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19 Apr 2021 at 01:34
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Bibliography on: Invasive Ductal Carcinoma


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RJR: Recommended Bibliography 19 Apr 2021 at 01:34 Created: 

Invasive Ductal Carcinoma

Invasive ductal carcinoma (IDC), also known as infiltrating ductal carcinoma, is cancer that began growing in a milk duct and has invaded the fibrous or fatty tissue of the breast outside of the duct. IDC is the most common form of breast cancer, representing 80 percent of all breast cancer diagnoses.

Created with PubMed® Query: ("invasive ductal carcinoma" OR IDC) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2021-04-17

Nobili S, Mannini A, Parenti A, et al (2021)

Establishment and characterization of a new spontaneously immortalized ER-/PR-/HER2+ human breast cancer cell line, DHSF-BR16.

Scientific reports, 11(1):8340.

Invasive ductal carcinoma (IDC) constitutes the most frequent malignant cancer endangering women's health. In this study, a new spontaneously immortalized breast cancer cell line, DHSF-BR16 cells, was isolated from the primary IDC of a 74-years old female patient, treated with neoadjuvant chemotherapy and disease-free 5-years after adjuvant chemotherapy. Primary breast cancer tissue surgically removed was classified as ER-/PR-/HER2+, and the same phenotype was maintained by DHSF-BR16 cells. We examined DHSF-BR16 cell morphology and relevant biological and molecular markers, as well as their response to anticancer drugs commonly used for breast cancer treatment. MCF-7 cells were used for comparison purposes. The DHSF-BR16 cells showed the ability to form spheroids and migrate. Furthermore, DHSF-BR16 cells showed a mixed stemness phenotype (i.e. CD44+/CD24-/low), high levels of cytokeratin 7, moderate levels of cytokeratin 8 and 18, EpCAM and E-Cadh. Transcriptome analysis showed 2071 differentially expressed genes between DHSF-BR16 and MCF-7 cells (logFC > 2, p-adj < 0.01). Several genes were highly upregulated or downregulated in the new cell line (log2 scale fold change magnitude within - 9.6 to + 12.13). A spontaneous immortalization signature, mainly represented by extracellular exosomes-, plasma membrane- and endoplasmic reticulum membrane pathways (GO database) as well as by metabolic pathways (KEGG database) was observed in DHSF-BR16 cells. Also, these cells were more resistant to anthracyclines compared with MCF-7 cells. Overall, DHSF-BR16 cell line represents a relevant model useful to investigate cancer biology, to identify both novel prognostic and drug response predictive biomarkers as well as to assess new therapeutic strategies.

RevDate: 2021-04-17

Rebollo Aguirre AC, Fernández Fernández J, Sánchez Sánchez R, et al (2021)

Radioguided surgery with iodine-125 seeds in breast cancer patients treated with neoadjuvant chemotherapy.

Revista espanola de medicina nuclear e imagen molecular pii:S2253-654X(21)00067-6 [Epub ahead of print].

OBJECTIVE: To evaluate the use of radioactive iodine-125 seed (RIS) in breast and/or axillary surgery, in patients with breast cancer treated with neoadjuvant chemotherapy (NAC).

MATERIAL AND METHODS: Prospective study between January 2016 and June 2020. 80 women T1-3,N0-2,M0: 30 RIS marking the breast tumor, 36 both the tumor and the biopsied positive axillary node, and 14 only the axilla. Age: 54.7±11.4 years. Tumor size: 34.1±14.6mm. Histological type: invasive ductal carcinoma 90.0%. Molecular subtypes: luminal-A 23.8%, luminal-B/HER2- 33.7%, luminal-B/HER2+ 18.8%, HER2+ 7.5%, basal-like 16,2%.

RESULTS: Of the 66 patients with RIS marking of the tumor (51 pre-NAC, 15 post-NAC), 92.1% had tumor-free surgical margins, with a specimen volume of 126.7±111.2 cm3. Of the 5 second local excisions, in 3 the resection margin was involved (1 mastectomy). Of the 50 patients N1 with RIS marking (MLN), 44 pre-NAC and 6 post-NAC, MLN was identified in 97.2%: negative 23, positive 26. In 45/50 patients, sentinel node biopsy (SNB) was performed and it was identified in 93.3%: negative 26, positive 16. In 1 case RIS was not placed correctly and SNB was not identified due to non-migration. In 61.9% of the patients, MLN was among the SNB identified in the surgery. In 5 patients with mismatched SNB and MLN, the pathological result of the SNB was negative and the MLN was positive. Axillary lymph node dissection was performed in 53.8% of the patients.

CONCLUSION: RIS allow to perform breast-conserving surgery and improve detection of residual axillary disease in patients treated with NAC.

RevDate: 2021-04-17

D'Iorio A, Esposito M, Maggi G, et al (2021)

Neuropsychological correlates of prospective memory: A comparison between tremor-dominant Parkinson's disease and cervical dystonia.

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 87:156-161.

Cervical Dystonia (CD) and Parkinson's disease, particularly tremor-dominant motor phenotype (TD-PD), showed a selective deficit of time-based prospective memory (TBPM). The two movement disorders are mainly characterized by dysfunctions of basal-ganglia and prefrontal cortex but it is reported that cerebellum also plays a key role in their pathogenesis. These cerebral structures are specifically involved in TBPM rather than in event-based PM (EBPM), but until now no study directly compared these two components of PM between CD and TD-PD patients. Therefore, the present study aimed at investigating if differences in PM functioning between CD and TD-PD patients might exist and if the type of movement disorder moderated the relationship between deficit of PM and deficit of executive functions and retrospective memory. Thirty TD-PD, 27CD patients and 29 healthy subjects (HCs), matched for demographic features, underwent neuropsychological tests for PM, executive functions, retrospective memory and self-rated questionnaires. The three groups did not differ on neuropsychological variables except for TBPM where TD-PD and CD patients performed worse than HCs; moreover, TD-PD performed worse than CD patients. Moderation analysis indicated that the type of movement disorder moderated the relationship between executive dysfunction and TBPM, but not EBPM. In conclusion, selective deficit of TBPM characterizes both CD and TD-PD but it is associated with executive dysfunction only in TD-PD. It might be possible to speculate that the involvement of the cerebellum, responsible for internal timing processes, could explain the impairment of TBPM in both movement disorders. This issue deserves to be explored in future neuroimaging studies.

RevDate: 2021-04-17

Alaref A, Hassan A, Sharma Kandel R, et al (2021)

Magnetic Resonance Imaging Features in Different Types of Invasive Breast Cancer: A Systematic Review of the Literature.

Cureus, 13(3):e13854.

Breast cancer is the most common malignancy affecting women worldwide, and early diagnosis of breast cancer is the key to its successful and effective treatment. Traditional imaging techniques such as mammography and ultrasound are used to detect and configure breast abnormalities; unfortunately, these modalities have low sensitivity and specificity, particularly in young patients with dense breast tissue, breast implants, or post-surgical scar/architecture distortions. Therefore, breast magnetic resonance imaging (MRI) has been superior in the characterization and detection of breast cancer, especially that with invasive features. This review article explores the importance of breast MRI in the early detection of invasive breast cancer versus traditional tools, including mammography and ultrasound, while also analyzing the use of MRI as a screening tool for high-risk women. We will also discuss the different MRI features for invasive ductal carcinoma and lobular carcinoma and the role of breast MRI in the detection of ductal carcinoma in situ with a focus on the utilization of new techniques, including MR spectroscopy and diffusion-weighted imaging.

RevDate: 2021-04-15

Li Q, Xiao Q, Yang M, et al (2021)

Histogram analysis of quantitative parameters from synthetic MRI: Correlations with prognostic factors and molecular subtypes in invasive ductal breast cancer.

European journal of radiology, 139:109697 pii:S0720-048X(21)00177-7 [Epub ahead of print].

PURPOSE: To evaluate intra-tumoral heterogeneity through a histogram analysis of quantitative parameters obtained from synthetic MRI (magnetic resonance imaging), and determine correlations of these histogram characteristics with prognostic factors and molecular subtypes of invasive ductal carcinoma (IDC).

METHODS: A total of 122 IDC from 122 women who underwent preoperative synthetic MRI and DCE (dynamic contrast enhancement)-MRI were investigated. The synthetic MRI parameters (T1, T2, and PD (proton density)) were obtained. For each parameter, the minimum, 10th percentile, mean, median, 90th percentile, maximum, skewness, and kurtosis values of tumor were calculated, and correlations with prognostic factors and subtypes were assessed. The Mann-Whitney U test or the Student's t test were utilized to analyze the association between the histogram features of synthetic MRI parameters and prognostic factors. The Kruskal-Wallis test followed by the post-hoc test was used to analyze differences of synthetic MRI parameters among molecular subtypes.

RESULTS: IDC with high histopathologic grade showed statistically higher PDmaxium, T1mean and T1median values than those with low grade (p = 0.003, p = 0.007, p = 0.003). The T110th were significantly higher in cancers with PR (progesterone receptor) negativity than those with PR positivity (p = 0.005). ER-negative cancers had significant higher values of T210th, T2mean, and T2median than ER-positive cancers (p = 0.006, 0.002, and 0.006, respectively). The values of PDmedian were significantly higher in IDC with HER2 (human epidermal growth factor receptor 2) positivity than those with HER2 negativity (p = 0.001). When discriminating molecular subtypes of IDC, the T2mean achieved the highest performance. The T2mean values of TN (triple-negative), luminal B and luminal A types are arranged in descending order (p < 0.0001).

CONCLUSIONS: Histogram features derived from synthetic MRI quantifies the distributions of tissue relaxation time and proton density, and may serve as a potential biomarker for discriminating histopathological grade, hormone receptor status, HER2 expression status and breast cancer subtypes.

RevDate: 2021-04-15

Powell M, Gate T, Kalake O, et al (2021)

Magnetic Seed Localization (Magseed) for excision of impalpable breast lesions-The North Wales experience.

The breast journal [Epub ahead of print].

The breast surgical community has faced huge challenges due to close working relationships with radiologists who are in short supply. Breast lesion localization is moving away from the traditional wire technique, which requires an on-site radiologist to support theater scheduling. In North Wales, the introduction of Magseed for impalpable breast lesion localization has facilitated theater scheduling in the absence of same day radiology presence. We audited our first 200 Magseed cases to assess the safety and efficacy of the technique, the ease of use, and patient experience. Data were entered prospectively into an excel data base relating to Magseed cases. Data collected included demographics, pre and postoperative lesion size, histology, margin positivity, and re-excision rates. Data were submitted in real time by the radiologist performing Magseed insertion to ascertain degree of difficulty. A PROMS questionnaire was designed and sent to patients undergoing Magseed vs wire localizations. Two hundred patients underwent Magseed-guided wide local excision between May 2018 and January 2020 across 2 district general hospital sites in North Wales. Histology: 69% IDC, 20% ILC, and 11% others. Mean preoperative size 12.3 mm, postoperative size 19 mm. Re-excision rate 15%. Re-excision for DCIS was significantly more likely than for invasive disease (p < 0.0001). A significant difference was also observed between radiological mean preoperative tumor size estimate and actual histological tumor size in patients undergoing margin re-excision (p = 0.000019). Wire-guided re-excision rate was 21% in the same unit. PROMs found the procedure well tolerated by patients. Surgeons and radiologists reported Magseed to be user-friendly with minimal learning curve. Magseed use for impalpable breast lesion localization is safe, user friendly, and well tolerated by patients. It produces favorable re-excision rates when compared to published figures for wire-guided excision. The presence of DCIS and preoperative radiological size underestimation was associated with margin re-excision.

RevDate: 2021-04-16

Thompson HK, PJ Spicer (2021)

Recurrent Breast Cancer Diagnosis Delayed by COVID-19 Pandemic.

We describe the case of a 65-year-old female with a history of left-sided ductal carcinoma in situ in 2008. Mammography in January 2020 demonstrated calcifications in the previously affected breast. Subsequent stereotactic biopsy results were benign. In the months that followed, the patient experienced breast changes but avoided returning to the facility as the COVID-19 pandemic worsened. In August of 2020, the patient returned for a repeat mammogram, which indicated two suspicious masses in the left breast. Further analysis through ultrasound-guided core biopsy ultimately led to a left mastectomy and lymph node biopsy, which were performed in September 2020. Pathology results revealed multifocal invasive ductal carcinoma stage IIB.

RevDate: 2021-04-14

Fayad R, Rojas MV, Partisani M, et al (2021)

EFA6B regulates a stop signal for collective invasion in breast cancer.

Nature communications, 12(1):2198.

Cancer is initiated by somatic mutations in oncogenes or tumor suppressor genes. However, additional alterations provide selective advantages to the tumor cells to resist treatment and develop metastases. Their identification is of paramount importance. Reduced expression of EFA6B (Exchange Factor for ARF6, B) is associated with breast cancer of poor prognosis. Here, we report that loss of EFA6B triggers a transcriptional reprogramming of the cell-to-ECM interaction machinery and unleashes CDC42-dependent collective invasion in collagen. In xenograft experiments, MCF10 DCIS.com cells, a DCIS-to-IDC transition model, invades faster when knocked-out for EFA6B. In addition, invasive and metastatic tumors isolated from patients have lower expression of EFA6B and display gene ontology signatures identical to those of EFA6B knock-out cells. Thus, we reveal an EFA6B-regulated molecular mechanism that controls the invasive potential of mammary cells; this finding opens up avenues for the treatment of invasive breast cancer.

RevDate: 2021-04-12

Davidson JL, Bergenstal RM, Conry JA, et al (2021)

Initiating Insulin in the Emergency Center and Urgent Care to Prevent Hospital Admission for Patients with Hyperglycemia: A Unique Insulin Starter Kit.

Journal of diabetes science and technology [Epub ahead of print].

BACKGROUND: Clinicians in the Emergency Center (EC) and Urgent Care (UC) can play a vital role in preventing hospital admissions and improving outcomes of patients with newly diagnosed diabetes or pre-existing diabetes who present with hyperglycemia and the need to initiate insulin.

METHODS: This article describes a unique EC/UC discharge insulin starter kit protocol with clinician instructions via an Electronic Medical Record (EMR) order set that includes: starting doses for insulin, a prescription for glucose monitoring supplies, and an emergent referral to diabetes education at International Diabetes Center. Patients receive insulin during the EC/UC visit and are provided an insulin pen to take home. Nurses from the EC or UC review and provide educational material on how to use an insulin pen, treating hypoglycemia and healthy eating. The Certified Diabetes Care and Education Specialist (CDCES) sees patients within 24-72 hours after the referral is placed.

RESULTS: Within our single healthcare system's EC and UC (multiple sites), the kit has enabled clinicians to metabolically stabilize patients and decrease the need for hospitalization without experiencing hypoglycemia. In the recent three years of use, of 42 patients given the insulin starter kit, there were only 2 patients with repeat EC/UC visits within the first six months (1 hyperglycemia and 1 hypoglycemia).

CONCLUSIONS: An insulin starter kit and EMR-based order set initiated in the EC/UC setting is a tool that can be used to improve the quality of care for people with newly diagnosed or pre-existing diabetes experiencing significant hyperglycemia.

RevDate: 2021-04-17

Hofstetter S, Zuiderbaan W, Heimler B, et al (2021)

Topographic maps and neural tuning for sensory substitution dimensions learned in adulthood in a congenital blind subject.

NeuroImage, 235:118029 pii:S1053-8119(21)00306-2 [Epub ahead of print].

Topographic maps, a key principle of brain organization, emerge during development. It remains unclear, however, whether topographic maps can represent a new sensory experience learned in adulthood. MaMe, a congenitally blind individual, has been extensively trained in adulthood for perception of a 2D auditory-space (soundscape) where the y- and x-axes are represented by pitch and time, respectively. Using population receptive field mapping we found neural populations tuned topographically to pitch, not only in the auditory cortices but also in the parietal and occipito-temporal cortices. Topographic neural tuning to time was revealed in the parietal and occipito-temporal cortices. Some of these maps were found to represent both axes concurrently, enabling MaMe to represent unique locations in the soundscape space. This case study provides proof of concept for the existence of topographic maps tuned to the newly learned soundscape dimensions. These results suggest that topographic maps can be adapted or recycled in adulthood to represent novel sensory experiences.

RevDate: 2021-04-12

Nash Y, Ganoth A, Borenstein-Auerbach N, et al (2021)

From virus to diabetes therapy: Characterization of a specific insulin-degrading enzyme inhibitor for diabetes treatment.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 35(5):e21374.

Inhibition of insulin-degrading enzyme (IDE) is a possible target for treating diabetes. However, it has not yet evolved into a medical intervention, mainly because most developed inhibitors target the zinc in IDE's catalytic site, potentially causing toxicity to other essential metalloproteases. Since IDE is a cellular receptor for the varicella-zoster virus (VZV), we constructed a VZV-based inhibitor. We computationally characterized its interaction site with IDE showing that the peptide specifically binds inside IDE's central cavity, however, not in close proximity to the zinc ion. We confirmed the peptide's effective inhibition on IDE activity in vitro and showed its efficacy in ameliorating insulin-related defects in types 1 and 2 diabetes mouse models. In addition, we suggest that inhibition of IDE may ameliorate the pro-inflammatory profile of CD4+ T-cells toward insulin. Together, we propose a potential role of a designed VZV-derived peptide to serve as a selectively-targeted and as an efficient diabetes therapy.

RevDate: 2021-04-14

Jung SU, Jung M, Choi JH, et al (2021)

Palbociclib with letrozole as second-line neo-systemic therapy after failure of neo-adjuvant chemotherapy for luminal type breast cancer: A case report.

Medicine, 100(14):e25175.

RATIONALE: Neo-adjuvant systemic therapy includes endocrine therapy and chemotherapy, which is widely used. Luminal breast cancer is resistant to chemotherapy and is more likely to not respond to chemotherapy before surgery. Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor. Palbociclib with letrozole combination therapy was an effective chemotherapy in metastatic luminal type breast cancer and had fewer side effects; however, the benefit of palbociclib in neoadjuvant systemic therapy is unclear.

PATIENT CONCERNS: A 50-year-old female patient visited our hospital with palpable lump in the right breast. The lymph nodes fixed in the ipsilateral axilla.

DIAGNOSIS: The patient was diagnosed with invasive ductal carcinoma of the right breast; the nuclear grade was moderate. The ipsilateral fixed lymph node was diagnosed as metastasis. The breast cancer subtype was luminal A type and was positive for estrogen receptor and progesterone receptor, and negative for HER2/neu and Ki-67 marker index <10% on immunohistochemistry.

INTERVENTIONS: Neo-systemic therapy was performed with 3 cycles of adriamycin with docetaxel. After follow-up study, the breast and axillary lesions progressed. Palbociclib with letrozole was administered as second neo-systemic therapy for 10 months. Subsequently, breast-conserving surgery with sentinel lymph node biopsy was performed.

OUTCOMES: In the postoperative pathologic result, 4 mm invasive lesion remained, and the sentinel lymph node biopsy was negative. The results achieved a residual cancer burden classification class 1.

CONCLUSION: Second-line neo-systemic therapy can further reduce the size of the tumor and increase the likelihood of avoiding the side effects of surgery. Palbociclib with letrozole may be a good treatment in the preoperative stage for luminal breast cancer that is resistant to chemotherapy.

RevDate: 2021-04-08

Hu A, Hong F, Li D, et al (2021)

KDM3B-ETF1 fusion gene downregulates LMO2 via the WNT/β-catenin signaling pathway, promoting metastasis of invasive ductal carcinoma.

Cancer gene therapy [Epub ahead of print].

