 2+/FISH− cases (p < 0.001). A poor concordance rate was found between IHC/FISH and qRT-PCR for HER2 0 and HER2-low cases (Cohen’s kappa 0.126, p < 0.001). No survival difference was observed among these groups, whether stratified by HER2 IHC/FISH status or mRNA level (all p > 0.05). Conclusions: HER2 1+ cases had similar clinicopathological features to HER2 0 breast cancers, and both were different from HER2 2+/FISH− cases. HER2 mRNA levels were comparable between HER2 0 and 1+ tumors, and both were significantly lower than IHC 2+/FISH− tumors. Neither IHC nor qRT-PCR may be optimal to quantify HER2-low expression, especially for HER2 1+ patients.}, } @article {pmid36074318, year = {2022}, author = {Pellegata, NS and Berriel Diaz, M and Rohm, M and Herzig, S}, title = {Obesity and cancer-extracellular matrix, angiogenesis, and adrenergic signaling as unusual suspects linking the two diseases.}, journal = {Cancer metastasis reviews}, volume = {41}, number = {3}, pages = {517-547}, pmid = {36074318}, issn = {1573-7233}, mesh = {Adipose Tissue ; *Adrenergic Agents ; Extracellular Matrix ; Humans ; *Neoplasms/epidemiology ; Obesity/complications ; }, abstract = {Obesity is an established risk factor for several human cancers. Given the association between excess body weight and cancer, the increasing rates of obesity worldwide are worrisome. A variety of obesity-related factors has been implicated in cancer initiation, progression, and response to therapy. These factors include circulating nutritional factors, hormones, and cytokines, causing hyperinsulinemia, inflammation, and adipose tissue dysfunction. The impact of these conditions on cancer development and progression has been the focus of extensive literature. In this review, we concentrate on processes that can link obesity and cancer, and which provide a novel perspective: extracellular matrix remodeling, angiogenesis, and adrenergic signaling. We describe molecular mechanisms involved in these processes, which represent putative targets for intervention. Liver, pancreas, and breast cancers were chosen as exemplary disease models. In view of the expanding epidemic of obesity, a better understanding of the tumorigenic process in obese individuals might lead to more effective treatments and preventive measures.}, } @article {pmid36072237, year = {2022}, author = {Ahmed, Y and Khan, AMH and Shaukat, F and Tahseen, R and Tariq, M and Mazhar, B and Abrar, S and Ali, N}, title = {Acute dermatitis in adult female patients receiving hypofractionated radiotherapy for breast cancer: experience from a low- and middle-income country.}, journal = {Ecancermedicalscience}, volume = {16}, number = {}, pages = {1412}, pmid = {36072237}, issn = {1754-6605}, abstract = {Radiotherapy (RT) is an important component of treatment in the management of breast cancer patients. The radiation treatment paradigm has been shifted towards hypofractionated RT. This study aims to determine the severity of acute dermatitis in patients receiving hypofractionated RT for breast cancer at a tertiary care university hospital in Pakistan. Patients with biopsy-proven invasive breast carcinoma or DCIS who were referred for radical radiotherapy after discussion in the breast tumour board were retrospectively reviewed. Physical assessment of the patients for evaluation of the severity of radiation dermatitis will be carried out in the first week, last week and on the first follow-up after 1 month of completion of RT, according to the Radiation Therapy Oncology Group/European Organisation For Research And Treatment Of Cancer (RTOG/EORTC) criteria. We identified 92 female patients in 6 months at Aga Khan University Hospital, with a mean age of 53.1 years. Most of the treated patients had clinical stage 3 (64%) cancer, while others were stage 2 (42%), stage 1 (2%) and stage 0 (2%). The surgeries performed were mastectomy in 59 patients and breast-conserving surgery in 33 patients. Histology was Intra Ductal Carcinoma (IDC) (95%), DCIS (3%) and Invasive Lobular Carcinoma (ILC) (2%). Most of the patients received chemotherapy (96%). Radiotherapy dose was 4256 cGy in 16 fractions, followed by a boost of 10 Gy. The radiation techniques used were intensity-modulated radiotherapy (47.8%) and three-dimensional conformal radiotherapy (52.2%). Most of the patients experienced no toxicity (59%), while grade I toxicity was observed in 29% of the patients and grade II toxicity was observed in 11%. Only 1% of the patients experienced grade III skin toxicity. Hypofractionated radiation therapy is beneficial because of the shorter overall treatment time which reduces the socio-economic burden, not only for patients but also for radiotherapeutic institutions. However, extended follow-up is to be reported for long-term toxicity and other consequences.}, } @article {pmid36068624, year = {2022}, author = {Kvopka, M and Smith, JR and Koczwara, B and Lake, SR}, title = {Bilateral intermediate uveitis following treatment with paclitaxel in a patient with invasive ductal carcinoma of the breast.}, journal = {International journal of retina and vitreous}, volume = {8}, number = {1}, pages = {63}, pmid = {36068624}, issn = {2056-9920}, abstract = {BACKGROUND: To report a case of bilateral intermediate uveitis without cystoid macular edema secondary to paclitaxel therapy, and its successful management with oral corticosteroids.

CASE PRESENTATION: A 66-year-old female developed bilateral intermediate uveitis with reduced best corrected visual acuity to 20/40 right and 20/200 left, following 12 cycles of paclitaxel therapy for breast carcinoma. Optical coherence tomography demonstrated no cystoid macular edema in either eye, and fundus fluorescein angiography showed localized retinal vascular leakage. Resolution of uveitis and improvement of visual acuity followed treatment with oral prednisolone for two months. Fourteen months after presentation, right and left visual acuities had returned to 20/32 and 20/40, respectively, and there was no recurrence of the uveitis.

CONCLUSIONS: This is the first reported case of bilateral intermediate uveitis in a patient treated with paclitaxel. Drug-induced uveitis should be considered in patients with visual symptoms in the setting of taxane chemotherapy, and oral corticosteroids are a safe and effective treatment.}, } @article {pmid36065403, year = {2022}, author = {Liu, Y and Jin, Z and Yu, X and Zheng, A and Jin, F and Wang, X}, title = {An insight into the invasion of breast ductal carcinoma in situ based on clinical, pathological and hematological data.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e13966}, pmid = {36065403}, issn = {2167-8359}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/diagnosis ; *Carcinoma, Ductal, Breast/diagnosis ; *Breast Neoplasms/diagnosis ; Neoplastic Processes ; Lymphatic Metastasis ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) has become a non-negligible part of breast cancers owing to the greatly increased incidence. While its natural history was not fully elucidated, which is the reason for current controversies in clinical treatment. Exploration of this issue from a clinical perspective is meaningful.

METHODS: Medical records of 389 patients diagnosed with DCIS or DCIS with invasive ductal carcinoma (IDC) were reviewed. All of them received appropriate medical care in our center. All 324 patients in training cohort were divided into invasion and non-invasion groups based on pathology. Differences in DCIS immunohistochemical markers and hematological indicators between them were analyzed. In the invasion group, differences between DCIS and matched IDC were compared to explore changes in the tumor heterogeneity during invasion. Conclusions are validated in the validation cohort of 65 patients.

RESULTS: Patients in invasion and non-invasion groups were balanced in baseline characteristics and no statistically significant differences were noticed for DCIS immunohistochemical markers. For hematological indicators, high expression of platelet >291.50) (odds ratio, 2.46; CI [1.35-4.46]; p = 0.003) and SII (>347.20) (odds ratio, 2.54; CI [1.56-4.12]; p < 0.001) were established as independent predictors for invasion by logistic analysis and were validated in the validation cohort. Ki-67 of IDC was significantly higher than that of matched DCIS (p < 0.001). HER2 expression and histological grade of DCIS were separately linearly related to those of IDC.

CONCLUSION: The change in hematological indicators is an independent predictor for invasion and can be incorporated into the treatment decision-making process for DCIS. Invasion tumor cells exhibit a stronger proliferative capacity compared with the in-situ ones. There are linear relationships in HER2 expression and histological grades between DCIS and matched IDC. DCIS subclones with different histological grades will develop into invasive carcinomas separately.}, } @article {pmid36065259, year = {2022}, author = {Malakzai, HA and Haidary, AM and Gulzar, S and Haidari, M and Ibrahimkhil, AS and Saadaat, R and Hakimi, A and Sadat Hofiani, SM and Rahmani, S and Abdul-Ghafar, J}, title = {Prevalence, Distribution, and Histopathological Features of Malignant Tumors Reported at Tertiary Level in Afghanistan: A 3-Year Study.}, journal = {Cancer management and research}, volume = {14}, number = {}, pages = {2569-2582}, pmid = {36065259}, issn = {1179-1322}, support = {001/WHO_/World Health Organization/International ; }, abstract = {PURPOSE: Cancer is one of the leading causes of mortality and morbidity, and therefore, tremendous research work is continuously being done around the world with consideration of etiopathogenesis as well as identification of therapeutic targets. Decades of continuous war in Afghanistan has left the medical infrastructure of the country in a miserable situation. There is a serious deficiency in research work in the fields of pathology and oncology at the moment with minimal data available to elaborate about the demographic characteristics of various malignant disorders in the country, which would be indispensable to pave the way for further research and development.

PATIENTS AND METHODS: A descriptive cross-sectional study was conducted to describe the prevalence, distribution, and important histopathological features of malignant tumors reported at tertiary level in Afghanistan.

RESULTS: Out of 2328 consecutive cases of solid malignant tumors included in our study, 93.8% were primary and 6.2% were metastatic. Breast was the most common site of origin for primary malignancy (29.5%) in females; however, in males, esophagus was the leading site for primary malignant tumors (16.3%). Invasive ductal carcinoma was the most common histologic type of malignancy in females (87.9%). However, in both genders, squamous cell carcinoma of esophagus and skin, osteosarcoma of bone and soft tissue, and glioblastoma of central nervous system were the most common histologic types of malignancies diagnosed. Small intestine was a frequently involved site affected by extranodal non-Hodgkin lymphomas. Overall, the majority of the cancers were diagnosed in stage-II.

CONCLUSION: Findings in our study were somewhat similar to data presented elsewhere in the world, with some significant differences that could be related to the local factors. Our study revealed that most of the malignant tumors were diagnosed in later stages of the disease, attributable to scarcity of specialized oncology institutions and public awareness.}, } @article {pmid36060830, year = {2022}, author = {Kroeze, E and Huijsman, R}, title = {One for All, All for One: A Mixed Methods Case Study into the Role Organisational and Personal Interests Play on Cooperation in Dutch Integrated Dementia Care Networks.}, journal = {International journal of integrated care}, volume = {22}, number = {3}, pages = {10}, pmid = {36060830}, issn = {1568-4156}, abstract = {INTRODUCTION: Cooperation is key to provide integrated dementia care. However, different kinds of (personal and organisational) interests will affect collaboration in integrated dementia care (IDC) networks. Hence, it is crucial to understand how interests influence relations in IDC-networks in order to shape future policies.

METHODS: A sequential mixed methods single case study design was used, in three phases: a Social Network Analysis (SNA) based on data from questionnaires (n = 24-26), explorative interviews with network partners (n = 14) and a focus group with network coordinators (n = 7) to explore the conceptual generalisability of the single case of the IDC-network.

RESULTS: The SNA revealed that highly connected organisations were often established care organisations that deliver case management, while smaller care organisations or welfare organisations tend to be less connected. Care-related, strategic, and financial interests influence participation of organisations in the IDC-network, while personal intrinsic motivations determine a representative's contribution to the network. Especially conflicting interests strongly influence the network structure.

DISCUSSION AND CONCLUSION: We conclude that conflicting interests in IDC-networks stand in the way of reaching the collective goal of an IDC-network, i.e., optimising the wellbeing of people with dementia and their informal caregivers in the region. Thus, IDC-networks should act to manage, resolve and prevent disputes arising from conflicting interests.}, } @article {pmid36052460, year = {2022}, author = {Isaogullari, SY and Topal, U and Ozturk, F and Gok, M and Oz, B and Akcan, AC}, title = {The relationship of patients, giving or not giving a pathological full response, wıth YAP (Yes Associated Protein) in breast cancer cases to which neo-adjuvant chemotherapy is applied.}, journal = {Annali italiani di chirurgia}, volume = {92}, number = {}, pages = {263-270}, pmid = {36052460}, issn = {2239-253X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor ; *Breast Neoplasms/pathology ; Chemotherapy, Adjuvant ; Female ; Humans ; Ki-67 Antigen ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local/drug therapy ; Erb-b2 Receptor Tyrosine Kinases/metabolism/therapeutic use ; Receptors, Estrogen/metabolism/therapeutic use ; Receptors, Progesterone/metabolism/therapeutic use ; Retrospective Studies ; YAP-Signaling Proteins ; }, abstract = {AIM: We aimed to evaluate (immunohistochemically) the YAP expression in breast cancer patients undergoing neoadjuvant chemotherapy and to clarify the relationship between the molecular characteristics, treatment response and survival data and the YAP expression, and hence, to clarify the prognostic significance.

MATERIAL AND METHODS: One hundred and four patients who were diagnosed with Breast Cancer between 2015-2020 and underwent Neo Adjuvant Chemotherapy were included in the study. Estrogen Receptor(ER), Progesterone Receptor(PR), Human Epidermal Growth Receptor-2(HER2) and Ki-67. Expression are routinely stained immunohistochemically. In this study, existing immunohistochemical markers were reviewed and also, the relationship of YAP with these biological markers was evaluated by using immunohistochemistry and its effect on prognosis has been investigated.

RESULTS: The average age of the patients was 52.37. While YAP was positive in 78 patients (75%), it was negative in 26 patients (25%). In the evaluation after neoadjuvant therapy, pathological complete response (MillerPayne Grade5 response) in 28 patients (26.9%), relapse in 6 patients (5.8%), and exitus in 6 patients (5.8%) were detected. In the pathological evaluation, invasive Ductal Carcinoma was the most common one observed in 88 patients (84.6%). As a result of the statistical evaluation, no significant result was obtained between the parameters and YAP negative/positive.

CONCLUSION: As a result of staining with additional YAP in patients who were diagnosed with breast cancer and routinely stained with ER, PR, Cerb B2 and Ki-67 in pathology samples, we could not reach a result that would contribute positively to survival. Longer studies to be conducted prospectively will be meaningful.

KEY WORDS: Breast Cancer, Chemotherapy, Neoadjuvant, Yes Associated Protein.}, } @article {pmid36051653, year = {2022}, author = {Yang, X and Chen, L and Shen, Y}, title = {Breast Metaplastic Carcinoma With Osteosarcomatous Differentiation: A Case Report and literature Review.}, journal = {Clinical pathology (Thousand Oaks, Ventura County, Calif.)}, volume = {15}, number = {}, pages = {2632010X221118056}, pmid = {36051653}, issn = {2632-010X}, abstract = {Metaplastic breast carcinoma (MBCs) is a rare heterogeneous group of malignancies. Herein, we report a case of metaplastic breast carcinoma, which had 2 components. One of them was typical invasive ductal carcinoma (IDC), the other one was presenting as osteosarcoma with lots of immature trabeculae. The results of immunohistochemistry showed different presentations between them. The majority of MBCs show triple-negativity for ER, PR, and HER-2 and are thus associated with poor prognosis. Our report shows that, it is necessary to describe the proportion of the components and the presentations of immunohistochemistry in the diagnosis, which will be important to develop specific and effective therapies.}, } @article {pmid36048457, year = {2022}, author = {Tannir, NM and Agarwal, N and Porta, C and Lawrence, NJ and Motzer, R and McGregor, B and Lee, RJ and Jain, RK and Davis, N and Appleman, LJ and Goodman, O and Stadler, WM and Gandhi, S and Geynisman, DM and Iacovelli, R and Mellado, B and Sepúlveda Sánchez, JM and Figlin, R and Powles, T and Akella, L and Orford, K and Escudier, B}, title = {Efficacy and Safety of Telaglenastat Plus Cabozantinib vs Placebo Plus Cabozantinib in Patients With Advanced Renal Cell Carcinoma: The CANTATA Randomized Clinical Trial.}, journal = {JAMA oncology}, volume = {8}, number = {10}, pages = {1411-1418}, pmid = {36048457}, issn = {2374-2445}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Male ; Female ; Middle Aged ; *Carcinoma, Renal Cell/drug therapy/mortality ; Nivolumab/therapeutic use ; Ipilimumab/therapeutic use ; Glutaminase/therapeutic use ; Double-Blind Method ; Immune Checkpoint Inhibitors ; Glutamine/therapeutic use ; Protein Kinase Inhibitors/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Glutamates/therapeutic use ; Anilides ; Pyridines ; }, abstract = {IMPORTANCE: Dysregulated metabolism is a hallmark of renal cell carcinoma (RCC). Glutaminase is a key enzyme that fuels tumor growth by converting glutamine to glutamate. Telaglenastat is an investigational, first-in-class, selective, oral glutaminase inhibitor that blocks glutamine utilization and downstream pathways. Preclinically, telaglenastat synergized with cabozantinib, a VEGFR2/MET/AXL inhibitor, in RCC models.

OBJECTIVE: To compare the efficacy and safety of telaglenastat plus cabozantinib (Tela + Cabo) vs placebo plus cabozantinib (Pbo + Cabo).

CANTATA was a randomized, placebo-controlled, double-blind, pivotal trial conducted at sites in the US, Europe, Australia, and New Zealand. Eligible patients had metastatic clear-cell RCC following progression on 1 to 2 prior lines of therapy, including 1 or more antiangiogenic therapies or nivolumab plus ipilimumab. The data cutoff date was August 31, 2020. Data analysis was performed from December 2020 to February 2021.

INTERVENTIONS: Patients were randomized 1:1 to receive oral cabozantinib (60 mg daily) with either telaglenastat (800 mg twice daily) or placebo until disease progression or unacceptable toxicity.

MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival (Response Evaluation Criteria in Solid Tumors version 1.1) assessed by blinded independent radiology review.

RESULTS: A total of 444 patients were randomized: 221 to Tela + Cabo (median [range] age, 61 [21-81] years; 47 [21%] women and 174 [79%] men) and 223 to Pbo + Cabo (median [range] age, 62 [29-83] years; 68 [30%] women and 155 [70%] men). A total of 276 (62%) patients had received prior immune checkpoint inhibitors, including 128 with prior nivolumab plus ipilimumab, 93 of whom had not received prior antiangiogenic therapy. Median progression-free survival was 9.2 months for Tela + Cabo vs 9.3 months for Pbo + Cabo (HR, 0.94; 95% CI, 0.74-1.21; P = .65). Overall response rates were 31% (69 of 221) with Tela + Cabo vs 28% (62 of 223) with Pbo + Cabo. Treatment-emergent adverse event (TEAE) rates were similar between arms. Grade 3 to 4 TEAEs occurred in 160 patients (71%) with Tela + Cabo and 172 patients (79%) with Pbo + Cabo and included hypertension (38 patients [17%] vs 40 patients [18%]) and diarrhea (34 patients [15%] vs 29 patients [13%]). Cabozantinib was discontinued due to AEs in 23 patients (10%) receiving Tela + Cabo and 33 patients (15%) receiving Pbo + Cabo.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, telaglenastat did not improve the efficacy of cabozantinib in metastatic RCC. Tela + Cabo was well tolerated with AEs consistent with the known risks of both agents.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03428217.}, } @article {pmid36045608, year = {2022}, author = {Flosdorf, N and Zenke, M}, title = {Dendritic cells generated from induced pluripotent stem cells and by direct reprogramming of somatic cells.}, journal = {European journal of immunology}, volume = {52}, number = {12}, pages = {1880-1888}, doi = {10.1002/eji.202149550}, pmid = {36045608}, issn = {1521-4141}, mesh = {Humans ; *Induced Pluripotent Stem Cells ; Dendritic Cells ; }, abstract = {Novel and exciting avenues allow generating dendritic cells (DC) by reprogramming of somatic cells. DC are obtained from induced pluripotent stem cells (iPS cells), referred to as ipDC, and by direct reprogramming of cells toward DC, referred to as induced DC (iDC). iPS cells represent pluripotent stem cells generated by reprogramming of somatic cells and can differentiate into all cell types of the body, including DC. This makes iPS cells and ipDC derived thereof useful for studying various DC subsets, acquiring high cell numbers for research and clinical use, or applying genome editing to generate DC with wanted properties. Thereby, ipDC overcome limitations in specific DC subsets, which are only found in low abundance in blood or lymphoid organs. iDC are generated by direct reprogramming of somatic cells with a specific set of transcription factors and offer an avenue to obtain DC without a pluripotent cell intermediate. ipDC and iDC retain patient and disease-specific mutations and this opens new perspectives for studying DC in disease. This review summarizes the current techniques used to generate ipDC and iDC, and the types and functionality of the DC generated.}, } @article {pmid36043708, year = {2022}, author = {Gadi, V and Shetty, SR}, title = {Potential of Anti-inflammatory Molecules in the Chemoprevention of Breast Cancer.}, journal = {Recent advances in inflammation & allergy drug discovery}, volume = {16}, number = {2}, pages = {60-76}, pmid = {36043708}, issn = {2772-2716}, mesh = {Humans ; Female ; *Breast Neoplasms/prevention & control ; Vascular Endothelial Growth Factor A ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Anti-Inflammatory Agents/pharmacology ; Chemoprevention ; *Anticarcinogenic Agents/pharmacology ; Phytochemicals/pharmacology ; }, abstract = {Breast cancer is a global issue, affecting greater than 1 million women per annum. Over the past two decades, there have been numerous clinical trials involving the use of various pharmacological substances as chemopreventive agents for breast cancer. Various pre-clinical as well as clinical studies have established numerous anti-inflammatory molecules, including nonsteroidal anti-inflammatory drugs (NSAIDs) and dietary phytochemicals as promising agents for chemoprevention of several cancers, including breast cancer. The overexpression of COX-2 has been detected in approximately 40% of human breast cancer cases and pre-invasive ductal carcinoma in-situ lesions, associated with aggressive elements of breast cancer such as large size of the tumour, ER/PR negative and HER-2 overexpression, among others. Anti-inflammatory molecules inhibit COX, thereby inhibiting the formation of prostaglandins and inhibiting nuclear factor-κBmediated signals (NF-kB). Another probable explanation entails inflammation-induced degranulation, with the production of angiogenesis-regulating factors, such as vascular endothelial growth factor, which can be possibly regulated by anti-inflammatory molecules. Apart from NSAIDS, many dietary phytochemicals have the ability to decrease, delay, or stop the progression and/or incidence of breast cancer by their antioxidant action, regulating inflammatory and proliferative cell signalling pathways as well as inducing apoptosis. The rapid progress in chemoprevention research has also established innovative strategies that can be implemented to prevent breast cancer. This article gives a comprehensive overview of the recent advancements in using antiinflammatory molecules in the chemoprevention of breast cancer along with their mechanism of action, supported by latest preclinical and clinical data. The merits of anti-inflammatory chemopreventive agents in the prevention of cardiotoxicity have been described. We have also highlighted the ongoing research and advancements in improving the efficacy of using antiinflammatory molecules as chemopreventive agents.}, } @article {pmid36040027, year = {2023}, author = {Thompson, LDR and Bishop, JA}, title = {Salivary Gland Intraductal Carcinoma: How Do 183 Reported Cases Fit Into a Developing Classification.}, journal = {Advances in anatomic pathology}, volume = {30}, number = {2}, pages = {112-129}, pmid = {36040027}, issn = {1533-4031}, mesh = {Humans ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Salivary Gland Neoplasms/pathology ; Transcription Factors ; Salivary Glands/pathology ; Biomarkers, Tumor/genetics ; }, abstract = {Salivary gland intraductal carcinoma (IDC) is a very uncommon group of neoplasms. Many names, variations in diagnostic criteria, and newly observed molecular findings (including NCOA4 :: RET , TRIM27 :: RET , HRAS point mutations, and PIK3CA pathway alterations) have generated further confusion in being able to recognize and categorize this group of tumors. Different histologic appearances and patterns of growth suggest there is more than one tumor category, with intercalated duct, apocrine, oncocytic, and hybrid features seen. Frankly destructive invasion further complicates the category, as the name "intraductal" would suggest an "in situ" neoplasm. Recent evidence on fusion-positive IDC demonstrates the same molecular underpinnings in both the ductal and the myoepithelial cells, which aids in further separating these tumors. This article summarizes the historical group of 183 neoplasms classified under the umbrella of IDC and highlights the unique histologic, immunohistochemistry, and molecular features that may further guide nomenclature standardization and harmonization.}, } @article {pmid36039062, year = {2022}, author = {Wu, Q and He, L and Luo, J and Jin, W and Xu, Y and Wang, C}, title = {Long-term remission under Disitamab Vedotin (RC48) in HR-positive/HER2-positive metastatic breast cancer with brain meningeal, and bone marrow involvement: A case report.}, journal = {Oncology letters}, volume = {24}, number = {4}, pages = {339}, pmid = {36039062}, issn = {1792-1082}, abstract = {Breast cancer (BC) with overexpression of human epidermal growth factor receptor 2 (HER2) is closely associated with an elevated risk of multiple distant metastases and unfavorable prognosis. Disitamab Vedotin (RC48) is a newly developed antibody-drug conjugate targeting HER2, which is comprised of hertuzumab coupled to monomethyl auristatin E via a cleavable linker. Pre-clinical studies indicated its strong anti-tumor activity in HER2-positive and low HER2 expression models of BC. The present study reported on the case of a 60-year-old postmenopausal female who suffered from fatigue and was diagnosed with a right-sided BC tumor. The diagnosis was stage IV (cT4N3M1) hormone receptor (HR)-positive and HER2-positive invasive ductal carcinoma with systemic metastases (brain included). The patient initially responded well to 26 cycles of the first-line anti-HER2 targeted therapy plus chemotherapy (trastuzumab+pertuzumab+nab-paclitaxel) combined with whole-brain radiotherapy. However, both extracranial and intracranial lesions achieved progressive disease (PD), which eventually occurred during 5 sequential cycles of maintenance therapy. Subsequently, 4 cycles of second-line treatment (trastuzumab + pyrotinib + capecitabin) were continued until the levels of blood tumor markers CEA, CA15-3 and CA125 were elevated, and systemic PD was able to be attained (the brain metastases were rated as stable disease). Finally, the patient received RC48 as the third-line therapy and achieved a durable and effective clinical response. To date, the patient has benefited from 12 cycles of RC48 without any severe adverse effects. The overall survival was >3 years. The present study showcased that RC48 was effective and tolerable for a patient with HR- and HER2-positive BMBC.}, } @article {pmid36034829, year = {2022}, author = {Pillai, SS and Pereira, DG and Bonsu, G and Chaudhry, H and Puri, N and Lakhani, HV and Tirona, MT and Sodhi, K and Thompson, E}, title = {Biomarker panel for early screening of trastuzumab -induced cardiotoxicity among breast cancer patients in west virginia.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {953178}, pmid = {36034829}, issn = {1663-9812}, abstract = {Cardiotoxicity is a well-known pathophysiological consequence in breast cancer patients receiving trastuzumab. Trastuzumab related cardiotoxicity typically results in an overall decline in cardiac function, primarily characterized by reduction in left ventricular ejection fraction (LVEF) and development of symptoms associated with heart failure. Current strategies for the monitoring of cardiac function, during trastuzumab therapy, includes serial echocardiography, which is cost ineffective as well as offers limited specificity, while offering limited potential in monitoring early onset of cardiotoxicity. However, biomarkers have been shown to be aberrant prior to any detectable functional or clinical deficit in cardiac function. Hence, this study aims to develop a panel of novel biomarkers and circulating miRNAs for the early screening of trastuzumab induced cardiotoxicity. Patients with clinical diagnosis of invasive ductal carcinoma were enrolled in the study, with blood specimen collected and echocardiography performed prior to trastuzumab therapy initiation at baseline, 3- and 6-months post trastuzumab therapy. Following 6-months of trastuzumab therapy, about 18% of the subjects developed cardiotoxicity, as defined by reduction in LVEF. Our results showed significant upregulation of biomarkers and circulating miRNAs, specific to cardiac injury and remodeling, at 3- and 6-months post trastuzumab therapy. These biomarkers and circulating miRNAs significantly correlated with the cardiac injury specific markers, troponin I and T. The findings in the present study demonstrates the translational applicability of the proposed biomarker panel in early preclinical diagnosis of trastuzumab induced cardiotoxicity, further allowing management of cardiac function decline and improved health outcomes for breast cancer patients.}, } @article {pmid36031887, year = {2022}, author = {Sogunro, O and Sayyed, AA and Aminpour, N and Towfighi, P and Maini, M and Masanam, M and Deldar, R and Murray, A and De La Cruz, L and Greenwalt, I and Son, JD}, title = {Triple negative breast cancer and reconstruction: Predictors of recurrence, complications, and mortality.}, journal = {Breast disease}, volume = {41}, number = {1}, pages = {343-350}, doi = {10.3233/BD-220005}, pmid = {36031887}, issn = {1558-1551}, mesh = {*Breast Neoplasms ; Female ; Humans ; *Mammaplasty ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local ; Retrospective Studies ; *Triple Negative Breast Neoplasms ; }, abstract = {BACKGROUND: Only 42% of all breast cancer patients undergoing mastectomy elect for breast reconstruction.

