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28 Sep 2021 at 01:45
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Bibliography on: Invasive Ductal Carcinoma


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RJR: Recommended Bibliography 28 Sep 2021 at 01:45 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: 2021-09-27

Kalhan S, Garg S, Satarkar R, et al (2021)

Correlation of Nuclear Morphometry with Clinicopathologic Parameters in Malignant Breast Aspirates.

South Asian journal of cancer, 10(2):64-68.

Objectives The primary objective of this study was to correlate nuclear morphometric parameters with clinicopathologic features such as cytologic grade, tumor size, lymph node status, mitotic index, and histopathologic grade. Secondary objective was to quantify nuclear changes on malignant breast aspirates using morphometry. Material and Methods Forty-five cases of carcinoma breast diagnosed on cytology were included in this study. These were graded into cytologic grades 1, 2, and 3 as per Robinson's cytologic grading system. Nuclear morphometry was done in all cases on smears stained with Papanicolaou stain. Clinicopathologic parameters including cytological grade, tumor size, lymph node status, mitotic count, and histological grade were correlated with nuclear morphometric parameters, namely, area, perimeter, shape, long axis, short axis, intensity, long-run emphasis, total run length, and T1 homogeneity. Results There were 9 cases in cytologic grade 1, 26 in grade 2, and 10 cases in cytologic grade 3. Histopathology showed 42 cases of infiltrating duct carcinoma, not otherwise specified (IDC, NOS) and 3 cases (6.7%) of ductal carcinoma in situ (DCIS). IDC (NOS) included 6, 27, and 9 cases in grades 1, 2, and 3, respectively. Majority of our cases had a tumor size less than 5 cm (n = 38, 84.4%) and had positive nodes (n = 30, 66.7%). Correlation of cytologic and histopathologic grades (including DCIS) with all morphometric features except long-run emphasis was statistically significant. Correlation of morphometry with tumor size yielded significant results for nuclear area, perimeter, long and short axes, and intensity with p < 0.05. Study of lymph node status (positive/negative) versus morphometry showed a highly significant statistical association with all the geometric as well as textural parameters. Mitotic count was significantly associated with all the geometric parameters and one textural parameter (total run length). Statistics Continuous variables were presented as mean ± standard deviation and compared using the two-tailed, independent sample t -test and one-way analysis of variance test. Tests were performed at significance level of 0.05. Conclusion Morphometry is an objective technique which holds immense promise in prognostication in breast carcinoma.

RevDate: 2021-09-27

Saeed U, Uppal SR, Piracha ZZ, et al (2021)

SARS-CoV-2 Spike Antibody Levels Trend among Sinopharm Vaccinated People.

Iranian journal of public health, 50(7):1486-1487.

RevDate: 2021-09-27

Onitilo AA, Engel J, Joseph AO, et al (2021)

Is oestrogen receptor-negative/progesterone receptor-positive (ER-/PR+) a real pathological entity?.

Ecancermedicalscience, 15:1278 pii:can-15-1278.

Background: The existence of oestrogen receptor-negative (ER-)/progesterone receptor-positive (PR+) breast cancer continues to be an area of controversy amongst oncologists and pathologists.

Methods: To re-evaluate breast cancers originally classified as ER-/PR+ via Oncotype DX® assay and compare molecular phenotype with Recurrence Score® (RS) result, clinicopathologic features and clinical outcomes were retrospectively obtained from electronic health records between January 1998 and June 2005. Archived formalin-fixed, paraffin-embedded (FFPE) tumour specimens were tested for the expression of ER, PR and human-epidermal-growth-factor-2. The number of positive ER-/PR+ samples confirmed by transcriptional analysis was the primary outcome of interest with event-free and overall survival as secondary outcomes. Biopsies from 26 patients underwent Oncotype DX testing and analysis.

Results: Approximately 60% were middle-aged (40-50 years old) women, and 84.6% had invasive ductal carcinoma. Based on the Oncotype DX assay, approximately 65% (N = 17) had ER+/PR+ status; 23% (N = 6) had ER-/PR- status; and 12% had a single hormone positive receptor (1 ER-/PR+, 2 ER+/PR-) status. Almost one-quarter of patients were stratified into the low-RS (<18) or intermediate-RS (18-30) results, and half of the patients had a high-RS (>30) result.

Conclusion: Our findings suggest the ER-/PR+ subtype is not a reproducible entity and emphasises the value of retesting this subtype via molecular methods for appropriate treatment selection and patient outcomes. Multigene assay analysis may serve as a second-line or confirming tool for clinical determination of ER/PR phenotype in breast cancer patients for targeted therapies.

RevDate: 2021-09-27

Pradhan P, Margolin W, TK Beuria (2021)

Targeting the Achilles Heel of FtsZ: The Interdomain Cleft.

Frontiers in microbiology, 12:732796.

Widespread antimicrobial resistance among bacterial pathogens is a serious threat to public health. Thus, identification of new targets and development of new antibacterial agents are urgently needed. Although cell division is a major driver of bacterial colonization and pathogenesis, its targeting with antibacterial compounds is still in its infancy. FtsZ, a bacterial cytoskeletal homolog of eukaryotic tubulin, plays a highly conserved and foundational role in cell division and has been the primary focus of research on small molecule cell division inhibitors. FtsZ contains two drug-binding pockets: the GTP binding site situated at the interface between polymeric subunits, and the inter-domain cleft (IDC), located between the N-terminal and C-terminal segments of the core globular domain of FtsZ. The majority of anti-FtsZ molecules bind to the IDC. Compounds that bind instead to the GTP binding site are much less useful as potential antimicrobial therapeutics because they are often cytotoxic to mammalian cells, due to the high sequence similarity between the GTP binding sites of FtsZ and tubulin. Fortunately, the IDC has much less sequence and structural similarity with tubulin, making it a better potential target for drugs that are less toxic to humans. Over the last decade, a large number of natural and synthetic IDC inhibitors have been identified. Here we outline the molecular structure of IDC in detail and discuss how it has become a crucial target for broad spectrum and species-specific antibacterial agents. We also outline the drugs that bind to the IDC and their modes of action.

RevDate: 2021-09-26

Twick M, DA Levy (2021)

Fractionating the episodic buffer.

Brain and cognition, 154:105800 pii:S0278-2626(21)00120-2 [Epub ahead of print].

The episodic buffer is a putative component of working memory proposed to account for several short-term memory functions, including unexpectedly preserved immediate prose recall by amnesic patients. Over the course of time, this component has increasingly become associated with binding functions. Considering recent findings regarding the performance of both memory-impaired and healthy individuals on the range of tasks purported to require the contribution of the episodic buffer, we suggest that it should be fractionated into two functional systems. One is a schematic store instantiated in brain areas responsible for conceptual and schema representations, which is likely to be hippocampus-independent, and preserved in the face of amnesia. In contrast, short-term maintenance of novel associative binding is likely to require the contribution of the hippocampus and may therefore not be functionally dissociable from long-term memory.