Breast cancer is the most common malignancy for women, with invasive ductal carcinoma being the largest subtype of breast cancers, accounting for 75-80% of cases. However, the underlying mechanism of invasive ductal carcinoma remains unclear. In this study, we investigate the possible effects KDM3B-ETF1 fusion gene has on breast cancer cell metastasis, invasion and its downstream signaling mediators as revealed from RNA sequence data analysis. As predicted, KDM3B-ETF1 expression was increased in breast cancer tissues and cells. Overexpression of KDM3B-ETF1 in cancer cell lines promoted the growth and invasion of breast cancer cells, while KDM3B-ETF1 knockdown showed the opposite effects on malignant cell growth and invasion both in vivo and in vitro as evidenced by cell counting kit-8, Transwell assay and tumor xenograft in nude mice. On the contrary, LIM Domain Only 2 (LMO2) expression was significantly reduced in breast cancer tissues and cells. According to chromatin immunoprecipitation and Western blot analysis, KDM3B-ETF1 targets LMO2 and reduced the expression of LMO2, leading to an increase in WNT/β-catenin signaling pathway and thus promoting invasion. In conclusion, fusion gene KDM3B-ETF1 inhibits LMO2, activates the Wnt/β-catenin signaling pathway that leads to increased breast cancer cell invasion and metastasis, providing a novel insight into developing therapeutic strategies. These results provide novel insights into the molecular mechanism of invasive ductal carcinomas, which may lead to potential therapeutic targets.

RevDate: 2021-04-08

Nehmeh WA, Derienne J, El Khoury L, et al (2021)

A 58-Year-Old Woman with Acute Gastric Perforation Due to Metastatic Ductal Carcinoma 18 Years Following Bilateral Mastectomy for Invasive Ductal Carcinoma of the Breast.

The American journal of case reports, 22:e927094 pii:927094.

BACKGROUND Invasive lobular carcinoma and ductal carcinoma of the breast can metastasize to all sites in the body, including the gastrointestinal tract. Late presentation of metastases of lobular carcinoma of the breast to the gastrointestinal tract have previously been reported, but late metastasis of ductal carcinoma of the breast to the gastric mucosa is rare. This report is of a 58-year-old Lebanese woman who presented with acute gastric perforation due to metastatic ductal carcinoma,18 years following bilateral mastectomy for invasive ductal carcinoma of the breast. CASE REPORT We present the case of a 58-year-old woman who underwent a right modified mastectomy for an invasive ductal carcinoma in 2002 combined with a contralateral prophylactic mastectomy for cosmetic purposes. She presented a secondary gastric lesion 18 years later. The clinical presentation resembled perforated ulcer. The choice of gastrectomy was denied due to retrogastric and pancreatic invasion by the tumor. A laparoscopic gastric closure failed to heal the perforation. A supraumbilical laparotomy incision was performed for the placement of a Pezzer tube in the gastric perforation and the installation of a feeding jejunostomy. CONCLUSIONS This report is of a rare presentation of metastatic ductal carcinoma of the breast to the gastric mucosa associated with gastric perforation that presented 18 years after bilateral mastectomy. This case highlights the importance of obtaining a full past medical history to identify previous primary malignancy, and also is a reminder that ductal carcinoma of the breast can present with metastatic involvement in the gastrointestinal tract several months, or even years, following mastectomy.

RevDate: 2021-04-08

Weaver KD, Isom J, Esnakula A, et al (2021)

Acinic Cell Carcinoma of the Breast: Report of a Case With Immunohistochemical and Next-Generation Sequencing Studies.

International journal of surgical pathology [Epub ahead of print].

Acinic cell carcinoma of the breast is a rare subtype of triple-negative breast cancer that recapitulates the appearance of tumors seen in salivary glands. We present the case of a 42-year-old woman with an irregular, nontender mass above the left nipple during routine obstetric appointment at 24 weeks gestation. She was subsequently diagnosed with triple-negative invasive ductal carcinoma of the left breast, Nottingham grade 3, via core needle biopsy. She was treated with neoadjuvant therapy (doxorubucin and cyclophosphamide) antenatally and paclitaxel in the postpartum period followed by left mastectomy with sentinel node biopsy. The carcinoma in the mastectomy specimen showed a spectrum of morphologic patterns with immunohistochemistry revealing strong positivity for alpha-1-antichymotrypsin, epithelial membrane antigen (EMA), lysozyme, and S100. The histomorphology paired with the immunoprofile led us to the diagnosis of acinic cell carcinoma. We retrospectively performed immunostains in the core biopsy specimen, which demonstrated GATA-3 and DOG-1 positivity. Next-generation sequencing of the postneoadjuvant specimen using a 70-gene panel revealed 2 single-nucleotide variant (SNV) mutations: tumor protein 53 (TP53) (c.747G>T) SNV mutation and rearranged during transfection (RET) (c.2899G>A) SNV mutation.

RevDate: 2021-04-08

Khanam R, Fanous IS, Fadhel EN, et al (2021)

Voltage-Gated Calcium Channel Antibody-Induced Oropharyngeal Dysphagia Presenting as a Paraneoplastic Neurological Complication in Breast Cancer.

Cureus, 13(3):e13677.

Paraneoplastic neurologic syndromes (PNS) are a group of disorders characterized by an autoimmune response against the nervous system due to cross-reactivity between malignant and normal neural tissue. The most commonly associated malignancies include small cell lung cancer, ovarian cancer, breast cancer, and lymphoma. Multiple PNS have been reported including paraneoplastic cerebellar degeneration, retinopathy, sensorimotor peripheral neuropathy, encephalopathy, opsoclonus-myoclonus syndrome, and stiff-person syndrome. We report a case of a 67-year-old woman with breast cancer who presented with a history of progressive oropharyngeal dysphagia as a paraneoplastic neurologic complication. She was diagnosed with invasive ductal carcinoma, nuclear grade 3 with moderate peritumoral lymphoid infiltrate. Hormone receptors were weakly positive for estrogen receptor (ER) (H score 15), weakly positive for progesterone receptor (PR) (H score 30), and negative for human epidermal growth factor receptor 2 (HER-2/NEU). The patient underwent a localized segmental mastectomy but declined any further adjuvant treatment. Three years after being diagnosed with invasive ductal carcinoma of the breast, she developed progressive oropharyngeal dysphagia that warranted percutaneous endoscopic gastrostomy (PEG) tube placement. Testing for onconeural antibodies was positive for voltage-gated calcium channel antibody. An extensive workup was negative for any alternative etiology that would explain her neurological symptoms. The patient declined further treatment and eventually succumbed to her illness.

RevDate: 2021-04-08

Hashmi AA, Zia S, Yaqeen SR, et al (2021)

Mucinous Breast Carcinoma: Clinicopathological Comparison With Invasive Ductal Carcinoma.

Cureus, 13(3):e13650.

Introduction Invasive ductal carcinoma (IDC) is the most common histological subtype of breast cancer. Conversely, many special types of breast carcinoma were described with varying prognosis and hormone receptor status. Mucinous carcinoma (MC) is a rare special subtype of breast cancer, and only a few studies have evaluated the clinicopathological and hormone receptor profile of this type of breast cancer. Therefore, in this study, we compared the clinicopathological characteristics of MC with IDC in our population. Methods A retrospective observational study was conducted in the Department of Histopathology, Liaquat National Hospital and Medical College, from January 2013 till December 2020, for eight years. During this period, 38 cases of MC were diagnosed and 1268 cases of IDC were identified. All specimens were grossed according to standard protocols and representative sections were submitted from tumors, resection margins, and lymph nodes. Slides were examined by histopathologists to determine tumor type and grade. Immunohistochemical (IHC) stains were applied to evaluate estrogen receptor (ER), progesterone receptor (PR), Ki67, and human epidermal growth factor receptor 2 (HER2/neu) statuses. Results The mean age of the patients with MC was 56.47±13.90 years, and most of the patients were above 50 years of age. The mean tumor size was 34.89±19.70 mm. Most tumors were grade 1 (68.4%) with a low mean Ki67 index (15.21±14.06%). Axillary metastasis was present in 31.6% of cases and all of them were nodal (N)-stage N1. ER, PR, and HER2/neu positivity were noted in 94.7%, 78.9, and 10.5% cases, respectively. Compared with IDC, a significant association of MC was noted with age, Ki67 index, tumor (T)-stage, N-stage, and tumor grade. MC cases had a higher mean age than IDC cases. Comparative analysis revealed that MC had a lower frequency of axillary metastasis, a lower mean Ki67 index, and a lower tumor grade than IDC. About biomarker status, MC was noted to have a higher frequency of ER and PR expression, and a lower frequency of HER2/neu expression than IDC. Conclusion MC is a rare subtype of breast cancer. However, it is important to recognize this subtype of breast cancer as it is associated with a prognostically better pathological profile, such as lower tumor grade and Ki67 index, lower frequency of axillary metastasis, higher expression of ER and PR, and lower expression of HER2/neu.

RevDate: 2021-04-07

Kricheli-Katz T, T Regev (2021)

The effect of language on performance: do gendered languages fail women in maths?.

NPJ science of learning, 6(1):9.

Research suggests that gendered languages are associated with gender inequality. However, as languages are embedded in cultures, evidence for causal effects are harder to provide. We contribute to this ongoing debate by exploring the relationship between gendered languages and the gender gap in mathematics achievements. We provide evidence for causality by exploiting the prominent (but not exclusive) practice in gendered languages of using masculine generics to address women. In an experiment on a large representative sample of the Hebrew-speaking adult population in Israel, we show that addressing women in the feminine, compared to addressing them in the masculine, reduces the gender gap in mathematics achievements by a third. These effects are stronger among participants who acquired the Hebrew language early in childhood rather than later in life, suggesting that it is the extent of language proficiency that generates one's sensitivity to being addressed in the masculine or in the feminine. Moreover, when women are addressed in the masculine, their efforts (in terms of time spent on the maths test) decrease and they report feeling that "science is for men" more than when addressed in the feminine. We supplement the analysis with two experiments that explore the roles of general and task-specific stereotypes in generating these effects.

RevDate: 2021-04-06

Vartholomatos G, Ηarissis Η, Andreou M, et al (2021)

Rapid Assessment of Resection Margins During Breast Conserving Surgery Using Intraoperative Flow Cytometry.

Clinical breast cancer pii:S1526-8209(21)00057-4 [Epub ahead of print].

BACKGROUND: Positive margins are the most important factor for recurrence of the disease after breast-conserving surgery. Several methods have been developed throughout the years to evaluate the margin status during surgery in an attempt to assist the surgeon in excising the whole tumor at once, a goal that has not yet been accomplished.

PATIENTS AND METHODS: In our study, we compared intraoperative flow cytometry (iFC) with cytology and pathology in order to evaluate 606 samples of margins and tumors corresponding to 99 patients with invasive ductal carcinoma of no special type and invasive lobular carcinoma obtained from breast-conserving surgeries.

RESULTS: Using the pathology as the gold standard, flow cytometry had 93.3% sensitivity, 92.4% specificity, and 92.5% accuracy. Cytology had 82.3% sensitivity, 94.6% specificity, and 94.2% accuracy.

CONCLUSIONS: Our data support the suggestion that iFC is a novel, reliable technique that allows rapid evaluation of the excision margins of lumpectomies, thus improving the precision of breast-conserving surgery. Among the advantages of iFC are that it does not rely on the expertise of a pathologist or cytologist, it is low cost, and it has no additional psychological effect on patients, because no re-operation is needed.

RevDate: 2021-04-15

Palgi Y, Bergman YS, Ben-David B, et al (2021)

No psychological vaccination: Vaccine hesitancy is associated with negative psychiatric outcomes among Israelis who received COVID-19 vaccination.

BACKGROUND: The widespread COVID-19 vaccination program, issued by the Israel Government, provides a unique opportunity to examine psychiatric morbidity and vaccine attitudes among individuals who have already been vaccinated. Accordingly, the current study examined how vaccine hesitancy contributes to clinical levels of depression, anxiety, and peritraumatic stress among individuals who had received COVID-19 vaccinations.

METHODS: We analyzed data obtained from 254 vaccinated individuals, and assessed vaccine hesitancy, depression, anxiety, and peritraumatic distress, as well as several demographic, health, and COVID-19-related factors.

RESULTS: Logistic regressions demonstrated that above and beyond socio-demographic, health, and COVID-19-related factors, COVID-19 vaccine hesitancy was the most prominent risk factor for anxiety, depression, and peritraumatic distress. Higher levels of vaccine hesitancy were found to double the risk for depression and peritraumatic stress (ORs > 2), and to triple the risk for anxiety (OR > 3).

LIMITATIONS: A cross-sectional design; a preliminary study requiring further investigation CONCLUSIONS: This study points to the importance of vaccine hesitancy among vaccinated populations and provides knowledge regarding its associations with negative psychiatric outcomes. These findings may offer important information for healthcare practitioners and policy makers in their attempt to encourage individuals to receive COVID-19 vaccinations and emphasize the need to further understand the underlying mechanisms of psychiatric morbidity among vaccinated individuals.

RevDate: 2021-04-05

Alyami H, Yoo TK, Cheun JH, et al (2021)

Clinical Features of Breast Cancer in South Korean Patients with Germline TP53 Gene Mutations.

Journal of breast cancer pii:24.e16 [Epub ahead of print].

PURPOSE: Li-Fraumeni syndrome (LFS) is a rare autosomal cancer syndrome caused by a germline mutation in the TP53 gene. Breast cancer in LFS patients is of various subtypes; however, limited data are available on the clinicopathological features of these subtypes and their appropriate treatments. This study aimed to review the clinical features and treatments for breast cancer in South Korean patients with germline TP53 mutations.

METHODS: Data on the clinicopathological features and treatment of all breast cancer patients with LFS were collected retrospectively from the available database of 4 tertiary hospitals in the Republic of Korea.

RESULTS: Twenty-one breast cancer cases in 12 unrelated women with confirmed germline TP53 mutations were included in the study. The median age at diagnosis was 33.5 years. The histopathological diagnosis included invasive ductal carcinoma (n = 16), ductal carcinoma in situ (n = 3), and malignant phyllodes tumor (n = 2). While 42% and 31% of the cases were positive for estrogen and progesterone receptors, respectively, 52.6% were human epidermal growth factor receptor 2 (HER2) positive, and 21% were triple-negative. The treatments included mastectomy (52%) and breast-conserving surgery (38%). Five patients underwent radiotherapy (RT). The median follow-up period was 87.5 (8-222) months. There were 3 ipsilateral and 4 contralateral breast recurrences during the follow-up, and 8 patients developed new primary cancers. In the post-RT subgroup, there were 2 ipsilateral and 2 contralateral breast recurrences in 1 patient, and 4 patients had a new primary cancer.

CONCLUSION: As reported in other countries, breast cancer in LFS patients in South Korea had an early onset and were predominantly but not exclusively positive for HER2. A multidisciplinary approach with adherence to the treatment guidelines, considering mastectomy, and avoiding RT is encouraged to prevent RT-associated sequelae in LFS patients.

RevDate: 2021-04-06

Jiang X, Wang X, Shen T, et al (2021)

FAPI-04 PET/CT Using [18F]AlF Labeling Strategy: Automatic Synthesis, Quality Control, and In Vivo Assessment in Patient.

Frontiers in oncology, 11:649148.

68Ga labeled FAPI is the current standard for FAPI-PET, but its batch activity is limited. [18F]AlF-NOTA-FAPI-04 is a promising alternative combining the advantages of a chelator-based radiolabeling method with the unique properties of fluorine-18. The objective of this study was to develop a quick automatic method for synthesis of [18F]AlF-NOTA-FAPI-04 using a AllinOne synthesis system, and perform PET imaging with [18F]AlF-NOTA-FAPI-04 on patients. [18F]AlF-NOTA-FAPI-04 was produced, and its quality control was conducted by HPLC equipped with a radioactive detector. [18F]AlF-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice (n = 3) and 4T1 breast cancer models (n = 3) to determine its biodistribution. Then [18F]AlF-NOTA-FAPI-04 and 18F-fluorodeoxyglucose (FDG) PET/CT imaging were performed in an invasive ductal carcinoma patient (female, 54 years old). The synthesis time of [18F]AlF-NOTA-FAPI-04 was about 25 min, and the radiochemical yield was 26.4 ± 1.5% (attenuation correction, n = 10). The radiochemical purity was above 99.0% and was above 98.0% after 6 h. The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was 49.41 ± 3.19 GBq/μmol. PET/CT imaging in mice showed that physiological uptake of [18F]AlF-NOTA-FAPI-04 was mainly in the biliary system and bladder, and [18F]AlF-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that [18F]AlF-NOTA-FAPI-04 obtained high tumor background ratio (TBR) value of 8.44 in segment V and VI, while TBR value was 2.55 by 18F-FDG. [18F]AlF-NOTA-FAPI-04 could be synthesized with high radiochemical yield and batch production by AllinOne module and show excellent diagnosis performance in cancer patients.

RevDate: 2021-04-06

Xu M, Tang Q, Li M, et al (2021)

An analysis of Ki-67 expression in stage 1 invasive ductal breast carcinoma using apparent diffusion coefficient histograms.

Quantitative imaging in medicine and surgery, 11(4):1518-1531.

Background: To investigate the value of apparent diffusion coefficient (ADC) histograms in differentiating Ki-67 expression in T1 stage invasive ductal breast carcinoma (IDC).

Methods: The records of 111 patients with pathologically confirmed T1 stage IDC who underwent magnetic resonance imaging prior to surgery were retrospectively reviewed. The expression of Ki-67 in tumor tissue samples from the patients was assessed using immunohistochemical (IHC) staining, with a cut-off value of 25% for high Ki-67 labeling index (LI). ADC images of the maximum lay of tumors were selected, and the region of interest (ROI) of each lay was delineated using the MaZda software and analyzed by histogram. The correlations between the histogram characteristic parameters and the Ki-67 LI were investigated. Additionally, the histogram characteristic parameters of the high Ki-67 group (n=54) and the low Ki-67 group (n=57) were statistically analyzed to determine the characteristic parameters with significant difference. Receiver operator characteristic (ROC) analyses were further performed for the significant parameters.

Results: The mean value, and the 1st, 10th, 50th, 90th, and 99th percentiles were found to be negatively correlated with the expression of Ki-67 (all P values <0.001), with a correlation coefficient of -0.624, -0.749, -0.717, -0.621, -0.500, and -0.410, respectively. In the high Ki-67 group, the mean value, and the 1st, 10th, 50th, 90th, and 99th percentiles extracted by the histogram were significantly lower (all P values <0.05) than that of the low Ki-67 group, with areas under the ROC curves ranging from 0.717-0.856. However, the variance, skewness, and kurtosis did not differ between the two groups (all P values >0.05).

Conclusions: Histogram-derived parameters for ADC images can serve as a reliable tool in the prediction of Ki-67 proliferation status in patients with T1 stage IDC. Among the significant ADC histogram values, the 1st and 10th percentiles showed the best predictive values.

RevDate: 2021-04-08

Ardila DC, Aggarwal V, Singh M, et al (2021)

Identifying Molecular Signatures of Distinct Modes of Collective Migration in Response to the Microenvironment Using Three-Dimensional Breast Cancer Models.

Cancers, 13(6):.