OBJECTIVE: We evaluate factors impacting complications, recurrence, and mortality in triple-negative breast cancer (TNBC) patients undergoing reconstruction.

METHODS: Reconstructive TNBC patients at a single institution from 2010 to 2020 were retrospectively reviewed. Patient demographics, cancer characteristics, reconstruction choice, and complications were collected. Statistical significance was defined at p < 0.05.

RESULTS: A total of 131 patients were identified. Average age was 47.8 years, 50.4% were Caucasian and 36.4% were African American. Most patients had invasive ductal carcinoma (90.8%), and most underwent nipple-sparing (41.2%) or skin-sparing (38.9%) mastectomies. Twenty-one patients (16.0%) experienced postoperative complications. Patients with complications tended to be older (52.1 versus 46.9 years, p = 0.052). At mean follow-up of 52.1 months, 14.5% experienced cancer recurrence and 5.3% died. Deceased patients were significantly younger at diagnosis (42.2 versus 48.5 years, p = 0.008) and had a lower BMI compared to surviving patients (21.2 versus 26.9 kg/m2; p = 0.014). Patients younger than age 45 years had higher Ki-67 than those older than 45 years (80.0% versus 60.0%, p = 0.013). Outcomes in autologous- versus implant-based reconstruction were not significantly different.

CONCLUSIONS: In TNBC post-mastectomy reconstruction patients, age and BMI were predictors of mortality while race, smoking history, reconstruction choice, or type of implant-based reconstruction had no significant effect on these outcomes.

SYNOPSIS: The purpose of this study is to evaluate factors that impact complications, recurrence, and mortality in triple negative breast cancer (TNBC) patients undergoing reconstruction. We identified BMI, neoadjuvant chemotherapy, and age as predictors of complications, recurrence, and mortality in TNBC.}, } @article {pmid36031387, year = {2022}, author = {Rios Garcia, M and Meissburger, B and Chan, J and de Guia, RM and Mattijssen, F and Roessler, S and Birkenfeld, AL and Raschzok, N and Riols, F and Tokarz, J and Giroud, M and Gil Lozano, M and Hartleben, G and Nawroth, P and Haid, M and López, M and Herzig, S and Berriel Diaz, M}, title = {Trip13 Depletion in Liver Cancer Induces a Lipogenic Response Contributing to Plin2-Dependent Mitotic Cell Death.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {9}, number = {29}, pages = {e2104291}, pmid = {36031387}, issn = {2198-3844}, support = {2015_A240//Else-Kröner-Fresenius-Stiftung/ ; //Helmholtz Future Topic AmPro/ ; 2016-PG068//Xunta de Galicia/ ; RTI2018-101840-B-I00//Ministerio de Economía y Competitividad (MINECO) co-funded by FEDER Program of EU/ ; }, mesh = {ATPases Associated with Diverse Cellular Activities/metabolism ; Cell Cycle Proteins/metabolism ; Cell Death ; Humans ; *Insulins/metabolism ; Lipids ; *Liver Neoplasms ; Mad2 Proteins/metabolism ; Paclitaxel/pharmacology ; Perilipin-2 ; Proto-Oncogene Proteins c-akt/metabolism ; Receptors, Thyroid Hormone/metabolism ; }, abstract = {Aberrant energy metabolism and cell cycle regulation both critically contribute to malignant cell growth and both processes represent targets for anticancer therapy. It is shown here that depletion of the AAA+-ATPase thyroid hormone receptor interacting protein 13 (Trip13) results in mitotic cell death through a combined mechanism linking lipid metabolism to aberrant mitosis. Diminished Trip13 levels in hepatocellular carcinoma cells result in insulin-receptor-/Akt-pathway-dependent accumulation of lipid droplets, which act as functional acentriolar microtubule organizing centers disturbing mitotic spindle polarity. Specifically, the lipid-droplet-coating protein perilipin 2 (Plin2) is required for multipolar spindle formation, induction of DNA damage, and mitotic cell death. Plin2 expression in different tumor cells confers susceptibility to cell death induced by Trip13 depletion as well as treatment with paclitaxel, a spindle-interfering drug commonly used against different cancers. Thus, assessment of Plin2 levels enables the stratification of tumor responsiveness to mitosis-targeting drugs, including clinically approved paclitaxel and Trip13 inhibitors currently under development.}, } @article {pmid36018614, year = {2022}, author = {Sun, Z and Li, L and Sun, C and Ni, Q and Zhao, Y and Wu, H and Jin, H}, title = {Active Control of Interface Dynamics in NASICON-Based Rechargeable Solid-State Sodium Batteries.}, journal = {Nano letters}, volume = {22}, number = {17}, pages = {7187-7194}, doi = {10.1021/acs.nanolett.2c02509}, pmid = {36018614}, issn = {1530-6992}, abstract = {Severe challenges are restraining the practical application of solid-state batteries, such as the dendrite growth and unsatisfactory compatibility between solid electrolyte and electrode. Here, we propose an interface dynamic control (IDC) strategy to ensure the stable operation of NASICON-based solid-state sodium batteries. First, we introduce intergranular phase (CuO) to effectively promote the densification of Na3Zr2Si2PO12 with an optimized ionic conductivity of 1.74 × 10[-3] S cm[-1] at 25 °C. Moreover, the kinetically formed Na-Cu-O interlayer reveals outstanding conductive capability. The dramatically reduced interfacial area-specific resistance (70 ohm cm[-2]) boosts the resistance to Na dendrite growth, ensuring the excellent cycling stability of symmetric Na cells at a current density of 0.4 mA cm[-2] and room temperature. All-solid-state sodium metal batteries with Na3V1.5Cr0.5(PO4)3 cathode and modified Na3Zr2Si2PO12 ceramic electrolyte reveal a high retention of 87.4% at 100 mA g[-1] over 300 cycles. This work opens up a new route for the rational interface design of NASICON-structure solid electrolyte toward the application in the high energy-density and high safety electrochemical energy storage devices.}, } @article {pmid36016722, year = {2022}, author = {Barker, T and D'hulst, P and Fong, E}, title = {Urethro-venous fistula following straddle injury: A case report and image series.}, journal = {Urology case reports}, volume = {45}, number = {}, pages = {102184}, pmid = {36016722}, issn = {2214-4420}, abstract = {We present a case of a 49-year-old man with an acute traumatic urethral injury after a fall onto a fence post. Retrograde contrast study showed a contrast leak and suspicion of a traumatic urethro-venous fistula. We successfully placed a urethral indwelling catheter (IDC) in the operating room and follow-up urethrocystoscopy showed healing of the injury. The patient remained asymptomatic during further follow-up visits.}, } @article {pmid36016067, year = {2022}, author = {Benmussa, C and Cauchard, JR and Yakhini, Z}, title = {Generating Alerts from Breathing Pattern Outliers.}, journal = {Sensors (Basel, Switzerland)}, volume = {22}, number = {16}, pages = {}, pmid = {36016067}, issn = {1424-8220}, mesh = {Humans ; Models, Statistical ; *Respiration ; *Respiratory Rate ; Rest ; }, abstract = {Analysing human physiological data allows access to the health state and the state of mind of the subject individual. Whenever a person is sick, having a panic attack, happy or scared, physiological signals will be different. In terms of physiological signals, we focus, in this manuscript, on monitoring breathing patterns. The scope can be extended to also address heart rate and other variables. We describe an analysis of breathing rate patterns during activities including resting, walking, running and watching a movie. We model normal breathing behaviours by statistically analysing signals, processed to represent quantities of interest. We consider moving maximum/minimum, the amplitude and the Fourier transform of the respiration signal, working with different window sizes. We then learn a statistical model for the basal behaviour, per individual, and detect outliers. When outliers are detected, a system that incorporates our approach would send a visible signal through a smart garment or through other means. We describe alert generation performance in two datasets-one literature dataset and one collected as a field study for this work. In particular, when learning personal rest distributions for the breathing signals of 14 subjects, we see alerts generated more often when the same individual is running than when they are tested in rest conditions.}, } @article {pmid36012443, year = {2022}, author = {Kmiecik, A and Ratajczak-Wielgomas, K and Grzegrzółka, J and Romanowicz, H and Smolarz, B and Dziegiel, P}, title = {Expression of NUCB2/NESF-1 in Breast Cancer Cells.}, journal = {International journal of molecular sciences}, volume = {23}, number = {16}, pages = {}, pmid = {36012443}, issn = {1422-0067}, support = {STM.A350.20.064//Wrocław Medical University/ ; }, mesh = {*Breast Neoplasms/genetics/metabolism ; *Carcinoma, Ductal, Breast/pathology ; Cytoplasm/metabolism ; Female ; Humans ; RNA, Messenger/genetics/metabolism ; }, abstract = {Recently, the expression of NUCB2/NESF-1 has been linked to tumor development. We report NUCB2/NESF-1 expression and its relation to clinicopathological parameters in breast cancer cells. Immunohistochemical reactions were conducted on 446 cases of invasive ductal carcinoma (IDC) and 36 cases of mastopathy. The expression of NUCB2/NESF-1 was also examined at the mRNA and protein levels in breast cancer cell lines. A statistically significant higher level of NUCB2/NESF-1 in IDC cells was noted compared to that in mastopathy samples. The level of NUCB2 expression in the cytoplasm of IDC cells decreased with the increasing degree of tumor malignancy (G). Higher NUCB2 expression was found in tumors with estrogen receptor (ER)-positive and progesterone receptor (PR)-positive phenotypes compared to that in estrogen-receptor-negative and progesterone-receptor-negative cases. Moreover, a higher expression was shown in ER(+) and PR(+) MCF-7 and T47D cell lines compared to that in triple-negative MDA-MB-468 and normal human breast epithelial cells. The analysis of the five-year survival rate indicated that a positive NUCB2/NESF-1 expression in tumor cells was also associated with longer patient survival. The study results suggest that NUCB2/NESF1 may play an important role in malignant transformation and may be a positive prognostic factor in IDC.}, } @article {pmid36010848, year = {2022}, author = {Kastora, SL and Kounidas, G and Speirs, V and Masannat, YA}, title = {Integrative, In Silico and Comparative Analysis of Breast Cancer Secretome Highlights Invasive-Ductal-Carcinoma-Grade Progression Biomarkers.}, journal = {Cancers}, volume = {14}, number = {16}, pages = {}, pmid = {36010848}, issn = {2072-6694}, support = {NER11101//NHS Grampian Endowment Fund/ ; }, abstract = {Globally, BC is the most frequently diagnosed cancer in women. The aim of this study was to identify novel secreted biomarkers that may indicate progression to high-grade BC malignancies and therefore predict metastatic potential. A total of 33 studies of breast cancer and 78 of other malignancies were screened via a systematic review for eligibility, yielding 26 datasets, 8 breast cancer secretome datasets, and 18 of other cancers that were included in the comparative secretome analysis. Sequential bioinformatic analysis using online resources enabled the identification of enriched GO_terms, overlapping clusters, and pathway reconstruction. This study identified putative predictors of IDC grade progression and their association with breast cancer patient mortality outcomes, namely, HSPG2, ACTG1, and LAMA5 as biomarkers of in silico pathway prediction, offering a putative approach by which the abovementioned proteins may mediate their effects, enabling disease progression. This study also identified ITGB1, FBN1, and THBS1 as putative pan-cancer detection biomarkers. The present study highlights novel, putative secretome biomarkers that may provide insight into the tumor biology and could inform clinical decision making in the context of IDC management in a non-invasive manner.}, } @article {pmid36010160, year = {2022}, author = {Cho, H and Cho, A and Kang, WJ}, title = {Prognosis Associated with Glycolytic Activity in Regional Lymph Nodes of Patients with Previously Untreated Metastatic Breast Cancer: A Preliminary Study.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {8}, pages = {}, pmid = {36010160}, issn = {2075-4418}, support = {2020M2D9A1093991//Ministry of Science ICT and Future Planning/ ; 6-2019-0112//Yonsei University College of Medicine/ ; }, abstract = {Better mechanisms of predicting prognoses in patients with metastatic breast cancer will improve the identification of patients for whom curative treatments may be the most effective. In this study, the prognostic value of [18]F-fluorodeoxyglucose positron emission tomography/computed tomography ([18]F-FDG PET/CT) was assessed in patients with metastatic breast cancer. A retrospective analysis of women who underwent [18]F-FDG PET/CT for staging of newly diagnosed metastatic breast cancer was conducted. In each patient, the maximum standardized uptake value (SUV) and total lesion glycolysis (TLG) of primary tumors and regional lymph nodes were measured and analyzed for association with survival using the Cox proportional hazards regression model. From 346 consecutive patients, 32 with metastatic invasive ductal carcinoma of the breast were included in the study. The median duration of follow-up was 22.5 months. Disease progression occurred in 26 patients, and 11 patients died. When multivariate analyses with a stepwise forward regression were applied, only the maximum SUV and TLG of regional lymph nodes showed a significant correlation with progression-free survival and overall survival, respectively. This study demonstrates that increased [18]F-FDG uptake in regional lymph nodes is a strong independent predictor of survival in women with metastatic invasive ductal carcinoma of the breast.}, } @article {pmid36009260, year = {2022}, author = {Pigazzani, F and Gorni, D and Dyar, KA and Pedrelli, M and Kennedy, G and Costantino, G and Bruno, A and Mackenzie, I and MacDonald, TM and Tietge, UJF and George, J}, title = {The Prognostic Value of Derivatives-Reactive Oxygen Metabolites (d-ROMs) for Cardiovascular Disease Events and Mortality: A Review.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {11}, number = {8}, pages = {}, pmid = {36009260}, issn = {2076-3921}, abstract = {Oxidative stress participates in the development and exacerbation of cardiovascular diseases (CVD). The ability to promptly quantify an imbalance in an individual reductive-oxidative (RedOx) state could improve cardiovascular risk assessment and management. Derivatives-reactive oxygen metabolites (d-ROMs) are an emerging biomarker of oxidative stress quantifiable in minutes through standard biochemical analysers or by a bedside point-of-care test. The current review evaluates available data on the prognostic value of d-ROMs for CVD events and mortality in individuals with known and unknown CVD. Outcome studies involving small and large cohorts were analysed and hazard ratio, risk ratio, odds ratio, and mean differences were used as measures of effect. High d-ROM plasma levels were found to be an independent predictor of CVD events and mortality. Risk begins increasing at d-ROM levels higher than 340 UCARR and rises considerably above 400 UCARR. Conversely, low d-ROM plasma levels are a good negative predictor for CVD events in patients with coronary artery disease and heart failure. Moreover, combining d-ROMs with other relevant biomarkers routinely used in clinical practice might support a more precise cardiovascular risk assessment. We conclude that d-ROMs represent an emerging oxidative-stress-related biomarker with the potential for better risk stratification both in primary and secondary cardiovascular prevention.}, } @article {pmid36008255, year = {2022}, author = {Cai, Q and Costa, DN and Metter, CK and Goldberg, K and Roehrborn, CG and Cadeddu, J and Pedrosa, I and Meng, X and Mostardeiro, TR and Shah, RB}, title = {Sensitivity of multiparametric MRI and targeted biopsy for detection of adverse pathologies (Cribriform gleason pattern 4 and intraductal carcinoma): Correlation of detected and missed prostate cancer foci with whole mount histopathology.}, journal = {Urologic oncology}, volume = {40}, number = {10}, pages = {452.e1-452.e8}, doi = {10.1016/j.urolonc.2022.07.012}, pmid = {36008255}, issn = {1873-2496}, mesh = {Biopsy ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Humans ; Image-Guided Biopsy/methods ; Magnetic Resonance Imaging/methods ; Male ; *Multiparametric Magnetic Resonance Imaging ; Neoplasm Grading ; *Prostatic Neoplasms/diagnostic imaging/surgery ; Retrospective Studies ; }, abstract = {PURPOSE: Accurate preoperative detection of prostate cancer (PCa) exhibiting "cribriform" morphology (intraductal carcinoma [IDC-P] or cribriform Gleason pattern 4 [CrP4]) is important as it is independently associated with a variety of adverse clinical outcomes. The sensitivity of multiparametric magnetic resonance imaging (mpMRI) in the detection of PCa exhibiting "cribriform" morphology remains controversial.

MATERIALS AND METHODS: A total of 117 eligible men with prospectively reported mpMRI who underwent in-bore MRI targeted biopsy followed by whole-mount radical prostatectomy (RP) were analyzed for lesion-level imaging-pathology correlation.

RESULTS: Of the 206 PCa foci at RP (117 index and 89 non-index), 74% (152/206) were detected by mpMRI. Of the 54 tumors missed by mpMRI, most were non-index (98%, 53/54), grade group (GG) 1 (68%, 37/54) or GG 2 (26%, 14/54), with a median size of 1.0 cm (range, 0.7-1.5 cm), and non-cribriform morphology (96%, 52/54). Cribriform morphology was detected in 26% (53/206) of all tumors, and although targeted biopsies identified 96% (51/53) of these cancers, the cribriform component was depicted in only 45% (24/53). Of these, mpMRI detected all (100%, 44/44) index and 78% (7/9) of the non-index tumors. At univariable analysis, tumor size greater than 5 mm, % pattern 4 > 5%, cribriform morphology, zone (transition versus peripheral zone), and region (apex versus mid/base) were significantly associated with tumor visibility at mpMRI. At multivariable analysis, only tumor size, presence of any pattern 4, and peripheral zone remained significant predictors for visibility by mpMRI.

CONCLUSION: At a lesion level, mpMRI offers high sensitivity for the detection of cribriform morphologies, however, the cribriform component is frequently missed by targeted biopsies. The MRI visibility is significantly associated with larger tumor size, presence of Gleason pattern 4, and peripheral zone location.}, } @article {pmid36002899, year = {2022}, author = {Molinaro, J and DeVries, P and Ha, J and Knight, JM}, title = {New-onset hallucinations with amiodarone: a case report.}, journal = {Annals of general psychiatry}, volume = {21}, number = {1}, pages = {34}, pmid = {36002899}, issn = {1744-859X}, abstract = {BACKGROUND: Amiodarone is a commonly used antiarrhythmic for the treatment of atrial fibrillation with a unique pharmacokinetic profile. While general side effects can be frequently associated with amiodarone, psychiatric adverse reactions to this medication are uncommon. The relationship between amiodarone and hallucinations independent of delirium has been rarely reported in the literature.

CASE PRESENTATION: We report the case of a 63-year-old female with a history of estrogen and progesterone receptor positive invasive ductal carcinoma with osseous metastases to the ribs and skull, major depressive disorder, and unspecified anxiety. She was diagnosed with invasive ductal carcinoma 12 years prior and underwent a lumpectomy with axillary lymph node dissection and radiation, currently maintained on anastrozole and trastuzumab for the past 11 years. Her symptoms of major depressive disorder and anxiety have remained in remission on a regimen of bupropion extended release, duloxetine, and trazodone without recent dose changes. This patient presented to the emergency department with dyspnea and was admitted to the general medical floor with new-onset atrial fibrillation. She was subsequently started on amiodarone for rhythm control. Shortly after its initiation, the patient developed new onset auditory and visual hallucinations with an unremarkable extensive medical evaluation. Auditory hallucinations consisted of music and unintelligible conversations, while visual hallucinations were of a family member crying on the floor and a man carrying a gun. The differential diagnoses included depression with psychotic features, delirium, and amiodarone-induced hallucinations. Given the lack of current depressive symptoms, absence of altered cognition, and the temporal relationship between the initiation of amiodarone and the onset of hallucinations, amiodarone was suspected to be probable etiology of her hallucinations. For this reason, amiodarone was replaced with dronedarone. Visual and auditory hallucinations ceased within less than 3 days after the discontinuation of amiodarone.

CONCLUSIONS: Psychiatric adverse events from amiodarone are uncommon, and associated isolated hallucinations have only been rarely reported in the literature. While the risk of visual and auditory hallucinations appears to be low with amiodarone initiation, clinicians should be aware of this potential side effect.}, } @article {pmid35999153, year = {2022}, author = {Carmon, E and Alster, T and Maly, B and Kadouri, L and Kleinman, TA and Sella, T}, title = {Preoperative MRI for Evaluation of Extent of Disease in IDC Compared to ILC.}, journal = {Clinical breast cancer}, volume = {22}, number = {7}, pages = {e745-e752}, doi = {10.1016/j.clbc.2022.07.007}, pmid = {35999153}, issn = {1938-0666}, mesh = {*Breast Neoplasms/diagnostic imaging/pathology/surgery ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/diagnostic imaging/pathology/surgery ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Retrospective Studies ; }, abstract = {OBJECTIVES: The purpose of this study was to assess the incremental value of preoperative breast MRI over mammography and US in depicting the accurate extent of disease in invasive duct carcinoma (IDC) compared to invasive lobular carcinoma (ILC).

PATIENTS AND METHODS: Retrospective analysis of pre-operative mammography, US and MRI was performed in 239 patients with either IDC (n = 193) or ILC (n = 46). Images were evaluated for solitary, multifocal or multi centric disease and compared for concordance with postsurgical pathology. Discordance was documented as either overestimation or underestimation. Two tailed paired T and Fischer's exact tests were used for analysis.

RESULTS: Multifocality was present on pathology in 35% and 61% of patients with IDC and ILC (P < .05) and multicentricity in 23% and 41% respectively (P = .84). In ILC, MRI demonstrated better concordance with pathology compared to mammography and US (89%, 44%, 49% for multifocality [P < .05] and 80.5%, 63%, 71% for multicentricity [P = .3]). For IDC, concordance with pathology for all modalities was similar (65%-76%). Among discordant cases, underestimation was significantly more common for mammography and US, while MRI more frequently overestimated disease extent. MRI very rarely overestimated multifocal disease in ILC (2%).

CONCLUSION: MRI demonstrates an 80% to 90% concordance rate with pathology for ILC, superior to mammography and US. The addition of MRI in IDC patients may decrease underestimation of disease extent and potentially contribute to a reduction in post-operative residual disease.}, } @article {pmid35996660, year = {2022}, author = {Shakuf, V and Ben-David, B and Wegner, TGG and Wesseling, PBC and Mentzel, M and Defren, S and Allen, SEM and Lachmann, T}, title = {Processing emotional prosody in a foreign language: the case of German and Hebrew.}, journal = {Journal of cultural cognitive science}, volume = {6}, number = {3}, pages = {251-268}, pmid = {35996660}, issn = {2520-1018}, abstract = {UNLABELLED: This study investigated the universality of emotional prosody in perception of discrete emotions when semantics is not available. In two experiments the perception of emotional prosody in Hebrew and German by listeners who speak one of the languages but not the other was investigated. Having a parallel tool in both languages allowed to conduct controlled comparisons. In Experiment 1, 39 native German speakers with no knowledge of Hebrew and 80 native Israeli speakers rated Hebrew sentences spoken with four different emotional prosodies (anger, fear, happiness, sadness) or neutral. The Hebrew version of the Test for Rating of Emotions in Speech (T-RES) was used for this purpose. Ratings indicated participants' agreement on how much the sentence conveyed each of four discrete emotions (anger, fear, happiness and sadness). In Experient 2, 30 native speakers of German, and 24 Israeli native speakers of Hebrew who had no knowledge of German rated sentences of the German version of the T-RES. Based only on the prosody, German-speaking participants were able to accurately identify the emotions in the Hebrew sentences and Hebrew-speaking participants were able to identify the emotions in the German sentences. In both experiments ratings between the groups were similar. These findings show that individuals are able to identify emotions in a foreign language even if they do not have access to semantics. This ability goes beyond identification of target emotion; similarities between languages exist even for "wrong" perception. This adds to accumulating evidence in the literature on the universality of emotional prosody.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s41809-022-00107-x.}, } @article {pmid35995898, year = {2022}, author = {Bridge, CP and Gorman, C and Pieper, S and Doyle, SW and Lennerz, JK and Kalpathy-Cramer, J and Clunie, DA and Fedorov, AY and Herrmann, MD}, title = {Highdicom: a Python Library for Standardized Encoding of Image Annotations and Machine Learning Model Outputs in Pathology and Radiology.}, journal = {Journal of digital imaging}, volume = {35}, number = {6}, pages = {1719-1737}, pmid = {35995898}, issn = {1618-727X}, support = {P41EB028741/EB/NIBIB NIH HHS/United States ; U01 CA242879/CA/NCI NIH HHS/United States ; R01 CA241817/CA/NCI NIH HHS/United States ; HHSN26110071/CA/NCI NIH HHS/United States ; U24 CA264044/CA/NCI NIH HHS/United States ; 5P41EB015902/NH/NIH HHS/United States ; 5R01CA235589/NH/NIH HHS/United States ; P41 EB028741/EB/NIBIB NIH HHS/United States ; P41 EB015902/EB/NIBIB NIH HHS/United States ; U01CA242879/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Ecosystem ; Data Curation ; *Radiology ; *Radiology Information Systems ; Tomography, X-Ray Computed ; Machine Learning ; }, abstract = {Machine learning (ML) is revolutionizing image-based diagnostics in pathology and radiology. ML models have shown promising results in research settings, but the lack of interoperability between ML systems and enterprise medical imaging systems has been a major barrier for clinical integration and evaluation. The DICOM[®] standard specifies information object definitions (IODs) and services for the representation and communication of digital images and related information, including image-derived annotations and analysis results. However, the complexity of the standard represents an obstacle for its adoption in the ML community and creates a need for software libraries and tools that simplify working with datasets in DICOM format. Here we present the highdicom library, which provides a high-level application programming interface (API) for the Python programming language that abstracts low-level details of the standard and enables encoding and decoding of image-derived information in DICOM format in a few lines of Python code. The highdicom library leverages NumPy arrays for efficient data representation and ties into the extensive Python ecosystem for image processing and machine learning. Simultaneously, by simplifying creation and parsing of DICOM-compliant files, highdicom achieves interoperability with the medical imaging systems that hold the data used to train and run ML models, and ultimately communicate and store model outputs for clinical use. We demonstrate through experiments with slide microscopy and computed tomography imaging, that, by bridging these two ecosystems, highdicom enables developers and researchers to train and evaluate state-of-the-art ML models in pathology and radiology while remaining compliant with the DICOM standard and interoperable with clinical systems at all stages. To promote standardization of ML research and streamline the ML model development and deployment process, we made the library available free and open-source at https://github.com/herrmannlab/highdicom .}, } @article {pmid35985745, year = {2022}, author = {Lerttiendamrong, B and Vongsaisuwon, M}, title = {First report of bilateral synchronous male accessory breast cancer.}, journal = {BMJ case reports}, volume = {15}, number = {8}, pages = {}, pmid = {35985745}, issn = {1757-790X}, mesh = {Axilla/pathology ; *Breast Diseases/surgery ; *Breast Neoplasms/pathology ; *Breast Neoplasms, Male/diagnostic imaging/surgery ; *Carcinoma, Ductal, Breast/surgery ; *Exanthema ; Humans ; Lymph Node Excision ; Male ; Mastectomy ; }, abstract = {Accessory breast occurs due to the persistence of milk line in the non-thoracic region. Malignant transformation in male accessory breast is very rare, with 16 reports documented across the world. No bilateral synchronous accessory male breast cancer has been reported. We present the first case reported globally of a man in his 70s with a complaint of left axillary lump and chronic rash for 3 years. About 1 year ago, additional reddish rash was detected in the right axilla. Initial skin biopsy from a private hospital confirmed mammary carcinoma with skin invasion. Subsequent left breast mastectomy with left axillary lymph node dissection and right wide excision was performed. Final pathological result was grade 2 invasive ductal carcinoma in the left accessory breast and Paget's disease in the contralateral axilla. Postoperative treatment of adjuvant paclitaxel and trastuzumab was prescribed, which was followed by adjuvant radiation therapy.}, } @article {pmid35983810, year = {2022}, author = {Kalemci, S and Kizilay, F and Simsir, A and Emre Ergun, K and Kose, T}, title = {The Influence of the Intraductal Carcinoma of the Prostate on the Short-Term Oncological Outcomes.}, journal = {Archivos espanoles de urologia}, volume = {75}, number = {5}, pages = {405-409}, doi = {10.37554/en-j.arch.esp.urol-20210522-3503-23}, pmid = {35983810}, issn = {0004-0614}, mesh = {Aged ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Humans ; Male ; Neoplasm Grading ; Prostate/pathology ; Prostatectomy ; *Prostatic Neoplasms/pathology ; Retrospective Studies ; }, abstract = {AIM: The presence of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy (RP) specimens correlates with adverse prognostic factors such as worse biochemical recurrence-free survival, higher grade and stage disease. This study aimed to investigate the effect of IDC-P in radical prostatectomy specimens on short-term oncological outcomes.