RevDate: 2021-09-25

Kumar V, PP Nawroth (2021)

Is the association between diabetes mellitus and pulmonary fibrosis real?.

Nature reviews. Endocrinology [Epub ahead of print].

RevDate: 2021-09-26

Wan D, Zhang Y, Yu Q, et al (2021)

14-3-3ζ promoted invasion and lymph node metastasis of breast invasive ductal carcinoma with HER2 overexpression.

Pathology, research and practice, 227:153619 pii:S0344-0338(21)00280-6 [Epub ahead of print].

BACKGROUND: HER2 was a recognized oncogene that promoted the development and metastasis of breast cancer, but its positive expression rate in invasive ductal carcinoma (IDC) was much lower than that in ductal carcinoma in situ (DCIS). The correlation between the occurrence and development of breast cancer and the amplification and overexpression of HER2 gene alone was still controversial. 14-3-3ζ had a strong protein binding ability and a variety of functions, mainly through the interaction with other proteins to exert its unique biological activities. However, influence and interaction relationship of the two proteins on the development of IDC was not clear. Furthermore, the mutual effect mechanism of synergy effect on lymph node metastasis of IDC was not known well too.

METHODS: Immunohistochemistry experiment was performed to detect expression status of 14-3-3ζ, HER2, TGF-β, p53 and Gli2 in paraffin-embedded samples respectively, including 30 cases of normal breast tissue, 30 cases of usual ductal hyperplasia (UDH), 30 cases of atypical ductal hyperplasia (ADH), 30 cases of DCIS and 120 cases of IDC.

RESULTS: The positive expression rates of 14-3-3ζ/HER2 in Normal group, UDH group, ADH group, DCIS group and IDC group were 30%/0.00%, 26.7%/0.00%, 53.3%/33.3%, 46.7%/53.3% and 50%/24.2%, respectively. Compared with Normal group or UDH group, the expression of 14-3-3ζ was significantly increased in ADH, DCIS and IDC groups. 14-3-3ζ was overexpressed in only 4 of the 16 DCIS cases with HER2 overexpression (25.0%, 4/16), but it was overexpressed in 7 of the 9 IDC cases with DCIS (77.8%, 7/9). Among HER2 overexpression cases, 14-3-3ζ overexpression was significantly different between DCIS group and IDC with DCIS group (P = 0.017). In 18 IDC cases with lymph node metastasis and HER2 overexpression, 14-3-3ζ was overexpressed in 15 cases (83.3%, 15/18), while in the 11 IDC cases without lymph node metastasis, 14-3-3ζ and HER2 were overexpressed in only 5 cases (45.5%, 5/11). Co-overexpression of 14-3-3ζ and HER2 was positively correlated with occurrence of lymph node metastasis (P = 0.048). TGF-β was overexpressed in both precancerous lesion group and IDC group compared with normal group. Compared with the IDC group without lymph node metastasis, TGF-β expression was significantly increased in the IDC group with lymph node metastasis (P = 0.015). In IDC cases with 14-3-3ζ and HER2 co-overexpression, the expression of p53 in IDC with lymph node metastasis was significantly decreased (P = 0.010), while the expression of Gli2 was significantly increased compared with IDC cases without lymph node metastasis (P = 0.038). The co-overexpression of 14-3-3ζ and HER2 was positively correlated with ER negative expression (P < 0.001) and PR negative expression (P = 0.038), respectively.

CONCLUSION: 14-3-3ζ synergistic with HER2 could promote the occurrence and development of breast IDC and induce the lymph node metastasis of IDC, suggesting that combined overexpression of 14-3-3ζ and HER2 would lead to higher invasion and metastasis risk of breast cancer. It was speculated that the combined detection of 14-3-3ζ and HER2 would be one of the key factors affecting the clinical treatment decision and prognosis.

RevDate: 2021-09-24

Han J, Harrison L, Patzelt L, et al (2021)

Imaging modalities for diagnosis and monitoring of cancer cachexia.

EJNMMI research, 11(1):94.

Cachexia, a multifactorial wasting syndrome, is highly prevalent among advanced-stage cancer patients. Unlike weight loss in healthy humans, the progressive loss of body weight in cancer cachexia primarily implicates lean body mass, caused by an aberrant metabolism and systemic inflammation. This may lead to disease aggravation, poorer quality of life, and increased mortality. Timely detection is, therefore, crucial, as is the careful monitoring of cancer progression, in an effort to improve management, facilitate individual treatment and minimize disease complications. A detailed analysis of body composition and tissue changes using imaging modalities-that is, computed tomography, magnetic resonance imaging, (18F) fluoro-2-deoxy-D-glucose (18FDG) PET and dual-energy X-ray absorptiometry-shows great premise for charting the course of cachexia. Quantitative and qualitative changes to adipose tissue, organs, and muscle compartments, particularly of the trunk and extremities, could present important biomarkers for phenotyping cachexia and determining its onset in patients. In this review, we present and compare the imaging techniques that have been used in the setting of cancer cachexia. Their individual limitations, drawbacks in the face of clinical routine care, and relevance in oncology are also discussed.

RevDate: 2021-09-24

Ruddock-Walker S, Shaaban S, Jacobson JL, et al (2021)

Improving Timeliness of Insulin Administration by Using an Insulin Dose Calculator.

Hospital pediatrics pii:hpeds.2020-003103 [Epub ahead of print].

OBJECTIVES: Insulin is a high-risk medication, and its dosing depends on the individualized clinical and nutritional needs of each patient. Our hospital implemented an insulin dose calculator (IDC) imbedded in the electronic medical record with the goal of decreasing average wait times in inpatient insulin ordering and administration. In this study, we evaluated whether implementation of an IDC decreased the average wait time for insulin administration for hospitalized pediatric patients.

METHODS: This pre- and postintervention cohort study measured wait times between point-of-care glucose testing and insulin administration. Patients admitted to the inpatient pediatric services who were treated with subcutaneous insulin during the study period were included. Additionally, nurses completed satisfaction surveys on the insulin administration process at our hospital pre- and post-IDC implementation. Descriptive statistics, χ2, Fisher's exact test, and Student t tests were used to compare groups. Statistical process control charts were used to analyze data trends.