Collective cell migration is a key feature of transition of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) among many other cancers, yet the microenvironmental factors and underlying mechanisms that trigger collective migration remain poorly understood. Here, we investigated two microenvironmental factors, tumor-intrinsic hypoxia and tumor-secreted factors (secretome), as triggers of collective migration using three-dimensional (3D) discrete-sized microtumor models that recapitulate hallmarks of DCIS-IDC transition. Interestingly, the two factors induced two distinct modes of collective migration: directional and radial migration in the 3D microtumors generated from the same breast cancer cell line model, T47D. Without external stimulus, large (600 µm) T47D microtumors exhibited tumor-intrinsic hypoxia and directional migration, while small (150 µm), non-hypoxic microtumors exhibited radial migration only when exposed to the secretome of large microtumors. To investigate the mechanisms underlying hypoxia- and secretome-induced directional vs. radial migration modes, we performed differential gene expression analysis of hypoxia- and secretome-induced migratory microtumors compared with non-hypoxic, non-migratory small microtumors as controls. We propose unique gene signature sets related to tumor-intrinsic hypoxia, hypoxia-induced epithelial-mesenchymal transition (EMT), as well as hypoxia-induced directional migration and secretome-induced radial migration. Gene Set Enrichment Analysis (GSEA) and protein-protein interaction (PPI) network analysis revealed enrichment and potential interaction between hypoxia, EMT, and migration gene signatures for the hypoxia-induced directional migration. In contrast, hypoxia and EMT were not enriched in the secretome-induced radial migration, suggesting that complete EMT may not be required for radial migration. Survival analysis identified unique genes associated with low survival rate and poor prognosis in TCGA-breast invasive carcinoma dataset from our tumor-intrinsic hypoxia gene signature (CXCR4, FOXO3, LDH, NDRG1), hypoxia-induced EMT gene signature (EFEMP2, MGP), and directional migration gene signature (MAP3K3, PI3K3R3). NOS3 was common between hypoxia and migration gene signature. Survival analysis from secretome-induced radial migration identified ATM, KCNMA1 (hypoxia gene signature), and KLF4, IFITM1, EFNA1, TGFBR1 (migration gene signature) to be associated with poor survival rate. In conclusion, our unique 3D cultures with controlled microenvironments respond to different microenvironmental factors, tumor-intrinsic hypoxia, and secretome by adopting distinct collective migration modes and their gene expression analysis highlights the phenotypic heterogeneity and plasticity of epithelial cancer cells.

RevDate: 2021-04-17

Nagasawa S, Kuze Y, Maeda I, et al (2021)

Genomic profiling reveals heterogeneous populations of ductal carcinoma in situ of the breast.

Communications biology, 4(1):438.

In a substantial number of patients, ductal carcinoma in situ (DCIS) of the breast will never progress to invasive ductal carcinoma, and these patients are often overtreated under the current clinical criteria. Although various candidate markers are available, relevant markers for delineating risk categories have not yet been established. In this study, we analyzed the clinical characteristics of 431 patients with DCIS and performed whole-exome sequencing analysis in a 21-patient discovery cohort and targeted deep sequencing analysis in a 72-patient validation cohort. We determined that age <45 years, HER2 amplification, and GATA3 mutation are possible indicators of relapse. PIK3CA mutation negativity and PgR negativity were also suggested to be risk factors. Spatial transcriptome analysis further revealed that GATA3 dysfunction upregulates epithelial-to-mesenchymal transition and angiogenesis, followed by PgR downregulation. These results reveal the existence of heterogeneous cell populations in DCIS and provide predictive markers for classifying DCIS and optimizing treatment.

RevDate: 2021-04-02
CmpDate: 2021-04-02

Yamamoto D, Yamamoto C, Okugawa H, et al (2021)

[The Treatment of Olaparib for BRCA Positive-Metastatic Breast Cancer Patient].

Gan to kagaku ryoho. Cancer & chemotherapy, 48(3):455-456.

Breast cancer patient(invasive ductal carcinoma, ER[+], PgR[+], HER2[3+], Ki-67: 30%)had neoadjuvant chemotherapy(FEC followed by docetaxel plus trastuzumab). After surgical operation(mastectomy and Ax)was performed and she received trastuzumab plus hormone therapy. After 2 years later, she had liver metastasis that showed IDC, ER(+), PgR (+), HER2(-). In addition, BRCA positive was shown. Therefore, the patient received olaparib tablets(300 mg twice daily). After 2 months later, liver metastasis reduced dramatically.

RevDate: 2021-04-02
CmpDate: 2021-04-02

Satoh E, Uchiyama D, Uehira D, et al (2021)

[A Useful Method of Nipple-Side HydroMARK-Marking before Neoadjuvant Chemotherapy in the Breast Preserving Surgery-A Case Report with pCR of the Triple Negative Breast Cancer].

Gan to kagaku ryoho. Cancer & chemotherapy, 48(3):440-442.

When the primary breast cancer disappears by neoadjuvant chemotherapy, it is often difficult to detect it during the breast preserving surgery. Before neoadjuvant chemotherapy, preoperative nipple-side HydroMARK-marking, which was made of titanium coil and hydrogel, was a very useful and effective method because of its fine detection by ultrasonography. We report a case of 51-year-old female with the triple negative breast cancer(TNBC). At first, the HydroMARK was inserted between the nipple and the tumor. Its distance was about 10 mm toward the nipple. EC therapy followed by docetaxel was performed for 6 months as neoadjuvant chemotherapy. After that, her left TNBC(T1N0M0, Stage Ⅰ, invasive ductal carcinoma, ER[-], PgR[-], HER2[-])was disappeared in all imagings and resected in August 2018. The HydroMARK was clearly detected by intraoperative ultrasonography and her right breast preserving surgery was completely performed. Its pathological finding was pCR(pathological complete response).

RevDate: 2021-04-02
CmpDate: 2021-04-02

Kimura A, Hashimoto N, Sawano T, et al (2021)

[Two Cases in Which Simultaneous Laparoscopic Surgery and Breast Cancer Surgery Using a Head-Mounted Monitor Were Useful].

Gan to kagaku ryoho. Cancer & chemotherapy, 48(3):403-406.

Herein, we report on how we were able to reduce the operation time by simultaneously performing laparoscopic surgery and breast cancer surgery using a head-mounted monitor(HMS-3000MT, Sony corporation). Case 1: 60s, female. A 5.5 cm leiomyoma was found in the central thoracic esophagus, and a 1 cm breast cancer was found in the C region of the left mammary gland. Subtotal esophagectomy with right thoracotomy and laparoscopy and a left partial mastectomy were performed. For the abdominal surgery, HMS-3000MT was used under hand-assisted laparoscopy, and a left partial mastectomy was performed concurrently. Operation time was 367 minutes(simultaneous surgery for 56 minutes). Esophagus: leiomyoma, 50×45 mm; and mammary gland: 16×15 mm, pTis(DCIS), pN0(sn), cM0, and pStage 0. Case 2: 70s, female. A 3 cm sized GIST was found on the posterior wall of the middle gastric body, and a breast cancer of 1.3 cm was also found in the B region of the right mammary gland. Using HMS-3000MT, laparoscopic local resection of the stomach and right total glandectomy were performed concurrently. Operation time was 114 minutes(simultaneous surgery for 58 minutes). Stomach: GIST, 25×22 mm, and modified Flecher classification low risk; and mammary gland: invasive ductal carcinoma, 15×15 mm, pT1c, pN0(sn), cM0, and pStage Ⅰ. Conclusion: In 2 fields of surgery, simultaneous surgery using HMS-3000MT was considered to be a useful method to shorten the operation time.

RevDate: 2021-04-02
CmpDate: 2021-04-02

Ishikawa H, Kouki T, Oda R, et al (2021)

Neoadjuvant Hyperthermia and Chemoradiotherapy for Borderline Resectable Pancreatic Cancer.

Gan to kagaku ryoho. Cancer & chemotherapy, 48(3):388-390.

Pancreatic cancer(PC)is associated with poor prognosis and low resectability rates. Currently, only 15-20% of all patients are candidates for upfront surgery at the time of diagnosis, which offers the chance of long-term survival. In recent years, patients with borderline resectable PC(BR-PC)have been treated with surgery following neoadjuvant chemoradiotherapy or intensive multi-agent chemotherapy. In PC, which is therapy resistant due to its hypoxic microenvironment, hyperthermia may enhance the effect of chemo(radio)therapy. An 84-year-old man with fatty stool was diagnosed with pancreatic head cancer according to the result of contrast computed tomography(CT), which showed a 37 mm irregular low-density area at the pancreatic head infiltrating nearly half of the superior mesenteric artery(SMA)plexus. There were no findings of lymph node metastasis or distant metastasis. The pretreatment diagnosis was BR-PC, cT3, N0, M0, cStage Ⅱ A. The patient was treated with hyperthermia plus S-1 and radiotherapy. The size of the tumor had reduced from 37 mm to 15 mm after the neoadjuvant therapy, and the infiltration into the SMA plexus had also reduced. Therefore, the patient underwent subtotal stomach-preserving pancreaticoduodenectomy(SSPPD)concomitant resection of the PV, SMV, SV confluence. The histopathological findings were invasive ductal carcinoma with R0 radical resection. There has been no recurrence 18 months after the surgery. Based on the above-mentioned findings, hyperthermia and chemoradiotherapy can be an effective option of neoadjuvant treatment for BR-PC.

RevDate: 2021-04-15

Garcia AM, Bishop EL, Li D, et al (2021)

Tolerogenic effects of 1,25-dihydroxyvitamin D on dendritic cells involve induction of fatty acid synthesis.

The Journal of steroid biochemistry and molecular biology, 211:105891 pii:S0960-0760(21)00084-4 [Epub ahead of print].

The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) is a potent regulator of immune function, promoting anti-inflammatory, tolerogenic T cell responses by modulating antigen presentation by dendritic cells (DC). Transcriptomic analyses indicate that DC responses to 1,25D involve changes in glycolysis, oxidative phosphorylation, electron transport and the TCA cycle. To determine the functional impact of 1,25D-mediated metabolic remodelling, human monocyte-derived DC were differentiated to immature (+vehicle, iDC), mature (+LPS, mDC), and immature tolerogenic DC (+1,25D, itolDC) and characterised for metabolic function. In contrast to mDC which showed no change in respiration, itolDC showed increased basal and ATP-linked respiration relative to iDC. Tracer metabolite analyses using 13C -labeled glucose showed increased lactate and TCA cycle metabolites. Analysis of lipophilic metabolites of 13C-glucose revealed significant incorporation of label in palmitate and palmitoleate, indicating that 1,25D promotes metabolic fatty acid synthesis in itolDC. Inhibition of fatty acid synthesis in itolDC altered itolDC morphology and suppressed expression of CD14 and IL-10 by these cells. These data indicate that the ability of 1,25D to induce tolerogenic DC involves metabolic remodelling leading to synthesis of fatty acids.

RevDate: 2021-04-05

Gaertner KM, Poornima IG, C Hilton (2021)

Trastuzumab and pertuzumab in hemodialysis: A case report.

Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners [Epub ahead of print].

INTRODUCTION: Trastuzumab and pertuzumab are recombinant humanized monoclonal antibodies targeting human epidermal growth factor receptor 2 (HER2). Currently, six reported cases on the use of trastuzumab in dialysis, and one on the use of pertuzumab, have been identified in the literature. This case is one of the first to describe the use of pertuzumab, and adds to currently available reports on the use of trastuzumab, in hemodialysis.

CASE REPORT: A female receiving hemodialysis three times per week was diagnosed with a clinical T2N1M0, hormone receptor-negative, HER2-positive, invasive ductal carcinoma of the breast. She received six cycles of neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab, with left ventricular ejection fraction (LVEF) remaining stable throughout. Following surgery, she continued dual HER2 blockade with trastuzumab and pertuzumab, after six cycles of which she was found on routine echocardiogram to have an asymptomatic decline in LVEF.Management & outcome: Following the decline in LVEF, trastuzumab and pertuzumab were held, and cardio-oncology was consulted. LVEF recovered within one month, after which she continued on single-agent trastuzumab to complete one year of HER2-directed therapy.

DISCUSSION: To our knowledge, this is one of the first published cases describing the use of pertuzumab in a patient receiving hemodialysis. Though our patient did experience a reversible decline in LVEF following twelve cycles of combination trastuzumab and pertuzumab, this case demonstrates the relatively safe and effective use of pertuzumab in a patient with end-stage renal disease undergoing hemodialysis, and lends additional support to the use of trastuzumab in this particular patient population.

RevDate: 2021-03-30

Komoroski RA, Lee JH, Welge JA, et al (2020)

1H MR Spectroscopy of Fine-Needle Aspiration Biopsy Specimens for the Discrimination of Breast Cancer.

Radiology. Imaging cancer, 2(6):e200033.

Purpose: To determine whether MR spectroscopic assessment of fine-needle aspiration (FNA) biopsy specimens from suspicious breast lesions could be used to improve the diagnostic utility of FNA biopsies for the characterization of breast lesions.

Materials and Methods: In this prospective study, a previously reported technique using high-spatial-resolution proton MR spectroscopy was modified and used to examine the utility of FNA biopsies in the evaluation of suspicious breast lesions. Tissue samples from 115 lesions (from 102 women; average age, 54 years) were excised by using FNA and core biopsies and were collected between September 7, 2012, and April 11, 2014. Histologic results from core biopsy specimens determined the lesions to be benign (n = 55), invasive ductal carcinoma (n = 51), invasive lobular carcinoma (n = 5), or ductal carcinoma in situ (n = 4). Measures of phosphocholine (PC), glycerophosphocholine, and choline relative to each other and to total creatine (tCr) were obtained from usable spectra. Planned comparisons among lesion groups were carried out using t test contrasts, and differences of each contrast level from zero were judged significant when the two-tailed P value was less than .05.

Results: Of the 115 samples, 69 (60%) yielded no usable MR spectra. Analysis of the 46 with usable spectra found that only the difference in PC/tCr between benign and cancer lesions was statistically significant (P = .028).

Conclusion: Given that 60% of FNA biopsy specimens yielded no usable spectra and that results were largely inconclusive when derived from usable spectra, the combined MR and FNA technique, as modified and implemented in this study, is of little value for detection and diagnosis of breast cancer.Keywords: Breast, MR-Spectroscopy, Neoplasms-Primary© RSNA, 2020.

RevDate: 2021-03-30

Hashmi AA, Munawar S, Rehman N, et al (2021)

Invasive Papillary Carcinoma of the Breast: Clinicopathological Features and Hormone Receptor Profile.

Cureus, 13(2):e13480.

Introduction Papillary neoplasms are a heterogeneous group of breast lesions, ranging from benign to in situ and invasive malignant tumors. The term invasive papillary carcinoma (IPC) is reserved for rare invasive breast tumors showing greater than 90% papillary morphology. The clinical, epidemiological and pathological characteristics of IPC are not widely described in the existing literature; therefore, in this study, we evaluated the clinicopathological features and biomarker profile of IPC and compared it with invasive ductal carcinoma (IDC) diagnosed in the same study duration. Methods A retrospective study was conducted in the Department of Histopathology, Liaquat National Hospital and Medical College, from January 2013 to December 2020. During the study period, 44 cases of IPC and 1,268 cases of IDC were diagnosed. Slides and blocks of all cases were retrieved and histopathological diagnosis was reviewed. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2/neu), and Ki67 immunohistochemical (IHC) stains were applied on representative tissue blocks. Results The mean age of the patients with IPC was 58.77±8.38 years, and the mean Ki67 index was 19.95±21.12%. The mean tumor size was 32.41±17.39 mm, and most tumors (59.1%) were tumor (T)-stage T2. Axillary metastasis was present in 13.6% cases, and 86.4% cases had nodal (N)-stage N0. ER and PR expression was noted in 72.7% cases, and HER2/neu positivity was seen in 13.6% cases. IPC cases had a higher mean age than IDC. Conversely, IPC had a lower mean Ki67 index than IDC. Similarly, IPC cases were found to have a lower frequency of axillary metastasis than IDC. IPC was noted to have a lower frequency of T3-stage and lymphovascular invasion than IDC. A higher expression of PR and lower frequency of HER2/neu expression was noted in IPC than IDC. Conclusion IPC is a rare malignant papillary breast tumor with a wide differential diagnosis and therefore poses a significant diagnostic challenge. We found that IPC had a favorable pathological profile than IDC, in terms of T-stage, Ki67 index, axillary metastasis, PR and HER2/neu expression.

RevDate: 2021-03-30

Sugimoto H, Oda G, Yokoyama M, et al (2021)

Hydronephrosis Caused by Metastatic Breast Cancer.

Case reports in oncology, 14(1):378-385.

Breast cancer metastasizes mainly to organs such as bone, lung, and liver, whereas metastases to the peritoneum and urinary tract are rare. Metastasis to the peritoneum or urinary tract may result in renal dysfunction, infection, and painful hydronephrosis. In our hospital, 1,409 breast cancer surgeries were performed between January 2004 and December 2015, and 7 cases of hydronephrosis associated with recurrence were observed. The median age of patients was 69 years (57-79 years). The median time from surgery to diagnosis of hydronephrosis was 47 months (20-70 months). Histology was invasive ductal carcinoma (IDC) in 6 cases and invasive lobular carcinoma (ILC) in 1 case. There were 6 bilateral cases and 1 unilateral case of hydronephrosis. The causes were retroperitoneal metastasis in 5 cases and lymph node metastasis in 2 cases. The hydronephrosis was untreated in 2 cases, and treated with a ureteral stent in 2 cases, nephrostomy in 1 case, and nephrostomy due to ureteral stent failure in 2 cases. The median survival from the onset of hydronephrosis was 12 months (3-57 months). Although the probability of hydronephrosis in breast cancer recurrence was not high, care must be taken to avoid renal dysfunction, infection, or pain, which may require treatment.

RevDate: 2021-03-30

Al-Gahmi A, Alhuthali M, Alrehaili M, et al (2021)

Unusual Synchronous Association of Solid Tumors with Hematological Malignancies in Multiple Primary Cancers: Case Series and Literature Review.

Case reports in oncology, 14(1):352-364.

The incidence of synchronous multiple primary malignancies (MPMs), which include both solid and hematological malignancy, is considered very rare. In addition, the involvement of sites such as brain, thyroid, and breast are among the least reported in such complex conditions. Here we report five different types of solid tumors including glioblastoma multiforme, thyroid papillary carcinoma, breast invasive ductal carcinoma, colon cancer, and gastric adenocarcinoma that were associated with synchronous five different hematological malignancies in the form of T-cell lymphoblastic non-Hodgkin lymphoma (NHL), nodal marginal zone NHL, diffuse large B-cell NHL, Hodgkin lymphoma, and gastric mucosa-associated lymphoid tissue marginal zone NHL, respectively. The diagnosis of MPMs can be challenging, and there is no standard treatment for such difficult primary malignancies. However, the management of these conditions should be individualized using tumor board discussion and ensuring multidisciplinary coordinated care, besides considering treatment of the more aggressive malignancy before that with the less malignant potential.

RevDate: 2021-03-27

Ali EA, Elmalik H, Omar NE, et al (2021)

Invasive ductal breast carcinoma preceded by CALR-positive essential thrombocythemia.

Clinical case reports, 9(3):1732-1736.

Persistent thrombocytosis in patients with cancer needs workup because it can be linked to essential thrombocytosis. The management should be individualized to start treatment for low-risk essential thrombocytosis due to the combined risk of thrombosis.

RevDate: 2021-03-26

Teh J, Dessauvagie B, Kessell M, et al (2021)

An atypically located pleomorphic adenoma: Radiological and pathological correlation.

Pleomorphic adenoma is a common benign salivary gland neoplasm which very rarely occurs in the breast. Its radiologic and pathologic appearance may be mistaken for other benign or malignant lesions such as a fibroadenoma or invasive ductal carcinoma. Due to the risk of local recurrence and, rarely, malignant transformation, wide local excision with clear margins is recommended. As such, a correct diagnosis of this lesion is important to ensure appropriate surgical treatment. We report a case of an atypically located pleomorphic adenoma with radiologic-pathologic correlation in an asymptomatic 63-year-old woman.

RevDate: 2021-04-15

Shimon-Raz O, Salomon R, Bloch M, et al (2021)

Mother brain is wired for social moments.

eLife, 10:.

Reorganization of the maternal brain upon childbirth triggers the species-typical maternal social behavior. These brief social moments carry profound effects on the infant's brain and likely have a distinct signature in the maternal brain. Utilizing a double-blind, within-subject oxytocin/placebo administration crossover design, mothers' brain was imaged twice using fMRI while observing three naturalistic maternal-infant contexts in the home ecology; 'unavailable', 'unresponsive', and 'social', when mothers engaged in synchronous peek-a-boo play. The social condition elicited greater neural response across the human caregiving network, including amygdala, VTA, hippocampus, insula, ACC, and temporal cortex. Oxytocin impacted neural response primarily to the social condition and attenuated differences between social and non-social stimuli. Greater temporal consistency emerged in the 'social' condition across the two imaging sessions, particularly in insula, amygdala, and TP. Findings describe how mother's brain varies by caregiving experiences and gives salience to moments of social synchrony that support infant development and brain maturation.