MATERIALS AND METHODS: Patients who underwent RP at our clinic for prostate cancer between May 2016 and November 2019 were included in the study. They were divided into two groups based on the presence of IDC-P in RP specimens. Their clinical, pathological, and oncologic data were evaluated retrospectively.

RESULTS: A total of 98 patients underwent RP with a mean age of 65.5 years (50-83) and a mean follow-up time of 31.2 months (6-52). Seventy and 28 patients were evaluated in the group without IDC-P and group with IDC-P, respectively. Surgical margin positivity (p=0.307) and lymph node metastasis (p=0.017) rates were higher in the group with IDC-P. Although there were no statistical differences between the groups, at follow-up biochemical recurrence rate (p=0.052) was higher, and mean time to biochemical recurrence rates were lower (p=0.057) in the group with IDC-P. The group with IDC-P was associated with a 3-fold increase in prostate cancer-specific mortality to the group without IDC-P (p=0.037).

CONCLUSIONS: Patients with IDC-P at RP specimens have more advanced disease, shorter biochemical recurrence-free, and cancerspecific survival than those without IDC-P. Defining the presence of IDC-P in RP specimens is critical in choosing the appropriate treatment strategy and predicting the prognosis.}, } @article {pmid35982591, year = {2022}, author = {Kovalenko, I and Roy, P and Soni, B and Sangha, L and Toom, S}, title = {Secretory Carcinoma of the Breast Mimicking Invasive Ductal Carcinoma: A Case Report.}, journal = {The American journal of case reports}, volume = {23}, number = {}, pages = {e936665}, pmid = {35982591}, issn = {1941-5923}, mesh = {*Breast Neoplasms/diagnosis/genetics/therapy ; *Carcinoma/pathology ; *Carcinoma, Ductal/genetics/surgery ; *Carcinoma, Ductal, Breast/diagnosis/therapy ; Female ; Humans ; In Situ Hybridization, Fluorescence/methods ; Mastectomy ; Translocation, Genetic ; }, abstract = {BACKGROUND Secretory breast carcinoma (SBC), an extremely rare malignancy, is related to a chromosomal translocation which leads to an ETV6-NTRK3 fusion mutation. SBC is characterized by eosinophilic secretions and is usually triple-negative, with a small number of patients demonstrating ER-positivity of the tumors. Diagnosis can be challenging and requires genomic testing for confirmation. CASE REPORT A 40-year-old woman presented with a breast mass found on mammography. She underwent an ultrasound-guided biopsy of the tumor. Initial pathology evaluation revealed features consistent with invasive ductal carcinoma. The immunochemistry report described an ER-positive, PR-negative, and HER2-negative tumor. The specimen was sent for oncotype scoring, which was not performed due to the specimen not meeting the criteria for invasive ductal carcinoma and displaying pathological features of SBC. A fluorescent in situ hybridization (FISH) study revealed ETV6 translocation, consistent with the diagnosis of SBC. The patient underwent lumpectomy followed by adjuvant radiotherapy and endocrine therapy. She remains in complete remission 3 years after treatment. CONCLUSIONS Accurately diagnosing SBC is of extreme importance as it has an indolent clinical course, but has a favorable prognosis if detected early. Due to nonspecific imaging findings, pathology evaluation with immunohistochemical staining followed by genomic testing is required. Our case highlights the challenges associated with SBC diagnosis requiring genomic testing due to equivocal pathological findings, along with increasing incidence of SBT in adults. There are no established guidelines for SBC management. The mainstay of treatment is partial or total mastectomy. Data on the benefits of adjuvant endocrine therapy, chemotherapy, and radiotherapy are inconclusive.}, } @article {pmid35978202, year = {2022}, author = {Birnbaum, GE and Zholtack, K and Ayal, S}, title = {Is Infidelity Contagious? Online Exposure to Norms of Adultery and Its Effect on Expressions of Desire for Current and Alternative Partners.}, journal = {Archives of sexual behavior}, volume = {51}, number = {8}, pages = {3919-3930}, pmid = {35978202}, issn = {1573-2800}, mesh = {Humans ; *Extramarital Relations ; *Sexual Partners ; Marriage ; Motivation ; Deception ; Interpersonal Relations ; Sexual Behavior ; }, abstract = {Research exploring the determinants of infidelity has mainly focused on individual and relationship characteristics that render relationships vulnerable, paying less attention to the external circumstances that increase the likelihood of straying. The present research examined whether online exposure to norms of adultery would affect expressions of desire for alternative mates. In three studies, romantically involved participants were exposed to others' cheating behavior and then thought of or encountered attractive strangers. Their relationship perceptions and reactions during these experiences (fantasmatic themes, expressed interest in alternative partners, and overt flirtation with them in Studies 1-3, respectively) were recorded. Results showed that following exposure to others' cheating behavior, participants were less likely to devalue the attractiveness of alternative partners and to be committed to their relationship. These findings suggest that exposure to adultery norms decreases the awareness of long-term priorities of relationship maintenance, lessening the resistance to the temptation of attractive alternatives.}, } @article {pmid35976519, year = {2023}, author = {Eum, SY and Schurhoff, N and Teglas, T and Wolff, G and Toborek, M}, title = {Circadian disruption alters gut barrier integrity via a ß-catenin-MMP-related pathway.}, journal = {Molecular and cellular biochemistry}, volume = {478}, number = {3}, pages = {581-595}, pmid = {35976519}, issn = {1573-4919}, support = {R01 MH128022/MH/NIMH NIH HHS/United States ; DA050528/DA/NIDA NIH HHS/United States ; DA047157/DA/NIDA NIH HHS/United States ; MH128022/MH/NIMH NIH HHS/United States ; R01 DA039576/DA/NIDA NIH HHS/United States ; R01 DA050528/DA/NIDA NIH HHS/United States ; R01 DA040537/DA/NIDA NIH HHS/United States ; DA044579/DA/NIDA NIH HHS/United States ; MH072567/MH/NIMH NIH HHS/United States ; R01 DA044579/DA/NIDA NIH HHS/United States ; DA039576/DA/NIDA NIH HHS/United States ; MH122235/MH/NIMH NIH HHS/United States ; R01 HL126559/HL/NHLBI NIH HHS/United States ; DA040537/DA/NIDA NIH HHS/United States ; R21 MH122235/MH/NIMH NIH HHS/United States ; R01 DA047157/DA/NIDA NIH HHS/United States ; HL126559/HL/NHLBI NIH HHS/United States ; R01 MH072567/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Catenins/genetics ; *Circadian Rhythm ; Gene Expression Regulation ; }, abstract = {We evaluated the mechanistic link between circadian rhythms and gut barrier permeability. Mice were subjected to either constant 24-h light (LL) or 12-h light/dark cycles (LD). Mice housed in LL experienced a significant increase in gut barrier permeability that was associated with dysregulated ß-catenin expression and altered expression of tight junction (TJ) proteins. Silencing of ß-catenin resulted in disruption of barrier function in SW480 cells, with ß-catenin appearing to be an upstream regulator of the core circadian components, such as Bmal1, Clock, and Per1/2. In addition, ß-catenin silencing downregulated ZO-1 and occludin TJ proteins with only limited or no changes at their mRNA levels, suggesting post transcriptional regulation. Indeed, silencing of ß-catenin significantly upregulated expression of matrix metallopeptidase (MMP)-2 and MMP-9, and blocking MMP-2/9 activity attenuated epithelial disruption induced by ß-catenin silencing. These results indicate the regulatory role of circadian disruption on gut barrier integrity and the associations between TJ proteins and circadian rhythms, while demonstrating the regulatory role of ß-catenin in this process.}, } @article {pmid35969492, year = {2022}, author = {Li, C and Su, N and Wu, H and Liu, C and Che, G and Dong, H}, title = {Synergies of Adjacent Sites in Atomically Dispersed Ruthenium toward Achieving Stable Hydrogen Evolution.}, journal = {Inorganic chemistry}, volume = {61}, number = {34}, pages = {13453-13461}, doi = {10.1021/acs.inorgchem.2c01908}, pmid = {35969492}, issn = {1520-510X}, abstract = {It is a challenge to fabricate atomically dispersed metal clusters in polymeric carbon nitride (PCN) for durable photocatalytic reactions owing to the thermodynamic stability limitation. Herein, atomically dispersed Ru clusters are implanted into the PCN skeleton matrix based on an ionic diffusion and coordination (IDC) strategy, the stability of which is improved owing to the robust Ru-N bonds in the formed RuN4 and RuN3 configurations. Additionally, RuN4 and RuN3 as charge transport bridges between two adjacent melon strands efficaciously conquer hydrogen bond restriction in the skeleton to facilitate the in-plane mobility and separation of charge carriers. Moreover, the synergistic effect of adjacent Ru atoms is triggered on the assembled RuN3-RuN4 and RuN3-RuN3 in the atomically dispersed Ru clusters to significantly decrease hydrogen adsorption energy. As a result, the optimal PCN-Ru photocatalyst achieves nearly 6 times higher than the photocatalytic hydrogen evolution (PHE) rate of the Pt/PCN benchmark and maintains the long-term stable running for 104 h of 26 cycles; its overall PHE performance is far superior to the most of single atoms supported on g-C3N4 photocatalysts reported. The findings here gain new insight into the preparation strategy, structure configuration, and reaction mechanism for atomically dispersed metal clusters supported on PCN, which further stimulates the intensive investigations toward developing more efficient and stable PCN-like photocatalytic materials.}, } @article {pmid35963427, year = {2022}, author = {Brecklinghaus, T and Albrecht, W and Duda, J and Kappenberg, F and Gründler, L and Edlund, K and Marchan, R and Ghallab, A and Cadenas, C and Rieck, A and Vartak, N and Tolosa, L and Castell, JV and Gardner, I and Halilbasic, E and Trauner, M and Ullrich, A and Zeigerer, A and Demirci Turgunbayer, Ö and Damm, G and Seehofer, D and Rahnenführer, J and Hengstler, JG}, title = {In vitro/in silico prediction of drug induced steatosis in relation to oral doses and blood concentrations by the Nile Red assay.}, journal = {Toxicology letters}, volume = {368}, number = {}, pages = {33-46}, doi = {10.1016/j.toxlet.2022.08.006}, pmid = {35963427}, issn = {1879-3169}, mesh = {*Chemical and Drug Induced Liver Injury/etiology ; *Drug-Related Side Effects and Adverse Reactions ; *Fatty Liver/chemically induced ; Hepatocytes ; Humans ; Oxazines/toxicity ; }, abstract = {The accumulation of lipid droplets in hepatocytes is a key feature of drug-induced liver injury (DILI) and can be induced by a subset of hepatotoxic compounds. In the present study, we optimized and evaluated an in vitro technique based on the fluorescent dye Nile Red, further named Nile Red assay to quantify lipid droplets induced by the exposure to chemicals. The Nile Red assay and a cytotoxicity test (CTB assay) were then performed on cells exposed concentration-dependently to 60 different compounds. Of these, 31 were known to induce hepatotoxicity in humans, and 13 were reported to also cause steatosis. In order to compare in vivo relevant blood concentrations, pharmacokinetic models were established for all compounds to simulate the maximal blood concentrations (Cmax) at therapeutic doses. The results showed that several hepatotoxic compounds induced an increase in lipid droplets at sub-cytotoxic concentrations. To compare how well (1) the cytotoxicity test alone, (2) the Nile Red assay alone, and (3) the combination of the cytotoxicity test and the Nile Red assay (based on the lower EC10 of both assays) allow the differentiation between hepatotoxic and non-hepatotoxic compounds, a previously established performance metric, the Toxicity Separation Index (TSI) was calculated. In addition, the Toxicity Estimation Index (TEI) was calculated to determine how well blood concentrations that cause an increased DILI risk can be estimated for hepatotoxic compounds. Our findings indicate that the combination of both assays improved the TSI and TEI compared to each assay alone. In conclusion, the study demonstrates that inclusion of the Nile Red assay into in vitro test batteries may improve the prediction of DILI compounds.}, } @article {pmid35962150, year = {2022}, author = {Berkowitz, SJ and Kwan, D and Cornish, TC and Silver, EL and Thullner, KS and Aisen, A and Bui, MM and Clark, SD and Clunie, DA and Eid, M and Hartman, DJ and Ho, K and Leontiev, A and Luviano, DM and O'Toole, PE and Parwani, AV and Pereira, NS and Rotemberg, V and Vining, DJ and Gaskin, CM and Roth, CJ and Folio, LR}, title = {Interactive Multimedia Reporting Technical Considerations: HIMSS-SIIM Collaborative White Paper.}, journal = {Journal of digital imaging}, volume = {35}, number = {4}, pages = {817-833}, pmid = {35962150}, issn = {1618-727X}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Communication ; Diagnostic Imaging ; Electronic Health Records ; Humans ; *Medicine ; Multimedia ; *Radiology Information Systems ; }, abstract = {Despite technological advances in the analysis of digital images for medical consultations, many health information systems lack the ability to correlate textual descriptions of image findings linked to the actual images. Images and reports often reside in separate silos in the medical record throughout the process of image viewing, report authoring, and report consumption. Forward-thinking centers and early adopters have created interactive reports with multimedia elements and embedded hyperlinks in reports that connect the narrative text with the related source images and measurements. Most of these solutions rely on proprietary single-vendor systems for viewing and reporting in the absence of any encompassing industry standards to facilitate interoperability with the electronic health record (EHR) and other systems. International standards have enabled the digitization of image acquisition, storage, viewing, and structured reporting. These provide the foundation to discuss enhanced reporting. Lessons learned in the digital transformation of radiology and pathology can serve as a basis for interactive multimedia reporting (IMR) across image-centric medical specialties. This paper describes the standard-based infrastructure and communications to fulfill recently defined clinical requirements through a consensus from an international workgroup of multidisciplinary medical specialists, informaticists, and industry participants. These efforts have led toward the development of an Integrating the Healthcare Enterprise (IHE) profile that will serve as a foundation for interoperable interactive multimedia reporting.}, } @article {pmid35960332, year = {2023}, author = {De Jaeghere, EA and Tuyaerts, S and Van Nuffel, AMT and Belmans, A and Bogaerts, K and Baiden-Amissah, R and Lippens, L and Vuylsteke, P and Henry, S and Trinh, XB and van Dam, PA and Aspeslagh, S and De Caluwé, A and Naert, E and Lambrechts, D and Hendrix, A and De Wever, O and Van de Vijver, KK and Amant, F and Vandecasteele, K and Denys, HG}, title = {Pembrolizumab, radiotherapy, and an immunomodulatory five-drug cocktail in pretreated patients with persistent, recurrent, or metastatic cervical or endometrial carcinoma: Results of the phase II PRIMMO study.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {72}, number = {2}, pages = {475-491}, pmid = {35960332}, issn = {1432-0851}, support = {1195919N//Fonds Wetenschappelijk Onderzoek/ ; T002218N//Fonds Wetenschappelijk Onderzoek/ ; ZKD5584//Kom op tegen Kanker/ ; G0H7516N//ERA-NET-Transcan-2/ ; SW/OPS/SUB 11719-0001//Nationale Loterij/ ; }, mesh = {Female ; Humans ; *Uterine Cervical Neoplasms/drug therapy ; Quality of Life ; Antibodies, Monoclonal, Humanized/therapeutic use ; *Endometrial Neoplasms/pathology ; }, abstract = {A phase II study (PRIMMO) of patients with pretreated persistent/recurrent/metastatic cervical or endometrial cancer is presented. Patients received an immunomodulatory five-drug cocktail (IDC) consisting of low-dose cyclophosphamide, aspirin, lansoprazole, vitamin D, and curcumin starting 2 weeks before radioimmunotherapy. Pembrolizumab was administered three-weekly from day 15 onwards; one of the tumor lesions was irradiated (8Gyx3) on days 15, 17, and 19. The primary endpoint was the objective response rate per immune-related response criteria (irORR) at week 26 (a lower bound of the 90% confidence interval [CI] of > 10% was considered efficacious). The prespecified 43 patients (cervical, n = 18; endometrial, n = 25) were enrolled. The irORR was 11.1% (90% CI 2.0-31.0) in cervical cancer and 12.0% (90% CI 3.4-28.2) in endometrial cancer. Median duration of response was not reached in both cohorts. Median interval-censored progression-free survival was 4.1 weeks (95% CI 4.1-25.7) in cervical cancer and 3.6 weeks (95% CI 3.6-15.4) in endometrial cancer; median overall survival was 39.6 weeks (95% CI 15.0-67.0) and 37.4 weeks (95% CI 19.0-50.3), respectively. Grade ≥ 3 treatment-related adverse events were reported in 10 (55.6%) cervical cancer patients and 9 (36.0%) endometrial cancer patients. Health-related quality of life was generally stable over time. Responders had a significantly higher proportion of peripheral T cells when compared to nonresponders (p = 0.013). In conclusion, PRIMMO did not meet its primary objective in both cohorts; pembrolizumab, radiotherapy, and an IDC had modest but durable antitumor activity with acceptable but not negligible toxicity.Trial registration ClinicalTrials.gov (identifier NCT03192059) and EudraCT Registry (number 2016-001569-97).}, } @article {pmid35958350, year = {2022}, author = {Fujita, K and Okamura, M and Imakita, T and Yamamoto, Y and Sawai, S and Moriyoshi, K and Mio, T}, title = {Natural course of pulmonary hyalinizing granuloma over a decade.}, journal = {Respiratory medicine case reports}, volume = {39}, number = {}, pages = {101715}, pmid = {35958350}, issn = {2213-0071}, abstract = {BACKGROUND: Pulmonary hyalinizing granuloma (PHG) is a very rare pulmonary disease characterized by multiple fibrosclerotic inflammatory lung nodules. The disease is supposedly caused by an unusual immune response.

CASE PRESENTATION: We present a case involving a 53-year-old female with a history of lumpectomy surgery due to invasive ductal carcinoma who was admitted for slowly progressive pulmonary nodules. The patient's elevated serum IgG4 level and the pathological findings obtained in surgical biopsy indicated IgG4-related lung disease. The nodules continued to enlarge despite administration of corticosteroid therapy, and we performed a second surgical biopsy to obtain a correct diagnosis. The pathological findings obtained in the second biopsy were different and consistent with the features of PHG.

CONCLUSIONS: In this report, the radiological follow-up data obtained after lumpectomy surgery demonstrate the very early stage of PHG and the following radiological changes over a decade, and the two surgical biopsies support us to realize the pathological change from previous diagnosed disease before PHG.}, } @article {pmid35953564, year = {2023}, author = {Telha, W and Abotaleb, B and Zhang, J and Bi, R and Zhu, S and Jiang, N}, title = {Correlation between mandibular anatomy and bad split occurrence during bilateral sagittal split osteotomy: a three-dimensional study.}, journal = {Clinical oral investigations}, volume = {27}, number = {3}, pages = {1035-1042}, pmid = {35953564}, issn = {1436-3771}, mesh = {Humans ; *Osteotomy, Sagittal Split Ramus/methods ; *Mandible/surgery ; Cortical Bone/anatomy & histology ; Molar ; Tooth Root ; Polymers ; }, abstract = {OBJECTIVES: This study aimed to find out the correlation between different anatomical parameters of the mandible and the occurrence of a bad split in patients who had undergone bilateral split sagittal ramus osteotomy (BSSRO).

MATERIALS AND METHOD: At both the distal roots of the first molar (1) and the retromolar area (2), we measured the distance from the buccal margin of the inferior dental canal (IDC) to the buccal margin of the cortical bone (MCBC), the thickness of both buccal cortical (WBCB) and cancellous bone (WBCA), distance from the superior border of IDC to the alveolar crest (MCAC), buccolingual thickness (BLT), and thickness of cancellous bone (WCA). At the ramus, the distances between the sigmoid notch to the upper part of the lingula (SL) and the inferior border of the mandible (SIBM), the thickness of the ramus at the level of the lingula (BLTR), and the anteroposterior width of the ramus (APWR) were measured. The paired and independent t-tests were used when applicable, and a P-value < 0.05 was considered significant.

RESULTS: MCBC1 showed a significant difference between bad and non-bad split sides (P = 0.037). Both WBCA1 and WBCA2 show the same significant difference (P = 0.023, 0.024). Similarly, WCA1 and WCA2 showed a statistical difference between the bad and non-bad split sides (P = 0.027, 0.036). There were no statistically significant differences between the compared sides of WBCB1, WBCB2, MCAC1, MCAC2, SIBM, APWR, SL, and BLTR.

CONCLUSION: Narrow space between IDC and the buccal cortical margin, along with the decrease in the thickness of both buccal cancellous bone and total cancellous bone at the inferior border of the mandible along the course of SSRO, has been implicated in the occurrence of bad split intraoperatively.}, } @article {pmid35950920, year = {2022}, author = {Nardone, A and Qiu, X and Spisak, S and Nagy, Z and Feiglin, A and Feit, A and Cohen Feit, G and Xie, Y and Font-Tello, A and Guarducci, C and Hermida-Prado, F and Syamala, S and Lim, K and Munoz Gomez, M and Pun, M and Cornwell, M and Liu, W and Ors, A and Mohammed, H and Cejas, P and Brock, JB and Freedman, ML and Winer, EP and Fu, X and Schiff, R and Long, HW and Metzger Filho, O and Jeselsohn, R}, title = {A Distinct Chromatin State Drives Therapeutic Resistance in Invasive Lobular Breast Cancer.}, journal = {Cancer research}, volume = {82}, number = {20}, pages = {3673-3686}, pmid = {35950920}, issn = {1538-7445}, support = {K08 CA191058/CA/NCI NIH HHS/United States ; P01 CA250959/CA/NCI NIH HHS/United States ; R01 CA193910/CA/NCI NIH HHS/United States ; R01 CA237414/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/drug therapy/genetics/metabolism ; Chromatin/genetics ; Drug Resistance, Neoplasm/genetics ; Female ; Humans ; Prognosis ; Receptors, Estrogen/metabolism ; Tamoxifen/pharmacology/therapeutic use ; }, abstract = {UNLABELLED: Most invasive lobular breast cancers (ILC) are of the luminal A subtype and are strongly hormone receptor-positive. Yet, ILC is relatively resistant to tamoxifen and associated with inferior long-term outcomes compared with invasive ductal cancers (IDC). In this study, we sought to gain mechanistic insights into these clinical findings that are not explained by the genetic landscape of ILC and to identify strategies to improve patient outcomes. A comprehensive analysis of the epigenome of ILC in preclinical models and clinical samples showed that, compared with IDC, ILC harbored a distinct chromatin state linked to gained recruitment of FOXA1, a lineage-defining pioneer transcription factor. This resulted in an ILC-unique FOXA1-estrogen receptor (ER) axis that promoted the transcription of genes associated with tumor progression and poor outcomes. The ILC-unique FOXA1-ER axis led to retained ER chromatin binding after tamoxifen treatment, which facilitated tamoxifen resistance while remaining strongly dependent on ER signaling. Mechanistically, gained FOXA1 binding was associated with the autoinduction of FOXA1 in ILC through an ILC-unique FOXA1 binding site. Targeted silencing of this regulatory site resulted in the disruption of the feed-forward loop and growth inhibition in ILC. In summary, ILC is characterized by a unique chromatin state and FOXA1-ER axis that is associated with tumor progression, offering a novel mechanism of tamoxifen resistance. These results underscore the importance of conducting clinical trials dedicated to patients with ILC in order to optimize treatments in this breast cancer subtype.

SIGNIFICANCE: A unique FOXA1-ER axis in invasive lobular breast cancer promotes disease progression and tamoxifen resistance, highlighting a potential therapeutic avenue for clinical investigations dedicated to this disease. See related commentary by Blawski and Toska, p. 3668.}, } @article {pmid35949419, year = {2022}, author = {Luo, Y and Ma, A and Huang, S and Yu, Y}, title = {Invasive Lobular Carcinoma Has Worse Outcome Compared with Invasive Ductal Carcinoma in Stage IV Breast Cancer with Bone-Only Metastasis.}, journal = {Breast care (Basel, Switzerland)}, volume = {17}, number = {3}, pages = {296-305}, pmid = {35949419}, issn = {1661-3791}, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is more likely to have bone metastasis than invasive ductal carcinoma (IDC). However, the prognosis for bone metastasis in ILC and IDC is barely known. So, the aim of this study was to investigate the difference of prognosis between ILC and IDC accompanied by bone metastasis.

METHODS: We evaluated the women with bone-only metastasis of defined IDC or ILC reported to the Surveillance, Epidemiology and End Results program from 2010 to 2016. Pearson's χ[2] test was used to compare the differences of clinicopathologic factors between IDC and ILC. Univariate and multivariate analyses were performed to verify the effects of histological types (IDC and ILC) and other clinicopathologic factors on the overall survival (OS) and cancer-specific survival (CSS).

RESULTS: Overall, 3,647 patients with IDC and 945 patients with ILC met the inclusion criteria and were analyzed in our study. The patients with ILC were more likely to be older and to have lower histological grade and a higher proportion of the HR*/HER2- subtype. However, less treatment was administered to ILC than IDC, such as surgery of the breast, radiation, and chemotherapy. Compared to patients with IDC, patients with ILC showed worse OS (median OS, 36 and 42 months, respectively, p < 0.001) and CSS (median CSS, 39 and 45 months, respectively, p < 0.001), especially in subgroups with HR*/HER2- subtype (OS, hazard ratio: 1.501, 95% CI 1.270-1.773, p < 0.001; CSS, hazard ratio: 1.529, 95% CI 1.281-1.825, p < 0.001), lower histological grade (I-II) (OS, hazard ratio: 1.411, 95% CI 1.184-1.683, p < 0.001; CSS, hazard ratio: 1.488, 95% CI 1.235-1.791, p < 0.001), or tumor burden, such as T0-2 (OS, hazard ratio: 1.693, 95% CI 1.368-2.096, p < 0.001; CSS, hazard ratio: 1.76, 95% CI 1.405-2.205, p < 0.001) and N1-2 (OS, hazard ratio: 1.451, 95% CI 1.171-1.799, p = 0.001; CSS, hazard ratio: 1.488, 95% CI 1.187-1.865, p = 0.001). Furthermore, older age, black race, unmarried status, higher tumor burden (T3-4 and N3), triple-negative subtype, and higher histological grade were independent risk factors for both OS and CSS. Surgery of the breast and chemotherapy could significantly improve the prognosis for patients.

CONCLUSION: Patients with ILC have worse outcomes compared to those with IDC when associated with bone-only metastasis, especially in subgroups with lower histological grade or tumor burden. More effective treatment measures may be needed for ILC, such as cyclin-dependent kinase 4/6 inhibitors, new targeted drugs, etc.}, } @article {pmid35949409, year = {2022}, author = {Aryal, V and Singh, M and Neupane, K and Marhatta, A and Amatya, KS and Dhakal, HP}, title = {Invasive ductal carcinoma of breast with neuroendocrine differentiation: A case report.}, journal = {Clinical case reports}, volume = {10}, number = {8}, pages = {e6171}, pmid = {35949409}, issn = {2050-0904}, abstract = {Primary invasive breast carcinoma with neuroendocrine differentiation is an uncommon presentation. We hereby report a case diagnosed as invasive ductal carcinoma with neuroendocrine differentiation in a 52-year-old female patient who presented with a painless right breast lump.}, } @article {pmid35945526, year = {2022}, author = {Xu, A and Chu, X and Zhang, S and Zheng, J and Shi, D and Lv, S and Li, F and Weng, X}, title = {Development and validation of a clinicoradiomic nomogram to assess the HER2 status of patients with invasive ductal carcinoma.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {872}, pmid = {35945526}, issn = {1471-2407}, support = {2021KY1161 and 2022KY1316//Medical and Health Research Project of Zhejiang Province/ ; 2021ZA138//Zhejiang Province Chinese Medicine Science Research Fund Project/ ; }, mesh = {Bayes Theorem ; *Breast Neoplasms/diagnostic imaging/genetics ; *Carcinoma, Ductal ; China ; Female ; Humans ; Ki-67 Antigen ; Nomograms ; Retrospective Studies ; }, abstract = {BACKGROUND: The determination of HER2 expression status contributes significantly to HER2-targeted therapy in breast carcinoma. However, an economical, efficient, and non-invasive assessment of HER2 is lacking. We aimed to develop a clinicoradiomic nomogram based on radiomics scores extracted from multiparametric MRI (mpMRI, including ADC-map, T2W1, DCE-T1WI) and clinical risk factors to assess HER2 status.