RESULTS: The preintervention cohort included 79 insulin doses for admitted pediatric patients. The postimplementation cohort included 128 insulin doses ordered via the IDC. Post-IDC implementation, the average wait time between point-of-care glucose testing and insulin administration decreased from 37 to 25 minutes (P < .05). The statistical process control chart revealed a 5-month run below the established mean after implementation of the IDC. Before IDC implementation, 15.6% of nurses expressed satisfaction in the insulin-dosing process compared with 69.2% postimplementation (P < .05).

CONCLUSIONS: Implementation of an IDC reduced the average wait time in ordering and administration of rapid-acting insulin and improved nursing satisfaction with the process.

RevDate: 2021-09-24

Mangiardi-Veltin M, Chamming's F, Jaffre A, et al (2021)

[Prophylactic mastectomy and occult cancer: a ten-year experience at a cancer center].

Bulletin du cancer pii:S0007-4551(21)00298-8 [Epub ahead of print].

INTRODUCTION: Women identified as high-risk for breast cancer may choose between close follow-up and radical mastectomy. Prophylactic mastectomy, as any other surgery, is associated with benefits and harms. The aim of this study was to assess the morbidity associated with prophylactic mastectomy and to evaluate the prevalence of occult cancers.

METHODS: All patients who underwent unilateral or bilateral prophylactic mastectomy between 2007 and 2017 in our institution were eligible for inclusion in this retrospective study. Medical history, type of surgery, occurrence of complication or reoperation and pathological reports were examined in medical charts.

RESULTS: 79 women underwent prophylactic mastectomy over the studied period of which 58.2% were contralateral after breast cancer. A genetic mutation was present in 86.1% of cases. Postoperative complications occurred in 43.0% of cases. An additional surgery for medical or esthetic purpose was needed in 72.1% of cases. Occult cancer was found in 11.4% of the pathological reports. Triple negative invasive ductal carcinoma was discovered in two cases (2.5%).

DISCUSSION: Prophylactic mastectomy is the only effective preventive action against breast cancer. Women must be clearly informed of possible complications, high reoperation rate and potential pathological findings. Identifying women most at risk for breast cancer would help to better target those who will benefit most from surgery.

RevDate: 2021-09-23

Giroud M, Jodeleit H, Prentice KJ, et al (2021)

Adipocyte function and the development of cardiometabolic disease.

The Journal of physiology [Epub ahead of print].

KEY POINTS: Obesity and the associated adipocyte pathology are risk factors for cardiovascular disease Translational research is possible but strongly depends on the mouse model used White adipose tissue inflammation contributes to metabolic and vascular dysfunction Brown adipose tissue thermogenesis supports metabolic and vascular function ABSTRACT: Obesity is a medical disorder caused by multiple mechanisms of dysregulated energy balance. A major consequence of obesity is an increased risk to develop diabetes, diabetic complications, and cardiovascular disease. While a better understanding of the molecular mechanisms linking obesity, insulin resistance, and cardiovascular disease is needed, translational research of the human pathology is hampered by the available cellular and rodent model systems. Major barriers are the species-specific differences in energy balance, vascular biology, and adipose tissue physiology, especially related to white and brown adipocytes, and adipose tissue browning. In rodents, non-shivering thermogenesis is responsible for a large part of energy expenditure, but humans possess much less thermogenic fat, which makes temperature is an important variable in translational research. Mouse models with predisposition to dyslipidaemia housed at thermoneutrality and fed a high-fat diet more closely reflect human physiology. Also, adipocytes play a key role in the endocrine regulation of cardiovascular function. Adipocytes secrete a variety of hormones, lipid mediators, and other metabolites that directly influence the local microenvironment as well as distant tissues. This is specifically apparent in perivascular depots, where adipocytes modulate vascular function and inflammation. Altogether, these mechanisms highlight the critical role of adipocytes in the development of cardiometabolic disease. Abstract figure legend While cardiometabolic health is associated with adipose tissue browning and beneficial adipokine profiles, obesity leads to adipose tissue whitening, inflammation, and atherosclerosis. This article is protected by copyright. All rights reserved.

RevDate: 2021-09-22

Greco CM, Koronowski KB, Smith JG, et al (2021)

Integration of feeding behavior by the liver circadian clock reveals network dependency of metabolic rhythms.

Science advances, 7(39):eabi7828.

[Figure: see text].

RevDate: 2021-09-23
CmpDate: 2021-09-23

Fujimoto A, Kosaka Y, Hasebe T, et al (2021)

Hidden breast cancer after breast augmentation, not presenting as a hypoechoic mass lesion, diagnosed using colour Doppler ultrasound.

BMJ case reports, 14(9): pii:14/9/e242742.

The main concern after breast augmentation with silicone injection is that silicone granulomas make it difficult to detect breast cancer. A case of breast cancer was diagnosed using colour Doppler ultrasound (CD) to detect an non-palpable mass not presenting as a hypoechoic mass lesion. An 83-year-old woman was incidentally found to have a lesion in her right breast, which was injected with silicone, showing 18F-fluorodeoxyglucose (FDG) uptake; the lesion was suspected to be breast cancer or silicone granuloma. A mass at the FDG uptake site was not detected on ultrasonography (US); however, observation using CD revealed a slightly hypoechoic area with hypervascularity. Core needle biopsy showed invasive ductal carcinoma. Patients in whom US does not reveal lesions after breast augmentation with silicone injection should undergo CD to detect hypervascularised tissue. To prevent false-negative biopsy results, CD is essential to detect cancer at suspected sites.

RevDate: 2021-09-22

Moghalu O, Stoffel JT, Elliott SP, et al (2021)

Time-Related Changes in Patient Reported Bladder Symptoms and Satisfaction after Spinal Cord Injury.

The Journal of urology [Epub ahead of print].

PURPOSE: Increased time after spinal cord injury (SCI) is associated with a migration to bladder managements with higher morbidity such as indwelling catheter (IDC). Still it is unclear how this affects bladder-related quality of life (QoL). We hypothesized that time from injury (TFI) would be associated with changes in bladder management, symptoms, and satisfaction.

MATERIALS AND METHODS: Cross-sectional analysis of time-related changes in patient-reported bladder management, symptoms, and satisfaction, using the Neurogenic Bladder Research Group SCI Registry. Outcomes included: Neurogenic Bladder Symptom Score (NBSS) and bladder-related satisfaction (NBSS-satisfaction). Multivariable regression was performed to assess associations between TFI and outcomes, adjusting for participant characteristics, injury specifics, and psychosocial aspects of health-related QoL. Participants with TFI <1 year were excluded and TFI was categorized 1-5 (reference), 6-10, 11-15, 16-20, and >20 years.