RevDate: 2021-04-03

Garg KK, Anantha KH, Venkataradha A, et al (2021)

Impact of Rainwater Harvesting on Hydrological Processes in a Fragile Watershed of South Asia.

Ground water [Epub ahead of print].

Agricultural water management (AWM) interventions play an important role in ensuring sustainable food production and mitigating climate risks. This study was carried out in a watershed located in a low rainfall (400-600 mm) region of western India. The Soil and Water Assessment Tool model was calibrated using surface runoff, soil loss, and reservoir storage levels, between the year 2000 and 2006. The investigation indicated that the various AWM interventions increased groundwater recharge from 30 mm/year to 80 mm/year and reduced surface runoff from 250 mm/year to 100 mm/year. The intervention structures were refilled two to three times during the monsoon season depending on rainfall intensity and duration. The interventions have the advantage of building a resilient system by enhancing groundwater availability even in dry years, stimulating crop intensification and protecting the landscape from severe erosion. The results indicate that soil erosion has been reduced by more than 75% compared to the nonintervention situation. Moreover, the AWM interventions led to the cultivation of 100-150 ha of fallow land with high-value crops (horticulture, vegetables, and fodder). Household income increased by several folds compared to the nonintervention situation. The study showed about 50% reduction in downstream water availability, which could be a major concern. However, there are a number of ecosystem trade-offs such as improved base flow to the stream and reduction in soil loss that should be considered. The study is of great importance to stakeholders to decide on the optimal design for AWM interventions to achieve sustainable development goals.

RevDate: 2021-03-28

Rodrigues MA, Caldeira-Brant AL, Gomes DA, et al (2021)

Characterization of neoplastic cells outlining the cystic space of invasive micropapillary carcinoma of the canine mammary gland.

BMC veterinary research, 17(1):130.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) is a rare malignant breast tumor and a variant form of invasive ductal carcinoma that is an aggressive neoplasm of the human breast and canine mammary gland. The importance of the tumor microenvironment in cancer development has gradually been recognized, but little is known about the cell types outlining the cystic space of canine IMPC. This study aimed to characterize the neoplastic cells outlining the cystic space of IMPC.

RESULTS: Immunohistochemistry (IHC), immunofluorescence (IF), superresolution and transmission electron microscopy (TEM) were used to assess the cell types in the cystic areas of IMPCs. Cells expressing the mesenchymal markers alpha-smooth muscle actin (αSMA), Vimentin, and S100A4 outlined the cystic space of IMPC. Furthermore, loss of epithelial cell polarity in IMPC was shown by the localization of MUC1 at the stroma-facing surface. This protein modulates lumen formation and inhibits the cell-stroma interaction. Immunohistochemical and IF staining for the myoepithelial cell marker p63 were negative in IMPC samples. Furthermore, associated with peculiar morphology, such as thin cytoplasmic extensions outlining cystic spaces, was observed under TEM. These observations suggested cells with characteristics of myoepithelial-like cells.

CONCLUSIONS: The cells outlining the cystic space of IMPC in the canine mammary gland were characterized using IHC, IF and TEM. The presence of cells expressing αSMA, Vimentin, and S100A4 in the IMPC stroma suggested a role for tumor-associated fibroblasts in the IMPC microenvironment. The reversal of cell polarity revealed by the limited basal localization of MUC1 may be an important factor contributing to the invasiveness of IMPC. For the first time, the cystic space of canine mammary gland IMPC was shown to be delimited by myoepithelial-like cells that had lost p63 expression. These findings may enhance our understanding of the cellular microenvironment of invasive tumors to improve cancer diagnosis and treatment.

RevDate: 2021-03-24

Martens TW, Lima JS, Johnson EA, et al (2021)

Trial of a New Diabetes Education Model: Closing the Gap in Health Disparity for People with Diabetes.

Journal of diabetes science and technology [Epub ahead of print].

BACKGROUND: Quality measures relating to diabetes care in America have not improved between 2005 and 2016, and have plateaued even in areas that outperform national statistics. New approaches to diabetes care and education are needed and are especially important in reaching populations with significant barriers to optimized care.

METHODS: A pilot quality improvement study was created to optimize diabetes education in a clinic setting with a patient population with significant healthcare barriers. Certified Diabetes Care and Education Specialists (CDCES) were deployed in a team-based model with flexible scheduling and same-day education visits, outside of the traditional framework of diabetes education, specifically targeting practices with underperforming diabetes quality measures, in a clinic setting significantly impacted by social determinants of health.

RESULTS: A team-based and flexible diabetes education model decreased hemoglobin A1C for individuals participating in the project (and having a second A1C measured) by an average of -2.3%, improved Minnesota Diabetes Quality Measures (D5) for clinicians participating in the project by 5.8%, optimized use of CDCES, and reduced a high visit fail rate for diabetes education.

CONCLUSIONS: Diabetes education provided in a team-based and flexible model may better meet patient needs and improve diabetes care metrics, in settings with a patient population with significant barriers.

RevDate: 2021-03-24

Zhang J, Zhou B, Sun J, et al (2021)

Betulin ameliorates 7,12-dimethylbenz(a)anthracene-induced rat mammary cancer by modulating MAPK and AhR/Nrf-2 signaling pathway.

Journal of biochemical and molecular toxicology [Epub ahead of print].

The aim of the present study is to explore the preventive efficacy of betulin (BE) in 7,12-dimethylbenz(a)anthracene (DMBA)-administered mammary cancer by modulating Ahr/Nrf2 signaling in experimental models. The mammary cancer was stimulated by the addition of DMBA (25 mg/kg/b.Wt) mixed in 1 ml of vehicle solution (sunflower oil and saline 1:1) through subcutaneous injection. The DMBA-exposed mammary tumor models showed low bodyweight, elevated quantities of lipid peroxidation molecules (TBARS and LOOH), and low enzymatic (GPx, SOD, and CAT), and nonenzymatic (GSH, vitamin C, and vitamin E) antioxidant activities in plasma and mammary tissues. Moreover, histopathological studies confirmed that invasive ductal carcinoma was observed in DMBA-induced mammary tissue of the experimental model. Dietary oral supplementation of BE prevents the loss of bodyweight, overproduces lipid peroxidation, and restores the antioxidant activities in DMBA-exposed experimental animals. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial antioxidant protein that involves preventing numerous cancers. Therefore, Nrf2-associated signaling concern is a significant target for preventing mammary cancer. This study observed an increased expression of MAPKs, Keap1, ARNT, AhR, and CYP1A1, whereas decreased expression of HO-1 and Nrf2 in DMBA-induced cancer-bearing experimental animals. The oral supplementation of BE effectively modulates the expression of MAPKs, AhR/Nrf2-associated protein expressions in DMBA-exposed experimental animals. This current study concluded that BE is a strong antioxidant, which triggers the MAPKs-mediated oxidative stress and inhibits proliferative markers by restoring the activity of Nrf2 signaling.

RevDate: 2021-04-06

Okun JG, Rusu PM, Chan AY, et al (2021)

Liver alanine catabolism promotes skeletal muscle atrophy and hyperglycaemia in type 2 diabetes.

Nature metabolism, 3(3):394-409.

Both obesity and sarcopenia are frequently associated in ageing, and together may promote the progression of related conditions such as diabetes and frailty. However, little is known about the pathophysiological mechanisms underpinning this association. Here we show that systemic alanine metabolism is linked to glycaemic control. We find that expression of alanine aminotransferases is increased in the liver in mice with obesity and diabetes, as well as in humans with type 2 diabetes. Hepatocyte-selective silencing of both alanine aminotransferase enzymes in mice with obesity and diabetes retards hyperglycaemia and reverses skeletal muscle atrophy through restoration of skeletal muscle protein synthesis. Mechanistically, liver alanine catabolism driven by chronic glucocorticoid and glucagon signalling promotes hyperglycaemia and skeletal muscle wasting. We further provide evidence for amino acid-induced metabolic cross-talk between the liver and skeletal muscle in ex vivo experiments. Taken together, we reveal a metabolic inter-tissue cross-talk that links skeletal muscle atrophy and hyperglycaemia in type 2 diabetes.

RevDate: 2021-04-09

Yoneyama K, Nakagawa M, A Hara (2021)

Bilateral nipple-sparing mastectomy and breast reconstruction in BRCA1 mutation-positive simultaneous bilateral breast cancer: A case study.

BACKGROUND: Mutation-positive patients who develop unilateral breast cancer require different treatments, such as prophylactic mastectomy of the contralateral breast, from those used for other breast cancer patients. If a mutation is found before surgery, it is necessary to consider a surgical procedure that includes reconstruction. For BRCA mutation-positive patients, a suitable treatment must be selected. In Japan, a test for BRCA mutation has been covered by health insurance since 2020, making it possible to preoperatively test patients who are suspected of being positive. We report a case of simultaneous bilateral breast cancer that was found to be BRCA mutation-positive preoperatively and underwent bilateral subcutaneous mastectomy and breast reconstruction.

CASE PRESENTATION: A 57-year-old woman was admitted to our hospital after a breast cancer screening revealed a mass in the left breast. She had a family history of breast cancer, including her sister, aunt, and cousin. She was suspected of being malignant with a mass on both sides of her breast on imaging. She underwent needle biopsy and was diagnosed as having bilateral invasive ductal carcinoma, for which she was placed on preoperative chemotherapy. Due to the strong family history of bilateral breast cancer, the patient was recommended to undergo a BRCA gene-mutation test and she consented. The result was positive for BRCA1 mutation. Although it was judged that bilateral breast-conserving surgery was sufficiently possible, bilateral subcutaneous mastectomy and breast reconstruction were performed based on BRCA mutation-positive status.

DISCUSSION: Performing a preoperative BRCA test may change the surgical procedure. BRCA tests are beneficial to patients, but the timing of the tests is important. Care must be taken not to force the patient.

CONCLUSIONS: Knowing whether the patient is BRCA mutation-positive is extremely important for selecting surgical procedures and treatment methods. BRCA testing should be recommended for patients who are strongly suspected of being positive, but the decision should be the patient's. It is therefore necessary to provide accurate information and engage in a dialogue with the patient, but the medical staff should not pressure the patient to have the test.

RevDate: 2021-03-23

Bergeron A, MacGrogan G, Bertaut A, et al (2021)

Triple-negative breast lobular carcinoma: a luminal androgen receptor carcinoma with specific ESRRA mutations.

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Epub ahead of print].

Primary triple-negative invasive lobular breast carcinomas (TN-ILCs), which do not express hormone receptors and HER2 at diagnosis, are rare and poorly known. In this study, we analyzed the largest TN-ILC series ever reported in the literature, in comparison to phenotypically similar breast tumor subtypes: triple-negative invasive ductal carcinoma (TN-IDC) and hormone receptor-positive invasive lobular carcinoma (HR + ILC). All primary TN-ILCs registered in our database between 2000 and 2018 (n = 38) were compared to tumors from control groups, matched by stage and Elston/Ellis grade, with regard to clinical, pathologic, and immunohistochemical characteristics. A comparative molecular analysis (whole-exome and RNA sequencing using next-generation technology) was also performed. We found that TN-ILC patients were older than those with HR + ILC (P = 0.002) or TN-IDC (P < 0.001). Morphologically, TN-ILCs had aggressive phenotypes, with more pleomorphism (P = 0.003) and higher nuclear grades than HR + ILCs (P = 0.009). Immunohistochemistry showed that TN-ILCs less frequently expressed basal markers (CK5/6, EGFR and SOX10) than TN-IDCs (P < 0.001), while androgen receptor (AR) positivity was more prevalent (P < 0.001). Survival curves analysis did not show differences between TN-ILC and TN-IDC patients, while overall and distant metastasis-free survival were significantly worse compared to those with HR + ILCs (P = 0.047 and P = 0.039, respectively). At a molecular level, we found that TN-ILCs had particular transcriptomic profiles, characterized by increased AR signaling, and associated with frequent alterations in the PI3K network and ERBB2. Interestingly, whole-exome analysis also identified three specific recurrent ESRRA hotspot mutations in these tumors, which have never been described in breast cancer to date and which were absent in the other two tumor subtypes. Our findings highlight that TN-ILC is a unique aggressive breast cancer associated with elderly age, which belong to the luminal androgen receptor subtype as determined by immunohistochemistry and transcriptomic profiling. Moreover, it harbors specific molecular alterations (PI3K, ERBB2 and ESRRA) which may pave the way for new targeted therapeutic strategies.

RevDate: 2021-03-23

Nakash O, Cruz-Gonzalez M, Lincoln AK, et al (2021)

Similarities in client-clinician perceptions of subjective social status and its association to similarities in the quality of working alliance and client anxiety symptoms.

Psychotherapy research : journal of the Society for Psychotherapy Research [Epub ahead of print].

Objective: Subjective social status (SSS) has largely been ignored within psychotherapy literature. We investigated the association between similarities in client-clinician perceptions of SSS, similarities in their report of the quality of working alliance, and resultant anxiety symptoms. Method: Participants represented a primarily low-income, culturally diverse sample of 312 clients receiving care from 68 clinicians at 13 outpatient mental health clinics in the Northeastern United States between September 2013 and August 2016. As part of a larger randomized controlled trial, clients and clinicians completed the MacArthur Scale of subjective social status and the Working Alliance Inventory (WAI), and clients completed the Generalized Anxiety Disorder 7-item Scale (GAD-7). Results: At the within-clinician level, client-clinician dyads with less similar perceptions of the client's SSS were characterized by less similar perceptions of their alliance, which in turn resulted in worsening anxiety symptoms. Conclusion: Clinicians' correct perception of their clients' social status might be important for sharing a similar view of the client-clinician level of alliance, which can, in turn, contribute to lowering the client's anxiety symptoms.

RevDate: 2021-03-22

Zhu Z, Chen C, Chen C, et al (2021)

Prediction of tumor size in patients with invasive ductal carcinoma using FT-IR spectroscopy combined with chemometrics: a preliminary study.

Analytical and bioanalytical chemistry [Epub ahead of print].

Precise detection of tumor size is essential for early diagnosis, treatment, and evaluation of the prognosis of breast cancer. However, there are some errors between the tumor size of breast cancer measured by conventional imaging methods and the pathological tumor size. Invasive ductal carcinoma (IDC) is a common pathological type of breast cancer. In this study, serum Fourier transform infrared spectroscopy (FT-IR) combined with chemometric methods was used to predict the maximum diameter and maximum vertical diameter of tumors in IDC patients. Three models were evaluated based on the pathological tumor size measured after surgery and included grid search support vector machine regression (GS-SVR), back propagation neural network optimized by genetic algorithm (GA-BP-ANN), and back propagation neural network optimized by particle swarm optimization (PSO-BP-ANN). The results show that three models can accurately predict tumor size. The GA-BP-ANN model provided the best fitting quality of the largest tumor diameter with the determination coefficients of 0.984 in test set. And the GS-SVR model provided the best fitting quality of the largest vertical tumor diameter with the determination coefficients of 0.982 in test set. The GS-SVR model had the highest prediction efficiency and the lowest time complexity of the models. The results indicate that serum FT-IR spectroscopy combined with chemometric methods can predict tumor size in IDC patients. In addition, compared with traditional imaging methods, we found that the experimental results of the three models are better than traditional imaging methods in terms of correlation and fitting degree. And the average fitting error of PSO-BP-ANN and GA-BP-ANN models was less than 0.3 mm. The minimally invasive detection method is expected to be developed into a new clinical diagnostic method for tumor size estimation to reduce the diagnostic trauma of patients and provide new diagnostic experience for patients. Graphical Abstract.

RevDate: 2021-03-22

Shenkman G, Ifrah K, D Shmotkin (2021)

The moderation of socio-demographics in physical and mental health disparities among Israeli gay and heterosexual middle-aged and older men.

Aging & mental health [Epub ahead of print].

OBJECTIVES: Physical and mental health disparities were explored among Israeli middle-aged and older gay and heterosexual men alongside the moderating role of age, relationship status, and place of birth.

METHOD: 173 middle-aged and older gay men were individually matched with 173 middle-aged and older heterosexual men at the age range of 50-86 (M = 60.56, SD = 8.42). All participants completed measures of doctor visits, physical health comorbidity, depressive symptoms, and anxiety.

RESULTS: Israeli middle-aged and older gay and heterosexual men did not significantly differ on physical or mental health indicators. However, a more differential analysis revealed that older age and relationship status had a moderating role, such that older gay men reported more physical health comorbidity in comparison to older heterosexual men. Similarly, gay men who were not in a steady relationship reported more frequent visits to the doctor and more anxiety in comparison to heterosexual men who were not in a steady relationship. Additionally, immigration history appeared as a potential resiliency factor, such that gay men who were not born in Israel reported less frequent doctor visits and less anxiety in comparison to heterosexual men who were not born in Israel.

CONCLUSIONS: This study presents a pioneering examination of physical and mental health disparities in an Israeli sample of middle-aged and older gay and heterosexual men. These results may call the attention of clinicians and policymakers to both vulnerabilities and strengths of middle-aged and older gay men.

RevDate: 2021-03-20

Kato E, Mori N, Mugikura S, et al (2021)

Value of ultrafast and standard dynamic contrast-enhanced magnetic resonance imaging in the evaluation of the presence and extension of residual disease after neoadjuvant chemotherapy in breast cancer.

Japanese journal of radiology [Epub ahead of print].

PURPOSE: To evaluate the diagnostic performance of ultrafast and standard dynamic contrast-enhanced (DCE)-MRI in evaluating the residual disease after neoadjuvant chemotherapy (NAC) for breast cancer.

MATERIALS AND METHODS: Sixty-seven consecutive patients underwent MRI after NAC. Visual analysis of enhancement was performed on ultrafast and standard DCE-MRI, and compared between no residual disease and residual disease groups. The lesion diameters measured on the last phase of ultrafast DCE-MRI and early and delayed phases of standard DCE-MRI were compared with pathological diameter of entire residual cancer and residual invasive ductal carcinoma (IDC).

RESULTS: The visual analysis in the delayed phase of standard DCE-MRI exhibited the highest sensitivity (90%), whereas ultrafast DCE-MRI revealed the highest positive predictive value (92%). There were no significant differences between the diameters in the delayed phase of the standard DCE-MRI and the pathological entire residual cancer (p = 0.97), and the diameters in ultrafast DCE-MRI and the pathological residual IDC (p = 0.97).

CONCLUSION: The delayed phase of standard DCE-MRI may be effective for detecting the residual disease and evaluating the extension of entire residual cancer. Enhancement in ultrafast DCE-MRI may be strongly suggestive of the presence of residual disease, and effective for evaluating the extension of residual IDC.

RevDate: 2021-04-05

Levin Y, Lev Bar-Or R, Forer R, et al (2021)

The association between type of trauma, level of exposure and addiction.

Addictive behaviors, 118:106889.

Exposure to trauma is considered a risk factor for the development of addictive disorders. Currently, there is a knowledge gap concerning specific links between types and levels of exposure to traumatic events and addiction.In this study we explored the associations between interpersonal trauma and risk of addictive behaviors, stratified by type of trauma (physical, weapon, sexual assault, and combat) and level of exposure (direct/indirect), focusing on a wide range of substances and behaviors. Data from an online representative sample of 4025 respondents were collected, including the Life Events Checklist (LEC-5), substance use disorders and behavioral addictions metrics, and sociodemographic data. Substantial differences were found between specific types of trauma and risk of addiction. Among those exposed to sexual assault, the risk of alcohol use disorder was found to 15.4%, 95%CI[14.4-16.4%], compared to 12.1%,95%CI[11.3-12.8] among those exposed to combat-related trauma. Both direct and indirect exposure to trauma were found to be significantly related with risk of addiction. While direct exposure was most highly associated with addictions across several types of trauma, in the case of combat-related trauma, indirect exposure was more highly associated with alcohol and pornography addiction (14.5%,95%CI[13.2-15.8%] and 10.0%, 95%CI[6.3-15.0%], respectively) compared to direct exposure (10.7%,95%CI[9.9-11.6%] and 7.4%, 95%CI[4.7-11.6%], respectively). Our findings emphasize the strong association between all types of trauma and the risk of several specific substance and behavioral addictions. Specifically, the role of indirect exposure to trauma is highlighted.