METHODS: We retrospectively collected 214 patients with pathologically confirmed invasive ductal carcinoma between January 2018 to March 2021 from Fudan University Shanghai Cancer Center, and randomly divided this cohort into training set (n = 128, 42 HER2-positive and 86 HER2-negative cases) and validation set (n = 86, 28 HER2-positive and 58 HER2-negative cases) at a ratio of 6:4. The original and transformed pretherapy mpMRI images were treated by semi-automated segmentation and manual modification on the DeepWise scientific research platform v1.6 (http://keyan.deepwise.com/), then radiomics feature extraction was implemented with PyRadiomics library. Recursive feature elimination (RFE) based on logistic regression (LR) and LASSO regression were adpoted to identify optimal features before modeling. LR, Linear Discriminant Analysis (LDA), support vector machine (SVM), random forest (RF), naive Bayesian (NB) and XGBoost (XGB) algorithms were used to construct the radiomics signatures. Independent clinical predictors were identified through univariate logistic analysis (age, tumor location, ki-67 index, histological grade, and lymph node metastasis). Then, the radiomics signature with the best diagnostic performance (Rad score) was further combined with significant clinical risk factors to develop a clinicoradiomic model (nomogram) using multivariate logistic regression. The discriminative power of the constructed models were evaluated by AUC, DeLong test, calibration curve, and decision curve analysis (DCA).

RESULTS: 70 (32.71%) of the enrolled 214 cases were HER2-positive, while 144 (67.29%) were HER2-negative. Eleven best radiomics features were retained to develop 6 radiomcis classifiers in which RF classifier showed the highest AUC of 0.887 (95%CI: 0.827-0.947) in the training set and acheived the AUC of 0.840 (95%CI: 0.758-0.922) in the validation set. A nomogram that incorporated the Rad score with two selected clinical factors (Ki-67 index and histological grade) was constructed and yielded better discrimination compared with Rad score (p = 0.374, Delong test), with an AUC of 0.945 (95%CI: 0.904-0.987) in the training set and 0.868 (95%CI: 0.789-0.948; p = 0.123) in the validation set. Moreover, calibration with the p-value of 0.732 using Hosmer-Lemeshow test demonstrated good agreement, and the DCA verified the benefits of the nomogram.

CONCLUSION: Post largescale validation, the clinicoradiomic nomogram may have the potential to be used as a non-invasive tool for determination of HER2 expression status in clinical HER2-targeted therapy prediction.}, } @article {pmid35943969, year = {2022}, author = {Boyd, CJ and Salibian, AA and Bekisz, JM and Axelrod, DM and Guth, AA and Shapiro, RL and Schnabel, FR and Karp, NS and Choi, M}, title = {Long-Term Cancer Recurrence Rates following Nipple-Sparing Mastectomy: A 10-Year Follow-Up Study.}, journal = {Plastic and reconstructive surgery}, volume = {150}, number = {}, pages = {13S-19S}, doi = {10.1097/PRS.0000000000009495}, pmid = {35943969}, issn = {1529-4242}, mesh = {*Breast Neoplasms/pathology ; Female ; Follow-Up Studies ; Humans ; *Mammaplasty/adverse effects ; Mastectomy/adverse effects ; *Mastectomy, Subcutaneous/adverse effects ; Neoplasm Recurrence, Local/pathology ; Nipples/pathology/surgery ; Retrospective Studies ; }, abstract = {BACKGROUND: Despite the increased use of nipple-sparing mastectomies, there are limited data examining long-term cancer recurrence rates in these patients. The objective of this study was to analyze breast cancer recurrence in patients who underwent therapeutic nipple-sparing mastectomy with a median of 10 years of follow-up.

METHODS: All patients undergoing nipple-sparing mastectomy at a single institution were retrospectively reviewed temporally to obtain a median of 10 years of follow-up. Patient demographic factors, mastectomy specimen pathologic findings, and oncologic outcomes were analyzed. Univariate analysis was performed to identify independent risk factors for locoregional recurrence.

RESULTS: One hundred twenty-six therapeutic nipple-sparing mastectomies were performed on 120 patients. The most frequently observed tumor histology included invasive ductal carcinoma (48.4 percent) and ductal carcinoma in situ (38.1 percent). Mean tumor size was 1.62 cm. Multifocal or multicentric disease and lymphovascular invasion were present in 31.0 percent and 10.3 percent of nipple-sparing mastectomy specimens, respectively. Sentinel lymph node biopsy was performed in 84.9 percent of nipple-sparing mastectomies, and 17.8 percent were positive. The rate of positive frozen subareolar biopsy was 7.3 percent (n = 82) and that of permanent subareolar pathology was 9.5 percent (n = 126). The most frequently observed pathologic tumor stages were stage I (44.6 percent) and stage 0 (33.9 percent). The incidence of recurrent disease was 3.17 percent per mastectomy and 3.33 percent per patient. On univariate analysis, no demographic, operative, or tumor-specific variables were independent risk factors for locoregional recurrence.

CONCLUSIONS: Overall recurrence rates are low in patients undergoing nipple-sparing mastectomy at a median follow-up of 10-years. Close surveillance should remain a goal for patients and their providers to promptly identify potential recurrence.

Risk, III.}, } @article {pmid35943964, year = {2022}, author = {Sorotos, M and Paolini, G and D'Orsi, G and Firmani, G and Timmermans, FW and Santanelli di Pompeo, F}, title = {Oncologic Outcome of 1000 Postmastectomy Breast Reconstructions with Fat Transfer: A Single-Center, Matched Case-Control Study.}, journal = {Plastic and reconstructive surgery}, volume = {150}, number = {}, pages = {4S-12S}, doi = {10.1097/PRS.0000000000009494}, pmid = {35943964}, issn = {1529-4242}, mesh = {Adipose Tissue/pathology ; *Breast Neoplasms/etiology ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; *Mammaplasty/adverse effects ; Mastectomy/adverse effects ; Neoplasm Recurrence, Local/epidemiology/etiology/prevention & control ; Retrospective Studies ; }, abstract = {BACKGROUND: Autologous fat transfer has an important role in breast reconstructive surgery. Nevertheless, some concerns remain with regard to its oncologic safety. The authors present a single-center, case-matching study analyzing the impact of autologous fat transfer in the cumulative incidence of local recurrences.

METHODS: From a prospectively maintained database, the authors identified 902 patients who underwent 1025 breast reconstructions from 2005 to 2017. Data regarding demographics, tumor characteristics, surgery details, and follow-up were collected. Exclusion criteria were patients with distant metastases at diagnosis, recurrent tumor, or incomplete data regarding primary tumor; and patients who underwent prophylactic mastectomies and breast-conserving operations. Statistical analysis was conducted to evaluate the impact of the variables on the incidence of local recurrence. A value of p < 0.05 was considered statistically significant.

RESULTS: After 1: n case-matching, we selected 919 breasts, of which 425 patients (46.2 percent) received at least one autologous fat transfer session versus 494 control cases (53.8 percent). Local recurrences had an overall rate of 6.8 percent, and we found local recurrences in 14 autologous fat transfer cases (3.0 percent) and 54 controls (9.6 percent). Statistical analysis showed that autologous fat transfer did not increase the risk of local recurrences (hazard ratio, 0.337; CI, 0.173 to 0.658; p = 0.00007). Multivariate analysis identified invasive ductal carcinoma subtype and lymph node metastases to have an increased risk of local recurrences (hazard ratio >1). Conversely, positive hormonal receptor status was associated with a reduced risk of events (hazard ratio <1).

CONCLUSIONS: Autologous fat transfer was not associated with a higher probability of locoregional recurrence in patients undergoing breast reconstruction; therefore, it can be safely used for total breast reconstruction or aesthetic refinements.

Risk, II.}, } @article {pmid35942356, year = {2022}, author = {Kufel, WD and Blaine, BE and Avery, LM}, title = {Pharmacy students' knowledge and confidence of COVID-19 following an interactive didactic class.}, journal = {Journal of the American College of Clinical Pharmacy : JACCP}, volume = {5}, number = {10}, pages = {1082-1087}, pmid = {35942356}, issn = {2574-9870}, abstract = {BACKGROUND: COVID-19 education for the pharmacy workforce is important to ensure pharmacists are optimizing patient care for the prevention and management of COVID-19. However, there are currently no reports to our knowledge of education and training experiences for COVID-19 prevention and management in the Doctor of Pharmacy (PharmD) curricula.

OBJECTIVE: To evaluate pharmacy students' knowledge and confidence regarding COVID-19 prevention and management before and after an interactive didactic class (IDC).

METHODS: A multicenter, quasi-experimental, cross-sectional survey study was performed among pharmacy students before and after IDC on COVID-19 at two schools of pharmacy. The IDC on COVID-19 consisted of student-led presentations on a COVID-19 drug, an infectious disease pharmacist faculty-led interactive lecture on COVID-19 prevention and management, and clinical case vignettes to assess COVID-19 management strategies. An anonymous, voluntary, electronic survey was distributed to students (n = 85) before and after. The pre- and postintervention survey contained 10 COVID-19 knowledge-based questions and multi-step, 5-point Likert scale statements related to COVID-19 prevention and management confidence. The postintervention survey also evaluated students' perceptions of the COVID-19 IDC. Descriptive statistics were performed, and Student t test was used to compare pre- and postintervention responses.

RESULTS: About 61 surveys were completed resulting in a response rate of 72%. COVID-19 knowledge scores (mean ± SD) increased overall following the IDC (5.9 ± 1.31 vs 8.6 ± 1.29). Pharmacy students' COVID-19 confidence scores (mean ± SD) also improved following the IDC (2.66 ± 0.75 vs 4.03 ± 0.53). Students performed well on the COVID-19 clinical case vignettes with a mean ± SD score of 22.41 ± 0.46 out of 25. Pharmacy students' perceptions of the IDC on COVID-19 were also positive overall.

CONCLUSION: Pharmacy students' knowledge and confidence of COVID-19 prevention and management improved following an IDC. This may be an effective strategy to provide COVID-19 education during the PharmD curricula.}, } @article {pmid35932126, year = {2022}, author = {Yaltirik Bilgin, E and Unal, O and Ciledag, N}, title = {Vasogenic Edema Pattern in Brain Metastasis.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {32}, number = {8}, pages = {1020-1025}, doi = {10.29271/jcpsp.2022.08.1020}, pmid = {35932126}, issn = {1681-7168}, mesh = {Brain/pathology ; *Brain Edema/diagnostic imaging/etiology ; *Brain Neoplasms/complications/diagnostic imaging/pathology ; Cross-Sectional Studies ; Edema/etiology ; Humans ; *Lung Neoplasms/complications ; Magnetic Resonance Imaging/methods ; Retrospective Studies ; }, abstract = {OBJECTIVE: To determine the relationship of the presence and amount of vasogenic edema with origin, type, and grade of primary cancer.

STUDY DESIGN: Cross-sectional study.

PLACE AND DURATION OF STUDY: Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Radiology Clinic, Ankara, Turkey, from July 2017 to October 2021.

METHODOLOGY: Brain MRI scans of 292 patients were retrospectively evaluated. Age, gender, origin, type, and grade of primary cancer were determined. Metastasis type, and presence of vasogenic edema accompanying metastatic lesion were questioned. In cases of vasogenic edema accompanying metastatic lesions, the largest diameter of the vasogenic edema mass complex was measured in T2 sequences. In the contrast-enhanced series, the largest diameter of the metastatic lesion was measured, and the edema-mass ratio (EMR) was calculated by proportioning the diameter of the edema mass complex to the diameter of the mass.

RESULTS: The frequency of vasogenic edema was found higher in patients with lung cancer compared to other primaries. The EMR was found statistically significantly higher in patients with primary lung cancer (p=0.001). This was particularly evident in the adenocarcinoma group. In the patient group with primary breast cancer, EMR was found significantly lower in patients with invasive ductal carcinoma. (IDC→1.95±0.66 vs. Other→2.48±0.52, Z=-2.301, p=0.021).

CONCLUSION: The amount and presence of vasogenic edema in patients with brain metastases may differ according to the origin and type of primary tumour.

KEY WORDS: Brain edema, Metastatic disease, Magnetic resonance imaging.}, } @article {pmid35929120, year = {2023}, author = {Kim, KN and Salerno, M and Shah, PD and Matro, J and LaRiviere, MJ}, title = {Severe acute radiation dermatitis after palbociclib therapy in the setting of palliative radiotherapy.}, journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners}, volume = {29}, number = {3}, pages = {764-767}, doi = {10.1177/10781552221118841}, pmid = {35929120}, issn = {1477-092X}, mesh = {Humans ; Female ; Middle Aged ; Retrospective Studies ; Pyridines/adverse effects ; *Breast Neoplasms/drug therapy/radiotherapy/metabolism ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; *Dermatitis/drug therapy/etiology ; Protein Kinase Inhibitors/therapeutic use ; Piperazines ; }, abstract = {INTRODUCTION: Cyclin-dependent-kinase 4/6(CDK4/6) inhibitors are widely used as a first-line systemic treatment for patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer. Although many patients with metastatic breast cancer require palliative radiotherapy (RT), there are limited data on the safety of combining a CDK4/6 inhibitor with palliative RT.

CASE REPORT: Presented is a case of acute high-grade radiation dermatitis with low-dose palliative RT following administration of palbociclib. A 49-year-old woman with newly diagnosed hormone receptor-positive invasive ductal carcinoma of the left breast presented with lytic bone lesions in the left femur and lumbar spine. The patient initiated treatment with goserelin, tamoxifen, and palbociclib. She underwent prophylactic surgical fixation of the left femur and received post-operative RT encompassing the entire surgical nail (30 Gy/10 fractions) and palliative RT to the lumbar spine for pain relief (20 Gy/5 fractions). During cycle 4, palbociclib was stopped 3 days prior to the start of RT to reduce the risk of toxicity risk. However, 16 days after starting RT, she developed painful erythematous papules and bullae with moist desquamation on the left groin and lumbar spine.

MANAGEMENT & OUTCOME: Her symptoms were managed with topical Aquaphor-lidocaine, silver sulfadiazine, and aluminum acetate soaks. Dermatitis subsided to dry desquamation within 2 weeks. The patient denied late toxicity at 11 months follow-up.

DISCUSSION: Larger retrospective or prospective studies are needed to further elucidate the safety of combined CDK4/6 inhibitors and RT. In the meantime, special precautions are warranted in patients receiving combined therapy.}, } @article {pmid35924707, year = {2022}, author = {Kamido, S and Kakuta, Y and Fukuhara, S and Fujita, K and Uemura, M and Kiuchi, H and Imamura, R and Miyagawa, Y and Nonomura, N}, title = {[A Rare Case of Adrenal Metastasis Diagnosed before Discovery of Invasive Ductal Breast Cancer which was Confirmed to Be the Primary Site].}, journal = {Hinyokika kiyo. Acta urologica Japonica}, volume = {68}, number = {7}, pages = {239-243}, doi = {10.14989/ActaUrolJap_68_7_239}, pmid = {35924707}, issn = {0018-1994}, mesh = {*Adrenal Gland Neoplasms/diagnostic imaging/surgery ; Adrenalectomy ; *Breast Neoplasms/pathology/surgery ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; }, abstract = {A 54-year-old female underwent open left adrenalectomy for a left adrenal tumor in 2013. The pathology showed metastatic poorly differentiated adenocarcinoma. Despite a close examination, the primary tumor could not be identified. During the follow-up, a computed tomographic scan showed a hyper vascular tumor in the left breast in2015. A left mastectomy was performed for diagnosis and treatment. The pathology showed invasive ductal carcinoma of the breast. Comparing the histopathology and immunohistochemistry of the breast tumor with the adrenal tumor, the adrenal tumor was finally confirmed as metastatic invasive ductal carcinoma. Adrenal gland metastasis from invasive ductal carcinoma is said to be extremely rare. To our knowledge, there have been no reports of cases in which metastatic invasive ductal carcinoma of the adrenal gland was found before the primary site. We report this case with some literature review.}, } @article {pmid35914749, year = {2022}, author = {Dang, X and Zhang, X and Gao, Y and Song, H}, title = {Assessment of Neoadjuvant Treatment Response Using Automated Breast Ultrasound in Breast Cancer.}, journal = {Journal of breast cancer}, volume = {25}, number = {4}, pages = {344-348}, pmid = {35914749}, issn = {1738-6756}, abstract = {Breast imaging techniques are used to assess the tumor response to neoadjuvant treatment (NAT), which is increasingly one of the preferred therapeutic options and increases the rate of breast conservation for breast cancer. Herein, we report a case in which a woman was diagnosed with invasive ductal carcinoma in the left breast and received NAT before surgery. Automated breast ultrasound (AB US) was regularly performed before and during the NAT to evaluate the tumor response to NAT by measuring diameter changes and volume reductions of the tumor. Images showed that the tumor size was significantly reduced and disappeared after 7 cycles of NAT, except for macrocalcification. Postoperative histopathological examination confirmed that there were no residual tumor cells. We found that AB US overcame the limitations of handheld US, such as operator dependence, poor reproducibility and limited field of view, and can be an alternative modality to assess the tumor response of NAT in the absence of magnetic resonance imaging (MRI) instruments.}, } @article {pmid35914650, year = {2022}, author = {Petrus, P and Cervantes, M and Samad, M and Sato, T and Chao, A and Sato, S and Koronowski, KB and Park, G and Alam, Y and Mejhert, N and Seldin, MM and Monroy Kuhn, JM and Dyar, KA and Lutter, D and Baldi, P and Kaiser, P and Jang, C and Sassone-Corsi, P}, title = {Tryptophan metabolism is a physiological integrator regulating circadian rhythms.}, journal = {Molecular metabolism}, volume = {64}, number = {}, pages = {101556}, pmid = {35914650}, issn = {2212-8778}, support = {U24 DK097771/DK/NIDDK NIH HHS/United States ; K99 HL138193/HL/NHLBI NIH HHS/United States ; R00 HL138193/HL/NHLBI NIH HHS/United States ; R21 AG053592/AG/NIA NIH HHS/United States ; R21 DK114652/DK/NIDDK NIH HHS/United States ; R35 GM148350/GM/NIGMS NIH HHS/United States ; P30 CA062203/CA/NCI NIH HHS/United States ; DP1 DK130640/DK/NIDDK NIH HHS/United States ; F31 GM117942/GM/NIGMS NIH HHS/United States ; R01 GM123558/GM/NIGMS NIH HHS/United States ; R01 AA029124/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; *Circadian Clocks ; *Circadian Rhythm/physiology ; Liver/metabolism ; Mammals ; Mice ; Suprachiasmatic Nucleus/metabolism ; Tryptophan/metabolism ; }, abstract = {OBJECTIVE: The circadian clock aligns physiology with the 24-hour rotation of Earth. Light and food are the main environmental cues (zeitgebers) regulating circadian rhythms in mammals. Yet, little is known about the interaction between specific dietary components and light in coordinating circadian homeostasis. Herein, we focused on the role of essential amino acids.

METHODS: Mice were fed diets depleted of specific essential amino acids and their behavioral rhythms were monitored and tryptophan was selected for downstream analyses. The role of tryptophan metabolism in modulating circadian homeostasis was studied using isotope tracing as well as transcriptomic- and metabolomic- analyses.

RESULTS: Dietary tryptophan depletion alters behavioral rhythms in mice. Furthermore, tryptophan metabolism was shown to be regulated in a time- and light- dependent manner. A multi-omics approach and combinatory diet/light interventions demonstrated that tryptophan metabolism modulates temporal regulation of metabolism and transcription programs by buffering photic cues. Specifically, tryptophan metabolites regulate central circadian functions of the suprachiasmatic nucleus and the core clock machinery in the liver.

CONCLUSIONS: Tryptophan metabolism is a modulator of circadian homeostasis by integrating environmental cues. Our findings propose tryptophan metabolism as a potential point for pharmacologic intervention to modulate phenotypes associated with disrupted circadian rhythms.}, } @article {pmid35910358, year = {2022}, author = {Xu, C and Liang, T and Liu, J and Fu, Y}, title = {RAB39B as a Chemosensitivity-Related Biomarker for Diffuse Large B-Cell Lymphoma.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {931501}, pmid = {35910358}, issn = {1663-9812}, abstract = {Background: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma with an increased tendency to relapse or refractoriness. RAB39B, a member of the Ras-oncogene superfamily, is associated with a variety of tumors. Nevertheless, the role of RAB39B in DLBCL is still unknown. This study aimed to identify the role of RAB39B in DLBCL using integrated bioinformatics analysis. Methods: RAB39B expression data were examined using TIMER, UCSC, and GEO databases. The LinkedOmics database was used to study the genes and signaling pathways related to RAB39B expression. A Protein-protein interaction network was performed in STRING. TIMER was used to analyze the correlation between RAB39B and infiltrating immune cells. The correlation between RAB39B and m6A-related genes in DLBCL was analyzed using TCGA data. The RAB39B ceRNA network was constructed based on starBase and miRNet2.0 databases. Drug sensitivity information was obtained from the GSCA database. Results: RAB39B was highly expressed in multiple tumors including DLBCL. The protein-protein interaction network showed enrichment of autophagy and RAS family proteins. Functional enrichment analysis of RAB39B co-expression genes revealed that RAB39B was closely related to DNA replication, protein synthesis, cytokine-cytokine receptor interaction, JAK-STAT signaling pathway, NF-kappa B signaling pathway, and autophagy. Immune infiltrate analysis showed that the amount of RAB39B was negatively correlated with iDC, Tem, and CD8 T-cell infiltration. CD4[+] T cell and DC were negatively correlated with CNV of RAB39B. DLBCL cohort analysis found that RAB39B expression was related to 14 m6A modifier genes, including YTHDC1, YTHDC2, YTHDF1, YTHDF2, YTHDF3, RBMX, ZC3H13, METTL14, METTL3, RBM15, RBM15B, VIRMA, FTO, and ALKBH5. We constructed 14 possible ceRNA networks of RAB39B in DLBCL. The RAB39B expression was associated with decreased sensitivity of chemotherapy drugs such as dexamethasone, doxorubicin, etoposide, vincristine, and cytarabine and poor overall survival in DLBCL. In vitro experiments showed that RAB39B was associated with proliferation, apoptosis, and drug sensitivity of DLBCL cells. Conclusion: RAB39B is abnormally elevated and related to drug resistance and poor OS in DLBCL, which may be due to its involvement in immune infiltration, m6A modification, and regulation by multiple non-coding RNAs. RAB39B may be used as an effective biomarker for the diagnosis and treatment of DLBCL.}, } @article {pmid35910265, year = {2022}, author = {Zhuang, J and Mei, H and Fang, F and Ma, X}, title = {What Is New in Classification, Diagnosis and Management of Chronic Musculoskeletal Pain: A Narrative Review.}, journal = {Frontiers in pain research (Lausanne, Switzerland)}, volume = {3}, number = {}, pages = {937004}, pmid = {35910265}, issn = {2673-561X}, abstract = {Chronic musculoskeletal pain (CMP) is the most common type of chronic pain, defined as persistent or recurrent pain condition deriving from musculoskeletal structures such as muscles, joints or bones that lasts for more than 3 months. CMP is multifactorial and severely affects people's quality of life. CMP may be influenced by a number of factors, including contextual factors, the presence of comorbidities, arthritis coping efficacy and access to CMP care. To deepen the comprehensive understanding of CMP, this narrative review provides the latest literature on disease classification, clinical diagnosis, treatment and basic research. In terms of the classification of the disease, here we introduce the 11th edition of the International Classification of Diseases (IDC-11), in which CMP is divided into chronic primary musculoskeletal pain and chronic secondary musculoskeletal pain. In the clinical diagnosis section, the progress of central sensitization in the diagnosis of CMP will also be summarized. In addition, we summarize some recent advances in clinical treatment and basic research.}, } @article {pmid35909232, year = {2023}, author = {Yang, ZJ and Liu, YX and Huang, Y and Chen, ZJ and Zhang, HZ and Yu, Y and Wang, X and Cao, XC}, title = {The regrouping of Luminal B (HER2 negative), a better discriminator of outcome and recurrence score.}, journal = {Cancer medicine}, volume = {12}, number = {3}, pages = {2493-2504}, pmid = {35909232}, issn = {2045-7634}, mesh = {Humans ; Female ; Ki-67 Antigen/metabolism ; *Erb-b2 Receptor Tyrosine Kinases/metabolism ; Retrospective Studies ; *Breast Neoplasms/pathology ; Disease-Free Survival ; Receptors, Progesterone/metabolism ; Biomarkers, Tumor/metabolism ; Prognosis ; }, abstract = {BACKGROUND: Breast cancer (BC) remains the leading cause of cancer-related deaths worldwide. High recurrence risk Luminal BC receives adjuvant chemotherapy in addition to standard hormone therapy. Considering the heterogeneity of Luminal B BC, a more accurate classification model is urgently needed.

METHODS: In this study, we retrospectively reviewed the data of 1603 patients who were diagnosed with HER2-negative breast invasive ductal carcinoma. According to the expression level of PR and Ki-67 index, the Luminal B (HER2-negative) BCs were divided into three groups: ER+PR-Ki67low (ER-positive, PR-negative, and Ki-67 index <20%), ER+PR+Ki67high (ER-positive, PR-positive, and Ki-67 index ≥20%), and ER+PR-Ki67high (ER-positive, PR-negative, and Ki-67 index ≥20%). The cox proportional hazards regression model was used to evaluate the correlation between each variable and outcomes. Besides, discriminatory accuracy of the models was compared using the area under the receiver operating characteristic curve and log-rank χ[2] value.