RESULTS: Of 1420 participants, mean age at injury was 29.7(SD13.4) years and mean TFI was 15.2(SD11.6) years. Participants grouped by TFI included 298 (21%) 1-5, 340 (24%) 6-10, 198 (14%) 11-15, 149 (10%) 16-20, and 435 (31%) >20 years. As TFI increased, clean intermittent catheterization (CIC) declined (55% 1-5 vs. 45% >20 years, p <0.001), and IDC increased (16% 1-5 vs. 21% >20 years, p <0.001). On multivariable analysis, increased TFI was associated with less bladder symptoms at >20 years from injury (-3.21 [CI-1.29,-5.14,p <0.001]) and better satisfaction (6-10 years -0.20 [CI-0.41,0.01,p=0.070], 11-15 years -0.36 [CI-0.60,-0.11,p=0.002], 16-20 years -0.59 [CI-0.86,-0.32,p <0.001], >20 years -0.85 [CI-1.07,-0.63, <0.001]).

CONCLUSION: After SCI, CIC decreases and IDC increases over time; however, increasing TFI is associated with reduced urinary symptoms, and improved bladder-related satisfaction.

RevDate: 2021-09-20

Chen Z, Pham H, Abreu A, et al (2021)

Prognostic value of cribriform size, percentage, and intraductal carcinoma in Gleason Score 7 prostate cancer with Cribriform Gleason Pattern 4.

Human pathology pii:S0046-8177(21)00163-5 [Epub ahead of print].

Cribriform Gleason pattern 4 (CGP4) is an indicator of poor prognosis in Gleason Score 7 prostate cancer, however, the significance of the size and percentage of this pattern and the presence of concomitant intraductal carcinoma (IDC) in these patients is unclear. To study the significance of these parameters in radical prostatectomy specimens, 165 cases with CGP4 were identified and reviewed (2017 to 2019). The size and percentage cribriform pattern and presence of IDC were noted and correlated with adverse pathological features and biochemical recurrence (BCR) free survival. On review, 156 cases had CGP4 (Grade Group 2: 87 and Grade Group 3: 69). Large cribriform pattern and cribriform percentage of >20% showed significant association with extraprostatic extension, surgical margin positivity and presence of IDC while presence of IDC was associated with all the analyzed adverse pathological features. BCR was seen in 22/111(20%) patients after a median follow up of 11 months and of these 21 had large cribriform pattern. On univariate analysis all parameters had significant predictive values for BCR free survival except for tertiary Gleason pattern 5. On multivariate analysis while > 20% cribriform pattern was trending to be an independent predictor only lymphovascular invasion was statistically significant. Large cribriform pattern, >20% cribriform and presence of IDC are additional pathologic parameters of potential value in identifying patients with high risk for early BCR.

RevDate: 2021-09-21

Wang XD, Su XJ, Chen YK, et al (2021)

Regression of intervertebral disc calcification combined with ossification of the posterior longitudinal ligament: A case report.

World journal of clinical cases, 9(24):7285-7291.

BACKGROUND: Intervertebral disc calcification (IDC) combined with ossification of the posterior longitudinal ligament (OPLL) in cervical discs is rarely reported. This case study presents a rare case of IDC combined with OPLL in the C2-C3 segment.

CASE SUMMARY: Here, we present a case of a 6-year-old Asian boy with severe neck pain and stiffness. Physical examination showed no neurological or other abnormalities. Digital radiography and computed tomography (CT) revealed a calcified intervertebral disc and OPLL at the C2-C3 vertebrae. The spinal canal compromise at C2-C3 was approximately 50% on magnetic resonance imaging. The final diagnosis was IDC combined with OPLL. We applied a neck brace for the patient to protect the neck. The patient's neck pain and stiffness recovered significantly within approximately 3 wk. At the 3 mo follow-up, the follow-up CT showed resolution of the ossified intervertebral disc herniation, and a small amount of calcification and slight OPLL remained at the involved segment.

CONCLUSION: IDC combined with OPLL is a relatively rare condition in children. However, the majority of patients could have a favorable outcome, and the ossified mass in the canal would be spontaneously resolved with conservative therapy.

RevDate: 2021-09-21

Das S, Bramhachari S, Halder A, et al (2021)

Synchronous Breast Carcinoma, Uterine Myoma, and Ovarian Teratoma in a Single Woman.

Cureus, 13(9):e17977.

Multiple primary tumors in a patient diagnosed with invasive ductal breast cancer are rarely reported in the literature. Here we present a case of invasive ductal carcinoma of the breast in a 42-year-old lady, with synchronous uterine leiomyoma (UL), ovarian teratoma and with prior history of follicular adenoma of thyroid in the same patient. The clinical presentation and management plan is discussed with a review of the literature. Breast cancer is the most common cancer in women where the concomitant occurrence of multiple primary tumors is a diagnostic and therapeutic challenge. In low- and middle-income countries, where facilities of genetic screening in all patients of synchronous neoplasia are limited due to scarcity of resources, strong clinical suspicion, multidisciplinary management, and follow-up remain important.

RevDate: 2021-09-20

Ramotar M, Chua MLK, Truong H, et al (2021)

Subpathologies and genomic classifier for treatment individualization of post-prostatectomy radiotherapy.

Urologic oncology pii:S1078-1439(21)00376-8 [Epub ahead of print].

PURPOSE/OBJECTIVE: Risk-stratification for post-prostatectomy radiotherapy (PORT) using conventional clinicopathologic indexes leads to substantial over- and under-treatment. Better patient selection could spare unnecessary toxicities and improve outcomes. We investigated the prognostic utility of unfavorable subpathologies intraductal carcinoma and cribriform architecture (IDC/CA), and a 22-gene Decipher genomic classifier (GC) in prostate cancer (PCa) patients receiving PORT.

MATERIAL/METHODS: A cohort of 302 men who received PORT at 2 academic institutions was pooled. PORT was predominately delivered as salvage (62% of cases); 20% received HT+PORT. Specimens were centrally reviewed for IDC/CA presence. In 104 cases, GC scores were determined. Endpoints were biochemical relapse-free (bRFR) and metastasis-free (mFR) rates.

RESULTS: After a median follow-up of 6.49-years, 135 (45%) and 40 (13%) men experienced biochemical relapse and metastasis, respectively. IDC/CA were identified in 160 (53%) of cases. Men harboring IDC/CA experienced inferior bRFR (HR 2.6, 95%CI 1.8-3.2, P<0.001) and mFR (HR 3.1, 95%CI 1.5-6.4, P = 0.0014). Patients with GC scores, 22 (21%) were stratified low-, 30 (29%) intermediate-, and 52 (50%) high-risk. GC low-risk was associated with superior bRFR (HR 0.25, 95%CI 0.1-0.5, P<0.001) and mFR (HR 0.15, 95%CI 0.03-0.8, P = 0.025). On multivariable analyses, IDC/CA and GC independently predicted for bRFR, corresponding to improved discrimination (C-index = 0.737 (95%CI 0.662-0.813)).