RevDate: 2021-03-18

Yaman ME, Kayili HM, Albayrak M, et al (2021)

Differential N-glycosylation profiling of formalin-fixed paraffin-embedded (FFPE) invasive ductal carcinoma tissues using MALDI-TOF-MS.

Molecular omics [Epub ahead of print].

Invasive ductal carcinoma (IDC) is the most common type of breast cancer. As dynamic changes of the glycome are closely associated with complex diseases, they have become a focal point of cancer research involving predictive and prognostic markers. Formalin-fixed paraffin-embedded (FFPE) clinical specimens are representative of the tumor environment and are thus utilized in studies on cancer related research and biomarker discovery. Further studies on differential N-glycosylation profiling of IDC cancer tissues are necessary in order to understand the biological role of glycans in cancer and to evaluate their predictive ability. In this study, matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS)-based analyses were conducted for determining differential N-glycosylation patterns of IDC. Two different derivatization methods, namely, 2-aminobenzoic acid (2-AA) labeling and linkage-specific sialic acid esterification, were used for the analysis of N-glycans. Forty-seven 2-AA labeled and fifty ethyl esterified N-glycans were identified by MALDI-MS. In statistical analyses conducted for 2-AA-labeled N-glycans, the relative amounts of 32 N-glycans and prevalence of 15 N-glycan traits showed significant (p < 0.05) differences between cancer and normal tissues; and in such analyses for the ethyl-esterified N-glycans, the relative amounts of 27 N-glycans and prevalence of 17 N-glycan traits showed significant (p < 0.05) differences between them. It was found that mainly high mannose N-glycans, including H5N2, H6N2, and H7N2, and two fucosylated compositions (H3N3F1 and H5N5F1) showed strong discrimination between IDC and controls. In addition, compared with the controls, high mannose N-glycans were observed to be up-regulated in IDC whereas bisecting N-glycans were down-regulated.

RevDate: 2021-04-01

Ginzburg K, Mikulincer M, Ohry A, et al (2021)

Echoes from the past: adjustment of aging former prisoners of war to the COVID-19 pandemic.

Psychological medicine [Epub ahead of print].

BACKGROUND: The aim of this study was to examine whether exposure to previous traumatic events is a risk factor for stress reactions during this pandemic. Capitalizing on a 29-year longitudinal study of Israeli ex-prisoners of war (ex-POWs) and combat veterans, we examined whether captivity is a risk factor for fear of coronavirus disease 2019 (COVID-19) and COVID-19-induced acute stress disorder (COVID-19 ASD) beyond the effects of combat exposure and other stressful life events. In addition, we examined the contribution of captivity experiences (severity of captivity, experience of solitary confinement, and suffering during captivity) and veterans' appraisal of the impact of their war-related experiences on adjustment to the current quarantine and isolation to fear of COVID-19 and COVID-19 ASD.

METHODS: One-hundred-and-twenty Israeli ex-POWs from 1973 Yom Kippur War and 65 matched controls (combat veterans from the same war) filled out self-report questionnaires 18 (T1), 35 (T2), 42 (T3), and 47 (T4) years after the war.

RESULTS: Findings revealed that although ex-POWs and controls did not differ in their level of exposure to COVID-19, ex-POWS reported higher levels of fear of COVID-19 and COVID-19 ASD than controls. Suffering during captivity, measured at 1991, and participants' appraisal of the extent to which their war-related experiences affected adjustment to COVID-19 were significantly associated with fear of COVID-19 and COVID-19 ASD.

CONCLUSIONS: The findings of the study demonstrate the long-term effects of exposure to traumatic experiences (captivity) during young adulthood on adjustment to an unrelated collective stress, such as COVID-19, 40 years later.

RevDate: 2021-03-17

Bar-Or RL, Kor A, Jaljuli I, et al (2021)

The Epidemiology of Substance Use Disorders among the Adult Jewish Population in Israel.

European addiction research pii:000513776 [Epub ahead of print].

INTRODUCTION: Substance use disorders (SUDs) are a leading cause of morbidity and mortality worldwide, having a profound and global impact on health, well-being, safety, and productivity. Although traditionally the prevalence of SUDs in Israel has been estimated to be lower than those in high-income countries, estimates and characteristics of individuals with SUDs in the past decade are lacking. In this work, we explored the prevalence of SUDs among the adult Jewish population in Israel, per different classes of substances across sex, age group, and other sociodemographic factors.

METHODS: Data from an online representative sample of 4,025 respondents were collected, including the alcohol, smoking, and substance involvement screening test (ASSIST) metric and sociodemographic data.

RESULTS: We found that the most common SUDs were alcohol (10.5% [9.5-11.4]), cannabis (9.0% [8.2-9.9]), and sedative (3.6% [3.0-4.2]) use disorders. Alcohol-cannabis (3.2% [2.7-3.7]) and alcohol-sedative (1.04% [0.7-1.35]) were the most prevalent co-occurring SUDs. Among those with cannabis use disorder, the prevalence of alcohol use disorder was found to be 35.3% [30.4-40.2]. The estimated risk for alcohol use disorder was found to be inversely proportional to age, cannabis use disorder increased, peaked, and decreased with age, and that of sedative use disorder increased with age, particularly among women. While older individuals (in the 51-60 years of age group) were at lower risk (OR = 0.5 [0.3, 0.8]) compared to those <20 years of age for alcohol use disorder, they were at increased risk for sedative use disorder (OR = 3.1 [1.2, 9.7]).

CONCLUSIONS: These findings represent substantially higher rates of SUDs in Israel than those previously reported and should affect resources allocated to addiction prevention and treatment. Further research on the role of gender, age, culture, and ethnicity in the propensity to develop SUDs is necessary for the development of more focused preventive and intervention measures. Focusing on non-Jewish populations in Israel and broadening the scope to include behavioral addictions should be addressed in future studies.

RevDate: 2021-03-20
CmpDate: 2021-03-18

Mallard SR, Clifford KA, Park R, et al (2021)

Role for colorectal teams to support non-colorectal teams to improve clinical outcomes and adherence to ERAS guidelines for segmental colectomy: a cohort study.

BMC surgery, 21(1):132.

BACKGROUND: To identify whether compliance with Enhanced Recovery After Surgery (ERAS) Society recommendations is associated with length of stay (LOS) in a New Zealand hospital for patients undergoing segmental colectomy in mixed acute and elective general surgery wards.

METHODS: Consecutive elective colorectal surgeries (n = 770) between October 2012 and February 2019 were audited. Patients with non-segmental colectomies, multi-organ surgeries, LOS > 14 days, and those who died were excluded. Logistic regression was used to determine the relationship between patient demographics, compliance with ERAS guidelines, and suboptimal LOS (> 4 days).

RESULTS: Analysis included 376 patients. Age, surgery prior to 2014, surgical approach, non-colorectal surgical team, operation type, and complications were significantly associated with suboptimal LOS. Non-compliance with ERAS recommendations for laparoscopy [OR 8.9, 95% CI (4.52, 19.67)], removal of indwelling catheters (IDC) [OR 3.14, 95% CI (1.85, 5.51)], use of abdominal drains [OR 4.27, 95% CI (0.99, 18.35)], and removal of PCA [OR 8.71, 95% CI (1.78, 157.27)], were associated with suboptimal LOS (univariable analysis). Multivariable analysis showed that age, surgical team, late removal of IDC, and open approach were independent predictors of suboptimal LOS.

CONCLUSIONS: Non-compliance with ERAS guidelines for laparoscopic approach and early removal of IDC was higher among procedures performed by non-colorectal surgery teams, and was also associated with adverse postoperative events and suboptimal LOS. This study demonstrates the importance of the surgical team's expertise in affecting surgical outcomes, and did not find significant independent associations between most individual ERAS guidelines and suboptimal LOS once adjusting for other factors.

RevDate: 2021-04-15
CmpDate: 2021-03-22

Oh BH, Woo CG, Lee YJ, et al (2021)

Brain metastasis with subtype conversion in a patient with male breast cancer: A case report.

Medicine, 100(11):e24373.

RATIONALE: Brain metastasis of male breast cancer is extremely rare, and the pathological changes between the primary tumor and the metastatic brain tumor have not been reported. Herein, we report for the first time a case of male breast cancer with metastasis to the parietal lobe with subtype conversion after metastasis.

PATIENT CONCERNS: we describe a 45-year-old male patient admitted for an incidentally found brain tumor after a motorcycle accident. The patient had been treated for breast cancer 5 years previously. The primary tumor was an invasive ductal carcinoma classified as pT1N1M0 with hormone receptor positivity (estrogen receptor ++, progesterone receptor +++, human epidermal growth factor receptor-type2 (HER2) +) and was treated with surgery, adjuvant chemotherapy, radiation therapy and endocrine therapy (tamoxifen).

DIAGNOSES: Magnetic resonance imaging revealed a well enhanced focal solid tumor in the right parietal lobe (5.0 × 4.2 cm in size), Immunohistochemical staining revealed cerebral metastases of breast cancer with HER2 subtype conversion (estrogen receptor +++, progesterone receptor +++, HER2 -).

INTERVENTIONS: The patient was successfully treated with surgery and whole brain irradiation (3 Gy × 10 fractions).

OUTCOMES: There was no additional complication after the surgery and the patient transferred to oncology department for chemotherapy. 2 years later, he had gamma knife radiosurgery due to the recurred brain lesion and after that he discontinued the treatment and opted for hospice care.

LESSONS: Male breast cancer with metastasis to the brain is an extremely rare condition. Although a few similar cases have been reported, subtype conversion in similar cases has not been reported. Therefore, we report this case of a male patient with brain metastasis of invasive ductal carcinoma with HER2 status conversion after metastasis.

RevDate: 2021-03-16

Parmeshwar N, Alcon A, EA Kim (2021)

A Dual-Surgeon Approach to Breast Cancer Surgery in a Transmale.

Annals of plastic surgery [Epub ahead of print].

With increasing numbers of gender-affirming chest surgery, new questions regarding breast cancer management and surgical practice arise. Guided by our case report, we present a comprehensive review of breast cancer surgery in a transman to educate both plastic and breast surgeons on various factors to consider when caring for these patients.Our case involves a 31-year-old transmale patient who presented for plastic surgery consultation for gender-affirming mastectomy but was subsequently found to have a right breast mass. This is the first case in the literature of a transmale on hormone therapy with breast cancer interested in gender-affirming surgery, thus requiring a dual-surgeon approach for oncologic and gender-affirming mastectomy. With a multidisciplinary patient-centered approach involving breast surgery, plastic surgery, medical oncology, and radiology, we devised a surgical plan to safely remove his breast tissue with consideration for his gender-affirming goals. He underwent a right skin-sparing mastectomy with sentinel node biopsy and left prophylactic skin-sparing mastectomy through skin markings by the plastic surgeon, with bilateral free nipple grafts. Final pathology confirmed estrogen and progesterone receptor-positive and androgen receptor-positive invasive ductal carcinoma with clear margins and negative sentinel node. The patient did not require adjuvant chemotherapy or radiation but was started on adjuvant hormone therapy targeting his hormone receptor positive cancer. He elected to stay on low-dose masculinizing hormone therapy with continued surveillance examinations.We follow our case with a review of the current literature involving breast cancer in transmales to explore current screening practices, surgical recommendations, adjuvant therapies, continuation of masculinizing hormone therapy, and postoperative surveillance guidelines in the hopes of informing plastic surgeons in having these discussions with their transmale patients and thus improving informed cancer care for this population.

RevDate: 2021-04-17

Bartels AK, Fadare O, Hasteh F, et al (2021)

Nonmass enhancement lesions of the breast on core needle biopsy: outcomes, frequency of malignancy, and pathologic findings.

Human pathology, 111:92-97 pii:S0046-8177(21)00044-7 [Epub ahead of print].

Nonmass enhancement (NME) on breast magnetic resonance imaging (MRI) is defined as an area whose internal enhancement characteristics can be distinguished from the normal surrounding breast parenchyma, without an associated mass in the Breast Imaging Reporting and Data System lexicon. In this study, we evaluated the pathologic correlates of NME lesions of the breast identified on MRI at our institution, including the frequency of atypical or malignant lesions in the core needle biopsies (CNBs), performed after such a radiologic finding. A retrospective study was performed on all CNBs performed for NME on breast MRI between 2010 and 2019. A total of 443 biopsies from 411 patients were identified, comprising 5.5% of all CNBs over the study period. The pathologic diagnoses were benign in the majority of the biopsies (68.0%), whereas 11.5% and 20.5% of the cases were atypical and malignant lesions, respectively. Of the malignant cases, 69.2% were ductal carcinoma in situ (DCIS) and 30.8% were invasive carcinomas. The most common invasive cancer was invasive ductal carcinoma (50%), followed by invasive lobular carcinoma (39.3%). NME identified on breast MRI carried a significant (32%) risk of atypia and malignancy in our cohort, which confirms that biopsy evaluation of these lesions is warranted. DCIS was the most commonly identified malignancy. Notably, among invasive cancers, invasive lobular carcinoma was identified at a substantially higher frequency that would be expected for that histotype.

RevDate: 2021-03-13

Abascal-Junquera JM, Fumadó-Ciutat L, Gasa-Galmes B, et al (2021)

Concomitant intraductal carcinoma of the prostate and response to hormonal therapy in metastatic prostate carcinoma.

Actas urologicas espanolas pii:S0210-4806(21)00008-5 [Epub ahead of print].

INTRODUCTION AND OBJECTIVE: Most prostate cancers are classified as acinar adenocarcinoma. Intraductal carcinoma of the prostate (IDC-P) is a distinct histologic entity that is believed to represent retrograde spread of invasive acinar adenocarcinoma into prostatic ducts and acini. We have analyzed the impact of IDC-P in hormonal naïve and castration resistant metastatic prostate cancer patients.

PATIENTS AND METHODS: We retrospectively evaluated 118 metastatic castration resistant prostate cancer (mCRPC) patients who were initially diagnosed with distant metastases from May 2010 to September 2018. Group 1 patients included 81 metastatic PCa patients with acinar adenocarcinoma and Group 2 included 37 metastatic PCa patients with IDC-P.

RESULTS: Mean age at presentation was 76 years (IQR 73.4-78.7) in group 1 and 74 years (68.5-80.6) in group 2. Mean PSA at diagnosis was 619 ng/mL (IQR 85-1113) and 868 ng/mL (IQR 186-1922), respectively. Time to castration resistance was 24.7 months (IQR 16.7-32.7) in group 1 and 10.2 months (IQR 4.2-16.2) in group 2 (p = 0.007). Time to progression in CPRC patients was: 10.6 months (IQR 5.6-15.6) and at 6.2 months (3.2-9.2), respectively (p = 0.05). Overall survival was 57.9 months in group 1(CI 95% 56.4-59.5) and 38 months (CI 95% 19.9-48.06) in group 2 (p = 0.001). In the multivariate analysis, adenocarcinoma subtype was statistically significant p 0.014, CI 95% (HR 0.058, 0.006-0.56).

CONCLUSIONS: IDC-P seems to be a subtype of prostate cancer that is associated with a shorter response to hormonal treatment when compared to acinar adenocarcinoma in metastatic patients. New drugs in CRPC scenario as abiraterone and enzalutamide also obtained less response in IDC-P patients. In daily clinical practice it might be interesting to take into account that patients with IDC-P may present shorter responses to first and second line hormonal treatments.

RevDate: 2021-03-29

Zhang J, Lu CY, Chen HM, et al (2021)

Neoadjuvant Chemotherapy or Endocrine Therapy for Invasive Ductal Carcinoma of the Breast With High Hormone Receptor Positivity and Human Epidermal Growth Factor Receptor 2 Negativity.

JAMA network open, 4(3):e211785.

Importance: Although neoadjuvant endocrine therapy (NET) is an alternative to chemotherapy for strongly hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (ERBB2)-negative breast cancer, evidence is currently lacking regarding the probable survival outcomes of NET in comparison with those of neoadjuvant chemotherapy (NACT) for this cancer.

Objective: To evaluate all-cause mortality among patients with strongly HR-positive and ERBB2-negative breast cancer treated with NET vs NACT.

This cohort study included patients with a diagnosis of invasive ductal carcinoma (IDC) with strong HR positivity and ERBB2 negativity, treated between January 1, 2009, and December 31, 2016, with follow-up from the index date (ie, date of IDC diagnosis) to December 31, 2018. The data came from the Taiwan Cancer Registry Database. Data were analyzed from January to November 2020.

Exposures: NET vs NACT for IDC with strong HR positivity and ERBB2 negativity.

Main Outcomes and Measures: The primary end point was all-cause mortality. Propensity score matching was performed, and Cox proportional hazard models were used to analyze all-cause mortality among patients undergoing different neoadjuvant treatments.

Results: A total of 640 patients (297 [46.4%] aged 20-49 years) undergoing NET (145 patients [22.7%]) or NACT (495 patients [77.3%]) were eligible for further analysis. In the multivariate Cox regression analyses, the adjusted hazard ratio (aHR) for all-cause mortality among the NET cohort compared with the NACT cohort was 2.67 (95% CI, 1.95-3.51; P < .001). The aHRs for age were 1.13 (95% CI, 1.03-2.24), 1.25 (95% CI, 1.13-2.45), and 1.37 (95% CI, 1.17-3.49) for all-cause mortality among patients aged 50 to 59, 60 to 69, and 70 years or older, respectively, compared with those aged 20 to 49 years (P = .002); the aHR for all-cause mortality among premenopausal women was 1.35 (95% CI, 1.13-1.56) compared with postmenopausal women (P < .001); and that of patients with a Charlson Comorbidity Index score of 2 or greater was 1.77 (1.37-2.26) compared with those with a score of 0 (P < .001). The aHRs of all-cause mortality for clinical tumor stage 2, 3, and 4 compared with 1 were 1.84 (95% CI, 1.07-3.40), 1.97 (95% CI, 1.03-3.77), and 2.49 (95% CI, 1.29-4.81), respectively (P = .009). The aHRs for all-cause mortality by clinical nodal (cN) stages were 1.49 (95% CI, 1.13-1.99) and 1.84 (95% CI, 1.31-2.61) for cN stage 1 and cN stages 2 or 3, respectively, compared with cN stage 0 (P = .005); those for differentiation were 1.77 (95% CI, 1.24-2.54) and 2.31 (95% CI, 1.61-3.34) for differentiation grade 2 and differentiation grade 3, respectively, compared with differentiation grade 1 (P < .001).

Conclusions and Relevance: The findings of this study suggest that for patients with strongly HR-positive and ERBB2-negative IDC, NACT may be considered the first choice for neoadjuvant treatment.

RevDate: 2021-03-13

Qian L, Lv Z, Zhang K, et al (2021)

Application of deep learning to predict underestimation in ductal carcinoma in situ of the breast with ultrasound.

Annals of translational medicine, 9(4):295.

Background: To develop an ultrasound-based deep learning model to predict postoperative upgrading of pure ductal carcinoma in situ (DCIS) diagnosed by core needle biopsy (CNB) before surgery.

Methods: Of the 360 patients with DCIS diagnosed by CNB and identified retrospectively, 180 had lesions upstaged to ductal carcinoma in situ with microinvasion (DCISM) or invasive ductal carcinoma (IDC) postoperatively. Ultrasound images obtained from the hospital database were divided into a training set (n=240) and validation set (n=120), with a ratio of 2:1 in chronological order. Four deep learning models, based on the ResNet and VggNet structures, were established to classify the ultrasound images into postoperative upgrade and pure DCIS. We obtained the area under the receiver operating characteristic curve (AUROC), specificity, sensitivity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) to estimate the performance of the predictive models. The robustness of the models was evaluated by a 3-fold cross-validation.