RESULTS: The analysis results showed that there was a significant correlation between subtypes using this newly defined classification and overall survival (p < 0.001) and disease-free survival (DFS) (p < 0.001). Interestingly, patients in the ER+PR-Ki67high subgroup have the worst survival outcome in Luminal B (HER2-negative) subtype, similar to Triple-negative patients. Besides, the ER+PR+Ki67high has worse 5-year DFS compared with Luminal A group. There was a significant relationship between the regrouping subtype and the recurrence score index (RI) (p < 0.001). Moreover, the results showed that patients in ER+PR-Ki67high subtype were more likely to have high RI for distance recurrence (RI-DR) and local recurrence (RI-LRR). Our newly defined classification has a better discrimination ability to predict survival outcome and recurrence score of Luminal B (HER2-negative) BC patients, which may help in clinical decision-making for individual treatment.}, } @article {pmid35909017, year = {2022}, author = {Rao, RA and Kozaily, E and Jawaid, O and Sabra, M and El-Am, EA and Chaaya, RGB and Woiewodski, L and Elsemesmani, H and Ramchandani, J and Shah, C and Guglin, M and Das, MK}, title = {Comparison of and Frequency of Mortality, Left Ventricular Assist Device Implantation, Ventricular Arrhythmias, and Heart Transplantation in Patients With Familial Versus Nonfamilial Idiopathic Dilated Cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {179}, number = {}, pages = {83-89}, doi = {10.1016/j.amjcard.2022.06.018}, pmid = {35909017}, issn = {1879-1913}, mesh = {Adult ; Aged ; Arrhythmias, Cardiac ; *Cardiomyopathy, Dilated ; *Heart Transplantation ; *Heart-Assist Devices ; Humans ; Male ; Middle Aged ; Stroke Volume ; Ventricular Remodeling ; }, abstract = {We postulated that familial idiopathic dilated cardiomyopathy (F-IDC) is associated with a worse prognosis than nonfamilial IDC (nonF-IDC). Patients with F-IDC had either a strong family history and/or proved genetic mutations. We studied long-term prognosis (mean follow-up: 6.1 ± 4.1 years) of 162 patients with IDC (age: 55.5 ± 17.9 years, men: 57.8%, 50% F-IDC) with an implantable cardioverter-defibrillator or cardiac resynchronization therapy. The primary end point was a composite of death, left ventricular (LV) assist device implant, or heart transplantation. The secondary end point was a ventricular arrhythmia event. There was no significant difference in the prevalence of diabetes, hypertension, New York Heart Association class, medical therapy, and years of follow-up between the F-IDC and nonF-IDC groups. Patients with F-IDC were younger than patients with nonF-IDC (49.1 ± 17.0 years vs 61.6 ± 16.5 years, p <0.001). Mean LV ejection fraction was significantly lower in F-IDC group than in the nonF-IDC group (26 ± 12% vs 31 ± 12%, p = 0.022). The primary end point was achieved in 54 patients in F-IDC group (66.7%) versus 19 in the nonF-IDC group (23.5%) (p <0.001). The Kaplan-Meier survival estimates for the composite end point and for ventricular arrhythmia were significantly lower in the F-IDC versus nonF-IDC (log-rank p ≤0.001 and 0.04, respectively). F-IDC was the only multivariable predictor of the primary composite end point (hazard ratio 3.419 [95% confidence interval 1.845 to 6.334], p <0.001). The likelihood of LV remodeling manifested by LV ejection fraction improvement (≥10%) was significantly lower in F-IDC than nonF-IDC (27.1% vs 44.8%, p = 0.042). In conclusion, F-IDC is a predictor of mortality, need for LV assist device, or heart transplantation. F-IDC is associated with significantly lower event-free survival for primary end point and ventricular arrhythmia than nonF-IDC. F-IDC has significantly lower likelihood of LV reverse remodeling than nonF-IDC.}, } @article {pmid35908296, year = {2022}, author = {Cerea, S and Doron, G and Manoli, T and Patania, F and Bottesi, G and Ghisi, M}, title = {Cognitive training via a mobile application to reduce some forms of body dissatisfaction in young females at high-risk for body image disorders: A randomized controlled trial.}, journal = {Body image}, volume = {42}, number = {}, pages = {297-306}, doi = {10.1016/j.bodyim.2022.07.010}, pmid = {35908296}, issn = {1873-6807}, mesh = {*Body Dissatisfaction ; *Body Dysmorphic Disorders/diagnosis/psychology/therapy ; Body Image/psychology ; Cognition ; *Feeding and Eating Disorders/prevention & control ; Female ; Humans ; *Mobile Applications ; }, abstract = {Body dissatisfaction has been related to Body Image Disorders (BIDs) such as Eating Disorders (EDs) and Body Dysmorphic Disorder (BDD). This study investigates the efficacy of a mHealth app in reducing body dissatisfaction, BDD/ED symptoms and related features. Ninety-five women who were identified as high-risk of developing BIDs (using the Structured Clinical Interview for DSM-5) were randomized into: immediate-use App (iApp group; n = 47) and delayed-use App (dApp group; n = 48). The iApp group started using the app at baseline for 16 days (T1). The dApp group started using the app at T1 for 16 days. Participants completed questionnaires at baseline (T0), 16 days from baseline (T1), and 32 days from baseline (T2). Repeated measure Multivariate Analysis of Variance (MANOVA) showed Group (iApp vs. dApp) × Time (T0 vs. T1) interactions indicating decrease in BDD symptoms and body dissatisfaction related to EDs in the iApp group at T1. The Reliable Change Index indicated changes on extreme body dissatisfaction/BDD symptoms for 34.74% of participants. Although preliminary, these findings highlight that a mHeatlh app might reduce BDD symptoms and body dissatisfaction related to EDs in women at high-risk for BIDs. Effects on ED symptoms and associated features seem more limited.}, } @article {pmid35907957, year = {2022}, author = {Oehler, D and Spychala, A and Gödecke, A and Lang, A and Gerdes, N and Ruas, J and Kelm, M and Szendroedi, J and Westenfeld, R}, title = {Full-length transcriptomic analysis in murine and human heart reveals diversity of PGC-1α promoters and isoforms regulated distinctly in myocardial ischemia and obesity.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {169}, pmid = {35907957}, issn = {1741-7007}, mesh = {Alternative Splicing ; Animals ; Humans ; Mice ; *Myocardial Ischemia/genetics ; Obesity/genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics/metabolism ; Protein Isoforms/genetics ; RNA, Messenger/metabolism ; *Transcriptome ; }, abstract = {BACKGROUND: Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) acts as a transcriptional coactivator and regulates mitochondrial function. Various isoforms are generated by alternative splicing and differentially regulated promoters. In the heart, total PGC-1α deficiency knockout leads to dilatative cardiomyopathy, but knowledge on the complexity of cardiac isoform expression of PGC-1α remains sparse. Thus, this study aims to generate a reliable dataset on cardiac isoform expression pattern by long-read mRNA sequencing, followed by investigation of differential regulation of PGC-1α isoforms under metabolic and ischemic stress, using high-fat-high-sucrose-diet-induced obesity and a murine model of myocardial infarction.

RESULTS: Murine (C57Bl/6J) or human heart tissue (obtained during LVAD-surgery) was used for long-read mRNA sequencing, resulting in full-length transcriptomes including 58,000 mRNA isoforms with 99% sequence accuracy. Automatic bioinformatic analysis as well as manual similarity search against exonic sequences leads to identification of putative coding PGC-1α isoforms, validated by PCR and Sanger sequencing. Thereby, 12 novel transcripts generated by hitherto unknown splicing events were detected. In addition, we postulate a novel promoter with homologous and strongly conserved sequence in human heart. High-fat diet as well as ischemia/reperfusion (I/R) injury transiently reduced cardiac expression of PGC-1α isoforms, with the most pronounced effect in the infarcted area. Recovery of PGC-1α-isoform expression was even more decelerated when I/R was performed in diet-induced obese mice.

CONCLUSIONS: We deciphered for the first time a complete full-length transcriptome of the murine and human heart, identifying novel putative PGC-1α coding transcripts including a novel promoter. These transcripts are differentially regulated in I/R and obesity suggesting transcriptional regulation and alternative splicing that may modulate PGC-1α function in the injured and metabolically challenged heart.}, } @article {pmid35906698, year = {2022}, author = {Lee, S and Osmanbeyoglu, HU}, title = {Chromatin accessibility landscape and active transcription factors in primary human invasive lobular and ductal breast carcinomas.}, journal = {Breast cancer research : BCR}, volume = {24}, number = {1}, pages = {54}, pmid = {35906698}, issn = {1465-542X}, support = {R00 CA207871/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology ; *Carcinoma, Lobular/genetics/pathology ; Chromatin/genetics ; Female ; Humans ; Transcription Factors/genetics ; }, abstract = {BACKGROUND: Invasive lobular breast carcinoma (ILC), the second most prevalent histological subtype of breast cancer, exhibits unique molecular features compared with the more common invasive ductal carcinoma (IDC). While genomic and transcriptomic features of ILC and IDC have been characterized, genome-wide chromatin accessibility pattern differences between ILC and IDC remain largely unexplored.

METHODS: Here, we characterized tumor-intrinsic chromatin accessibility differences between ILC and IDC using primary tumors from The Cancer Genome Atlas (TCGA) breast cancer assay for transposase-accessible chromatin with sequencing (ATAC-seq) dataset.

RESULTS: We identified distinct patterns of genome-wide chromatin accessibility in ILC and IDC. Inferred patient-specific transcription factor (TF) motif activities revealed regulatory differences between and within ILC and IDC tumors. EGR1, RUNX3, TP63, STAT6, SOX family, and TEAD family TFs were higher in ILC, while ATF4, PBX3, SPDEF, PITX family, and FOX family TFs were higher in IDC.

CONCLUSIONS: This study reveals the distinct epigenomic features of ILC and IDC and the active TFs driving cancer progression that may provide valuable information on patient prognosis.}, } @article {pmid35904971, year = {2022}, author = {Wan, M and Song, S and Feng, W and Shen, H and Luo, Y and Wu, W and Shen, J}, title = {Metal-Organic Framework (UiO-66)-Based Temperature-Responsive Pesticide Delivery System for Controlled Release and Enhanced Insecticidal Performance against Spodoptera frugiperda.}, journal = {ACS applied bio materials}, volume = {5}, number = {8}, pages = {4020-4027}, doi = {10.1021/acsabm.2c00549}, pmid = {35904971}, issn = {2576-6422}, mesh = {Animals ; Delayed-Action Preparations/pharmacology ; *Insecticides/pharmacology ; *Metal-Organic Frameworks ; *Pesticides/pharmacology ; Phthalic Acids ; Spodoptera ; Temperature ; }, abstract = {Spodoptera frugiperda is a global pest that brings about great disasters to crops. Conventional pesticide formulations often suffer from poor water solubility, low stability, burst release, weak leaf adhesion, and low efficiency. To improve the insecticidal activity of pesticides, a stimuli-responsive controlled release pesticide delivery system (PDS) has attracted extensive attention in recent years. This paper reports a temperature-responsive controlled release PDS based on poly(N-isopropyl acrylamide) (PNIPAm)-modified indoxacarb (IDC)-loaded UiO-66-(COOH)2 (IDC@UiO-66-(COOH)2-PNIPAm) and studies its insecticidal activities against S. frugiperda. The UiO-66-(COOH)2 nanocarrier has an excellent pesticide loading performance, and the loading rate for IDC is 78.69%. The as-prepared PDS has good stability, temperature-responsive controllable release performance, and enhanced leaf affinity, so it can effectively improve the utilization rate of IDC. The insecticidal experiment indicates that the PDS has an enhanced control effect against S. frugiperda. In addition, biosafety analysis further verifies that the PDS exhibits no obvious negative effects on the germination of maize seeds and the growth of maize seedlings. In view of this, we believe that this PDS will have a broad application in the field of pesticide formulation innovation, pest management, and sustainable agricultural development.}, } @article {pmid35903710, year = {2022}, author = {Bhimani, F and Johnson, K and Brodin, NP and Tomé, WA and Fox, J and Mehta, K and McEvoy, M and Feldman, S}, title = {Case Report: Can Targeted Intraoperative Radiotherapy in Patients With Breast Cancer and Pacemakers be the New Standard of Care?.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {927174}, pmid = {35903710}, issn = {2234-943X}, abstract = {BACKGROUND: Partial breast irradiation with Intra-operative radiotherapy (IORT) has become a popular management option as opposed to whole breast radiation using external beam radiotherapy for breast cancer patients. While previous studies have highlighted the use of IORT in breast cancer patients, there is a scarcity of literature on the use of IORT in those who also have ipsilateral pacemakers. Thus, the aim of our case report is to highlight the applicability of IORT in breast cancer patients who also have a pacemaker.

CASE REPORTS: Two female patients with an implanted dual-chamber pacemaker presented with a diagnosis of left-sided invasive ductal carcinoma on mammogram. Mammography of the left breast revealed a 10 mm and 7 mm spiculated mass, respectively, further confirmed with an ultrasound-guided core biopsy that was conclusive of clinical Stage I T1 N0 grade 2, ER +, PR + Her2 - invasive ductal carcinoma. They met our eligibility criteria for IORT, which is being performed as a registry trial. These patients underwent a wide excision lumpectomy along with IORT.

CONCLUSION: Our findings underscore the successful use of targeted IORT for breast-conserving surgery in a patient with invasive ductal carcinoma and pacemaker, hence eliminating the necessity for relocating pacemaker surgeries in these patients. Furthermore, no device failure or malfunction for the pacemaker was recorded before, during, or after the surgery, demonstrating the safety of using IORT in patients with preinstalled pacemaker despite a lack of evidence on safe radiation dosage or manufacturer guidelines. Nonetheless, the effects of IORT on pacemaker < 10 cm were not studied in our patients and further clinical studies are recommended to reinforce the applicability and safe distance of IORT in breast cancer patients with pacemaker.}, } @article {pmid35900825, year = {2022}, author = {Nitsan, G and Baharav, S and Tal-Shir, D and Shakuf, V and Ben-David, BM}, title = {Speech Processing as a Far-Transfer Gauge of Serious Games for Cognitive Training in Aging: Randomized Controlled Trial of Web-Based Effectivate Training.}, journal = {JMIR serious games}, volume = {10}, number = {3}, pages = {e32297}, pmid = {35900825}, issn = {2291-9279}, abstract = {BACKGROUND: The number of serious games for cognitive training in aging (SGCTAs) is proliferating in the market and attempting to combat one of the most feared aspects of aging-cognitive decline. However, the efficacy of many SGCTAs is still questionable. Even the measures used to validate SGCTAs are up for debate, with most studies using cognitive measures that gauge improvement in trained tasks, also known as near transfer. This study takes a different approach, testing the efficacy of the SGCTA-Effectivate-in generating tangible far-transfer improvements in a nontrained task-the Eye tracking of Word Identification in Noise Under Memory Increased Load (E-WINDMIL)-which tests speech processing in adverse conditions.

OBJECTIVE: This study aimed to validate the use of a real-time measure of speech processing as a gauge of the far-transfer efficacy of an SGCTA designed to train executive functions.

METHODS: In a randomized controlled trial that included 40 participants, we tested 20 (50%) older adults before and after self-administering the SGCTA Effectivate training and compared their performance with that of the control group of 20 (50%) older adults. The E-WINDMIL eye-tracking task was administered to all participants by blinded experimenters in 2 sessions separated by 2 to 8 weeks.

RESULTS: Specifically, we tested the change between sessions in the efficiency of segregating the spoken target word from its sound-sharing alternative, as the word unfolds in time. We found that training with the SGCTA Effectivate improved both early and late speech processing in adverse conditions, with higher discrimination scores in the training group than in the control group (early processing: F1,38=7.371; P=.01; ηp[2]=0.162 and late processing: F1,38=9.003; P=.005; ηp[2]=0.192).

CONCLUSIONS: This study found the E-WINDMIL measure of speech processing to be a valid gauge for the far-transfer effects of executive function training. As the SGCTA Effectivate does not train any auditory task or language processing, our results provide preliminary support for the ability of Effectivate to create a generalized cognitive improvement. Given the crucial role of speech processing in healthy and successful aging, we encourage researchers and developers to use speech processing measures, the E-WINDMIL in particular, to gauge the efficacy of SGCTAs. We advocate for increased industry-wide adoption of far-transfer metrics to gauge SGCTAs.}, } @article {pmid35900570, year = {2022}, author = {Bansal, VY and Bansal, VV and Shah, SV and Bellige, AR}, title = {Primary ectopic breast carcinoma arising in the inguinal region in a male patient.}, journal = {Journal of cancer research and therapeutics}, volume = {18}, number = {3}, pages = {837-839}, doi = {10.4103/jcrt.JCRT_777_20}, pmid = {35900570}, issn = {1998-4138}, mesh = {Aged ; *Breast Neoplasms/drug therapy ; *Carcinoma, Ductal, Breast/drug therapy/therapy ; Humans ; Male ; Neoplasm, Residual ; Tamoxifen/therapeutic use ; }, abstract = {Carcinoma arising in ectopic breast tissue is a rare entity, especially in males, in whom the diagnosis is often delayed due to a low index of suspicion. Conventional imaging techniques fail to characterize the tumor, adding further to the diagnostic dilemma. We report the first case in our knowledge of an extramammary primary breast carcinoma arising in the inguinal region in a male. Our patient, a 69-year-old male, presented with a swelling in the left inguinal region, which was excised and diagnosed as luminal A type invasive ductal carcinoma. He received adjuvant external beam radiotherapy (50 Gy administered in 25 fractions) and tamoxifen. A follow-up examination performed 6 months after the completion of the last dose of radiotherapy showed no residual disease. The modalities of treatment for such tumors have been discussed, with emphasis on surgery and radiotherapy, given the aggressive nature of the disease.}, } @article {pmid35899956, year = {2023}, author = {Shi, J and Chen, L and Wang, B and Zhang, H and Xu, L and Ye, J and Liu, Y and Shao, Y and Sun, X and Zou, Y}, title = {Diagnostic Value of Ultrasound Elastography in the Differentiation of Breast Invasive Ductal Carcinoma and Ductal Carcinoma In situ.}, journal = {Current medical imaging}, volume = {19}, number = {3}, pages = {286-291}, doi = {10.2174/1573405618666220721091940}, pmid = {35899956}, issn = {1573-4056}, mesh = {Female ; Humans ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology ; *Carcinoma, Ductal, Breast/diagnostic imaging ; *Elasticity Imaging Techniques ; Breast/pathology ; *Breast Neoplasms/diagnostic imaging/pathology ; }, abstract = {BACKGROUND: Ultrasound elastography (US-E) has been shown superior to the conventional US in diagnosing benign and malignant breast lesions. In contrast, the role of US-E in the differentiation of breast invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) has been poorly described.

OBJECTIVE: This study was designed to examine the diagnostic value of US-E in the differentiation of IDC and DCIS.

METHODS: Medical records of all patients who underwent preoperative US-E evaluation and were diagnosed with IDC or DCIS at our hospital from April-December 2019 were retrieved and analyzed. Those who had prior surgical treatment, chemotherapy or radiotherapy were excluded.

RESULTS: Twenty women with DCIS and 111 women with IDC were included in this study. There were no significant differences in age, maximum lesion diameter and tumor volume between the two groups. While shear wave velocity (SWV) inside the lesion and in the surrounding tissue, strain ratio and tumor area ratio were not substantially different between the two groups, SWV at the edge of the lesion was significantly higher in IDC cases, which had an AUC value of 0.66 with a sensitivity of 65.8% and a specificity of 60.0% for the differential diagnosis of IDC and DCIS.

CONCLUSION: Edge SWV is significantly higher in IDC than that in DCIS, which had a moderate diagnostic value for the differentiation of IDC and DCIS, similar to the performance of diffusion-weighted magnetic resonance imaging as reported in the literature. In terms of cost-effectiveness, US-E could be very useful while waiting for further evaluations to determine whether US-E combined with other diagnostic modalities improves the diagnostic performance.}, } @article {pmid35898837, year = {2023}, author = {Suzuki, Y and Hoshi, K and Tominaga, K and Inaba, Y and Yoshinaga, T and Kojimahara, S and Maki, R and Nemoto, R and Tetsuka, Y and Kawata, Y and Yamamiya, A and Sugaya, T and Iso, Y and Takada-Owada, A and Ishida, K and Goda, K and Irisawa, A}, title = {A case of obstructive jaundice caused by metastasis of breast cancer to the intra/extrahepatic bile duct.}, journal = {DEN open}, volume = {3}, number = {1}, pages = {e144}, pmid = {35898837}, issn = {2692-4609}, abstract = {A 38-year-old woman was admitted to our hospital for a detailed examination of jaundice. Three years before, she had undergone a right total mastectomy and axillary lymph node dissection of her right breast because of cancer. Histopathological evaluation revealed invasive ductal carcinoma. Postoperatively, because multiple bone metastases were found, she underwent chemoradiotherapy. Endoscopic retrograde cholangiopancreatography was performed, which revealed widespread multiple stenoses with a smooth surface from the intrahepatic to the extrahepatic bile duct. A transpapillary biliary biopsy was performed. Histopathological examination revealed adenocarcinoma extending into the subepithelium of the bile duct. The obtained cancer cells were similar to those of the earlier invasive breast cancer. This rare case demonstrates bile duct metastasis of breast cancer with specific endoscopic retrograde cholangiopancreatography findings.}, } @article {pmid35893780, year = {2022}, author = {Jolivet, L and Ait Mohamed Amar, I and Horiot, C and Boursin, F and Colas, C and Letast, S and Denevault-Sabourin, C and Allard-Vannier, E and Joubert, N and Aubrey, N}, title = {Intra-Domain Cysteines (IDC), a New Strategy for the Development of Original Antibody Fragment-Drug Conjugates (FDCs).}, journal = {Pharmaceutics}, volume = {14}, number = {8}, pages = {}, pmid = {35893780}, issn = {1999-4923}, abstract = {Antibody-drug conjugates (ADCs) derived from a full immunoglobulin-G (IgG) are associated with suboptimal solid-tumor penetration and Fc-mediated toxicities. Antibody fragment-drug conjugates (FDCs) could be an alternative. Nevertheless, innovative solutions are needed to implant cysteines as conjugation sites in the single-chain fragment variable (scFv) format, which is the backbone from which many other antibody formats are built. In addition, the bioconjugation site has the utmost importance to optimize the safety and efficacy of bioconjugates. Our previous intra-tag cysteine (ITC) strategy consisted of introducing a bioconjugation motif at the C-terminal position of the 4D5.2 scFv, but this motif was subjected to proteolysis when the scFv was produced in CHO cells. Considering these data, using three intra-domain cysteine (IDC) strategies, several parameters were studied to assess the impact of different locations of a site-specific bioconjugation motif in the variable domains of an anti-HER2 scFv. In comparison to the ITC strategy, our new IDC strategy allowed us to identify new fragment-drug conjugates (FDCs) devoid of proteolysis and exhibiting enhanced stability profiles, better affinity, and better ability to kill selectively HER2-positive SK-BR-3 cells in vitro at picomolar concentrations. Thus, this work represents an important optimization step in the design of more complex and effective conjugates.}, } @article {pmid35892151, year = {2022}, author = {Lee, WP and Shetty, SS and Seah, CMJ and Tan, PT and Tan, SM}, title = {Does concomitant ductal carcinoma in situ affect the clinical outcome in breast cancer patients with invasive ductal carcinoma: An Asian perspective.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {5}, number = {9}, pages = {e1646}, pmid = {35892151}, issn = {2573-8348}, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology/therapy ; *Carcinoma, Intraductal, Noninfiltrating/pathology/therapy ; Disease Progression ; Female ; Humans ; Prognosis ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) is an established precursor to invasive ductal carcinoma (IDC) and its coexistence with IDC appear to favor reduced biological aggressiveness. Its prognostic implication and ability to affect clinical outcome has been understudied in Asia. This study aims to explore if concomitant DCIS affects the clinical behavior and outcomes among Asians.

AIM: Stages I to III breast cancer patients with histological proven IDC, diagnosed and treated in a single institution from June 1, 2004 to June 30, 2014 were included in this study. Statistical analyses were conducted using Χ[2] test, independent t test, multivariate logistic regression and Kaplan-Meier test.

METHODS AND RESULTS: A total of 818 patients were identified, including 224 and 594 patients with isolated IDC (No-DCIS) and IDC with coexisting DCIS (IDC-DCIS) respectively. Patients with IDC-DCIS were found to have smaller tumors (median: 22 mm, p ≤ .01), estrogen receptor positivity (p = .001), progesterone receptor positivity (p < .001) and associated with better pathological stage (p = .001). Patients with No-DCIS were 1.6 times more likely to develop disease progression (95% CI: 1.1-2.3, p = .027) and subsequently associated with distant recurrences (20.5% vs. 13.6%, p = .02). The breast cancer specific 5 year overall survival rate for patients with No-DCIS and those with IDC-DCIS was 90.9% (95% CI: 86.2%-94.5%) and 93.7% (95% CI: 91.4%-95.5%), respectively (p = .202).

CONCLUSION: The presence of DCIS component in IDC among Asians is associated with favorable tumor biological profile, thereby indicating reduced disease aggressiveness. Our study is the first to report the clinical significance in terms of disease progression and distant recurrences among Asians.}, } @article {pmid35891814, year = {2022}, author = {Javed, A and Medina, Y and Bux, A and Sahra, S and Rojas-Marte, G}, title = {Rare Case of Reversible Pulmonary Arterial Hypertension Secondary to Cyclophosphamide and Doxorubicin Chemotherapy.}, journal = {Cureus}, volume = {14}, number = {6}, pages = {e26207}, pmid = {35891814}, issn = {2168-8184}, abstract = {Pulmonary arterial hypertension (PAH), characterized as a resting mean pulmonary artery pressure greater than 25 mmHg, is due to the narrowing of the pulmonary arteries, which can be idiopathic, inherited, or drug-related. Alkylating agents, including cyclophosphamide, are a risk factor for developing the pulmonary veno-occlusive disease. Drug-induced PAH is extremely rare. A 59-year-old female with newly diagnosed invasive ductal carcinoma of the right breast and high-grade ductal carcinoma in situ of the left breast was initiated treatment with doxorubicin and cyclophosphamide. About one week after receiving the first cycle, the patient developed worsening lower extremity edema and shortness of breath. She was then hospitalized, and a transthoracic echocardiogram and coronary angiogram revealed PAH. The team then changed the breast cancer treatment regimen to Taxol and carboplatin, and PAH was resolved in a follow-up echocardiogram after five months. This report has described the first case of PAH directly related to cyclophosphamide and doxorubicin. It is imperative to promptly recognize this rare but important side-effect as early diagnosis and response can potentially reverse the disease progression.}, } @article {pmid35890415, year = {2022}, author = {Deguchi, S and Kadowaki, R and Otake, H and Taga, A and Nakazawa, Y and Misra, M and Yamamoto, N and Sasaki, H and Nagai, N}, title = {Combination of Lanosterol and Nilvadipine Nanosuspensions Rescues Lens Opacification in Selenite-Induced Cataractic Rats.}, journal = {Pharmaceutics}, volume = {14}, number = {7}, pages = {}, pmid = {35890415}, issn = {1999-4923}, support = {21K06656//The Ministry of Education, Culture, Sports, Science, and Technology of Japan/ ; }, abstract = {It has recently been reported that lanosterol (LAN) plays a preventive role against lens opacification through the reversal of crystalline aggregation. However, the effect of LAN is not sufficient to restore lens transparency. In this study, we designed ophthalmic nanosuspensions (LAN-ONSs and NIL-ONSs) based on LAN and nilvadipine (NIL), which can counteract cataract-related factors (e.g., enhanced Ca[2+] and calpain levels), and investigated whether the combination of LAN-ONSs and NIL-ONSs can restore the nuclear lens opacity in sodium-selenite-induced cataractic rats (cataractic rats). The mean particle sizes of the LAN-ONSs and NIL-ONSs were 108.8 nm and 89.0 nm, respectively. The instillation of the LAN-ONSs or NIL-ONSs successfully delivered the drugs (LAN or NIL) into the lenses of the rats, although the instillation of LAN-ONSs or NIL-ONSs alone did not increase lens transparency in the cataractic rats. On the other hand, the cataract-related factors (enhanced Ca[2+] and calpain levels) were significantly alleviated by the combination of LAN-ONSs and NIL-ONSs; furthermore, the perinuclear refractile ring in the lens nucleus and enhanced number of swollen fibers were attenuated by the LAN-ONS and NIL-ONS combination. Moreover, the opacity levels in the cataractic rats were reduced after treatment with the combination of LAN-ONSs and NIL-ONSs. It is possible that the combination of LAN and NIL will be useful for the treatment of lens opacification in the future.}, } @article {pmid35884039, year = {2022}, author = {Aggius-Vella, E and Gori, M and Campus, C and Petri, S and Tinelli, F}, title = {Motor Influence in Developing Auditory Spatial Cognition in Hemiplegic Children with and without Visual Field Disorder.}, journal = {Children (Basel, Switzerland)}, volume = {9}, number = {7}, pages = {}, pmid = {35884039}, issn = {2227-9067}, support = {9848349//European Union/ ; RC Finalizzata 2021 and 5x1000 volountary contribution//Governo Italiano/ ; }, abstract = {Spatial representation is a crucial skill for everyday interaction with the environment. Different factors seem to influence spatial perception, such as body movements and vision. However, it is still unknown if motor impairment affects the building of simple spatial perception. To investigate this point, we tested hemiplegic children with (HV) and without visual field (H) disorders in an auditory and visual-spatial localization and pitch discrimination task. Fifteen hemiplegic children (nine H and six HV) and twenty with typical development took part in the experiment. The tasks consisted in listening to a sound coming from a series of speakers positioned at the front or back of the subject. In one condition, subjects were asked to discriminate the pitch, while in the other, subjects had to localize the position of the sound. We also replicated the spatial task in a visual modality. Both groups of hemiplegic children performed worse in the auditory spatial localization task compared with the control, while no difference was found in the pitch discrimination task. For the visual-spatial localization task, only HV children differed from the two other groups. These results suggest that movement is important for the development of auditory spatial representation.}, } @article {pmid35880762, year = {2022}, author = {Billeter, AT and Scheurlen, KM and Israel, B and Straub, BK and Schirmacher, P and Kopf, S and Nawroth, PP and Müller-Stich, BP}, title = {Gastric Bypass Resolves Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Low-BMI Patients: A Prospective Cohort Study.}, journal = {Annals of surgery}, volume = {276}, number = {5}, pages = {814-821}, pmid = {35880762}, issn = {1528-1140}, mesh = {Adipokines ; Adolescent ; Adult ; Aged ; Blood Glucose/metabolism ; Body Mass Index ; C-Peptide ; *Diabetes Mellitus, Type 2/complications ; *Gastric Bypass ; *Gastrointestinal Hormones/metabolism ; Glucagon ; Glycated Hemoglobin/metabolism ; Humans ; Insulin ; *Liver Diseases/complications ; Middle Aged ; *Obesity, Morbid/complications/metabolism/surgery ; Prospective Studies ; Sirtuin 1 ; Young Adult ; }, abstract = {OBJECTIVE: Metabolic dysfunction-associated fatty liver disease (MAFLD) reflects the multifactorial pathogenesis of fatty liver disease in metabolically sick patients. The effects of metabolic surgery on MAFLD have not been investigated. This study assesses the impact of Roux-en-Y gastric bypass (RYGB) on MAFLD in a prototypical cohort outside the guidelines for obesity surgery.

METHODS: Twenty patients were enrolled in this prospective, single-arm trial investigating the effects of RYGB on advanced metabolic disease (DRKS00004605). Inclusion criteria were an insulin-dependent type 2 diabetes, body mass index of 25 to 35 kg/m 2 , glucagon-stimulated C-peptide of >1.5 ng/mL, glycated hemoglobin >7%, and age 18 to 70 years. A RYGB with intraoperative liver biopsies and follow-up liver biopsies 3 years later was performed. Steatohepatitis was assessed by expert liver pathologists. Data were analyzed using the Wilcoxon rank sum test and a P value <0.05 was defined as significant.