CONCLUSIONS: IDC/CA subpathologies and GC predict for biochemical relapse and metastasis beyond conventional clinicopathologic indexes in the PORT setting. Patients harboring IDC/CA are at higher risk of relapse after maximal local therapies, thus warranting consideration for treatment intensification strategies. Conversely, for men with absence of IDC/CA and low GC scores, de-intensification strategies could be explored.

RevDate: 2021-09-18

Lin X, He Y, Fu S, et al (2021)

The Ultrasonographic Characteristics of Focal Fibrocystic Change of the Breast and Analysis of Misdiagnosis.

Clinical breast cancer pii:S1526-8209(21)00241-X [Epub ahead of print].

INTRODUCTION: To investigate ultrasonographic features and analyze causes of misdiagnosis of focal fibrocystic change (FC) of the breast.

MATERIALS AND METHODS: The ultrasonographic features of 95 women (104 lesions) with postoperatively pathologically confirmed focal FC (Group 1) were retrospectively analyzed and compared with those of 105 women (107 lesions) with ductal carcinoma in situ (DCIS) (Group 2), and 164 women (177 lesions) with invasive ductal carcinoma (IDC) (Group 3).

RESULTS: There were significant differences in 12 features among groups. The sizes and distributions of cystic changes among the groups were significantly different. In group 1, the incidence of cystic changes was 75%(78/104), and the main manifestation was scattered cystic changes (88.5%, 69/78) and microcapsules (81.8%, 63/78). Among focal FC lesions, 36.5% were preoperative BI-RADS classifications 4b-5 (30.8% 4b and 4c). Lesions misdiagnosed as malignant showed solid or cystic solid mixed echoes, and 70.2% of group 1 were irregularly shaped, and 63.5% had unclear edges. In group 1, 5 cases had "hyperechoic halo," 11.5% (12/104) appeared echo attenuation behind the mass, and 21 cases appeared punctate hyperechoic.

CONCLUSION: FC frequently exhibits low heterogeneity, scattered microcapsules with posterior enhancement, "pit-like" or "grid-like" changes, posterior enhancement, rare hyperechoic halo, calcification, and lack of blood supply. Certain focal FC are irregularly shaped with unclear edges, with malignant signs such as crab feet and burr, hyperechoic halo, and calcification, which ultrasound BI-RADS classification may easily misdiagnose as malignant. Local magnification function should be considered, and the internal structure should be carefully observed to prevent misdiagnosis.

RevDate: 2021-09-17

Fritsche A, Wagner R, Heni M, et al (2021)

Different effects of lifestyle intervention in high- and low-risk prediabetes.

Diabetes pii:db21-0526 [Epub ahead of print].

Lifestyle intervention (LI) can prevent type 2 diabetes, but response to LI varies depending on risk subphenotypes. We tested if prediabetic individuals with low risk benefit from conventional LI and individuals with high risk benefit from an intensification of LI in a multi-center randomized controlled intervention over 12 months with 2 years follow up. 1105 prediabetic individuals based on ADA glucose criteria were stratified into a high- and low-risk phenotype, based on previously described thresholds of insulin secretion, insulin sensitivity and liver fat content. Low-risk individuals were randomly assigned to conventional LI according to the DPP protocol or control (1:1), high-risk individuals to conventional or intensified LI with doubling of required exercise (1:1). A total of 908 (82%) participants completed the study. In high-risk individuals, the difference between conventional and intensified LI in post-challenge glucose change was -0.29 mmol/l [CI:-0.54;-0.04], p=0.025. Liver fat (-1.34 percentage points [CI:-2.17;-0.50], p=0.002) and cardiovascular risk (-1.82[CI:-3.13-0.50],p=0.007) underwent larger reductions with intensified than with conventional LI. During a follow up of 3 years, intensified compared to conventional LI had a higher probability to normalize glucose tolerance (p=0.008). In conclusion, it is possible in high-risk individuals with prediabetes to improve glycemic and cardiometabolic outcomes by intensification of LI. Individualized, risk-phenotype-based LI may be beneficial for the prevention of diabetes.

RevDate: 2021-09-16

Trontzas IP, Syrigos NK, EA Kotteas (2021)

A case of trastuzumab-induced dermatomyositis.

Journal of cancer research and therapeutics, 17(4):1112-1114.

Human epidermal growth factor receptor 2 (HER-2) is a checkpoint, controlling cell proliferation and differentiation. Trastuzumab, a humanized monoclonal antibody directed against HER-2, is nowadays standard treatment for breast cancer patients whose tumors express HER-2. It is generally well tolerated, with a small number of patients developing mild adverse reactions. Dermatomyositis is a rare adverse event of trastuzumab therapy not well described in the literature. We herein present a case of a patient treated for hormone-sensitive invasive ductal carcinoma, who presented with symptoms of proximal muscle weakness, arthralgias, skin rash, and generalized fatigue. The symptoms started after the sixth cycle of trastuzumab and progressively deteriorated. The patient's medical and family history was unremarkable. Disease progression as a possible cause of dermatomyositis had been ruled out, and laboratory evaluation revealed moderate elevation of serum muscle proteins and acute-phase reactants. Trastuzumab treatment was discontinued, and 3 months later, the patient was free of symptoms without any further intervention.

RevDate: 2021-09-17

Loft A, Herzig S, SF Schmidt (2021)

Purification of GFP-tagged nuclei from frozen livers of INTACT mice for RNA- and ATAC-sequencing.

STAR protocols, 2(3):100805.

Isolation of nuclei tagged in specific cell types (INTACT) allows for stress-free and high-throughput analyses of cellular subpopulations. Here, we present an improved protocol for isolation of pure and high-quality GFP-labeled nuclei from frozen livers of INTACT mice, as well as protocols for downstream sequencing analyses. The adaptation to frozen tissue provides a pause point that allows sampling at multiple time points and/or phenotypic characterization of livers prior to nuclei isolation and downstream analyses. For complete details on the use of this protocol, please refer to Loft et al. (2021).

RevDate: 2021-09-17

Fujimoto A, Matsuura K, Kawasaki T, et al (2021)

Early HER2-positive breast cancer arising from a fibroadenoma: a case report.

Oxford medical case reports, 2021(9):omab083.