Results: Clinical features were not significantly different between the training set and the test set (P value >0.05). The area under the receiver operating characteristic curve of our models ranged from 0.724 to 0.804. The sensitivity, specificity, and accuracy of the optimal model were 0.733, 0.750, and 0.742, respectively. The three-fold cross-validation results showed that the model was very robust.

Conclusions: The ultrasound-based deep learning prediction model is effective in predicting DCIS that will be upgraded postoperatively.

RevDate: 2021-03-13

Mastrototaro G, Zaghi M, Massimino L, et al (2021)

TBL1XR1 Ensures Balanced Neural Development Through NCOR Complex-Mediated Regulation of the MAPK Pathway.

Frontiers in cell and developmental biology, 9:641410.

TBL1XR1 gene is associated with multiple developmental disorders presenting several neurological aspects. The relative protein is involved in the modulation of important cellular pathways and master regulators of transcriptional output, including nuclear receptor repressors, Wnt signaling, and MECP2 protein. However, TBL1XR1 mutations (including complete loss of its functions) have not been experimentally studied in a neurological context, leaving a knowledge gap in the mechanisms at the basis of the diseases. Here, we show that Tbl1xr1 knock-out mice exhibit behavioral and neuronal abnormalities. Either the absence of TBL1XR1 or its point mutations interfering with stability/regulation of NCOR complex induced decreased proliferation and increased differentiation in neural progenitors. We suggest that this developmental unbalance is due to a failure in the regulation of the MAPK cascade. Taken together, our results broaden the molecular and functional aftermath of TBL1XR1 deficiency associated with human disorders.

RevDate: 2021-03-13

Tajima Y, Sone Y, Yaguchi H, et al (2021)

Very-Late-Onset Neuromyelitis Optica Spectrum Disorder in a Patient with Breast Cancer and Parkinson Disease.

Case reports in neurology, 13(1):53-58.

Anti-aquaporin-4 (anti-AQP-4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder resulting in severe, recurrent optic neuritis, transverse myelitis, brain stem syndrome, and other types of neurological involvement. Its median age of onset has been reported to be around 40 years. We report herein a case of very-late-onset NMOSD (76 years of age) and try to promote its awareness as a type of neurological deterioration in elder patients. A 76-year-old woman suffering from Parkinson disease was admitted to our hospital because of consciousness disturbance. Cranial magnetic resonance imaging revealed the presence of fluid-attenuated inversion recovery high-signal-intensity lesions in the right peri- and intralateral ventricle. Part of this lesion and the meninges showed gadolinium enhancement. Physical examination revealed the presence of a tumor in the right breast, which was later diagnosed as invasive ductal carcinoma. In addition, laboratory examinations led to the detection of anti-AQP-4 antibodies in her serum; consequently, the patient was diagnosed as having NMOSD. She received initial pulsed steroid therapy, followed by right mastectomy. Although the patient's consciousness improved significantly, she developed abrupt-onset bilateral leg weakness and multiple longitudinal spinal cord lesions. Additional steroid therapy ameliorated the patient's leg weakness and reduced the swelling of the spinal cord.

RevDate: 2021-04-05

Grant M, de Graaf E, S Teunissen (2021)

A systematic review of classifications systems to determine complexity of patient care needs in palliative care.

Palliative medicine, 35(4):636-650.

BACKGROUND: Providing the right care for each individual patient is a key element of quality palliative care. Complexity is a relatively new concept, defined as the nature of patients' situations and the extent of resulting needs. Classifying patients according to the complexity of their care needs can guide integration of services, anticipatory discussions, health service planning, resource management and determination of needs for specialist or general palliative care. However, there is no consistent approach to interpreting and classifying complexity of patient needs.

AIM: The aim of this article is to identify and describe classification systems for complexity of patient care needs in palliative care.

DESIGN: Narrative systematic review (PROSPERO registration number CRD42020182102).

DATA SOURCES: MEDLINE, Embase, CINAHL and PsychINFO databases were searched without time limitations. Articles were included that described classification systems for complexity of care requirements in populations with palliative care needs.

RESULTS: In total, 4301 records were screened, with nine articles identified reporting the use of patient classification systems in populations with palliative care needs. These articles included the use of six classification systems: HexCom, Perroca Scale, AN-SNAP, Hui Major Criteria, IDC-Pal and PALCOM. These systems were heterogenous in the manner they determined complexity of care needs. The HexCom and IDC-Pal systems contained items that covered all domains of complexity as described by Hodiamont; personal, social support, health care team and environment.

CONCLUSION: Although six classification systems have been developed, they access differing aspects of care needs and their application has been limited. The HexCOM and IDC-Pal systems offer the broadest determinations of complexity from an individual perspective. Further research is needed to apply these systems to populations external to those in which they were developed, and to appreciate how they may integrate with, and impact, clinical care.

RevDate: 2021-03-11

Nachoum R, Moed A, Madjar N, et al (2021)

Prenatal childbearing motivations, parenting styles, and child adjustment: A longitudinal study.

Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43) pii:2021-25907-001 [Epub ahead of print].

To have a child is among individuals' most important and meaningful decisions, with far-reaching implications. Despite evidence linking this decision to a wide variety of consequences, little is known about what motivates people to have children, and even less so about the long-term effects of different childbearing motivations on parenting and child adjustment. This study took a self-determination theory (SDT) perspective, examining how prenatal maternal autonomous and controlled childbearing motivations are related to child behavior problems through parenting styles. The rationale was that prenatal autonomous (sense of volition and self-fulfillment) and controlled (feeling pressured) childbearing motivations would shape later parental styles (autonomy-supportive vs. controlling, respectively) and, consequently, child adjustment. Over a period of 2 years beginning at pregnancy, 326 Israeli mothers reported their prenatal childbearing motivations, as well as parental styles and child behavior problems 20 months postpartum. Results of a path analysis revealed that prenatal autonomous childbearing motivation predicted autonomy-supportive parenting, yet the latter was not associated with children's behavior problems. Prenatal controlled motivation predicted controlling parenting, which, in turn, predicted children's internalizing and externalizing problems. No direct effects of childbearing motivation on children's behavior problems are observed, suggesting that childbearing motivation is a distal antecedent operating through more proximal factors such as parenting style. Findings were robust to children's temperamental tendencies and sociodemographic risk factors such as maternal age, high-risk pregnancy, and preterm birth. These findings have theoretical and practical implications for the discourse on motivations underlying the childbearing decision and their effects on parenting and child adjustment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

RevDate: 2021-03-14

Bondy S, Tajzler C, Hotte SJ, et al (2020)

Genomic and Clinical Correlates of Adrenocortical Carcinoma in an Adult Patient with Li-Fraumeni Syndrome: A Case Report.

Current oncology (Toronto, Ont.), 28(1):226-232.

Li-Fraumeni Syndrome (LFS) is defined by germline mutations of the p53 tumour suppressor gene. Adrenocortical carcinoma (ACC) is a rare aggressive malignancy that is commonly associated with LFS. Most LFS-linked ACC cases occur in children, and limited research has been dedicated to the clinical outcomes and genomics of adult cases with LFS-linked ACC. We report on a 34-year-old female who was diagnosed with three separate malignancies: stage III invasive ductal carcinoma of the right breast, metastatic ACC from the right adrenal gland, and grade 2 pleomorphic sarcoma of the left hand. Her invasive breast ductal carcinoma was treated with neoadjuvant chemotherapy, and she received a bilateral mastectomy after her LFS was confirmed with genetic blood testing. Adrenal ACC was initially treated with a right nephrectomy and adrenalectomy, followed by adjuvant mitotane and two lines of chemotherapy after disease recurrence. Her hand sarcoma was treated by second ray amputation. Further, we conducted deep next-generation sequencing of each of her unique tumour tissue samples using FoundationONE CDx. A whole-genome shot capture followed by in vitro sequencing performed by the Illumina® HiSeq platform revealed a germline P191fs*18 TP53 mutation across all three tissue samples. This case provides insight into the genomics and clinical characteristics of LFS-linked adult-onset ACC and demonstrated that p53 mutations were preserved throughout each malignancy, without apparent treatment pressures on genomic profiling. This case reinforces the critical importance of adopting best practices for LFS, which include the implementation of highly vigilant screening and management of care in a multidisciplinary setting.

RevDate: 2021-03-12

Togashi K, Nishitsuka K, Hayashi S, et al (2021)

Metastatic Orbital Tumor From Breast Ductal Carcinoma With Neuroendocrine Differentiation Initially Presenting as Ocular Symptoms: A Case Report and Literature Review.

Frontiers in endocrinology, 12:625663.

Background: Orbital metastases from cancers of various organs can arise via the hematogenous route, and many originate from breast, prostate, and lung cancers. Such metastatic orbital tumors may be diagnosed before the primary tumor. We have encountered a case of breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and responded to chemotherapy, with improvement in visual function.

Case Presentation: A woman in her fifties visited our ophthalmology department with a chief complaint of foreign body sensation and exophthalmos in her right eye. An elastic soft mass was palpated from the lateral orbit to the temporal region. A systemic examination revealed breast cancer and a metastatic orbital tumor. Excisional biopsy of the breast revealed a diagnosis of invasive ductal carcinoma with neuroendocrine differentiation, and immunohistochemical examination was negative for cytokeratin 7, making the case unusual. Chemotherapy was remarkably effective, and the tumor size decreased, resulting in improvement of visual function. Her general condition and quality of life are still good at present. We searched the PubMed English language literature focusing on metastatic orbital tumors from breast cancer in which ocular symptoms had been the initial presenting sign. No previous reports have documented neuroendocrine differentiation or cytokeratin 7 expression in isolated orbital metastases from breast cancer. Although it is not possible to be certain from this case alone, we speculated that some such cases might involve cytokeratin 7-negative invasive breast cancer with neuroendocrine differentiation.

Conclusion: We have described our experience of a very rare case of cytokeratin 7 negative breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and formed a solitary giant tumor initially manifesting as ocular symptoms.

RevDate: 2021-03-11

Iwamoto M, Takei H, Ninomiya J, et al (2021)

Neoadjuvant endocrine therapy in women with operable breast cancer: A retrospective analysis of real-world use.

Journal of Nippon Medical School = Nippon Ika Daigaku zasshi [Epub ahead of print].

BACKGROUND: A retrospective study of the real-world use of neoadjuvant endocrine therapy (NET) is important for standardizing its role in breast cancer care.

MATERIALS AND METHODS: In a consecutive series of women with operable breast cancer who received NET for ≥28 days, NET objectives, NET outcomes, adjuvant chemotherapy use after NET, and survivals, were examined for the correlation with clinicopathological factors.

RESULTS: NET objectives were for surgery extent reduction in 49 patients, surgery avoidance in 31, and treatment until scheduled surgery in 8. The mean duration of NET was 349.5 (range, 34-1923), 869.8 (range, 36-4859), and 55.8 (range, 39-113) days in the above cohorts (success: 79.6%, 64.5%, and 100%), respectively, with significant difference. In patients of the former two cohorts, better progression-free survival was significantly correlated with stage 0 or I, ductal carcinoma in situ or invasive ductal carcinoma, ≥71% estrogen receptor (ER) positivity, and the surgery extent reduction cohort than the other counterparts. Postoperative chemotherapy use was significantly correlated with lymph node metastasis, a high Ki67 labeling index, lymphovascular invasion, and a high Preoperative Endocrine Prognostic Index, at surgery after NET. Better recurrence-free survival after surgery was significantly correlated with high ER expression after NET and high PgR expression before and after NET.

CONCLUSIONS: NET can help to reduce the surgery extent or to avoid surgery in women with breast cancer of early-stage, ductal carcinoma, or high ER expression. NET may also contribute to appropriate decision of postoperative systemic therapy to improve survivals.

RevDate: 2021-03-19
CmpDate: 2021-03-19

Greenbaum D (2021)

Making Compassionate Use More Useful: Using real-world data, real-world evidence and digital twins to supplement or supplant randomized controlled trials.

Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing, 26:38-49.

The coronavirus pandemic has placed renewed focus on expanded access (EA) programs to provide compassionate use exceptions to the waves of patients seeking medical care in treating the novel disease. While commendable, justifiable, and compassionate, EA programs are not designed to collect the necessary vital clinical data that can be later used in the New Drug Application process before the U.S. Food and Drug Administration (FDA). In particular, they lack the necessary rigor of properly crafted and controlled randomized controlled trials (RCT) which ensure that each patient closely monitored for side effects and other potential dangers associated with the drug, that the data is documented, stable and are traceable and that the patient population is well defined with the defined target condition. Overall, while RCTs is deemed to be of the most reliable methodologies within evidence-based medicine, morally, however, they are problematic in EA programs. Nevertheless, actionable data ought to be collected from EA patients. To this end, we look to the growing incorporation of real-world data real-world evidence as increasingly useful substitutes for data collected via RCTs, including the ethical, legal and social implications thereof. Finally, we suggest the use of digital twins as an additional method to derive causal inferences from real-world trials involving expanded access patients.

RevDate: 2021-03-10

Parikh P, Rose T, Jeong D, et al (2021)

Diffuse intrasinusoidal hepatic metastasis from breast cancer: Multimodality imaging with pathology correlation.

Radiology case reports, 16(5):1005-1009.

Metastatic disease to the liver is a known and common site of breast cancer spread, classically presenting as either hypovascular or hypervascular masses. Rarely, hepatic metastatic disease may have an atypical diffuse and intrasinusoidal pattern of involvement, which may be radiographically occult or extremely challenging to diagnose even with multiphase contrast enhanced techniques. We report a case of a 28-year-old female with stage III invasive ductal carcinoma of the breast, who recently discontinued treatment due to pregnancy, presenting with progressive signs and symptoms of rapidly decompensating liver failure due to sinusoidal obstruction. Multimodality imaging was performed without evidence for focal hepatic metastatic disease; however, intrahepatic vein (IVC) compression was noted. Hepatic sinusoidal tumor infiltration was confirmed by liver biopsy. After palliative chemotherapy the disease became less infiltrative and more conspicuous on imaging, revealing itself as hepatic metastases, with decreased compression of the intrahepatic IVC and resolution of signs and symptoms of sinusoidal obstruction syndrome.

RevDate: 2021-03-10

Carone N, Bos HMW, Shenkman G, et al (2021)

Editorial: LGBTQ Parents and Their Children During the Family Life Cycle.

Frontiers in psychology, 12:643647.

RevDate: 2021-03-12

Ji L, Cheng L, Zhu X, et al (2021)

Risk and prognostic factors of breast cancer with liver metastases.

BMC cancer, 21(1):238.

BACKGROUND: Liver metastasis is a significant adverse predictor of overall survival (OS) among breast cancer patients. The purpose of this study was to determine the risk and prognostic factors of breast cancer with liver metastases (BCLM).

METHODS: Data on 311,573 breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database and 1728 BCLM patients from Fudan University Shanghai Cancer Center (FUSCC) were included. Logistic regression was used to identify risk factors for liver metastasis. Cox proportional hazards regression model was adopted to determine independent prognostic factors in BCLM patients.

RESULTS: Young age, invasive ductal carcinoma, higher pathological grade, and subtype of triple-negative and human epidermal growth factor receptor 2 positive (HER2+) were risk factors for developing liver metastasis. The median OS after liver metastasis was 20.0 months in the SEER database and 27.3 months in the FUSCC dataset. Molecular subtypes also played a critical role in the survival of BCLM patients. We observed that hormone receptor-positive (HR+)/HER2+ patients had the longest median OS (38.0 for SEER vs. 34.0 months for FUSCC), whereas triple-negative breast cancer had the shortest OS (9.0 vs. 15.6 months) in both SEER and FUSCC. According to the results from the FUSCC, the subtype of HR+/HER2+ (hazard ratio (HR) = 2.62; 95% confidence interval (CI) = 1.88-3.66; P < 0.001) and HR-/HER2+ (HR = 3.43; 95% CI = 2.28-5.15; P < 0.001) were associated with a significantly increased death risk in comparison with HR+/HER2- patients if these patients did not receive HER2-targeted therapy. For those who underwent HER2-targeted therapy, however, HR+/HER2+ subtype reduced death risk compared with HR+/HER2- subtype (HR = 0.74; 95% CI = 0.58-0.95; P < 0.001).

CONCLUSIONS: Breast cancer patients at a high risk for developing liver metastasis deserve more attention during the follow-up. BCLM patients with HR+/HER2+ subtype displayed the longest median survival than HR+/HER2- and triple-negative patients due to the introduction of HER2-targeted therapy and therefore it should be recommended for HER2+ BCLM patients.

RevDate: 2021-03-16

Irelli A, Sirufo MM, Quaglione GR, et al (2021)

Invasive Ductal Breast Cancer with Osteoclast-Like Giant Cells: A Case Report Based on the Gene Expression Profile for Changes in Management.

Journal of personalized medicine, 11(2):.

We report the case of a 49-year-old woman diagnosed with a rare histotype of early breast cancer (BC), invasive ductal carcinoma with osteoclast-like giant cells (OGCs), from the perspective of gene profile analysis tests. The patient underwent a quadrantectomy of the right breast with removal of 2 cm neoplastic nodule and three ipsilateral sentinel lymph nodes. The Oncotype Dx gave a recurrence score (RS) of 23, and taking into account the patient's age, an RS of 23 corresponds to a chemotherapy benefit of 6.5%. After a multidisciplinary collegial discussion, and in consideration of the patient's age, the absence of comorbidity, the premenopausal state, the rare histotype and the Oncotype Dx report, the patient was offered adjuvant chemotherapy treatment followed by hormone therapy. This case may be an example of the utility of integrating gene expression profiling tests into clinical practice in the adjuvant treatment decision of a rare histotype BC. The Oncotype Dx test required to supplement the histological examination made us opt for the proposal of a combined treatment of adjuvant chemotherapy followed by adjuvant hormone therapy. It demonstrates the importance of considering molecular tests and, in particular, the Oncotype Dx, in estimating the risk of disease recovery at 10 years in order to identify patients who benefit from hormone therapy alone versus those who benefit from the addition of chemotherapy, all with a view toward patient-centered oncology. Here, we discuss the possible validity and limitations of the Oncotype Dx in a rare luminal A-like histotype with high infiltrate of stromal/inflammatory cells.

RevDate: 2021-04-13

Rand D, Ravid O, Atrakchi D, et al (2021)

Endothelial Iron Homeostasis Regulates Blood-Brain Barrier Integrity via the HIF2α-Ve-Cadherin Pathway.

Pharmaceutics, 13(3):.

The objective of this study was to investigate the molecular response to damage at the blood brain barrier (BBB) and to elucidate critical pathways that might lead to effective treatment in central nervous system (CNS) pathologies in which the BBB is compromised. We have used a human, stem-cell derived in-vitro BBB injury model to gain a better understanding of the mechanisms controlling BBB integrity. Chemical injury induced by exposure to an organophosphate resulted in rapid lipid peroxidation, initiating a ferroptosis-like process. Additionally, mitochondrial ROS formation (MRF) and increase in mitochondrial membrane permeability were induced, leading to apoptotic cell death. Yet, these processes did not directly result in damage to barrier functionality, since blocking them did not reverse the increased permeability. We found that the iron chelator, Desferal© significantly decreased MRF and apoptosis subsequent to barrier insult, while also rescuing barrier integrity by inhibiting the labile iron pool increase, inducing HIF2α expression and preventing the degradation of Ve-cadherin specifically on the endothelial cell surface. Moreover, the novel nitroxide JP4-039 significantly rescued both injury-induced endothelium cell toxicity and barrier functionality. Elucidating a regulatory pathway that maintains BBB integrity illuminates a potential therapeutic approach to protect the BBB degradation that is evident in many neurological diseases.

RevDate: 2021-03-17

Abramczyk H, Brozek-Pluska B, Kopec M, et al (2021)

Redox Imbalance and Biochemical Changes in Cancer by Probing Redox-Sensitive Mitochondrial Cytochromes in Label-Free Visible Resonance Raman Imaging.