RESULTS: MAFLD completely resolved in all patients 3 years after RYGB while fibrosis improved as well. Fifty-five percent were off insulin therapy with a significant reduction in glycated hemoglobin (8.45±0.27% to 7.09±0.26%, P =0.0014). RYGB reduced systemic and hepatic nitrotyrosine levels likely through upregulation of NRF1 and its dependent antioxidative and mitochondrial genes. In addition, central metabolic regulators such as SIRT1 and FOXO1 were upregulated while de novo lipogenesis was reduced and β-oxidation was improved in line with an improvement of insulin resistance. Lastly, gastrointestinal hormones and adipokines secretion were changed favorably.

CONCLUSIONS: RYGB is a promising therapy for MAFLD even in low-body mass index patients with insulin-treated type 2 diabetes with complete histologic resolution. RYGB restores the oxidative balance, adipose tissue function, and gastrointestinal hormones.}, } @article {pmid35880695, year = {2023}, author = {Zhang, J and Lin, H and Hou, L and Xiao, H and Gong, X and Guo, X and Cao, X and Liu, Z}, title = {Exploration of the breast ductal carcinoma in situ signature and its prognostic implications.}, journal = {Cancer medicine}, volume = {12}, number = {3}, pages = {3758-3772}, pmid = {35880695}, issn = {2045-7634}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating ; Prognosis ; Prospective Studies ; *Breast Neoplasms/pathology ; Kaplan-Meier Estimate ; Biomarkers, Tumor/genetics ; *Carcinoma, Ductal, Breast/pathology ; Protein Serine-Threonine Kinases ; NIMA-Related Kinases ; }, abstract = {Following the implementation of breast screening programs, the occurrence of ductal carcinoma in situ (DCIS) as an early type of neoplasia has increased. Although the prognosis is promising, 20%-50% of DCIS patients will progress to invasive ductal carcinoma (IDC) if not treated. It is essential to look for promising biomarkers for predicting DCIS prognosis. The Gene Expression Omnibus (GEO) database was used to explore the expression of genes that differed between DCIS and normal tissue in this investigation. Enrichment analysis was performed to characterize the biological role and intrinsic process pathway. The Cancer Genome Atlas Breast Cancer Dataset was used to categorize the hub genes, and the results were confirmed using the Cytoscape plugin CytoHubba and MCODE. The prognostic ability of the core gene signature was determined through time-dependent receiver operating characteristic (ROC), Kaplan-Meier survival curve, Oncomine databases, and UALCAN databases. In addition, the prognostic value of core genes was verified in proliferation assays. We identified 217 common differentially expressed genes (DEGs) in the present study, with 101 upregulated and 138 downregulated genes. The top genes were obtained from the PPI network (protein-protein interaction). A unique six-gene signature (containing GAPDH, CDH2, BIRC5, NEK2, IDH2, and MELK) was developed for DCIS prognostic prediction. Centered on the Cancer Genome Atlas (TCGA) cohort, the ROC curve showed strong results in prognosis prediction. The six core gene signatures is often overexpressed in DCIS, with a weak prognosis. Furthermore, when breast cancer cells are transfected with small interfering RNAs, downregulation of core gene expression substantially inhibits cell proliferation, revealing a high potential for employing core genes in DCIS prognosis. In conclusion, the current investigation verified the six core genes signatures for prospective DCIS biomarkers, which may aid clinical decision-making for individual care.}, } @article {pmid35879144, year = {2023}, author = {Song, YQ and Hong, J and Wang, JY and Peng, J and Han, JH and Luo, HL}, title = {Dosimetric comparison of different intensity-modulated radiotherapy techniques for whole-breast irradiation of right-breast cancer.}, journal = {Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique}, volume = {27}, number = {1}, pages = {11-16}, doi = {10.1016/j.canrad.2022.04.009}, pmid = {35879144}, issn = {1769-6658}, mesh = {Humans ; Female ; *Breast Neoplasms/radiotherapy/surgery ; *Radiotherapy, Intensity-Modulated/methods ; Radiotherapy Planning, Computer-Assisted/methods ; Breast ; Radiometry ; Radiotherapy Dosage ; Organs at Risk/radiation effects ; }, abstract = {PURPOSE: This study compared the dosimetric parameters of field-in-field forward intensity-modulated radiotherapy (FIF-IMRT) and fixed-field inversely optimized intensity-modulated radiotherapy (FFIO-IMRT) for the whole-breast irradiation of patients undergoing right-breast lumpectomy.

MATERIAL AND METHODS: A total of 30 patients with pT1-2N0M0 right-breast invasive ductal carcinoma were enrolled in this study. Two different treatment plans, i.e., FIF-IMRT and FFIO-IMRT, were designed for each patient. The dosimetric parameters of the two treatment plans were compared including ipsilateral lung and heart, conformity index (CI), and the homogeneity index (HI) of the planning target volume (PTV).

RESULTS: Fixed-field inversely optimized intensity-modulated radiotherapy was found to significantly improve CI (83.302% vs. 60.146%) and HI (11.837% vs. 19.280%), and significantly reduced V25 (18.038% vs. 19.653%) and V30 (15.790% vs. 18.492%) of the ipsilateral lung. It also significantly increased V5 (69.791% vs. 32.615%) of the ipsilateral lung and V5 (61.579% vs. 3.829%), V10 (14.130% vs. 0.381%), V20 (1.843% vs. 0.051%), and Dmean (5.211Gy vs. 1.870Gy) of the heart.

CONCLUSION: Regardless of improving the conformity and homogeneity of PTV and reducing the ipsilateral lung irradiation volume at high doses, FFIO-IMRT significantly raised the ipsilateral lung irradiated volume at low doses, as well as the irradiation volume and mean radiation doses to the heart. This limits its use in patients with early-stage right breast cancer.}, } @article {pmid35875050, year = {2022}, author = {Liu, WC and Li, MX and Wu, SN and Tong, WL and Li, AA and Sun, BL and Liu, ZL and Liu, JM}, title = {Using Machine Learning Methods to Predict Bone Metastases in Breast Infiltrating Ductal Carcinoma Patients.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {922510}, pmid = {35875050}, issn = {2296-2565}, mesh = {Bayes Theorem ; *Breast Neoplasms ; *Carcinoma, Ductal ; Female ; Humans ; Machine Learning ; Quality of Life ; }, abstract = {Breast cancer (BC) was the most common malignant tumor in women, and breast infiltrating ductal carcinoma (IDC) accounted for about 80% of all BC cases. BC patients who had bone metastases (BM) were more likely to have poor prognosis and bad quality of life, and earlier attention to patients at a high risk of BM was important. This study aimed to develop a predictive model based on machine learning to predict risk of BM in patients with IDC. Six different machine learning algorithms, including Logistic regression (LR), Naive Bayes classifiers (NBC), Decision tree (DT), Random Forest (RF), Gradient Boosting Machine (GBM), and Extreme gradient boosting (XGB), were used to build prediction models. The XGB model offered the best predictive performance among these 6 models in internal and external validation sets (AUC: 0.888, accuracy: 0.803, sensitivity: 0.801, and specificity: 0.837). Finally, an XGB model-based web predictor was developed to predict risk of BM in IDC patients, which may help physicians make personalized clinical decisions and treatment plans for IDC patients.}, } @article {pmid35873268, year = {2022}, author = {Cohen, R and Slobodin, O}, title = {An Authentic Inner Compass and Need Satisfaction as Wellbeing Resources in Bedouin Teaching Students During the COVID-19.}, journal = {Frontiers in psychiatry}, volume = {13}, number = {}, pages = {870764}, pmid = {35873268}, issn = {1664-0640}, abstract = {A growing body of literature suggests that students from underserved backgrounds are more vulnerable to the adverse economic, emotional, and academic effects of the current COVID-19 pandemic. While this vulnerability was attributed to multiple structural and socio-cultural barriers, little attention has been paid to the role of psychological resources in preserving wellbeing in times of crisis and change. Guided by the Self-Determination Theory (SDT), the current study examined the role of the authentic inner compass (AIC) and need-satisfaction in predicting the wellbeing of Bedouin students attending teachers' higher education institutes in the south of Israel during the COVID-19. Participants were 84 Bedouin teaching students (84.1% female) who completed online questionnaires addressing the sense of AIC, need-based experiences, psychological distress, and positive affect. Consistent with the propositions of the SDT, we found that a strong and clear sense of AIC, as well as high need satisfaction and low need frustration, were associated with lower distress and higher positive effect in Bedouin teaching students. We have also found that need satisfaction moderated the effect of the AIC on students' wellbeing so that AIC better predicted lower distress and higher positive effect when students' levels of need satisfaction were higher. Our findings lend further support to the importance of the AIC and need satisfaction to optimal functioning even in collectivist cultural contexts that do not prioritize values of autonomy. The current study provides insight into the interplay between AIC and need-based experience by describing the conditions under which AIC may be beneficial for wellbeing in times of crisis.}, } @article {pmid35869577, year = {2022}, author = {Chen, Z and Salibay, C and Elatre, W and Naritoku, WY and Ma, Y and Martin, SE and Wang, T}, title = {Performance of breast fine needle aspiration as an initial diagnostic tool: A large academic hospital experience.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {33}, number = {6}, pages = {707-715}, pmid = {35869577}, issn = {1365-2303}, mesh = {Biopsy, Fine-Needle ; Breast/abnormalities ; *Breast Neoplasms/diagnosis/pathology ; Female ; *Fibroadenoma/diagnosis ; Hospitals ; Humans ; Hypertrophy ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: The clinical performance of the Yokohama reporting system for breast cytology remains uncertain.

METHODS: In this study, we retrospectively evaluated 318 breast fine needle aspirations (FNABs) from Los Angeles County Hospital over a five-year period, analysing data for breast cytology, histology, and radiology.

RESULTS: Among 318 breast FNAB cases, 78.3% (249/318) were benign and 5.3% (17/318) malignant. Of 83 cases with follow-up histology, 14.5% (12/83) were insufficient, 66.3% (55/83) were benign, and 16.9% (17/83) were malignant. Of 55 benign cases, 61.8% (34/55) were fibroadenoma and 9 (9/55, 16.4%) were fibrocystic changes. Two cases were diagnosed as "atypical" but confirmed "benign" on core needle biopsy (CNB). No "suspicious" cases were found. Seventeen malignant cases were confirmed by CNB, including 70.6% (12/17) invasive ductal carcinoma, 11.8% (2/17) invasive lobular carcinoma, and one malignant phyllodes tumour. Receptor studies on cell blocks of three malignant cases showed concordant results with CNB results. In addition, 82.2% (148/180) of lesions with Breast Imaging-Reporting and Data System (BI-RADS) scores of 2 or 3 were benign and 92.3% (12/13) BI-RADS score 5 lesions were malignant on FNAB. Finally, 90% (67/74) of BI-RADS 4a lesions were benign, and 97% (36/37) of fibroadenomas were BI-RADS score 4a.

CONCLUSION: This, by far the largest U.S. breast cytology study, showed 93.3% sensitivity, 100% specificity, 100% positive predictive value, and 98.2% negative predictive value for breast FNAB. Women with breast lesions of BI-RADS score 3 or less have a low risk of malignancy; FNAB would contribute to the reduction of excisional biopsies. FNAB can be considered as an initial diagnostic tool for BI-RADS 4 mass/lesions and satellite lesions, as well as for triaging patients.}, } @article {pmid35868130, year = {2022}, author = {Ou, Q and Li, YD and Chen, J and Yuan, LL and Li, W}, title = {A Very rare case report of male invasive micropapillary breast carcinoma in China and review of literature.}, journal = {International journal of surgery case reports}, volume = {97}, number = {}, pages = {107408}, pmid = {35868130}, issn = {2210-2612}, abstract = {INTRODUCTION: To report a rare case of male breast micropapillary carcinoma (MBMC) with early metastasis of axillary lymph nodes, the molecular characteristics were further studied in both primary and metastatic foci. In addition, we have reviewed similar published cases in the literature and tried to outline the molecular characteristics of this disease.

PRESENTATION OF CASE: A 63-year-old male patient presented with a painless mass on the medial side of left breast and was pathologically diagnosed with MBMC. Postoperative examination revealed 80 % invasive ductal carcinoma (IDC) and 20 % invasive micropapillary carcinoma (IMPC) in the mass, with a histological grade WHO III. There were 25 axillary lymph nodes, 11 of which were metastatic, including 5 macrometastasis and 1 micrometastasis, with a lymph node metastasis rate of 44 % (11/25). Pathological TNM stage: pT2N2M0. Immunohistochemical results in primary foci: AR (90 %, +), HER- 2 (1 +) and ER (90 %, +), PR (60 %, +), E - cadherin (+), EGFR (-), GATA - 3 (90 %, 3 +), Ki - 67 (50 %). Lymph node metastasis: AR (40 %, strong +), HER-2 (2+), ER (90 %, strong +), PR (40 %, strong +), Ki-67 (50 %). AR and Ki-67 were obviously expressed in both primary and metastatic foci. A mixture of IDC and IMPC was found in lymph node metastases, both of which expressed varying degrees of AR and Ki-67.

CLINICAL DISCUSSION: MBMC is easy to early metastasized to lymph node. In this case, there was no significant difference between primary and metastatic cancer in molecular results. It is positive for ER and PR, but negative for HER-2 in this patient. There is few data on male HER-2 expression, HER-2 expression is deficient in this case. AR is found to be positive in 50 % of MBMC cases, although their clinical relevance has not been established yet. The significance of EGFR in the prognosis of MBMC remains unclear, however, EGFR positive expression is not found in this patient.

CONCLUSIONS: MBMC is a rare disease characterized by early lymph node metastasis, high histological grade, positive ER and PR, and generally negative HER-2. The molecular biological characteristics and prognostic significance of MBMC need to be further studied in order to develop the optimal treatment strategy.}, } @article {pmid35866222, year = {2022}, author = {Khanam, R and Islam, S and Rahman, S and Ahmed, S and Islam, A and Hasan, T and Hasan, E and Chowdhury, NH and Roy, AD and Jaben, IA and Nehal, AA and Yoshida, S and Manu, AA and Raqib, R and McCollum, ED and Shahidullah, M and Jehan, F and Sazawal, S and Bahl, R and Baqui, AH}, title = {Sero-prevalence and risk factors for Severe Acute Respiratory Syndrome Coronavirus 2 infection in women and children in a rural district of Bangladesh: A cohort study.}, journal = {Journal of global health}, volume = {12}, number = {}, pages = {05030}, pmid = {35866222}, issn = {2047-2986}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Antibodies, Viral ; Bangladesh/epidemiology ; *COVID-19/epidemiology ; Child ; Cohort Studies ; Communicable Disease Control ; Female ; Humans ; Male ; Prevalence ; Risk Factors ; SARS-CoV-2 ; Seroepidemiologic Studies ; }, abstract = {BACKGROUND: Bangladesh reported its first COVID-19 case on March 8, 2020. Despite lockdowns and promoting behavioural interventions, as of December 31, 2021, Bangladesh reported 1.5 million confirmed cases and 27 904 COVID-19-related deaths. To understand the course of the pandemic and identify risk factors for SARs-Cov-2 infection, we conducted a cohort study from November 2020 to December 2021 in rural Bangladesh.

METHODS: After obtaining informed consent and collecting baseline data on COVID-19 knowledge, comorbidities, socioeconomic status, and lifestyle, we collected data on COVID-like illness and care-seeking weekly for 54 weeks for women (n = 2683) and their children (n = 2433). Between March and July 2021, we tested all participants for SARS-CoV-2 antibodies using ROCHE's Elecsys® test kit. We calculated seropositivity rates and 95% confidence intervals (95% CI) separately for women and children. In addition, we calculated unadjusted and adjusted relative risk (RR) and 95% CI of seropositivity for different age and risk groups using log-binomial regression models.

RESULTS: Overall, about one-third of women (35.8%, 95% CI = 33.7-37.9) and one-fifth of children (21.3%, 95% CI = 19.2-23.6) were seropositive for SARS-CoV-2 antibodies. The seroprevalence rate doubled for women and tripled for children between March 2021 and July 2021. Compared to women and children with the highest household wealth (HHW) tertile, both women and children from poorer households had a lower risk of infection (RR, 95% CI for lowest HHW tertile women (0.83 (0.71-0.97)) and children (0.75 (0.57-0.98)). Most infections were asymptomatic or mild. In addition, the risk of infection among women was higher if she reported chewing tobacco (RR = 1.19,95% CI = 1.03-1.38) and if her husband had an occupation requiring him to work indoors (RR = 1.16,  95% CI = 1.02-1.32). The risk of infection was higher among children if paternal education was >5 years (RR = 1.37, 95% CI = 1.10-1.71) than in children with a paternal education of ≤5 years.

CONCLUSIONS: We provided prospectively collected population-based data, which could contribute to designing feasible strategies against COVID-19 tailored to high-risk groups. The most feasible strategy may be promoting preventive care practices; however, collecting data on reported practices is inadequate. More in-depth understanding of the factors related to adoption and adherence to the practices is essential.}, } @article {pmid35864546, year = {2022}, author = {Zhu, S and Zhao, J and Nie, L and Yin, W and Zhang, Y and Zhao, F and Ni, Y and Zhang, X and Wang, Z and Dai, J and Liu, Z and Chen, J and Zeng, Y and Wang, Z and Sun, G and Liang, J and Zhao, X and Zhu, X and Tao, R and Yang, J and He, B and Chen, N and Shen, P and Zeng, H}, title = {Homologous recombination deficiency (HRD) score in aggressive prostatic adenocarcinoma with or without intraductal carcinoma of the prostate (IDC-P).}, journal = {BMC medicine}, volume = {20}, number = {1}, pages = {237}, pmid = {35864546}, issn = {1741-7015}, mesh = {*Adenocarcinoma/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Homologous Recombination/genetics ; Humans ; Male ; Prostate/pathology ; *Prostatic Neoplasms/pathology ; }, abstract = {BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is a subtype of prostate cancer featured by poor prognosis. Previous studies suggested IDC-P could have a potentially unstable genome. Homologous recombination deficiency (HRD) score is a result-oriented method to describe the genomic instability status. This study investigates the association of HRD scores with IDC-P and other clinicopathological factors and the prognostic implication of HRD scores in an aggressive prostate cancer cohort.

METHODS: This study involved 123 PCa patients, including high-risk localized (M0) and de novo metastatic (M1) diseases. HRD score is calculated based on over 10,000 single-nucleotide polymorphisms distributed across the human genome. We explored the association between HRD scores and clinicopathological characteristics, genomic alterations, and patients' prognoses using rank-sum tests, chi-square tests, Kaplan-Meier curves, and Cox proportional hazards method.

RESULTS: The median HRD score of this cohort is 21.0, with 65 (52.8%) patients showing HRD score≥21. Tumors with IDC-P displayed higher HRD scores than adenocarcinoma (P=0.002); other high HRD score-related factors included M1 (P =0.008) and high ISUP grades (4-5) (P=0.001). MYC mutations were associated with high HRD scores (P<0.001) in the total cohort. TP53 mutations (P=0.010) and HRR pathway mutations (P=0.028) corresponded to high HRD scores in IDC-P positive and non-IDC-P patients, respectively, but not vice versa. HRD scores higher than 21 indicated significantly worse survival in the total cohort.

CONCLUSIONS: M1, high Gleason score, and IDC-P pathology represent higher HRD scores in PCa. Tumors with IDC-P might have different driven mechanisms for high HRD scores than non-IDC-P. HRD score displayed prognostic value in this aggressive prostate cancer cohort.}, } @article {pmid35863289, year = {2022}, author = {Angellotti, G and Tomasicchio, G and Montanaro, AE and Telgrafo, M and Mastropasqua, MG and Punzo, C}, title = {Osteoclast-like stromal giant cells in invasive ductal breast cancer: A case series.}, journal = {International journal of surgery case reports}, volume = {97}, number = {}, pages = {107421}, pmid = {35863289}, issn = {2210-2612}, abstract = {INTRODUCTION: Breast Cancer with osteoclast-like stromal giant cells (OLGCs) is a rare pattern of invasive non-special type ductal carcinoma. The OLGCs are specific type of macrophage and are likely distinct from true osteoclasts. The aim of this case series was to describe the characteristics of this invasive ductal carcinoma rare histotype.

PRESENTATION OF CASES: The authors present the cases of two young women that, during national screening, discovered with mammography X-ray a breast lump suspected for malignancy. The core needle biopsy confirmed the malignancy of both nodule and in one patient the histological analysis revealed pre-operative OLGCs. In both cases the sentinel lymph node biopsy was negative therefore a quadrantectomy without axillary lymphadenectomy was done. The definitive histopathological examination was positive for invasive ductal carcinoma with OLGCs and CD 68 marker positivity. After surgery, patients underwent adjuvant therapy and multidisciplinary follow-up.

DISCUSSION: The origin and mechanism for developing osteoclast-like giant cells is unknown. The OLGCs directly descend from the precursors of the monocyte-macrophage. The rarity of this entity often promotes a misleading diagnosis, with >50 % of erroneous diagnosis of benign lesion. The prognostic significance of OLGCs in breast cancer is controversial, however it doesn't seem to influence the axillary lymph nodes spread. The presence of preoperative OLGCs didn't modify our surgical and oncological approach.

CONCLUSION: Breast Cancer with OLGCs is a rare tumour that has a similar prognosis to other carcinomas of identical grade and stage in most cases. The rarity and characteristics of this neoplasm require personalized treatments, discussed by a multidisciplinary team.}, } @article {pmid35860832, year = {2022}, author = {Chang, PH and Lee, CH and Wu, TM and Yeh, KY and Wang, HM and Huang, WK and Chan, SC and Chou, WC and Kuan, FC and Kuo, HC and Kuo, YC and Hu, CC and Hsieh, JC}, title = {Association of early changes of circulating cancer stem-like cells with survival among patients with metastatic breast cancer.}, journal = {Therapeutic advances in medical oncology}, volume = {14}, number = {}, pages = {17588359221110182}, pmid = {35860832}, issn = {1758-8340}, abstract = {BACKGROUND: This study aimed to investigate the role of circulating tumor cells (CTCs) and circulating cancer stem-like cells (cCSCs) before and after one cycle of chemotherapy and assessed the effects of early changes in CTCs and cCSCs on the outcomes of patients with metastatic breast cancer.

METHODS: Patients with stage IV invasive ductal carcinoma of the breast who received first-line chemotherapy between April 2014 and January 2016 were enrolled. CTCs and cCSCs were measured before the first cycle of chemotherapy (baseline) and on day 21, before the second cycle of chemotherapy commenced; a negative selection strategy and flow cytometry protocol were employed.

RESULTS: CTC and cCSC counts declined in 68.8 and 45.5% of patients, respectively. Declines in CTCs and cCSCs following the first chemotherapy cycle were associated with superior chemotherapy responses, longer progression-free survival (PFS), and longer overall survival (OS). An early decline in cCSCs remained an independent prognostic indicator for OS and PFS in multivariate analysis.

CONCLUSIONS: A cCSC decline after one cycle of chemotherapy for metastatic breast cancer is predictive of a superior chemotherapy response and longer PFS and OS, implying that cCSC dynamic monitoring may be helpful in early prediction of treatment response and prognosis.}, } @article {pmid35855704, year = {2022}, author = {Bhatia, JK and Chaudhary, T and Boruah, D and Bharadwaj, R}, title = {Study of angiogenesis in invasive breast carcinoma by morphometry and immunohistochemistry.}, journal = {Medical journal, Armed Forces India}, volume = {78}, number = {3}, pages = {345-354}, pmid = {35855704}, issn = {0377-1237}, abstract = {BACKGROUND: Breast cancer is the leading cause of cancer-related deaths in Asia and is emerging as the commonest female malignancy. Angiogenesis or neovascularization is important for the growth and spread of malignant tumors, and quantitative assessment of angiogenesis may prove valuable in prognostication. This study was undertaken to quantify and explore angiogenesis with immunohistochemistry with CD 34, CD 105, and vascular endothelial growth factor (VEGF), as well as morphometric analysis and correlate with the grades of the invasive breast carcinoma.

METHODS: Angiogenesis was assessed by morphometry and immunohistochemistry. Seventy cases of invasive ductal carcinoma (IDC) and twenty-five benign cases as controls were included in the study. Morphometry was performed on the CD34 and CD105 (Endoglin) stained representative histologic sections with the use of a computerized digital photomicrograph system using image analyzing software. Morphometric analysis and evaluation of vascular parameters, i.e. microvessel density (MVD), microvessel caliber (VC), and total microvessel boundary density (TVBD), were calculated. Semiquantitative assessment of angiogenesis of VEGF-stained sections was done by scoring. Immunohistochemical staining was correlated with the histological grade of the tumors. MVD, mean VC, TVBD with their mean values, SD, and range were calculated using Statistical Package for The Social Sciences (Version 20). One-way analysis of variance (ANOVA) with Tukey HSD was performed to assess the difference of the parameters for the groups. Spearman rank correlation coefficients ρ were calculated.

RESULTS: The vascular parameters were significantly more in malignant lesions as compared to benign lesions and showed differences with increasing grade. Grades of breast carcinoma showed a mild positive correlation with VEGF (ρ = 0.467), MVD-CD34 (ρ = 0.422) and VC-CD34 (ρ = 0.482); and moderate positive correlation with TVBD-CD34 (ρ = 0.615), VC-CD105 (ρ = 0.527), and TVBD-CD105 (ρ = 0.354). When these parameters were compared with each other for all four groups, VEGF showed a mild positive correlation with MVD-CD34 (ρ = 0.295), TVBD-CD34 (ρ = 0.339), and TVBD-CD105 ((ρ = 0.277). MVD-CD105 showed a mild positive correlation with MVD-CD34 TVBD-CD105 also showed a strong positive correlation with MVD-CD34. VC-CD105 showed a moderate positive correlation with VC-CD34. CD 105 stained fewer but larger caliber vessels.

CONCLUSIONS: In this study, vascular parameters showed significant differences in three grades of IDC with CD34. Differences were seen in vascular parameters stained with CD105 in three grades of IDC. Expression of VEGF also showed significant differences with positive correlations in the three grades of IDC. CD34 highlighted both old and newly formed microvessels. CD 105 stained fewer but larger caliber microvessels. VC-CD105 can be an extremely useful adjunct along with VEGF and CD34 to study angiogenesis of vessels in IDC.}, } @article {pmid35855193, year = {2022}, author = {Somashekhar, SP and Jaiswal, R and Kumar, R and Ashok, BC and Rakshit, S and Rauthan, A and Patil, P and Yashas, N and Karthik, HK and Prasad, A and Islam, H and Ashwin, KR}, title = {An Overview of the Impact of Body Mass Index on Pathological Complete Response Following Neoadjuvant Chemotherapy in Operable Breast Cancer in a Tertiary Care Centre in South India.}, journal = {European journal of breast health}, volume = {18}, number = {3}, pages = {271-278}, pmid = {35855193}, issn = {2587-0831}, abstract = {OBJECTIVE: The incidence of female breast cancer in the world is 11.7% with a mortality rate of 6.9%. According to Globocon 2020, breast cancer is the most commonly diagnosed cancer (24.5%) and the leading cause of cancer-related death amongst women worldwide. The purpose of this study was to analyze the impact of Body Mass Index (BMI) on pathological complete response (pCR) rates for operable breast cancer after neoadjuvant chemotherapy (NACT). The primary endpoint was to assess histopathological features of the surgical specimen in response to NACT and to investigate the relationship with pre-chemotherapy BMI taking into account the various molecular subtypes of breast cancer.

MATERIALS AND METHODS: Patients with biopsy-proven breast carcinoma who underwent surgery after NACT between January 2017 and May 2021 were included. All patients were initially divided into three groups depending on their pre-chemotherapy BMI. With BMI <22.9 as normal or underweight category, BMI of 23-27.4, was taken as overweight category and BMI ≥27.5 as obese category.

RESULTS: The study included 184 patients. Normal weight patients had the highest rate of pCR (75%) and the lowest was seen in the obese category (33.75%). Furthermore, the subtype most likely to achieve pCR was HER2+/ER negative followed by triple negative BC with odds ratios of 3.46 and 2.21, respectively.