Breast cancer arising from fibroadenoma (FA) is rare, in which almost all reported cases are human epidermal growth factor receptor 2 (HER2)-negative. This is the first report to describe a case of HER2-positive breast cancer arising from FA that was treated with chemotherapy plus anti-HER2 therapy. In this early case, upfront surgery outcomes guided the selection of appropriate systemic therapy. A 31-year-old woman previously diagnosed with FA experienced tumor growth. Core needle biopsy and imaging studies confirmed a diagnosis of stage IIA HER2-positive invasive ductal carcinoma (IDC) with no evidence of lymph node metastasis (cT2N0M0). Breast-conserving surgery was performed. Pathological diagnosis revealed stage IA IDC with a predominant intraductal component (pT1aN0M0), arising from FA. In conclusion, we encountered an extremely rare case of HER2-positive breast cancer arising from FA in which pathological infiltration was difficult to predict based on preoperative imaging.

RevDate: 2021-09-16

Chen X, Chen J, Liao S, et al (2021)

Invasive ductal carcinoma and small lymphocytic lymphoma/chronic lymphocytic leukemia manifesting as a collision breast tumor: A case report and literature review.

Open life sciences, 16(1):867-871.

Collision breast tumors, consisting of breast cancer (BC) and non-Hodgkin's lymphoma (NHL), are extremely rare. Here we report the case of a 64-year-old woman with a collision tumor in her left breast mass that was composed of invasive ductal carcinoma and small lymphocytic lymphoma/chronic lymphocytic leukemia. In addition, we reviewed the published comparable English-language literature. Collision breast tumor composed of BC and NHL is extremely rare. For that reason, there is a lack of consensus about the underlying mechanism, and diagnosing it without delay remains a complex clinical challenge. We found that post-menopausal, age-related estrogen levels changes and Epstein-Barr virus infection are possible pathogenic factors. However, the symptoms are almost identical, and it is difficult to distinguish a simple breast tumor from a breast collision tumor. In this study, we reviewed the clinical features of all patients with BC and NHL colliding breast tumors; this information might enable early identification and prevention of misdiagnosis.

RevDate: 2021-09-24

Wj H, As E, Js R, et al (2021)

Rates of margin positive resection with breast conservation for invasive breast cancer using the NCDB.

Breast (Edinburgh, Scotland), 60:86-89 pii:S0960-9776(21)00442-2 [Epub ahead of print].

BACKGROUND: Previous studies suggest the rate of positive surgical margin (PSM) after lumpectomy for breast cancer is approximately 20 %. The risk of PSM at time of resection is often a source of fear for patients, driving some to elect to undergo mastectomy. This study describes rates and predictors of positive margins for invasive breast cancers in the National Cancer Database (NCDB).

MATERIALS AND METHODS: From 2004 to 2013, patients with non-metastatic invasive breast cancers who underwent breast conservation surgery were identified from the NCDB. Patients' demographic, clinical, and facility of treatment characteristics were collected and compared. Per SSO-ASTRO-ASCO criteria, margin negative is defined as no gross or microscopic disease (i.e. no tumor on ink). Bivariate tests and multivariate logistic regression were conducted to identify independent predictors of patients with PSM at the time of resection.

RESULTS: A total of 707,798 patients were identified with non-metastatic invasive breast tumors who underwent lumpectomy. Rate of PSM across the entire cohort was 5.02 %. Over time, the rate of PSM decreased significantly from 6.54 % in 2004 to 3.91 % in 2013 (p < 0.001). Pure lobular histology predicted for the highest rate of PSM compared with IDC (8.63 vs 4.55 %; p < 0.001). In adjusted analysis, high grade, non-ductal histology and HER2 amplification were significantly associated with PSM with breast conservation while estrogen and progesterone status were not.

CONCLUSION: This study demonstrates a 5 % risk of PSM at time of breast conservation surgery using a large, modern national database. Patients with invasive lobular and mixed histology have a nearly two-fold risk of PSM compared to invasive ductal cancers. These results provide important data points to help appropriately counsel patients regarding the risk of PSM.

RevDate: 2021-09-13

Mills MN, Russo NW, Fahey M, et al (2021)

Increased Risk for Ipsilateral Breast Tumor Recurrence in Invasive Lobular Carcinoma after Accelerated Partial Breast Irradiation Brachytherapy.

The oncologist [Epub ahead of print].

BACKGROUND: The suitability criteria for accelerated partial breast irradiation (APBI) from the American Brachytherapy Society (ABS), American Society of Therapeutic Radiology and Oncology (ASTRO), and the European Society for Radiotherapy and Oncology (GEC-ESTRO) have significant differences.

MATERIALS AND METHODS: This is a single institution retrospective review of 946 consecutive patients with invasive breast cancer who underwent lumpectomy and APBI intracavitary brachytherapy from 2003 to 2018. Overall survival (OS), breast cancer-specific survival (BCSS), relapse-free survival (RFS), and ipsilateral breast tumor recurrence (IBTR) were estimated with Kaplan-Meier method.

RESULTS: Median follow-up time was 60.2 months. Median age was 68 years (46-94 years). The majority of patients had estrogen receptor (ER)-positive disease (94%). There were 821 (87%) cases of invasive ductal carcinoma and 68 cases (7%) of invasive lobular carcinoma (ILC). The 5-year OS, BCSS, RFS, and IBTR was 93%, 99%, 90%, and 1.5%, respectively. Upon univariate analysis, ILC (HR 4.6, p=0.008) and lack of nodal evaluation (HR 6.9, p=0.01) were risk factors for IBTR. The 10-year IBTR was 2.5% for IDC and 14% for ILC. Patients deemed unsuitable by the ABS or ASTRO criteria, or high risk by the ESTRO criteria, were not at increased risk for IBTR or RFS.

CONCLUSIONS: These results show that APBI is an effective treatment for patients with invasive breast cancer. Expansion of the current eligibility criteria should be considered, though prospective validation is needed. Caution is required when considering APBI for patients with ILC.

IMPLICATIONS FOR PRACTICE: In a large retrospective review of 946 patients with early breast cancer treated with partial mastectomy and APBI intracavitary brachytherapy, we demonstrate durable local control. Patients deemed unsuitable or high risk by the American Brachytherapy Society, American Society of Therapeutic Radiation Oncology, and European Society for Radiotherapy and Oncology guidelines were not at increased risk for IBTR, suggesting that expansion of the current criteria should be considered. Importantly, however, our results demonstrate that caution should be taken when considering APBI for patients with invasive lobular carcinoma, as these patients had relatively high risk for IBTR (10-year IBTR 14%).

RevDate: 2021-09-14

Brink HM, Rubin G, Benn CA, et al (2021)

An audit of patients clinically deemed as high risk for malignant breast pathology at the Helen Joseph Hospital Breast Clinic.

South African journal of surgery. Suid-Afrikaanse tydskrif vir chirurgie, 59(3):102-107.

BACKGROUND: The Helen Joseph Hospital Breast Clinic has implemented a clinical triage system for patients presenting with a variety of breast concerns. The goal of this system is to expedite the process from initial presentation to radiological assessment of patients with suspected breast malignancy or breast abscess in a resource limited setting. The objective was to assess the clinical, imaging and histological diagnoses of breast disease in these patients with malignancy and sepsis.