Cancers, 13(5):.

To monitor redox state changes and biological mechanisms occurring in mitochondrial cytochromes in cancers improving methods are required. We used Raman spectroscopy and Raman imaging to monitor changes in the redox state of the mitochondrial cytochromes in ex vivo human brain and breast tissues at 532 nm, 633 nm, 785 nm. We identified the oncogenic processes that characterize human infiltrating ductal carcinoma (IDC) and human brain tumors: gliomas; astrocytoma and medulloblastoma based on the quantification of cytochrome redox status by exploiting the resonance-enhancement effect of Raman scattering. We visualized localization of cytochromes by Raman imaging in the breast and brain tissues and analyzed cytochrome c vibrations at 750, 1126, 1337 and 1584 cm-1 as a function of malignancy grade. We found that the concentration of reduced cytochrome c becomes abnormally high in human brain tumors and breast cancers and correlates with the grade of cancer. We showed that Raman imaging provides additional insight into the biology of astrocytomas and breast ductal invasive cancer, which can be used for noninvasive grading, differential diagnosis.

RevDate: 2021-04-12

He B, Chen J, Song W, et al (2021)

miR-646/TET1 mediated demethylation of IRX1 promoter upregulates HIST2H2BE and promotes the progression of invasive ductal carcinoma.

Genomics, 113(3):1469-1481 pii:S0888-7543(21)00079-3 [Epub ahead of print].

BACKGROUND: This study aimed to explore role of miR-646 in breast IDC.

METHODS: miR-646, TET1, IRX1, and HIST2H2BE expression was detected by RT-qPCR and/or Western blot analysis. The methylation status of IRX1 promoter region was evaluated by methylation specific PCR. ChIP assay was used to determine the enrichment of TET1 at IRX1 promoter region. Loss- and gain-of functions were performed to determine the roles of miR-646, TET1, IRX1, and HIST2H2BE in cell proliferation, migration, invasion, and apoptosis. The tumor growth, volume, weight, and apoptosis status were measured.

RESULTS: miR-646 was upregulated while TET1 was downregulated in IDC tissues. miR-646 targeted TET1. Downregulated TET1 impairs demethylation of IRX1 promoter region resulting in reduced expression of IRX1, which subsequently leads to upregulation of HIST2H2BE in IDC. Consequently, elevated HIST2H2BE promotes progression of IDC.

CONCLUSION: Our study has demonstrated that miR-646 facilitates the tumorigenesis of IDC via regulating TET1/IRX1/HIST2H2BE axis.

RevDate: 2021-04-13

Schwartz CJ, Boroujeni AM, Khodadadi-Jamayran A, et al (2021)

Molecular analysis of encapsulated papillary carcinoma of the breast with and without invasion.

Human pathology, 111:67-74 pii:S0046-8177(21)00030-7 [Epub ahead of print].

Encapsulated papillary carcinomas (EPCs) of the breast are a unique variant of papillary carcinoma confined to a cystic space with absent or attenuated myoepithelial cell layer. Although staged as an in situ lesion, it can be associated with invasive ductal carcinoma (IDC). We sought to compare the genomic characteristics of pure EPC and EPC with associated invasive carcinoma (EPCi) at the genomic level. All cases of EPCi harbored recurrent hotspot mutations in PIK3CA. PIK3CA, KMT2A, and CREBBP deleterious somatic events were found across both tumor groups, irrespective of invasion status. At the whole transcriptomic level, EPCi cases displayed remarkably similar mRNA profiles when compared to EPC. When EPCi cases were compared with their corresponding IDC, despite significant overlap, we identified differential gene expression in 39 genes with enrichment of multiple pathways including extracellular matrix regulation, cell adhesion, and collagen fibril organization. Despite morphologic, genotypic, and transcriptomic overlap between pure EPC and EPCi, the latter tumors are likely advanced lesions with PIK3CA activating mutations and enrichment of stromal-related genes implicated in the switch to IDC.

RevDate: 2021-04-09

Hartleben G, Schorpp K, Kwon Y, et al (2021)

Combination therapies induce cancer cell death through the integrated stress response and disturbed pyrimidine metabolism.

EMBO molecular medicine, 13(4):e12461.

By accentuating drug efficacy and impeding resistance mechanisms, combinatorial, multi-agent therapies have emerged as key approaches in the treatment of complex diseases, most notably cancer. Using high-throughput drug screens, we uncovered distinct metabolic vulnerabilities and thereby identified drug combinations synergistically causing a starvation-like lethal catabolic response in tumor cells from different cancer entities. Domperidone, a dopamine receptor antagonist, as well as several tricyclic antidepressants (TCAs), including imipramine, induced cancer cell death in combination with the mitochondrial uncoupler niclosamide ethanolamine (NEN) through activation of the integrated stress response pathway and the catabolic CLEAR network. Using transcriptome and metabolome analyses, we characterized a combinatorial response, mainly driven by the transcription factors CHOP and TFE3, which resulted in cell death through enhanced pyrimidine catabolism as well as reduced pyrimidine synthesis. Remarkably, the drug combinations sensitized human organoid cultures to the standard-of-care chemotherapy paclitaxel. Thus, our combinatorial approach could be clinically implemented into established treatment regimen, which would be further facilitated by the advantages of drug repurposing.

RevDate: 2021-03-20

Varshney B, Kumar A, Deka L, et al (2021)

Bilateral alveolar rhabdomyosarcoma of breast: a rare entity.

BMJ case reports, 14(3): pii:14/3/e237134.

Sarcomas of breast constitute less than 1% of all malignant breast tumours. Alveolar rhabdomyosarcoma (RMS) is very rare in breast with limited case reports in literature, and primary alveolar RMS arising from breast is still less common than metastatic RMS. Here, we report a case of primary bilateral alveolar RMS of breast in an adolescent female where the correct diagnosis was obfuscated by an overlap in the histological features of RMS and high-grade invasive ductal carcinoma.

RevDate: 2021-03-10

Mills MN, Walker C, Thawani C, et al (2021)

Trastuzumab Emtansine (T-DM1) and stereotactic radiation in the management of HER2+ breast cancer brain metastases.

BMC cancer, 21(1):223.

BACKGROUND: Due to recent concerns about the toxicity of trastuzumab emtansine (T-DM1) with stereotactic radiation, we assessed our institutional outcomes treating HER2-positive breast cancer brain metastases (BCBM) with T-DM1 and stereotactic radiation.

METHODS: This is a single institution series of 16 patients with HER2-positive breast cancer who underwent 18 stereotactic sessions to 40 BCBM from 2013 to 2019 with T-DM1 delivered within 6 months. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), distant intracranial control (DIC), and systemic progression-free survival (sPFS) from the date of SRS. A neuro-radiologist independently reviewed follow-up imaging.

RESULTS: One patient had invasive lobular carcinoma, and 15 patients had invasive ductal carcinoma. All cases were HER2-positive, while 10 were hormone receptor (HR) positive. Twenty-four lesions were treated with stereotactic radiosurgery (SRS) to a median dose of 21 Gy (14-24 Gy). Sixteen lesions were treated with fractionated stereotactic radiation (FSRT) with a median dose of 25 Gy (20-30Gy) delivered in 3 to 5 fractions. Stereotactic radiation was delivered concurrently with T-DM1 in 19 lesions (48%). Median follow up time was 13.2 months from stereotactic radiation. The 1-year LC, DIC, sPFS, and OS were 75, 50, 30, and 67%, respectively. There was 1 case of leptomeningeal progression and 1 case (3%) of symptomatic radionecrosis.

CONCLUSIONS: We demonstrate that stereotactic radiation and T-DM1 is well-tolerated and effective for patients with HER2-positive BCBM. An increased risk for symptomatic radiation necrosis was not noted in our series.

RevDate: 2021-03-16

Mohamed RI, Bargal SA, Mekawy AS, et al (2021)

The overexpression of DNA repair genes in invasive ductal and lobular breast carcinomas: Insights on individual variations and precision medicine.

PloS one, 16(3):e0247837.

In the era of precision medicine, analyzing the transcriptomic profile of patients is essential to tailor the appropriate therapy. In this study, we explored transcriptional differences between two invasive breast cancer subtypes; infiltrating ductal carcinoma (IDC) and lobular carcinoma (LC) using RNA-Seq data deposited in the TCGA-BRCA project. We revealed 3854 differentially expressed genes between normal ductal tissues and IDC. In addition, IDC to LC comparison resulted in 663 differentially expressed genes. We then focused on DNA repair genes because of their known effects on patients' response to therapy and resistance. We here report that 36 DNA repair genes are overexpressed in a significant number of both IDC and LC patients' samples. Despite the upregulation in a significant number of samples, we observed a noticeable variation in the expression levels of the repair genes across patients of the same cancer subtype. The same trend is valid for the expression of miRNAs, where remarkable variations between patients' samples of the same cancer subtype are also observed. These individual variations could lie behind the differential response of patients to treatment. The future of cancer diagnostics and therapy will inevitably depend on high-throughput genomic and transcriptomic data analysis. However, we propose that performing analysis on individual patients rather than a big set of patients' samples will be necessary to ensure that the best treatment is determined, and therapy resistance is reduced.

RevDate: 2021-03-05

Santamaría-García H, Baez S, Aponte-Canencio DM, et al (2021)

Uncovering social-contextual and individual mental health factors associated with violence via computational inference.

Patterns (New York, N.Y.), 2(2):100176.

The identification of human violence determinants has sparked multiple questions from different academic fields. Innovative methodological assessments of the weight and interaction of multiple determinants are still required. Here, we examine multiple features potentially associated with confessed acts of violence in ex-members of illegal armed groups in Colombia (N = 26,349) through deep learning and feature-derived machine learning. We assessed 162 social-contextual and individual mental health potential predictors of historical data regarding consequentialist, appetitive, retaliative, and reactive domains of violence. Deep learning yields high accuracy using the full set of determinants. Progressive feature elimination revealed that contextual factors were more important than individual factors. Combined social network adversities, membership identification, and normalization of violence were among the more accurate social-contextual factors. To a lesser extent the best individual factors were personality traits (borderline, paranoid, and antisocial) and psychiatric symptoms. The results provide a population-based computational classification regarding historical assessments of violence in vulnerable populations.

RevDate: 2021-03-03

Nakamura R, Oyama T, Inokuchi M, et al (2021)

Neural EGFL like 2 expressed in myoepithelial cells and suppressed breast cancer cell migration.

Pathology international [Epub ahead of print].

Breast tissue has a branching structure that contains double-layered cells, consisting primarily of luminal epithelial cells inside and myoepithelial cells outside. Ductal carcinoma in situ (DCIS) still has myoepithelial cells surrounding the cancer cells. However, myoepithelial cells disappear in invasive ductal carcinoma. In this study, we detected expression of neural EGFL like (NELL) 2 and one of its receptors, roundabout guidance receptor (ROBO) 3, in myoepithelial and luminal epithelial cells (respectively) in normal breast tissue. NELL2 also was expressed in myoepithelial cells surrounding the non-cancerous intraductal proliferative lesions and DCIS. However, the expression level and proportion of NELL2-positive cells in DCIS were lower than those in normal and non-cancerous intraductal proliferative lesions. ROBO3 expression was decreased in invasive ductal carcinoma compared to that in normal and non-cancerous intraductal proliferative lesions. An evaluation of NELL2's function in breast cancer cell lines demonstrated that full-length NELL2 suppressed cell adhesion and migration in vitro. In contrast, the N-terminal domain of NELL2 increased cell adhesion in the early phase and migration in vitro in some breast cancer cells. These results suggested that full-length NELL2 protein, when expressed in myoepithelial cells, might serve as an inhibitor of breast cancer cell migration.

RevDate: 2021-03-02

He X, Zhou J, Ye S, et al (2021)

Differences in tumour heterogeneity based on dynamic contrast-enhanced MRI between tumour and peritumoural stroma for predicting Ki-67 status of invasive ductal carcinoma.

Clinical radiology pii:S0009-9260(21)00003-9 [Epub ahead of print].

AIM: To evaluate and compare the heterogeneity of intratumour and peritumour areas in the prediction of Ki-67 of invasive ductal carcinoma (IDC) and the predictive accuracy of different contrast frames based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

MATERIALS AND METHODS: This study included 88 patients with histologically confirmed IDC with 57 patients with high Ki-67 status and 31 patients with low Ki-67 status. All patients underwent DCE-MRI before surgery. A grey-level co-occurrence matrix (GLCM) was performed on slice-matched images from six frames by drawing the region of the interest (ROI) on the inner and outer regions of the tumours. The correlations between texture characteristics and Ki-67 status of lesions were analysed, using the Mann-Whitney test and receiver operating characteristic curve analysis.

RESULTS: In the high-Ki-67 group, the entropy was significantly higher than that of the low-Ki-67 group (p<0.001). The entropy obtained, based on the tumour boundary as a band-like area inside and outside at the first post-contrast series, revealed the highest receiver operating characteristic (AUC = 0.765). In the multivariate analysis, a higher entropy value (>4.305; p<0.001) remained independently associated with a high-Ki-67 status after adjustment for menopausal status, tumour size, histologic grade, oestrogen receptor (ER) status, and progesterone receptor (PR) status. The other parameters did not show significant differences between the high- and low-Ki-67 groups.

CONCLUSION: Heterogeneity analysis based on DCE-MRI could discriminate between high- and low-Ki-67 status. Texture characteristics from the band-like region inside and outside the tumour boundary could predict the Ki-67 status and showed higher accuracy.

RevDate: 2021-04-05

Efrati Y, Y Amichai-Hamburger (2021)

Adolescents who solely engage in online sexual experiences are at higher risk for compulsive sexual behavior.

Addictive behaviors, 118:106874.

In addition to its expression offline, sexual behavior is frequently expressed online. Some adolescents solely engage in online sexual activities, whereas others in offline and online activities, or have no sexual experience at all. In the current research, we examined whether those who solely engage in online sexual activities are at greater risk for compulsive sexual behavior. In Study 1 (n = 164), we examined differences in compulsive sexual behavior (CSB) and risky sexual action tendencies between study groups. In Study 2 (n = 713), we statistically replicated the classification into different sexual behaviors and examined differences between the clusters in CSB, social tendencies and socio-demographic measures. Results indicated that adolescents who only engaged in online sexual activities had significantly higher percentage of clinical CSB, were less likely boys and more likely to be religious. There were not more prone to risky sexual behavior, however. The current research expands the knowledge about offline or online sexually related activities among adolescence.

RevDate: 2021-03-11
CmpDate: 2021-03-11

Da Costa I, Belnou P, Soulier A, et al (2021)

Impact of delayed patient flow on surgical outcomes after hip fracture: An observational study.

European journal of anaesthesiology, 38 Suppl 1:S67-S68.

RevDate: 2021-03-01

Gunizi OC, H Calis (2021)

A Collision Tumor with Squamous Cell Carcinoma of Skin Overlying Breast and Invasive Breast Carcinoma.

Journal of the College of Physicians and Surgeons--Pakistan : JCPSP, 31(2):225-227.

Invasive breast cancer is the most common carcinoma in women. Invasive ductal carcinoma, not otherwise specified (NOS), is the largest group of invasive breast cancers. The second most common cancer of skin is squamous cell carcinoma (SCC). Collision tumor is a very rare and unusual tumor. It is defined as the concrescence of two distinct primary neoplasms at one site. Herein, we report a 56-year- female patient who had a collision tumor in the right breast, composed of moderately differentiated squamous cell carcinoma (SCC) and invasive breast carcinoma NOS. In the literature, collision tumors in the breast are very rare and reported in various combinations, but there is only one reported case with SCC and invasive breast cancer, the same as in our case. Key Words: Collision tumor, Squamous cell carcinoma, Invasive breast carcinoma.

RevDate: 2021-03-04

Caffery LJ, Rotemberg V, Weber J, et al (2020)

The Role of DICOM in Artificial Intelligence for Skin Disease.

Frontiers in medicine, 7:619787.

There is optimism that artificial intelligence (AI) will result in positive clinical outcomes, which is driving research and investment in the use of AI for skin disease. At present, AI for skin disease is embedded in research and development and not practiced widely in clinical dermatology. Clinical dermatology is also undergoing a technological transformation in terms of the development and adoption of standards that optimizes the quality use of imaging. Digital Imaging and Communications in Medicine (DICOM) is the international standard for medical imaging. DICOM is a continually evolving standard. There is considerable effort being invested in developing dermatology-specific extensions to the DICOM standard. The ability to encode relevant metadata and afford interoperability with the digital health ecosystem (e.g., image repositories, electronic medical records) has driven the initial impetus in the adoption of DICOM for dermatology. DICOM has a dedicated working group whose role is to develop a mechanism to support AI workflows and encode AI artifacts. DICOM can improve AI workflows by encoding derived objects (e.g., secondary images, visual explainability maps, AI algorithm output) and the efficient curation of multi-institutional datasets for machine learning training, testing, and validation. This can be achieved using DICOM mechanisms such as standardized image formats and metadata, metadata-based image retrieval, and de-identification protocols. DICOM can address several important technological and workflow challenges for the implementation of AI. However, many other technological, ethical, regulatory, medicolegal, and workforce barriers will need to be addressed before DICOM and AI can be used effectively in dermatology.

RevDate: 2021-03-16

Pramod N, Nigam A, Basree M, et al (2021)

Comprehensive Review of Molecular Mechanisms and Clinical Features of Invasive Lobular Cancer.

The oncologist [Epub ahead of print].

Invasive lobular carcinoma (ILC) accounts for 10% to 15% of breast cancers in the United States, 80% of which are estrogen receptor (ER)-positive, with an unusual metastatic pattern of spread to sites such as the serosa, meninges, and ovaries, among others. Lobular cancer presents significant challenges in detection and clinical management given its multifocality and multicentricity at presentation. Despite the unique features of ILC, it is often lumped with hormone receptor-positive invasive ductal cancers (IDC); consequently, ILC screening, treatment, and follow-up strategies are largely based on data from IDC. Despite both being treated as ER-positive breast cancer, querying the Cancer Genome Atlas database shows distinctive molecular aberrations in ILC compared with IDC, such as E-cadherin loss (66% vs. 3%), FOXA1 mutations (7% vs. 2%), and GATA3 mutations (5% vs. 20%). Moreover, compared with patients with IDC, patients with ILC are less likely to undergo breast-conserving surgery, with lower rates of complete response following therapy as these tumors are less chemosensitive. Taken together, this suggests that ILC is biologically distinct, which may influence tumorigenesis and therapeutic strategies. Long-term survival and clinical outcomes in patients with ILC are worse than in stage- and grade-matched patients with IDC; therefore, nuanced criteria are needed to better define treatment goals and protocols tailored to ILC's unique biology. This comprehensive review highlights the histologic and clinicopathologic features that distinguish ILC from IDC, with an in-depth discussion of ILC's molecular alterations and biomarkers, clinical trials and treatment strategies, and future targets for therapy. IMPLICATIONS FOR PRACTICE: The majority of invasive lobular breast cancers (ILCs) are hormone receptor (HR)-positive and low grade. Clinically, ILC is treated similar to HR-positive invasive ductal cancer (IDC). However, ILC differs distinctly from IDC in its clinicopathologic characteristics and molecular alterations. ILC also differs in response to systemic therapy, with studies showing ILC as less sensitive to chemotherapy. Patients with ILC have worse clinical outcomes with late recurrences. Despite these differences, clinical trials treat HR-positive breast cancers as a single disease, and there is an unmet need for studies addressing the unique challenges faced by patients diagnosed with ILC.

RevDate: 2021-03-22

Bajpai J, Simha V, Shylasree TS, et al (2021)

Pregnancy associated breast cancer (PABC): Report from a gestational cancer registry from a tertiary cancer care centre, India.

Breast (Edinburgh, Scotland), 56:88-95.

BACKGROUND: Pregnancy associated breast cancer (PABC) is a rare entity and defined as breast cancer diagnosed during pregnancy or one-year post-partum. There is sparse data especially from low and middle-income countries (LMIC) and merits exploration.