CONCLUSION: This retrospective study established that overweight and obese patients suffering from breast carcinoma had a lessened pCR rate following NACT in comparison with those who were under-/normal weight.}, } @article {pmid35852797, year = {2022}, author = {Tokura, M and Nakayama, J and Prieto-Vila, M and Shiino, S and Yoshida, M and Yamamoto, T and Watanabe, N and Takayama, S and Suzuki, Y and Okamoto, K and Ochiya, T and Kohno, T and Yatabe, Y and Suto, A and Yamamoto, Y}, title = {Single-Cell Transcriptome Profiling Reveals Intratumoral Heterogeneity and Molecular Features of Ductal Carcinoma In Situ.}, journal = {Cancer research}, volume = {82}, number = {18}, pages = {3236-3248}, doi = {10.1158/0008-5472.CAN-22-0090}, pmid = {35852797}, issn = {1538-7445}, mesh = {Biomarkers ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Female ; Gene Expression Profiling ; Humans ; }, abstract = {UNLABELLED: Ductal carcinoma in situ (DCIS) is a precursor to invasive breast cancer. The frequency of DCIS is increasing because of routine mammography; however, the biological features and intratumoral heterogeneity of DCIS remain obscure. To address this deficiency, we performed single-cell transcriptomic profiling of DCIS and invasive ductal carcinoma (IDC). DCIS was found to be composed of several transcriptionally distinct subpopulations of cancer cells with specific functions. Several transcripts, including long noncoding RNAs, were highly expressed in IDC compared with DCIS and might be related to the invasive phenotype. Closeness centrality analysis revealed extensive heterogeneity in DCIS, and the prediction model for cell-to-cell interactions implied that the interaction network among luminal cells and immune cells in DCIS was comparable with that in IDC. In addition, transcriptomic profiling of HER2+ luminal DCIS indicated HER2 genomic amplification at the DCIS stage. These data provide novel insight into the intratumoral heterogeneity and molecular features of DCIS, which exhibit properties similar to IDC.

SIGNIFICANCE: Investigation of the molecular features of ductal carcinoma in situ at single cell resolution provides new insights into breast cancer biology and identifies candidate therapeutic targets and diagnostic biomarkers.}, } @article {pmid35851387, year = {2022}, author = {Thennavan, A and Garcia-Recio, S and Liu, S and He, X and Perou, CM}, title = {Molecular signatures of in situ to invasive progression for basal-like breast cancers: An integrated mouse model and human DCIS study.}, journal = {NPJ breast cancer}, volume = {8}, number = {1}, pages = {83}, pmid = {35851387}, issn = {2374-4677}, support = {R01 CA148761/CA/NCI NIH HHS/United States ; P50 CA058223/CA/NCI NIH HHS/United States ; R01 CA195740/CA/NCI NIH HHS/United States ; RO1-CA148761//Breast Cancer Research Foundation (BCRF)/ ; P30 CA016086/CA/NCI NIH HHS/United States ; RO1-CA195740//Breast Cancer Research Foundation (BCRF)/ ; }, abstract = {Ductal carcinoma in situ (DCIS) of the breast is a non-obligate precursor of Invasive Ductal Carcinoma (IDC) and thus the identification of features that may predict DCIS progression would be of potential clinical value. Experimental mouse models can be used to address this challenge by studying DCIS-to-IDC biology. Here we utilize single cell RNA sequencing (scRNAseq) on the C3Tag genetically engineered mouse model that forms DCIS-like precursor lesions and for which many lesions progress into end-stage basal-like molecular subtype IDC. We also perform bulk RNAseq analysis on 10 human synchronous DCIS-IDC pairs comprised of estrogen receptor (ER) positive and ER-negative subsets and utilize 2 additional public human DCIS data sets for comparison to our mouse model. By identifying malignant cells using inferred DNA copy number changes from the murine C3Tag scRNAseq data, we show the existence of cancer cells within the C3Tag pre-DCIS, DCIS, and IDC-like tumor specimens. These cancer cells were further classified into proliferative, hypoxic, and inflammatory subpopulations, which change in frequency in DCIS versus IDC. The C3Tag tumor progression model was also associated with increase in Cancer-Associated Fibroblasts and decrease in activated T cells in IDC. Importantly, we translate the C3Tag murine genomic findings into human DCIS where we find common features only with human basal-like DCIS, suggesting there are intrinsic subtype unique DCIS features. This study identifies several tumor and microenvironmental features associated with DCIS progression and may also provide genomic signatures that can identify progression-prone DCIS within the context of human basal-like breast cancers.}, } @article {pmid35847444, year = {2022}, author = {Minagawa, T and Sugiura, T and Okamura, Y and Ito, T and Yamamoto, Y and Ashida, R and Ohgi, K and Sasaki, K and Uesaka, K}, title = {Clinical implications of lymphadenectomy for invasive ductal carcinoma of the body or tail of the pancreas.}, journal = {Annals of gastroenterological surgery}, volume = {6}, number = {4}, pages = {531-542}, pmid = {35847444}, issn = {2475-0328}, abstract = {AIM: The appropriate extent of lymphadenectomy for pancreatic cancer of the body/tail has not been standardized worldwide. The present study evaluated the optimal extent of harvesting lymph nodes.

METHODS: Patients who underwent distal pancreatectomy for invasive ductal carcinoma of the pancreas between 2007 and 2018 were retrospectively reviewed. Patients were subclassified into three groups depending on the tumor location: pancreatic body (Pb), proximal pancreatic tail (Ptp), and distal pancreatic tail (Ptd). The pancreatic tail was further divided into even sections of Ptp and Ptd. Patterns of lymph node metastasis and the impact of lymph node metastasis on the prognosis were examined.

RESULTS: A total of 120 patients were evaluated. Fifty-eight patients had a tumor in the Pb, 38 in the Ptp, and 24 in the Ptd. No patients with a Ptd tumor had metastasis beyond the peripancreatic and splenic hilar lymph nodes (LN-PSH). All patients with metastasis to the lymph nodes along the common hepatic artery (LN-CHA) or along the left lateral superior mesenteric artery (LN-SMA) also had metastasis to the LN-PSH. Recurrence after surgery occurred significantly earlier in this population. In a multivariate analysis, metastasis to the LN-CHA or LN-SMA (hazard ratio [HR] 3.3; P = .04) was an independent risk factor for overall survival. Furthermore, high levels of preoperative serum CA19-9 (HR 10.9; P = .013) were a predictive factor for metastasis to the LN-CHA or LN-SMA.

CONCLUSIONS: Metastasis to the LN-CHA or LN-SMA was rare but a significant prognostic factor in patients with pancreatic body/tail cancer.}, } @article {pmid35846408, year = {2023}, author = {Chen, XY and Thike, AA and Lim, JX and Bay, BH and Tan, PH}, title = {More microinvasive foci in larger tumours of breast ductal carcinoma in situ.}, journal = {Singapore medical journal}, volume = {64}, number = {8}, pages = {493-496}, pmid = {35846408}, issn = {2737-5935}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating ; Prognosis ; Disease-Free Survival ; Progression-Free Survival ; *Breast Neoplasms ; *Carcinoma, Ductal, Breast/pathology ; Neoplasm Invasiveness ; }, abstract = {INTRODUCTION: Microinvasion (Mi) is often thought to be an interim stage between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. This study aimed to investigate the potential influence of Mi on survival and assess its correlations with clinicopathological parameters, prognosis and molecular markers.

METHODS: The number of Mi foci in a cohort of 66 DCIS-Mi cases was assessed from haematoxylin and eosin-stained sections. Disease-free survival, clinicopathological parameters and biomarker expression were correlated with the number of Mi foci.

RESULTS: Higher numbers of Mi foci were found in larger tumours (P = 0.031).

CONCLUSION: Greater extent of DCIS is associated with multifocal Mi.}, } @article {pmid35846138, year = {2022}, author = {Niu, X and Ren, L and Wang, S and Gao, D and Ma, M and Hu, A and Qi, H and Zhang, S}, title = {High Prolyl 4-Hydroxylase Subunit Alpha 3 Expression as an Independent Prognostic Biomarker and Correlated With Immune Infiltration in Gastric Cancer.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {952335}, pmid = {35846138}, issn = {1664-8021}, abstract = {Background: Gastric cancer (GC) has a high mortality rate and is particularly prevalent in China. The extracellular matrix protein, prolyl 4-hydroxylase subunit alpha 3 (P4HA3), has been implicated in various cancers. We aimed to assess the diagnostic and prognostic value of P4HA3 in GC and investigate its correlation with immune cell infiltration. Methods: The present study used microarray data from the Cancer Genome Atlas (TCGA) to analyze the association of P4HA3 expression with clinicopathological features. Data from the Gene Expression Omnibus (GEO) were used for validation. Receiver operating characteristic (ROC) and Kaplan-Meier curves were constructed to determine the diagnostic and prognostic value of P4HA3 in GC. Univariate and multivariate regression analyses were performed to assess the impact of P4HA3 on overall survival (OS) rates. A protein-protein interaction (PPI) network was generated and functional enrichment evaluated. Single-sample gene set enrichment analysis (ssGSEA) was conducted to correlate P4HA3 expression with immune cell infiltration. The correlation between P4HA3 and immune check point genes was studied. Results: P4HA3 was over-expressed in GC, along with 15 other types of cancer, including breast invasive carcinoma and cholangiocarcinoma. P4HA3 showed high diagnostic and prognostic value in GC and was an independent prognostic factor. P4HA3, TNM (tumor, node, metastases) stage, pathological stage and age all correlated with OS rates. Genes related to P4HA3 were enriched in the lumen of the endoplasmic reticulum and included procollagen-proline 3-dioxygenase activity. P4HA3 expression correlated with numbers of macrophages, natural killer (NK) cells, immature dendritic cells (iDC), mast cells, eosinophils, effective memory T cells (Tem), T-helper 1 (Th1) cells and dendritic cells (DC). P4HA3 was positively correlated with hepatitis A virus cellular receptor 2 (HAVCR2) and programmed cell death 1 ligand 2 (PDCD1LG2). Conclusion: P4HA3 is a potential independent biomarker for prognosis of GC and may be an immunotherapy target in the treatment of GC.}, } @article {pmid35842661, year = {2022}, author = {Zhang, WT and Zhu, GL and Xu, WQ and Zhang, W and Wang, HZ and Wang, YB and Li, YX}, title = {Association of PD-1/PD-L1 expression and Epstein--Barr virus infection in patients with invasive breast cancer.}, journal = {Diagnostic pathology}, volume = {17}, number = {1}, pages = {61}, pmid = {35842661}, issn = {1746-1596}, support = {No.2008085QH408//Natural Science Foundation of Anhui Province/ ; No.81874063//National Natural Science Foundation of China/ ; }, mesh = {B7-H1 Antigen/metabolism ; Biomarkers, Tumor/analysis ; *Breast Neoplasms ; *Epstein-Barr Virus Infections/complications ; Female ; Herpesvirus 4, Human ; Humans ; Ligands ; Prognosis ; Programmed Cell Death 1 Receptor ; }, abstract = {PURPOSE: Causative factors of breast cancer include infections, such as Epstein-Barr virus (EBV) infection. The aim of this study was to analyze the clinicopathological features of EBV-positive (IBC) and determine if EBV affects programmed cell death receptor 1 (PD-1)/PD ligand 1 (PD-L1) expression in IBC, similar to other EBV-infected tumors with PD-L1/PD-1 expression.

METHODS: We collected 140 samples of IBC tissues and 25 samples of adjacent tissues. All patients were followed-up by telephone from the day of surgery to December 2020. Chromogenic in-situ hybridization was performed to evaluate EBV-encoded RNA (EBER). Immunohistochemistry was performed to evaluate PD-L1 and PD-1 expressions. The correlation between PD1/PDL1 expression and clinicopathological features was also analyzed.

RESULTS: EBER was detected in 57 of 140 (40.7%) IBC tissues and not detected in any adjacent tissue (P < 0.05). Clinicopathologic features of patients were consistent with EBV-associated IBC. EBV infection was correlated with the mass size, menopausal status, axillary lymph node metastasis, vascular invasion, Ki-67 index, clinical stage, and estrogen receptor and progesterone receptor expressions (all P < 0.05), but not with the histological type, invasive ductal carcinoma histological grade, or human epidermal growth factor receptor 2 (HER2) expression (all P > 0.05). The positive rate of PD-1/PD-L1 expression was higher in the EBV-positive group than in the EBV-negative group (P < 0.05). The Kaplan-Meier univariate survival analysis showed that EBV was associated with poor disease-free survival and overall survival in patients with IBC. PD-L1/PD-1 expression could predict a poor prognosis.

CONCLUSIONS: In this study, clinicopathologic characteristics of patients were consistent with EBV-infected IBC. Patients with EBV-positive breast cancer were more likely to have elevated PD-1/PDL-1 expression compared to those with EBV-negative breast cancer. This finding could serve as a basis to explore therapeutic targets, particularly immunotherapy, for patients with IBC.}, } @article {pmid35837116, year = {2022}, author = {Yang, L and Li, Z and Liang, X and Xu, J and Cai, Y and Huang, C and Zhang, M and Yao, J and Song, B}, title = {Radiomic Machine Learning and External Validation Based on 3.0 T mpMRI for Prediction of Intraductal Carcinoma of Prostate With Different Proportion.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {934291}, pmid = {35837116}, issn = {2234-943X}, abstract = {PURPOSE: To assess the association of radiomics features based on multiparametric MRI (mpMRI) with the proportion of intraductal carcinoma of prostate (IDC-P) and validate the predictive models.

MATERIALS AND METHODS: We retrospectively included pre-treatment MR images of prostate cancer (PCa) with IDC components of high proportion (≥10%, hpIDC-P), low proportion (<10%, lpIDC-P), and pure acinar adenocarcinoma (PAC) from our institution for training and internal validation and cooperated cohort for external validation. Normalized images of T2WI, diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) map, and dynamic contrast enhanced (DCE) sequences were used for radiomics modeling. The clinical model was built based on serum total prostate specific antigen (tPSA) and Gleason score (GS), and the integrated model was the combination of Rad-score and clinicopathological data. The discrimination ability was assessed by area under the receiver operating characteristic curve (ROC-AUC) in the internal and external validation sets and compared by DeLong test.

RESULTS: Overall, 97 patients with hpIDC-P, 87 lpIDC-P, and 78 PAC were included for training and internal validation, and 11, 16, and 19 patients for external validation. The integrated model for predicting hpIDC-P got the best ROC-AUC of 0.88 (95%CI = 0.83-0.93) in internal and 0.86 (95%CI = 0.72-1.0) in external validation, which both outperformed clinical models (AUC=0.78, 95% CI = 0.72-0.85, AUC=0.69, 95% CI = 0.5-0.85, respectively) based solely on GS, and the radiomics model (AUC=0.85, 95% CI = 0.79-0.91) was slightly inferior to the integrated model and better than the clinical model in internal dataset. The integrated model for predicting lpIDC-P outperformed both radiomics and clinical models in the internal dataset, while slightly inferior to the integrated model for predicting hpIDC-P.

CONCLUSIONS: Radiomics signature improved differentiation of both hpIDC-P and lpIDC-P versus PAC when compared with the clinical model based on Gleason score, and was validated in an external cohort.}, } @article {pmid35836477, year = {2022}, author = {Wu, X and Liu, Y and Zhu, J and Yu, W and Lin, X}, title = {A Prospective Trial of the Microneedle Fractional Radiofrequency System Application in the Treatment of Infraorbital Dark Circles.}, journal = {Clinical, cosmetic and investigational dermatology}, volume = {15}, number = {}, pages = {1293-1300}, pmid = {35836477}, issn = {1178-7015}, abstract = {BACKGROUND: Infraorbital dark circles (IDC) are commonly consulted in aesthetic practice. There is not yet a multifactorial approach to facilitating their treatment.

OBJECTIVE: To investigate the safety and efficacy of the microneedle fractional radiofrequency (MRF) system for the treatment of IDC.

METHODS: A prospective, split-face, evaluator-blind clinical trial was conducted to study the change in the overall appearance, color, and wrinkles in 21 female patients with mixed type IDC before and after MFR treatment.

RESULTS: Both patients and independent evaluators found significant improvement on the global aesthetic scales after the MFR treatment, especially on periorbital wrinkles (p=0.031). Trends in decreased melanin density in the IDC area were found, but no statistical differences were established. No side effects were observed.

CONCLUSION: MFR is a safe and effective modality for improving mixed type IDC by correcting the structural factors.}, } @article {pmid35834927, year = {2022}, author = {Syamsu, SA and Setiady, R and Smaradania, N and Prihantono, and Irsandy, F and Faruk, M}, title = {Synchronous breast cancer and non-Hodgkin lymphoma: A case report.}, journal = {International journal of surgery case reports}, volume = {97}, number = {}, pages = {107398}, pmid = {35834927}, issn = {2210-2612}, abstract = {INTRODUCTION: Among women, breast cancer (BC) is the most prevalent type of cancer and the top cause of cancer deaths. Although non-Hodgkin lymphoma (NHL) is the most prevalent hematological cancer, it is rarely reported synchronous with BC. Moreover, which malignancy appears first can rarely be explained because they are usually detected incidentally while diagnosing and treating other malignancies. This paper reports a case of invasive ductal carcinoma (IDC) concomitant with NHL.

PRESENTATION OF CASE: A 35-year-old woman presented with simultaneous IDC in the left breast and NHL in a lymph node in the neck. The patient underwent a modified radical mastectomy for stage IIIA IDC and received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy for stage I NHL.

CLINICAL DISCUSSION: Treating BC and NHL remains challenging due to their significantly different management, the lack of guidelines for treating BC and lymphoma simultaneously, and uncertainty about whether synchronous tumors should be treated separately as distinct clinical entities or as one disease with treatment covering both. Therefore, the best approach continues to be focusing on the most biologically aggressive malignancies.

CONCLUSION: The enlargement of lymph nodes not in the lymphatic drainage of the primary tumor should be suspected of indicating multiple primary malignancies until proven otherwise. For patients with luminal-B BC, NHL chemotherapy can involve receiving the R-CHOP regimen, including doxorubicin and cyclophosphamide, which can help to mitigate BC.}, } @article {pmid35821630, year = {2022}, author = {Ciudad, P and Escandón, JM and Manrique, OJ and Gutierrez-Arana, J and Mayer, HF}, title = {Lymphedema prevention and immediate breast reconstruction with simultaneous gastroepiploic vascularized lymph node transfer and deep inferior epigastric perforator flap: A case report.}, journal = {Microsurgery}, volume = {42}, number = {6}, pages = {617-621}, doi = {10.1002/micr.30939}, pmid = {35821630}, issn = {1098-2752}, mesh = {*Breast Neoplasms/complications/surgery ; Female ; Humans ; Lymph Nodes/blood supply ; *Lymphedema/etiology/prevention & control/surgery ; *Mammaplasty/adverse effects/methods ; Mastectomy/adverse effects ; Middle Aged ; *Perforator Flap/blood supply ; }, abstract = {Breast cancer-related lymphedema following axillary lymph node dissection (ALND) has been documented in 6%-55% of patients, mostly occurring within the next 3 years after radiation or surgery. We present a case of a 53-year-old patient with hormone positive, stage IB, left breast invasive ductal carcinoma treated with immediate lymphatic and microvascular breast reconstruction (MBR) using vascularized lymph node transfer (VLNT) for lymphedema prevention. A deep inferior epigastric perforator (DIEP) flap (18.3 × 11.2-cm) and simultaneous prophylactic gastroepiploic-VLNT (7 × 3-cm), orthotopically inset in the axilla, were used for reconstruction following mastectomy and radical ALND. The procedure was uneventful. The patient did not display increased postoperative arm circumferences. ICG lymphography did not show any changes at 2- and 3-years after surgery. Preventive lymphatic reconstruction with GE-VLNT and immediate MBR using the DIEP flap offers a new possibility for the primary prevention of lymphedema and simultaneous immediate autologous breast reconstruction without the risk of iatrogenic lymphedema. Further studies will be directed to unveil the external validity of these findings and the risk reduction rate of this approach.}, } @article {pmid35810223, year = {2022}, author = {Abel, MK and Shui, AM and Chien, AJ and Rugo, HS and Melisko, M and Baehner, F and Mukhtar, RA}, title = {The 21-Gene Recurrence Score in Clinically High-Risk Lobular and Ductal Breast Cancer: A National Cancer Database Study.}, journal = {Annals of surgical oncology}, volume = {29}, number = {12}, pages = {7739-7747}, pmid = {35810223}, issn = {1534-4681}, support = {K08 CA256047/CA/NCI NIH HHS/United States ; K08CA256047/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/pathology ; Cohort Studies ; Databases, Factual ; Female ; Humans ; Middle Aged ; }, abstract = {OBJECTIVE: The aim of this study was to evaluate whether patients with invasive lobular carcinoma (ILC) are more likely to have discordant clinical and genomic risk than those with invasive ductal carcinoma (IDC) when using the 21-gene recurrence score (RS), and to assess overall survival outcomes of patients with 1-3 positive nodes and RS ≤25 with and without chemotherapy, stratified by histology.

METHODS: We performed a cohort study using the National Cancer Database and included patients with hormone receptor-positive, HER2-negative, stage I-III invasive breast cancer who underwent 21-gene RS testing. Our primary outcome was rate of discordant clinical and genomic risk status by histologic subtype. Propensity score matching was used to compare 60-month overall survival in individuals with 1-3 positive nodes and RS ≤25 who did and did not receive chemotherapy.

RESULTS: Overall, 186,867 patients were included in our analysis, including 37,685 (20.2%) patients with ILC. There was a significantly higher rate of discordant clinical and genomic risk in patients with ILC compared with IDC. Among patients with 1-3 positive nodes and RS ≤25, there was no significant difference in survival between those who did and did not receive chemotherapy in the IDC or ILC cohorts. Unadjusted exploratory analyses of patients under age 50 years with 1-3 positive nodes and RS ≤25 showed improved overall survival in IDC patients who received chemotherapy, but not among those with ILC.

CONCLUSION: Our findings highlight the importance of lobular-specific tools for stratifying clinical and genomic risk, as well as the need for histologic subtype-specific analyses in randomized trials.}, } @article {pmid35805604, year = {2022}, author = {Shenkman, G and Levy, S and Winkler, ZB and Bass, D and Geller, S}, title = {Higher Levels of Postnatal Depressive Symptomatology, Post-Traumatic Growth, and Life Satisfaction among Gay Fathers through Surrogacy in Comparison to Heterosexual Fathers: A Study in Israel in Times of COVID-19.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {13}, pages = {}, pmid = {35805604}, issn = {1660-4601}, mesh = {*COVID-19 ; Fathers/psychology ; Female ; Heterosexuality/psychology ; Homosexuality, Male/psychology ; Humans ; Israel/epidemiology ; Male ; Personal Satisfaction ; *Posttraumatic Growth, Psychological ; Pregnancy ; *Sexual and Gender Minorities ; Gestational Carriers/psychology ; }, abstract = {This study aimed to explore the psychological welfare, as indicated by postnatal depressive symptomatology, life satisfaction, and posttraumatic growth (growth after contending with stressful birth events), of Israeli gay fathers through surrogacy in comparison to heterosexual fathers. For that purpose, a sample of 167 Israeli fathers (M = 35.6, SD = 4.4) was recruited (68 identified as gay fathers through surrogacy and 99 as heterosexual fathers). Participants completed questionnaires assessing their postnatal depressive symptomatology, life satisfaction, and sense of posttraumatic growth after becoming fathers. Results indicated that gay fathers through surrogacy reported higher levels of life satisfaction and posttraumatic growth than heterosexual fathers. Yet, gay fathers also reported higher levels of postnatal depressive symptomatology than heterosexual fathers when life satisfaction or posttraumatic growth values were low or medium. The findings were interpreted in light of the hardships associated with cross-border surrogacy and the psychological outcomes associated with succeeding to become fathers after contending with them. The study contributes to the limited literature on postnatal depressive symptomatology and posttraumatic growth among gay fathers through surrogacy and provides clinicians and policymakers with relevant information on the psychological strengths and potential difficulties associated with cross-border surrogacy among gay fathers.}, } @article {pmid35804316, year = {2022}, author = {Chang, C and Zhu, J and Li, H and Yang, Q}, title = {Enhanced magnetic resonance imaging manifestations of paediatric intervertebral disc calcification combined with ossification of the posterior longitudinal ligament: case report and literature review.}, journal = {BMC pediatrics}, volume = {22}, number = {1}, pages = {400}, pmid = {35804316}, issn = {1471-2431}, mesh = {*Calcinosis/diagnostic imaging ; Cervical Vertebrae/diagnostic imaging ; Child ; Female ; Humans ; *Intervertebral Disc/diagnostic imaging/pathology ; Longitudinal Ligaments/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; *Ossification of Posterior Longitudinal Ligament/complications/diagnostic imaging ; Osteogenesis ; }, abstract = {BACKGROUND: Since the first description of paediatric intervertebral disc calcification (IDC) by Báron in 1924, only approximately 400 cases have been reported in the literature. Paediatric IDC combined with ossification of the posterior longitudinal ligament (OPLL) is an even rarer condition, with only 8 cases described in detail to date. In this paper, we present a review of the disease characteristics described in the relevant English language literature and discuss the possible mechanisms of lesion enhancement in contrast-enhanced magnetic resonance imaging (MRI).

CASE PRESENTATION: In May 2020, a 6-year-old Han nationality girl presented with the chief complaint of neck pain that had lasted for a week. She did not report a history of trauma or a past illness. On admission, there was no personal and family history, congenital diseases, or non-specific infections such as tuberculosis, among others. Further physical examination revealed that the movement of her cervical spine was limited. Computed tomography (CT) and MRI revealed ossification of the intervertebral discs and posterior longitudinal ligament (PLL) at the C4/5 levels and an absence of obvious spinal cord compression. When contrast-enhanced MRI was performed, significant enhancement was observed in the intervertebral discs and PLL at the C4/5 level. We adopted a non-interventional approach and performed an imaging re-examination 8 months later. Both the plain and contrast-enhanced MRI scans indicated swelling in the C4/5 intervertebral discs and disappearance of the previously observed enhancement in the nucleus pulposus (NP) and PLL at the corresponding levels; CT examination revealed that the ossified lesions had been completely resorbed.

CONCLUSION: Obvious lesion enhancement in contrast-enhanced MRI is an extremely rare manifestation of paediatric IDC combined with OPLL. However, the exact mechanisms of this phenomenon remain unclear. We surmise that it may be caused by a series of biophysical changes related to vertebral endplate injury and repair, but further research will be required for in-depth investigation.}, } @article {pmid35803346, year = {2022}, author = {de Barros, HA and Remmers, S and Luiting, HB and van Leenders, GJLH and Roobol, MJ and Bekers, EM and Amin, A and Haynes, AM and Delprado, W and Stricker, PD and van der Poel, HG and van der Kwast, TH and van Leeuwen, PJ}, title = {Predictive Value of Cribriform and Intraductal Carcinoma for the Nomogram-based Selection of Prostate Cancer Patients for Pelvic Lymph Node Dissection.}, journal = {Urology}, volume = {168}, number = {}, pages = {156-164}, doi = {10.1016/j.urology.2022.04.043}, pmid = {35803346}, issn = {1527-9995}, mesh = {Humans ; Male ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Retrospective Studies ; Lymph Nodes/pathology ; Lymph Node Excision ; Nomograms ; *Prostatic Neoplasms/pathology ; Lymphatic Metastasis/pathology ; }, abstract = {OBJECTIVE: To assess the predictive value of biopsy-identified cribriform carcinoma and/or intraductal carcinoma (CR/IDC) within the Briganti and MSKCC nomograms predicting lymph node metastasis (LNM) in patients with primary prostate cancer (PCa).

METHODS: We retrospectively included 393 PCa patients who underwent radical prostatectomy with extended pelvic lymph node dissection at 3 tertiary referral centers. We externally validated 2 prediction tools: the Briganti 2012 nomogram and the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. Both nomograms were augmented with CR/IDC. The original model was compared with the CR/IDC-updated model using the likelihood ratio test. The performance of the prediction tools was assessed using calibration, discrimination, and clinical utility.

RESULTS: Overall, 109 (28%) men were diagnosed with LNM. Calibration plots of the Briganti and MSKCC nomograms demonstrated an underestimation of the LNM risk across clinically relevant thresholds (≤15%). The addition of CR/IDC to the Briganti nomogram increased the fit of the data (χ[2](1) = 4.30, P = .04), but did not improve the area under the curve (AUC) (0.69, 95% CI 0.63-0.75 vs 0.69, 95% CI 0.64-0.75). Incorporation of CR/IDC in the MSKCC nomogram resulted in an increased fit on the data (χ[2](1) = 10.04, P <.01), but did not increase the AUC (0.66, 95% CI 0.60-0.72 vs 0.68, 95% CI 0.62-0.74). The addition of CR/IDC to the Briganti and MSKCC nomograms did not improve the clinical risk prediction.