METHODS: A retrospective audit of patients clinically deemed high risk for malignant breast pathology referred to the breast imaging unit (BIU) in 2018. Patients were triaged based on strict clinical criteria: presence of a breast mass with or without lymph nodes or a breast abscess. Patients that were subsequently referred for mammography/ultrasound were identified using the patient files in the BIU. Results were recorded on Microsoft Excel and analysed using SAS version 9.2.

RESULTS: Three hundred and twenty-five patients were included in this study. Eighty-seven (26.8%) were diagnosed with breast cancer and 236 (72.6%) with benign disease. The most common presenting complaint was a palpable mass (n = 227; 69.9%). Ninety-five per cent of patients characterised as BI-RADS 5 had malignant disease. 55.8% of malignancies diagnosed on ultrasound had locally advanced disease. The most common histological diagnosis of malignancy was invasive ductal carcinoma (n = 67, 77%). The most commonly diagnosed benign disease was breast abscess (n = 42, 17.8%).

CONCLUSION: BI-RADS findings correspond to similar studies, however, a large number of benign breast disease was diagnosed. This may indicate heightened clinical awareness of breast cancer diagnosis and early detection. A significant percentage of malignancies presented as locally advanced. Except for a lower number of invasive lobular carcinoma, the histological spectrum of malignant disease is similar to comparative studies.

RevDate: 2021-09-14

Vijayaraghavan GR, Kona M, Maheswaran A, et al (2021)

Ultrasound Imaging Morphology is Associated with Biological Behavior in Invasive Ductal Carcinoma of the Breast.

Journal of clinical imaging science, 11:48.

Objectives: Ultrasound (US) is commonly used for diagnostic evaluation of breast lesions. The objective of this study was to investigate the association between US imaging morphology from routine radiologists' interpretation and biological behavior such as receptor status and tumor grade determined from histopathology in invasive ductal carcinoma (IDC).

Material and Methods: This retrospective study included 453 patients with pathology-verified diagnosis of IDC who had undergone US imaging and had surgery over a 5-year period. US and surgical pathology reports were reviewed and compiled. Correlation analyses and age-adjusted multivariable models were used to determine the association between US imaging morphology and receptor status, tumor grade, and germ line mutation of the breast cancer genes (BRCA1 and BRCA2). The odds ratio (OR), area under receiver operating characteristic curve (AUC), and 95% confidence intervals (CI) were obtained.

Results: The likelihood for high-grade cancer increased with size (OR: 1.066; CI: 1.042-1.091) and hypo-echogenicity (OR: 2.044; CI: 1.337-3.126), and decreased with angular or spiculated margins (OR: 0.605; CI: 0.393-0.931) and posterior acoustic shadowing (OR: 0.352; CI: 0.238-0.523). These features achieved an AUC of 0.799 (CI: 0.752-0.845) for predicting high-grade tumors. The likelihood for Estrogen Receptor-positive tumors increased with posterior acoustic shadowing (OR: 3.818; CI: 2.206-6.607), angulated or spiculated margins (OR: 2.596; CI: 1.159-5.815) and decreased with US measured tumor size (OR: 0.959; CI: 0.933-0.986) and hypoechoic features (OR: 0.399; CI: 0.198- 0.801), and achieved an AUC of 0.787 (CI: 0.733-0.841). The likelihood for Progesterone Receptor-positive tumors increased with posterior acoustic shadowing (OR: 2.732; CI: 1.744-4.28) and angulated or spiculated margins (OR: 2.618; CI: 1.412-4.852), and decreased with US measured tumor size (OR: 0.961; CI: 0.937-0.985) and hypoechoic features (OR: 0.571; CI: 0.335-0.975), and achieved an AUC of 0.739 (CI: 0.689-0.790). The likelihood for Human epidermal growth factor receptor 2-positive tumors increased with heterogeneous echo texture (OR: 2.141; CI: 1.17- 3.919) and decreased with angulated or spiculated margins (OR: 0.408; CI: 0.177-0.944), and was marginally associated with hypoechoic features (OR: 2.101; CI: 0.98-4.505) and circumscribed margins (OR: 4.225; CI: 0.919-19.4). The model with the aforementioned four US morphological features and achieved an AUC of 0.686 (CI: 0.614-0.758). The likelihood for triple-negative breast cancers increased with hypo-echogenicity (OR: 2.671; CI: 1.249-5.712) and decreased with posterior acoustic shadowing (OR: 0.287; CI: 0.161-0.513), and achieved an AUC of 0.739 (CI: 0.671- 0.806). No statistical association was observed between US imaging morphology and BRCA mutation.

Conclusion: In this study of over 450 IDCs, significant statistical associations between tumor grade and receptor status with US imaging morphology were observed and could serve as a surrogate imaging marker for the biological behavior of the tumor.

RevDate: 2021-09-16

Dias R, Mendes ÂB, Lages N, et al (2021)

Ultrasound-guided fascial plane blocks as unique anesthetic technique for total mastectomy in a covid-19 era: A case report.

Revista espanola de anestesiologia y reanimacion, 68(7):408-413.

INTRODUCTION: Regional anesthesia techniques were recently introduced to provide analgesia for breast surgery. These techniques are rarely used as the primary anesthesia due to the complexity of breast innervation, with numerous structures that can potentially be disrupted during breast surgery.

CASE REPORT: A female patient in her sixties diagnosed with invasive ductal carcinoma on her left breast was scheduled for a simple mastectomy. After anesthetic evaluation, identification of high risk perioperative cardiovascular complications, it was proposed to perform the surgery only with regional anesthesia. A combination of pectoral nerve block (Pecs II), pecto-intercostal fascial block (PIFB) and supraclavicular nerve block ultrasound-guided were successfully performed.

CONCLUSION: This is the first case reporting a novel approach in a patient with severe cardiopulmonary disease who underwent breast surgery in a COVID-19 era.

RevDate: 2021-09-25

Greenwood HI, Price ER, Lee AY, et al (2021)

Outcomes of screening mammography performed prior to fertility treatment in women ages 40-49.

Clinical imaging, 80:359-363 pii:S0899-7071(21)00362-4 [Epub ahead of print].

OBJECTIVE: There are currently various conflicting recommendations for breast cancer screening with mammography in women between ages 40-49. There are no specific guidelines for breast cancer screening in women of this age group prior to assisted reproductive technology (ART) for the treatment of infertility. The purpose of our study was to evaluate outcomes of screening mammography, specifically ordered for the purpose of pre-fertility treatment clearance in women aged 40-49 years old.