METHODS: The study (2013-2020) evaluated demographics, treatment patterns and outcomes of PABC.

RESULTS: There were 104 patients, median age of 31 years; 43 (41%) had triple-negative disease, 31(29.8%) had hormone-receptor (HR) positive and HER2 negative, 14 (13.5%) had HER2-positive and HR negative and 16(15.4%) had triple positive disease. 101(97%) had IDC grade III tumors and 74% had delayed diagnosis. 72% presented with early stage (24, EBC) or locally advanced breast cancer (53, LABC) and received either neoadjuvant (n = 49) or adjuvant (n = 26) chemotherapy and surgery. Trastuzumab, tamoxifen, and radiotherapy were administered post-delivery. At a median follow up of 27 (IQR:19-35) months, the estimated 3-year event-free survival (EFS) for EBC and LABC was 82% (95% CI: 65.2-100) and 56% (95% CI: 42-75.6%) and for metastatic 24% (95% CI: 10.1%-58.5%) respectively. Of the 104 patients, 34 were diagnosed antepartum (AP) and 15 had termination, 2 had preterm and 16 had full-term deliveries(FTDs). Among postpartum cohort (n = 70), 2 had termination, 1 had preterm, 67 had FTDs. 83(including 17 from AP) children from both cohorts were experiencing normal milestones.

CONCLUSION: Data from the first Indian PABC registry showed that the majority had delayed diagnosis and aggressive features(TNBC, higher grade). Treatment was feasible in majority and stage matched outcomes were comparable to non-PABCs.

RevDate: 2021-03-22

Salita A, Rosado M, Mack K, et al (2021)

Metastatic lobular carcinoma of the breast found incidentally on pathology following cholecystectomy for chronic cholecystitis: A case report.

International journal of surgery case reports, 80:105612.

BACKGROUND: Traditional oncologic pattern of spread of breast cancer is metastasis to axillary lymph nodes, lung, liver and bone (Doval et al., 2006 [1]). Here we present a case of unknown synchronous breast cancer in a patient that was revealed on histopathologic assessment following elective cholecystectomy.

CASE SUMMARY: A 57 year old female presented for an elective laparoscopic cholecystectomy secondary to biliary colic. Histopathologic assessment of the gallbladder revealed metastatic adenocarcinoma with signet ring features, consistent with metastatic lobular carcinoma. The patient went on to have a complete oncologic workup that revealed invasive ductal carcinoma with components of high grade ductal carcinoma in situ in the left breast, lobular carcinoma in the right breast, and metastatic lobular carcinoma to left and right axillary lymph nodes as well as diffuse osseous metastatic disease.

CONCLUSIONS: Metastatic disease to the gallbladder found incidentally on elective cholecystectomy is a rare presentation of synchronous breast cancer.

RevDate: 2021-02-26

Zhang J, Lemberskiy G, Moy L, et al (2021)

Measurement of cellular-interstitial water exchange time in tumors based on diffusion-time-dependent diffusional kurtosis imaging.

NMR in biomedicine [Epub ahead of print].

PURPOSE: To assess the feasibility of using diffusion-time-dependent diffusional kurtosis imaging (tDKI) to measure cellular-interstitial water exchange time (τex) in tumors, both in animals and in humans.

METHODS: Preclinical tDKI studies at 7 T were performed with the GL261 glioma model and the 4T1 mammary tumor model injected into the mouse brain. Clinical studies were performed at 3 T with women who had biopsy-proven invasive ductal carcinoma. tDKI measurement was conducted using a diffusion-weighted STEAM pulse sequence with multiple diffusion times (20-800 ms) at a fixed echo time, while keeping the b-values the same (0-3000 s/mm2) by adjusting the diffusion gradient strength. The tDKI data at each diffusion time t were used for a weighted linear least-squares fit method to estimate the diffusion-time-dependent diffusivity, D(t), and diffusional kurtosis, K(t).

RESULTS: Both preclinical and clinical studies showed that, when diffusion time t ≥ 200 ms, D(t) did not have a noticeable change while K(t) decreased monotonically with increasing diffusion time in tumors and t ≥ 100 ms for the cortical ribbon of the mouse brain. The estimated τex averaged median and interquartile range (IQR) of GL261 and 4T1 tumors were 93 (IQR = 89) ms and 68 (78) ms, respectively. For the cortical ribbon, the estimated τex averaged median and IQR were 41 (34) ms for C57BL/6 and 30 (17) ms for BALB/c. For invasive ductal carcinoma, the estimated τex median and IQR of the two breast cancers were 70 (94) and 106 (92) ms.

CONCLUSION: The results of this proof-of-concept study substantiate the feasibility of using tDKI to measure cellular-interstitial water exchange time without using an exogenous contrast agent.

RevDate: 2021-02-25

Min X, Zhu J, Shang M, et al (2021)

Stiffness Could be a Predictor of AJCC Prognostic Stage Groups in Preoperative Invasive Ductal Carcinoma.

Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine [Epub ahead of print].

OBJECTIVES: This study aimed to evaluate the stiffness of 2-dimensional (2D) shear wave elastography (SWE) in preoperatively predicting the prognostic stage groups of invasive ductal carcinoma (IDC).

METHODS: Eighty-six newly diagnosed lesions on 83 patients with IDCs were analyzed. All parameters from conventional ultrasound and stiffness to virtual touch tissue imaging and quantification were collected, and mean shear wave velocity (SWVmean) was calculated. Data on maximum diameter, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), histologic grading system and Tumor Node Metastasis (TNM) stages were collected. The levels of maximum shear wave velocity (SWVmax), minimum shear wave velocity (SWVmin) and SWVmean were compared. In receiver operating characteristic (ROC) curves analysis, the diagnostic efficacy was found in area under the curve (AUC). Parallel mode was used to improve the predictive value of sensitivity.

RESULTS: The median stiffness of SWVmax and SWVmean for IDCs were 9.38 and 6.32 m/s for late stage (stages II, III, IV) and 6.39 m/s and 4.72 m/s for early stage (stage I) of the prognostic stage groups, respectively. The median stiffness values in the late stage were significantly higher than those in the early stage (P = .003, P = .005). The optimal cutoff stiffness of SWVmax and SWVmean were 8.62 and 6.13 m/s, respectively. In ROC curves analysis, the AUC for SWVmax was 0.742, and it showed a better diagnostic value than SWVmean (0.725). In predictive diagnosis, the sensitivity for SWVmax and SWVmean were both 62.50%. The parallel mode improved the prediction power of sensitivity to 68.75%.

CONCLUSIONS: Preoperative SWV level may serve as a promising prognostic imaging indicator for breast IDCs.

RevDate: 2021-03-13

Santos CS, Rodrigues E, Ferreira S, et al (2021)

Foliar application of 3-hydroxy-4-pyridinone Fe-chelate [Fe(mpp)3 ] induces responses at the root level amending iron deficiency chlorosis in soybean.

Physiologia plantarum [Epub ahead of print].

Iron (Fe) deficiency chlorosis (IDC) affects the growth of several crops, especially when growing in alkaline soils. The application of synthetic Fe-chelates is one of the most commonly used strategies in IDC amendment, despite their associated negative environmental impacts. In a previous work, the Fe-chelate tris(3-hydroxy-1-(H)-2-methyl-4-pyridinonate) iron(III) [Fe(mpp)3 ] has shown great potential for alleviating IDC in soybean (Glycine max) in the early stages of plant development under hydroponic conditions. Herein, its efficacy was verified under soil conditions in soybean grown from seed to full maturity. Chlorophyll levels, plant growth, root and shoot mineral accumulation (K, Mg, Ca, Na, P, Mn, Zn, Ni, and Co) and FERRITIN expression were accessed at V5 phenological stage. Compared to a commonly used Fe chelate, FeEDDHA, supplementation with [Fe(mpp)3 ] led to a 29% higher relative chlorophyll content, 32% higher root biomass, 36% higher trifoliate Fe concentration, and a twofold increase in leaf FERRITIN gene expression. [Fe(mpp)3 ] supplementation also resulted in increased accumulation of P, K, Zn, and Co. At full maturity, the remaining plants were harvested and [Fe(mpp)3 ] application led to a 32% seed yield increase when compared to FeEDDHA. This is the first report on the use of [Fe(mpp)3 ] under alkaline soil conditions for IDC correction, and we show that its foliar application has a longer-lasting effect than FeEDDHA, induces efficient root responses, and promotes the uptake of other nutrients.

RevDate: 2021-02-26

Sarawagi A, J Maxwell (2021)

Chyle Leak after Right Axillary Lymph Node Dissection in a Patient with Breast Cancer.

Case reports in surgery, 2021:8812315.

Background: A female patient was diagnosed with a right-sided chyle leak following right skin sparing mastectomy, axillary lymph node dissection, and immediate tissue expander placement in the setting of invasive ductal carcinoma status post neoadjuvant chemotherapy. Summary. Our patient underwent a level I and II right axillary lymph node dissection followed by an axillary drain placement. On the first postoperative day, a change from serosanguinous to milky fluid in this drain was noted. The patient was diagnosed with a chyle leak based on the milky appearance and elevated triglyceride levels in the fluid. While chyle leaks are rare after an axillary dissection and even rarer to present on the right side, it is a complication of which breast surgeons should be aware. The cause of this complication is thought to be due to injury of the main thoracic duct, its branches, the subclavian duct, or its tributaries. Management is usually conservative; however, awareness of this potential complication even on the right side is of the utmost importance.

Conclusion: Chyle leaks are an uncommon complication of axillary node dissections and even rarer for them to present on the right side. It can be diagnosed by monitoring the drainage for changes in appearance and volume and by conducting supporting laboratory tests. Conservative management is generally suggested.

RevDate: 2021-02-26

Rouillé E, Bilbault H, Levin C, et al (2021)

Characterization of an interdigitating dendritic cell hyperplasia case in a lymph node of a control C57BL/6 mouse.

Journal of toxicologic pathology, 34(1):101-106.

Interdigitating dendritic cell (IDC) hyperplasia is considered a benign spontaneous condition occasionally observed in the lymph nodes of mice. It has been rarely reported and, to the best of our knowledge, it has never been characterized using immunohistochemistry. The present work describes a spontaneous IDC hyperplasia case in a lymph node of a 16-week-old control female C57BL/6 mouse. Microscopically, the lymph node architecture was completely effaced by the proliferation of eosinophilic spindle cells with an abundant pale cytoplasm forming trabecule admixed lymphocyte infiltrates. The spindle cell population was positive for F4/80, partially positive for S100 calcium-binding protein A4 (S100A4), slightly positive for E-cadherin, and negative for α-Smooth muscle actin (SMA) and cytokeratin. Lymphocytes were positive for CD3, CD4, CD20 and negative for CD8. Spindle cells were considered to be originated from the myeloid lineage, based on the immunohistochemistry (IHC) results, but their precise origin remains unclear (IDC or macrophages); even if macrophage origin is most likely based on F4/80 positivity, this remains to be further clarified using other markers.

RevDate: 2021-02-25

Morigny P, Boucher J, Arner P, et al (2021)

Lipid and glucose metabolism in white adipocytes: pathways, dysfunction and therapeutics.

Nature reviews. Endocrinology [Epub ahead of print].

In mammals, the white adipocyte is a cell type that is specialized for storage of energy (in the form of triacylglycerols) and for energy mobilization (as fatty acids). White adipocyte metabolism confers an essential role to adipose tissue in whole-body homeostasis. Dysfunction in white adipocyte metabolism is a cardinal event in the development of insulin resistance and associated disorders. This Review focuses on our current understanding of lipid and glucose metabolic pathways in the white adipocyte. We survey recent advances in humans on the importance of adipocyte hypertrophy and on the in vivo turnover of adipocytes and stored lipids. At the molecular level, the identification of novel regulators and of the interplay between metabolic pathways explains the fine-tuning between the anabolic and catabolic fates of fatty acids and glucose in different physiological states. We also examine the metabolic alterations involved in the genesis of obesity-associated metabolic disorders, lipodystrophic states, cancers and cancer-associated cachexia. New challenges include defining the heterogeneity of white adipocytes in different anatomical locations throughout the lifespan and investigating the importance of rhythmic processes. Targeting white fat metabolism offers opportunities for improved patient stratification and a wide, yet unexploited, range of therapeutic opportunities.

RevDate: 2021-03-26

Lozano R, Salles DC, Sandhu S, et al (2021)

Association between BRCA2 alterations and intraductal and cribriform histologies in prostate cancer.

European journal of cancer (Oxford, England : 1990), 147:74-83.

BACKGROUND: Intraductal (IDC) and cribriform (CRIB) histologies in prostate cancer have been associated with germline BRCA2 (gBRCA2) mutations in small retrospective series, leading to the recommendation of genetic testing for patients with IDC in the primary tumour.

PATIENTS AND METHODS: To examine the association of gBRCA2 mutations and other tumour molecular features with IDC and/or cribriform (CRIB) histologies, we conducted a case-control study in which primary prostate tumours from 58 gBRCA2 carriers were matched (1:2) by Gleason Grade Group and specimen type to 116 non-carriers. Presence/absence of IDC and CRIB morphologies was established by two expert uropathologists blinded to gBRCA2 status. Fluorescent in-situ hybridization (FISH) and next-generation sequencing (NGS) were used to detect BRCA2 alterations, PTEN deletions and TMPRSS2-ERG fusions. Chi-squared tests were used to compare the frequency of IDC and CRIB in gBRCA2 carriers and controls and to assess associations with other variables. Logistic regression models were constructed to identify independent factors associated with both histology patterns.

RESULTS: No significant differences between gBRCA2 carriers and non-carriers were observed in the prevalence of IDC (36% gBRCA2 versus 50% non-carriers, p = 0.085) or CRIB (53% gBRCA2 versus 43% non-carriers p = 0.197) patterns. However, IDC histology was independently associated with bi-allelic BRCA2 alterations (OR 4.3, 95%CI 1.1-16.2) and PTEN homozygous loss (OR 5.2, 95%CI 2.1-13.1). CRIB morphology was also independently associated with bi-allelic BRCA2 alterations (OR 5.6, 95%CI 1.7-19.3).

CONCLUSIONS: While we found no association between gBRCA2 mutations and IDC or CRIB histologies, bi-allelic BRCA2 loss in primary prostate tumours was significantly associated with both variant morphologies, independently of other clinical-pathologic factors.

RevDate: 2021-04-05

Chandrika M, Chua PJ, Muniasamy U, et al (2021)

Prognostic significance of phosphoglycerate dehydrogenase in breast cancer.

Breast cancer research and treatment, 186(3):655-665.

PURPOSE: Breast cancer is the most common type of cancer affecting women worldwide. Phosphoglycerate dehydrogenase (PHGDH) is an oxidoreductase in the serine biosynthesis pathway. Although it has been reported to affect growth of various tumors, its role in breast cancer is largely unknown. This study aimed to analyze the expression of PHGDH in breast cancer tissue samples and to determine if PHGDH regulates breast cancer cell proliferation.

METHODS: Tissue microarrays consisting of 305 cases of breast invasive ductal carcinoma were used for immunohistochemical evaluation of PHGDH expression. The role of PHGDH in breast cancer was investigated in vitro by knocking down its expression and determining the effect on cell proliferation and cell cycling, and in ovo by using a chorioallantoic membrane (CAM) assay.

RESULTS: Immunohistochemical examination showed that PHGDH is mainly localized in the cytoplasm of breast cancer cells and significantly associated with higher cancer grade, larger tumor size, increased PCNA expression, and lymph node positivity. Analysis of the GOBO dataset of 737 patients demonstrated that increased PHGDH expression was associated with poorer overall survival. Knockdown of PHGDH expression in breast cancer cells in vitro resulted in a decrease in cell proliferation, reduction in cells entering the S phase of the cell cycle, and downregulation of various cell cycle regulatory genes. The volume of breast tumor in an in ovo CAM assay was found to be smaller when PHGDH was silenced.

CONCLUSION: The findings suggest that PHGDH has a regulatory role in breast cancer cell proliferation and may be a potential prognostic marker and therapeutic target in breast cancer.

RevDate: 2021-04-12

Nakash O, Nagar M, Razon L, et al (2021)

Association Between Attachment Patterns and Personality Disorders: A Multimethod Multi-Informant Study Using a Clinical Sample.

The Journal of nervous and mental disease, 209(5):386-394.

ABSTRACT: We investigated the association between personality disorders (PDs) and attachment patterns, and examined the construct validity of attachment patterns against adaptive functioning. We used a multimeasure multi-informant approach, which allowed us to disentangle the effects of the methods and to examine the utility of the various methods for measuring these constructs. The participants included 80 clinicians and 170 clinical outpatients, recruited via convenience sampling. Results showed that secure attachment was positively associated with adaptive functioning, whereas insecure patterns were negatively associated with adaptive functioning. Both categorical and dimensional PD diagnoses were associated with insecure attachment patterns. However, after controlling for comorbidity among the PD diagnoses, only some findings remained significant, most notably the association between borderline PD and the clinicians' assessment of preoccupied and incoherent/disorganized attachment, and the patients' self-reported attachment anxiety. Our findings underscore the importance of controlling for comorbidity in examining the associations between attachment patterns and PDs.

RevDate: 2021-04-12

Gupta V, Agarwal P, P Deshpande (2021)

Impact of RASSF1A gene methylation on clinico-pathological features of tumor and non-tumor tissue of breast cancer.

Annals of diagnostic pathology, 52:151722 pii:S1092-9134(21)00022-8 [Epub ahead of print].

BACKGROUND: Breast cancer is the most common malignancy in women caused by genetic and epigenetic changes. Promoter DNA methylation in tumor suppressor gene plays a major role in breast cancer. The study determined the association of promoter DNA methylation of RASSF1A gene with clinicopathological features in tumor and non-tumor tissue.

MATERIALS AND METHODS: A cross sectional study was conducted in the Department of Pathology, Government Institute of Medical Sciences, Greater Noida and Molecular Pathology Laboratory, Department of Pathology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences. Two sections, one from tumor and the other from non-tumor tissue, were obtained and processed for DNA extraction and bisulphite conversion. Methylation specific PCR was done and results of RASSF1A promoter methylation were statistically correlated with clinicopathological features.

RESULTS: Of the 27 breast cancer tissue, 22 showed invasive ductal carcinoma, one showed invasive lobular carcinoma, another showed ductal carcinoma in situ and three cases showed malignant phyllodes tumor of breast. DNA promoter methylation was found in all the cases. 93% of tumor tissue samples and 67% of the non-tumor tissue samples were found to be aberrantly methylated. Tumor size and histological grade were found to be significantly (p-val <0.05) associated with the RASSF1A gene promoter methylation.

CONCLUSION: A significant association of higher tumor size and tumor histological grade with promoter methylation of RASSF1A gene exists suggestive of its being an important determinant of prognostic staging. This critical event in tumorigenesis may be of clinical utility in assessing breast cancer progression.

MICRO ABSTRACT: The study focuses on the RASSF1A gene promoter methylation and its impact on the clinicopathological features in Indian breast cancer patients highlighting the differences from other genetically different population. We found that RASFF1A gene methylation has significant impact on tumor size and tumor grade. The work carries high significance because it addresses the DNA methylation of tumor suppressor gene in relevance of breast cancer. It may also be the first such report on Indian patients with breast cancer.


RJR Experience and Expertise


Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.


Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.


Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.


Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.


While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.


Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.


Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.


Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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Cancer is the generic name for more than 100 diseases in which cells begin to grow and divide in an uncontrolled manner. Usually, when cells get too old or damaged, they die and new cells take their place. Cancer begins when genetic changes impair this orderly process so that some cells start to grow uncontrollably. The Emperor of All Maladies is a "biography" of cancer — from its first documented appearances thousands of years ago through the epic battles in the twentieth century to cure, control, and conquer it to a radical new understanding of its essence. This is a must read book for anyone with an interest in cancer. R. Robbins

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Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

Research Gate page for R J Robbins

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

short personal version

Curriculum Vitae for R J Robbins

long standard version

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