CONCLUSION: Incorporation of CR/IDC into the 2 clinically most used pre-radical prostatectomy nomograms does not improve LNM prediction in a multinational, contemporary PCa cohort.}, } @article {pmid35801025, year = {2022}, author = {Yang, SY and Li, Y and Nie, JY and Yang, ST and Yang, XJ and Wang, MH and Zhang, J}, title = {Metaplastic breast cancer with chondrosarcomatous differentiation combined with concurrent bilateral breast cancer: A case report.}, journal = {World journal of clinical cases}, volume = {10}, number = {15}, pages = {5064-5071}, pmid = {35801025}, issn = {2307-8960}, abstract = {BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare subtype of invasive breast cancer comprising malignant epithelial and mesenchymal cells. Compared with other invasive breast cancers, MBC is not only histologically distinctly heterogeneous but also has a rapid and aggressive growth pattern, which leads to a significant risk of recurrence and mortality.

CASE SUMMARY: In this study, we report the case of a patient with a large left breast mass diagnosed with bilateral invasive ductal carcinoma in both breasts after a preoperative core needle aspiration biopsy of the bilateral breast mass. The patient received neoadjuvant chemotherapy and underwent bilateral breast modified radical mastectomy. Postoperative pathology suggested carcinosarcoma with predominantly chondrosarcoma in the left breast and invasive ductal carcinoma (luminal B) in the right breast. As the patient did not achieve complete pathological remission after six cycles of neoadjuvant chemotherapy, we administered six months of intensive capecitabine treatment. Then the patient was switched to continuous treatment with endocrine therapy using letrozole + goserelin, and the patient is currently in stable condition. However, as MBC of the breast is concurrently diagnosed with chondrosarcoma differentiation, our case is sporadic.

CONCLUSION: Given the variety of immunohistochemical types of bilateral breast cancer, achieving effective chemotherapy should be a key research focus.}, } @article {pmid35797677, year = {2022}, author = {Kapatia, G and Kaur, S and Kumar, S and Laroiya, I and Singh, G and Sharma, M and Bal, A and Luthra-Guptasarma, M}, title = {Expression of Proteinase-activated Receptor 2 (PAR2) as a Correlate of Concern in Triple-negative Breast Cancer (TNBC).}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {30}, number = {6}, pages = {446-452}, doi = {10.1097/PAI.0000000000001025}, pmid = {35797677}, issn = {1533-4058}, mesh = {Adult ; Biomarkers, Tumor/metabolism ; Female ; Humans ; Mastectomy ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; *Receptor, PAR-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; *Triple Negative Breast Neoplasms/diagnosis/pathology ; }, abstract = {PURPOSE: Triple-negative breast cancer (TNBC), a highly aggressive cancer with poor outcome and lacking specific diagnostic, prognostic, or targeted therapeutic strategies, constitutes roughly 20% of all breast cancer cases. TNBC cells lack receptors for estrogen, progesterone, and human epidermal growth factor. The effort continues to find a suitable correlate that could serve as a TNBC biomarker, or as therapeutic target, or both.

MATERIALS AND METHODS: A retrospective study was performed with 88 TNBC and 74 non-TNBC patients who had undergone mastectomy/lumpectomy with axillary clearance for carcinoma breast. Immunohistochemical staining was carried out for levels of proteinase-activated receptor 2 (PAR2), encoded by F2RL1 gene, and staining scores were calculated, based on intensity and percentage positivity.

RESULTS: PAR2 levels were markedly upregulated in TNBC patients, compared with patients with other breast cancer subtypes. Amongst different non-TNBC subtypes, higher expression was noted in luminal B (88.8%) and HER2+ (100%), compared with luminal A (52.5%). PAR2 levels were significantly high in TNBC patients with age more than 40 years than corresponding patients of non-TNBC group (P=0.0017). Furthermore, there was a statistically significant increase in levels of PAR2 expression in lymph node negative (P=0.0096) and early stage (P=0.005) of TNBC versus non-TNBC patients. PAR2 staining of ductal carcinoma in situ and invasive ductal carcinoma revealed lower expression in invasive component.

CONCLUSIONS: Our data suggest that PAR2 levels constitute a correlate of concern for TNBC, tying in with a recent report that higher levels of F2RL1 gene expression correlate with poorer disease-free, as well as overall survival in TNBCs.}, } @article {pmid35794948, year = {2022}, author = {Tholany, J and Kobayashi, T and Marra, AR and Schweizer, ML and Samuelson, RJ and Suzuki, H}, title = {Impact of Infectious Diseases Consultation on the Outcome of Patients With Enterococcal Bacteremia: A Systematic Literature Review and Meta-analysis.}, journal = {Open forum infectious diseases}, volume = {9}, number = {7}, pages = {ofac200}, pmid = {35794948}, issn = {2328-8957}, abstract = {BACKGROUND: Enterococcal bacteremia carries significant mortality. While multiple studies have evaluated the impact of infectious disease consultation (IDC) on this condition, these studies were limited by the low numbers of patients enrolled. This systemic literature review and meta-analysis was conducted to determine whether IDC is associated with a mortality benefit among patients with enterococcal bacteremia.

METHODS: We performed a systematic literature search using 5 databases for studies evaluating IDC among patients with enterococcal bacteremia. We conducted a meta-analysis to assess whether IDC was associated with reduced mortality. Random-effects models were used to calculate pooled odds ratios (pORs). Heterogeneity was evaluated using I [2] estimation and the Cochran's Q statistic test.

RESULTS: The systematic literature review revealed 6496 reports, from which 18 studies were evaluated in the literature review and 16 studies in the meta-analysis. When all studies were pooled, the association between IDC and mortality was not statistically significant with a pOR of 0.81 (95% CI, 0.61-1.08) and substantial heterogeneity (I [2] = 58%). When the studies were limited to those reporting multivariate analysis including IDC, there was a significant protective effect of IDC (pOR, 0.40; 95% CI, 0.24-0.68) without heterogeneity (I [2] = 0%). Some studies also showed additional benefits to IDC, including appropriate antibiotic therapy and improved diagnostic use.

CONCLUSIONS: IDC was associated with 60% lower odds of mortality when patients were well-matched, potentially through improvement in the care of patients with enterococcal bacteremia. IDC should be considered part of routine care for patients with enterococcal bacteremia.}, } @article {pmid35789311, year = {2022}, author = {Martinez, EO and Jorns, JM and Kong, AL and Kijak, J and Lee, WY and Huang, CC and Cortina, CS}, title = {Primary Breast Neuroendocrine Tumors: An Analysis of the National Cancer Database.}, journal = {Annals of surgical oncology}, volume = {29}, number = {10}, pages = {6339-6346}, pmid = {35789311}, issn = {1534-4681}, support = {UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1TR001436/TR/NCATS NIH HHS/United States ; UL1TR001436/TR/NCATS NIH HHS/United States ; }, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; Hormones ; Humans ; Male ; *Neuroendocrine Tumors/epidemiology/therapy ; Retrospective Studies ; }, abstract = {BACKGROUND: Primary breast neuroendocrine tumors (BNETs) represent < 1% of breast cancers. Diagnosing BNETs can be challenging, and a limited amount of cohort data currently exists in literature. We aimed to describe primary BNET characteristics, treatment modalities, and survival outcomes through the National Cancer Database (NCDB).

METHODS: A retrospective cohort analysis was performed using the NCDB from 2004 to 2017. BNET cases were compared with patients with invasive ductal carcinoma (IDC). A matched IDC cohort was created by matching patient age, race, and disease stage. Kaplan-Meier analysis was performed, and hazard ratios (HR) were calculated through the bootstrap sampling method.

RESULTS: A total of 1389 BNET and 1,967,401 IDC cases were identified. When compared with IDC patients, BNET patients were older, had more comorbidities, and were more often male (p < 0.01). BNETs were larger, higher grade, and more frequently hormone receptor negative (p < 0.01). While BNET patients were treated with surgery and radiotherapy (p < 0.01) less often compared with IDC patients, they presented at later disease stage (p < 0.001) and received systemic treatment more frequently (53.5% vs. 40%, p < 0.01). Patients with BNET had increased mortality compared with the matched IDC cohort: stage 1 HR 1.8, stage 2 HR 2.0, stage 3 HR 1.8, and stage 4 HR 1.5 (p < 0.001 for all).

CONCLUSION: Patients with BNET tend to present at higher clinical stages, are more frequently hormone receptor negative, and have inferior overall survival compared with patients with IDC. Further treatment strategies and studies are needed to elucidate optimal therapies to maximize patient outcomes.}, } @article {pmid35785686, year = {2022}, author = {Al Laham, O and Atia, F and Ibrahim, D and Shaheen, J and Hokouk, B}, title = {An exceedingly rare simultaneous incidental occurrence of synchronous primary malignancies; Invasive Ductal Carcinoma and Renal Cell Carcinoma in a male - A Case Report.}, journal = {International journal of surgery case reports}, volume = {96}, number = {}, pages = {107367}, pmid = {35785686}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Synchronous malignancies are defined as the emergence of one or more tumors which either occur simultaneously or within 6 months of each other. Populations older than 50 years of age are the most vulnerable. Documented prevalence rates of synchronous neoplasia are 4.5-11.7 %. To the best of our knowledge, ours is the first documented case of synchronous primary incidental occurrence of Invasive Ductal Carcinoma (IDC) and Renal Cell Carcinoma (RCC) in a Middle Eastern male. This type of co-occurrence must be borne in mind because such neoplastic occurrence is potentially fatal. Documentation is essential to raise awareness and to decrease the resultant morbidity and mortality.

CASE PRESENTATION: We present a case of a 61-year-old male who presented to our clinic with a 22-day-history of gradual, painless, and disproportionate hypertrophy of his left breast. CT scan revealed incidental breast and right kidney masses. Therapeutic intervention included a modified radical mastectomy with Sentinel lymph node excision along with right radical nephrectomy.

CLINICAL DISCUSSION: Treatment of our patient was multimodal. Accurate radiological studying together with clinical examination helped us in making a diagnosis. Treatment options for this pathology consist of a combination of surgery and/or adjuvant therapy.

CONCLUSION: Synchronous IDC and RCC are an extremely rare co-occurrence, especially in males, particularly Middle Eastern males, and more specifically, those presenting asymptomatically as incidental findings. It is vital to further document and study such cases to establish innovative surgical techniques, screening modalities for males, and to overcome the consequential morbidity and mortality.}, } @article {pmid35784659, year = {2022}, author = {Saeed, M and Abdulshakour, BM and Bantan, NAA and Falemban, AH and Abdulla, M and Melibary, EM and Mufti, AH and Taher, MM}, title = {Profile of Male Breast Cancer in Makkah Region of Saudi Arabia: A 4-Year Retrospective Analysis of Radiology and Histopathology.}, journal = {International journal of breast cancer}, volume = {2022}, number = {}, pages = {8831011}, pmid = {35784659}, issn = {2090-3170}, abstract = {BACKGROUND: Mammography is a method widely used for the diagnosis of breast disorders in women and may help detect breast cancer in its early stages. Male breast cancer often remains undiagnosed or is poorly controlled until serious complications arise; therefore, the use of screening methods is needed to help with early diagnosis.

METHODS: From a total of 1,667 registered mammography cases screened, 17 male breast disease cases were included in this study. Mammography and ultrasound data were analyzed by Statistical Package of Social Sciences v.22 (SPSS). Diagnosis was made following biopsy in suspicious cases, and histopathological and immunological findings of all such patients were obtained for final diagnosis.

RESULTS: The mean age of the patients was 35 years (range, 14-70 years); 17.6% of the cases were aged 37 yrs, and 2 cases were aged 51 and 52 yrs. Of the 17 cases, 11 had breast lesions, and skin thickening was observed in only 1 case. The different patterns of lesions detected were asymmetry of the parenchyma, mastitis, and hamartoma (n = 1 each), malignant lesions (n = 2), and gynecomastia (n = 6). According to the BI-RADS categorization, 8 cases were benign, one case was probably benign, and 2 cases were likely malignant. In the 2 cases with malignant lesions, pathological diagnosis was made after hematoxylin and eosin and immunocytochemistry examination as invasive ductal carcinoma (IDC) of no special type (NST), grade II and grade III.

CONCLUSIONS: Most breast lesions in this study population were benign, while IDC was the most common malignancy encountered. Mammography is currently the most accurate and cost-effective method for detecting breast lesions. The findings of our study may help increase awareness of male breast cancer and encourage Saudi men at risk to perform self-breast exam and undergo routine breast screening.}, } @article {pmid35779088, year = {2023}, author = {Sadeghipour, N and Tseng, J and Anderson, K and Ayalasomayajula, S and Kozlov, A and Ikeda, D and DeMartini, W and Hori, SS}, title = {Tumor volume doubling time estimated from digital breast tomosynthesis mammograms distinguishes invasive breast cancers from benign lesions.}, journal = {European radiology}, volume = {33}, number = {1}, pages = {429-439}, pmid = {35779088}, issn = {1432-1084}, support = {W81XWH-18-1-0342//U.S. Department of Defense/ ; R25 CA217729/CA/NCI NIH HHS/United States ; T15 LM007033/LM/NLM NIH HHS/United States ; R25 CA217729//National Cancer Institute/ ; R25 CA217729//National Cancer Institute/ ; T15 LM007033//U.S. National Library of Medicine/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Retrospective Studies ; Tumor Burden ; Mammography/methods ; Breast Density ; Early Detection of Cancer/methods ; }, abstract = {OBJECTIVES: The aim of this study was to determine whether lesion size metrics on consecutive screening mammograms could predict malignant invasive carcinoma versus benign lesion outcome.

METHODS: We retrospectively reviewed suspicious screen-detected lesions confirmed by biopsy to be invasive breast cancers or benign that were visible on current and in-retrospect prior screening mammograms performed with digital breast tomosynthesis from 2017 to 2020. Four experienced radiologists recorded mammogram dates, breast density, lesion type, lesion diameter, and morphology on current and prior exams. We used logistic regression models to evaluate the association of invasive breast cancer outcome with lesion size metrics such as maximum dimension, average dimension, volume, and tumor volume doubling time (TVDT).

RESULTS: Twenty-eight patients with invasive ductal carcinoma or invasive lobular carcinoma and 40 patients with benign lesions were identified. The mean TVDT was significantly shorter for invasive breast cancers compared to benign lesions (0.84 vs. 2.5 years; p = 0.0025). Patients with a TVDT of less than 1 year were shown to have an odds ratio of invasive cancer of 6.33 (95% confidence interval, 2.18-18.43). Logistic regression adjusted for age, lesion maximum dimension, and lesion volume demonstrated that shorter TVDT was the size variable significantly associated with invasive cancer outcome.

CONCLUSION: Invasive breast cancers detected on current and in-retrospect prior screening mammograms are associated with shorter TVDT compared to benign lesions. If confirmed to be sufficiently predictive of benignity in larger studies, lesions visible on mammograms which in comparison to prior exams have longer TVDTs could potentially avoid additional imaging and/or biopsy.

KEY POINTS: • We propose tumor volume doubling time as a measure to distinguish benign from invasive breast cancer lesions. • Logistic regression results summarized the utility of the odds ratio in retrospective clinical mammography data.}, } @article {pmid35776828, year = {2022}, author = {Liu, M and Hu, L and Tang, Y and Wang, C and He, Y and Zeng, C and Lin, K and He, Z and Huo, W}, title = {A Deep Learning Method for Breast Cancer Classification in the Pathology Images.}, journal = {IEEE journal of biomedical and health informatics}, volume = {26}, number = {10}, pages = {5025-5032}, doi = {10.1109/JBHI.2022.3187765}, pmid = {35776828}, issn = {2168-2208}, mesh = {Breast/diagnostic imaging/pathology ; *Breast Neoplasms/diagnostic imaging/pathology ; *Deep Learning ; Diagnosis, Computer-Assisted/methods ; Female ; Humans ; Neural Networks, Computer ; }, abstract = {Breast cancer is the most common female cancer in the world, and it poses a huge threat to women's health. There is currently promising research concerning its early diagnosis using deep learning methodologies. However, some commonly used Convolutional Neural Network (CNN) and their variations, such as AlexNet, VGGNet, GoogleNet and so on, are prone to overfitting in breast cancer classification, due to both small-scale breast pathology image datasets and overconfident softmax-cross-entropy loss. To alleviate the overfitting issue for better classification accuracy, we propose a novel framework for breast pathology classification, called the AlexNet-BC model. The model is pre-trained using the ImageNet dataset and fine-tuned using an augmented dataset. We also devise an improved cross-entropy loss function to penalize overconfident low-entropy output distributions and make the predictions suitable for uniform distributions. The proposed approach is then validated through a series of comparative experiments on BreaKHis, IDC and UCSB datasets. The experimental results show that the proposed method outperforms the state-of-the-art methods at different magnifications. Its strong robustness and generalization capabilities make it suitable for histopathology clinical computer-aided diagnosis systems.}, } @article {pmid35776197, year = {2022}, author = {Rakshit, S and Sunny, JS and George, M and Hanna, LE and Leela, KV and Sarkar, K}, title = {T helper cell-mediated epitranscriptomic regulation via m6A RNA methylation bridges link between coronary artery disease and invasive ductal carcinoma.}, journal = {Journal of cancer research and clinical oncology}, volume = {148}, number = {12}, pages = {3421-3436}, pmid = {35776197}, issn = {1432-1335}, support = {ECR/2016/000965//Science and Engineering Research Board/ ; }, mesh = {Humans ; Female ; Methylation ; *Coronary Artery Disease/genetics ; Tumor Suppressor Protein p53 ; RNA/genetics ; T-Lymphocytes, Helper-Inducer ; Lactate Dehydrogenases ; *Carcinoma, Ductal ; }, abstract = {PURPOSE: Invasive ductal carcinoma (IDC) and coronary artery disease (CAD), remains the greatest cause of death annually in women, driven by complex signalling pathways and shared several predisposing risk factors together. Therefore, it is important to find out the common epigenetic modifications which are responsible for possible disease progression from CAD to IDC.

METHODS: CD4+T cell isolation by MACS, RT2 profiler PCR array, Gene ontology study, m6A RNA methylation, ChIP-qPCR, Q-PCR, CRISPR/Cas9-mediated knockout/overexpression, Lactate dehydrogenase release assay, RDIP-qPCR.

RESULTS: We have identified several epigenetic regulators (e.g., VEGFA, AIMP1, etc.) which are mainly involved in inflammatory pathways in both the diseased conditions. Epitranscriptomic alterations such as m6A RNA methylation found abnormal in CD4+T helper cells in both IDC as well as CAD. CRISPR-Cas9 mediated knockout/overexpression of specific gene (BRCA1) are promising therapeutic approaches in diseased conditions by regulating m6A RNA methylation and also tumor suppressor gene P53. It also affected the R-loop formation which is vulnerable to DNA damage and BRCA1 can also induce CTL mediated cytotoxicity in breast cancer cells.

CONCLUSIONS: Therefore, by understanding the modifications of epigenetic mechanisms, their alterations and interactions will aid in the development of newer therapeutic approaches to stop the possible spread from one disease to another.}, } @article {pmid35775660, year = {2022}, author = {Morin, B and Ahmadi, M and Rector, L and Allen, G}, title = {Development of an integrated duty cycle test method to assess cordwood stove performance.}, journal = {Journal of the Air & Waste Management Association (1995)}, volume = {72}, number = {7}, pages = {629-646}, doi = {10.1080/10962247.2022.2057615}, pmid = {35775660}, issn = {2162-2906}, mesh = {*Air Pollutants/analysis ; Heating/methods ; *Household Articles ; Household Products ; Particulate Matter/analysis ; }, abstract = {The US Environmental Protection Agency's (EPA's) New Source Performance Standards (NSPS) for Residential Wood Heaters (RWH) require certification emission testing of prototype appliances. In 2015, EPA revised those standards to further reduce particulate matter emissions from this critical source. However, to achieve that goal, lower emissions measured in certification tests must reflect lower emissions when the appliance is operated in homes. Woodstove certification tests have used either the Federal Reference Method (FRM), a crib wood method, or a cordwood testing method developed by ASTM International that was designated as a broadly applicable Alternative Test Method (ATM) by the EPA until December 2021, when that status was revoked. There is broad agreement that the FRM and ASTM procedures do not simulate typical fueling and operating of wood stoves in the field, raising questions about the efficacy of the current program. Effective emission reduction efforts require robust, accurate, and reproducible test methods. With input from a range of stakeholders, the Northeast States for Coordinated Air Use Management (NESCAUM) developed the Integrated Duty Cycle Test Method for Certification of Wood-Fired Stoves Using Cordwood (IDC), a cordwood testing protocol designed to improve the efficacy of residential wood heater certification testing. That method was approved by EPA as a broadly applicable ATM in 2021. IDC test runs assess appliance performance under a range of operating and fueling conditions representative of typical consumer use patterns. Unlike previous test methods, the IDC protocol requires three replicate runs to assess appliance performance variability. Including variable fueling and operating conditions, along with the requirement for replicates runs, will increase the effectiveness of certification testing and promote the development of improved wood stove technology. This paper reports on experiments conducted to develop and test the IDC method.Implications: Residential wood heating is one of the largest sources of primary particulate matter pollution nationwide. EPA's New Source Performance Standards (NSPS) establish emission limits for this source category and require certification testing of prototype wood appliances to demonstrate compliance with those limits. However, the operating and fueling requirements in NSPS compliance testing protocols do not represent typical conditions in the field. We developed a new testing approach, the Integrated-Duty Cycle (IDC) Test Method, to address the shortcomings of current certification test approaches. The IDC procedure for cordwood stoves, which was approved by EPA as a broadly applicable alternative test method in 2021, assesses appliance operations over various operating and fueling conditions representing typical consumer use patterns in an integrated run and requires three replicate runs to enable the assessment of variability in stove performance. Stoves certified with this method will be equipped to meet the NSPS limits consistently in field operation.}, } @article {pmid35770272, year = {2022}, author = {Tayubi, IA and Madar, IH}, title = {Biomineralization associated alkaline phosphatase as a potential marker of bone metastasis in the patients with invasive breast cancer.}, journal = {Saudi journal of biological sciences}, volume = {29}, number = {8}, pages = {103340}, pmid = {35770272}, issn = {1319-562X}, abstract = {Breast Cancer is the most predominant form of cancer among women worldwide. It has been rigorously studied for biomarker identifications and therapeutic targets. However, various potential genes and their clinical relevance to breast cancer remain unexplored. The heterogeneity of breast cancer is one of the major challenges in early detection. Several studies have reported the significant role of alkaline phosphate (ALP) in the regulation of tumor growth and overall free survival in the pathogenesis of different cancer, including breast cancer which may offer unique therapeutic targets. Therefore, these findings demand a comprehensive study for the biogenesis of ALP genes. This study aims to expression profiling of alkaline phosphate genes in breast cancer and to identify the key pathways and molecular mechanisms underlying breast cancer proliferation and progression. In this study, the transcriptome profiling of invasive breast carcinoma samples was performed and analyzed. We identified that all the ALP genes were downregulated in both Invasive Lobular and Invasive Ductal Carcinoma patients. To understand the underlying molecular mechanism and the clinical significance for these genes in breast cancer, the expression values of genes were measured in adjacent normal and tumor tissues of patients followed by network analysis and functional enrichment analysis. The overall analysis revealed the highly aberrant expression of ALPL gene among all four ALP genes. We identified the functional significance of RUNX2 and WNT3A in deregulating ALPL. Therefore, our findings suggests that downregulation of ALPL could be a potential marker gene for invasive breast carcinoma progression towards bone metastasis.}, } @article {pmid35765108, year = {2022}, author = {Ogbu, TJ and Scales, SE and de Almeida, MM and van Loenhout, JAF and Speybroeck, N and Guha-Sapir, D}, title = {Predictors of exceeding emergency under-five mortality thresholds using small-scale survey data from humanitarian settings (1999 - 2020): considerations for measles vaccination, malnutrition, and displacement status.}, journal = {Archives of public health = Archives belges de sante publique}, volume = {80}, number = {1}, pages = {160}, pmid = {35765108}, issn = {0778-7367}, abstract = {BACKGROUND: Quantifying the effect of measles containing vaccine (MCV) coverage and the prevalence of global acute malnutrition (GAM) on mortality levels in populations of displaced and crisis-affected resident children is important for intervention programming in humanitarian emergencies.

METHODS: A total of 1597 surveys containing data on under-five death rate, population status (internally displaced, refugee, or crisis-affected resident), measles containing vaccine coverage, and global acute malnutrition were extracted from the Complex Emergency Database (CE-DAT). Under-five mortality rates were dichotomized to those exceeding critical levels or otherwise. A Bayesian multivariable mixed-effect logistic regression model was used to assess the association between an under-five death rate (U5DR) exceeding this threshold and population status (i.e., internally displaced, refugees or residents), GAM prevalence (proxy for food security), and MCV coverage.

RESULTS: The prevalence of GAM, MCV and U5DR were higher in internally displaced children (IDC) with values of 14.6%, 69.9% and 2.07 deaths per 10 000 per day, respectively. Refugee populations had lower average under-five mortality rate (0.89 deaths per 10 000 per day), GAM of 12.0% and the highest measles containing vaccine coverage (80.0%). In crisis-affected residents the prevalence of GAM, MCV and average U5DR are 11.1%, 65.5% and 1.20 deaths per 10 000 per day respectively. In mixed-effect logistic model taking 2 deaths per 10 000 children less than five years old per as emergency threshold (Model III); MCV (AOR = 0.66, 95% Highest Density Interval (HDI): 0.57, 0.78), GAM (AOR = 1.79, 95% HDI: 1.52, 2.12) were associated with a reduction of the odds of U5DR exceeding critical level accounting for country-specific levels of variability. The odds of U5DR exceeding critical level (2/10000/day) in crisis-affected resident children and refugees were 0.36 (95% HDI: 0.22, 0.58) and 0.25(95% HDI: 0.11, 0.55) less than amongst IDP children adjusting for GAM and MCV. In considering country specific yearly median U5DR (model IV) the odds of U5DR exceeding twice the median U5DR were associated with MCV (AOR = 0.72, 95% HDI: 0.64, 0.82), GAM (AOR = 1.53, 95%HDI: 1.34, 1.76). The odds of U5DR exceeding critical level in crisis-affected resident children was 0.30(95% HDI: 0.20, 0.45) less than IDP children, after adjusting for MCV and GAM. We found no difference between the odds of U5DR exceeding twice the country level median U5DR in the refugee population compared to the IDPs.

CONCLUSIONS: In this study vaccination coverage and global acute malnutrition (proxy for food security) were associated with U5DR exceeding critical level. The emergency threshold for IDPs and affected residents is significantly different and consistent across the different outcomes, whereas the result is inconsistent for IDPs and refugees. Continued improvement in measles vaccination coverage and reduction of malnutrition in humanitarian emergencies have the potential to minimize the deterioration of mortality level amongst children in emergency settings. To generate a robust understanding of the critical level of child mortality in displaced and affected resident populations, studies accounting for the impact of the duration of displacement, contextual factors in humanitarian settings, and the level of humanitarian assistance provided are needed.}, } @article {pmid35761974, year = {2022}, author = {Chen, S and Yang, L and Li, Y}, title = {Clinicopathological Features of 166 Cases of Invasive Ductal Breast Carcinoma and Effect of Primary Tumor Location on Prognosis after Modified Radical Mastectomy.}, journal = {Emergency medicine international}, volume = {2022}, number = {}, pages = {3158956}, pmid = {35761974}, issn = {2090-2840}, abstract = {OBJECTIVE: To investigate the clinicopathological features of 166 cases of invasive ductal carcinoma (IDC) of the breast and to analyze the effect of the location of the primary tumor on the prognosis of modified radical mastectomy.

MATERIALS AND METHODS: The clinical data of 166 patients with IDC who underwent modified radical mastectomy in our hospital from May 2015 to May 2017 were retrospectively analyzed. The clinicopathological features of IDC patients were recorded. Univariate analysis and the multivariate logistic regression model were used to analyze the relationship between the location of the primary tumor and the prognosis of IDC patients after modified radical surgery. The effect of primary tumor location on the prognosis of modified radical resection was used with Survival curve analysis.

RESULTS: Among the patients in the central region, 13.33% had tumors >5 cm in diameter, which was higher than those in the other four groups. Among the patients in the upper inner quadrant, 59.38% received hormone therapy after operation, which was higher than those in the other four groups (P < 0.05). There were no significant differences in age, menopause, histological grading, molecular typing, lymph node metastasis, vascular invasion, radiation therapy, and chemotherapy among different groups (P > 0.05). Univariate analysis showed that molecular typing, lymph node metastasis, vascular invasion, and location of the primary tumor were all related to the prognosis of IDC patients after modified radical surgery, and the differences were statistically significant (P < 0.05). Logistic regression analysis showed that molecular typing, lymph node metastasis, vascular invasion, and primary tumor location were all independent influencing factors for prognosis of IDC patients after modified radical surgery (P < 0.05). As of 31 May 2021, there were 11 patients with recurrence and metastasis and 20 patients with death. The median survival time in the outer upper quadrant group was 80 months, which was higher than that in the outer lower quadrant group by 72 months, the median survival time in the central region group by 71 months,