MATERIALS AND METHODS: This was an IRB approved retrospective study of women aged 40-49 presenting for screening mammography prior to ART between January 2010 and October 2018. Clinical history, imaging, and pathology results were gathered from the electronic medical record. Descriptive statistics were performed.

RESULTS: Our study cohort consisted of 118 women with a mean age of 42 years (range 40-49). Sixteen of 118 (14%) women were recalled from screening for additional diagnostic work-up. Five of the 16 (31%) were recommended for biopsy (BI-RADS 4 or 5). One of 5 biopsies yielded a malignant result (PPV 20%). Overall cancer detection rate was 0.85% or 8.5 women per 1000 women screened. The single cancer in this cohort was an ER+ PR+ HER2- invasive ductal carcinoma.

CONCLUSION: Screening mammography in women 40-49 performed prior to initiation of ART may identify asymptomatic breast malignancy. In accordance with ACR and SBI guidelines to screen women of this age group, women of this age group should undergo screening mammography prior to ART.

RevDate: 2021-09-13

Patzelt L, Junker D, Syväri J, et al (2021)

MRI-Determined Psoas Muscle Fat Infiltration Correlates with Severity of Weight Loss during Cancer Cachexia.

Cancers, 13(17):.

PURPOSE: To evaluate the suitability of psoas and erector spinae muscle proton density fat fraction (PDFF) and fat volume as biomarkers for monitoring cachexia severity in an oncological cohort, and to evaluate regional variances in muscle parameters over time.

METHODS: In this prospective study, 58 oncological patients were examined by a 3 T MRI receiving between one and five scans. Muscle volume and PDFF were measured, segmentation masks were divided into proximal, middle and distal muscle section.

RESULTS: A regional variation of fat distribution in erector spinae muscle at baseline was found (p < 0.01). During follow-ups significant relative change of muscle parameters was observed. Relative maximum change of erector spinae muscle showed a significant regional variation. Correlation testing with age as a covariate revealed significant correlations for baseline psoas fat volume (r = -0.55, p < 0.01) and baseline psoas PDFF (r = -0.52, p = 0.02) with maximum BMI change during the course of the disease.

CONCLUSION: In erector spinae muscles, a regional variation of fat distribution at baseline and relative maximum change of muscle parameters was observed. Our results indicate that psoas muscle PDFF and fat volume could serve as MRI-determined biomarkers for early risk stratification and disease monitoring regarding progression and severity of weight loss in cancer cachexia.

RevDate: 2021-09-13

Cheung YC, Chen K, Yu CC, et al (2021)

Contrast-Enhanced Mammographic Features of In Situ and Invasive Ductal Carcinoma Manifesting Microcalcifications Only: Help to Predict Underestimation?.

Cancers, 13(17):.

BACKGROUND: The contrast-enhanced mammographic features of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) manifesting microcalcifications only on mammograms were evaluated to determine whether they could predict IDC underestimation.

METHODS: We reviewed patients who underwent mammography-guided biopsy on suspicious breast microcalcifications only and received contrast-enhanced spectral mammography (CESM) within 2 weeks before the biopsy. Those patients who were proven to have cancers (DCIS or IDC) by biopsy and subsequently had surgical treatment in our hospital were included for analysis. The presence or absence, size, morphology and texture of enhancement on contrast-enhanced spectral mammography were reviewed by consensus of two radiologists.

RESULTS: A total of 49 patients were included for analysis. Forty patients (81.6%) showed enhancement, including 18 (45%) DCIS and 22 (55%) IDC patients. All nine unenhanced cancers were pure DCIS. Pure DCIS showed 72.22% nonmass enhancement and 83.33% pure ground glass enhancement. IDC showed more mass (72.2% vs. 27.8%) and solid enhancements (83.33% vs. 16.67%). The cancer and texture of enhancement were significantly different between pure DCIS and IDC, with moderate diagnostic performance for the former (p-value < 0.01, AUC = 0.66, sensitivity = 93%, specificity = 39%) and the latter (p-value < 0.01, AUC = 0.74, sensitivity = 65%, specificity = 83%). Otherwise, pure DCIS showed a significant difference in enhanced texture compared with upgraded IDC and IDC (p = 0.0226 and 0.0018, respectively).

CONCLUSIONS: Nonmass and pure ground glass enhancements were closely related to pure DCIS, and cases showing mass and unpurified solid enhancements should be suspected as IDC. Unenhanced DCIS with microcalcifications only has a low DCIS upgrade rate. The CESM-enhanced features could feasibly predict IDC underestimation.

RevDate: 2021-09-13

Gawin M, Kurczyk A, Niemiec J, et al (2021)

Intra-Tumor Heterogeneity Revealed by Mass Spectrometry Imaging Is Associated with the Prognosis of Breast Cancer.

Cancers, 13(17):.

Intra-tumor heterogeneity (ITH) results from the coexistence of genetically distinct cancer cell (sub)populations, their phenotypic plasticity, and the presence of heterotypic components of the tumor microenvironment (TME). Here we addressed the potential association between phenotypic ITH revealed by mass spectrometry imaging (MSI) and the prognosis of breast cancer. Tissue specimens resected from 59 patients treated radically due to the locally advanced HER2-positive invasive ductal carcinoma were included in the study. After the on-tissue trypsin digestion of cellular proteins, peptide maps of all cancer regions (about 380,000 spectra in total) were segmented by an unsupervised approach to reveal their intrinsic heterogeneity. A high degree of similarity between spectra was observed, which indicated the relative homogeneity of cancer regions. However, when the number and diversity of the detected clusters of spectra were analyzed, differences between patient groups were observed. It is noteworthy that a higher degree of heterogeneity was found in tumors from patients who remained disease-free during a 5-year follow-up (n = 38) compared to tumors from patients with progressive disease (distant metastases detected during the follow-up, n = 21). Interestingly, such differences were not observed between patients with a different status of regional lymph nodes, cancer grade, or expression of estrogen receptor at the time of the primary treatment. Subsequently, spectral components with different abundance in cancer regions were detected in patients with different outcomes, and their hypothetical identity was established by assignment to measured masses of tryptic peptides identified in corresponding tissue lysates. Such differentiating components were associated with proteins involved in immune regulation and hemostasis. Further, a positive correlation between the level of tumor-infiltrating lymphocytes and heterogeneity revealed by MSI was observed. We postulate that a higher heterogeneity of tumors with a better prognosis could reflect the presence of heterotypic components including infiltrating immune cells, that facilitated the response to treatment.

RevDate: 2021-09-09

Mikulincer M, PR Shaver (2021)

Enhancing the "broaden-and-build" cycle of attachment security as a means of overcoming prejudice, discrimination, and racism.

Attachment & human development [Epub ahead of print].

Attachment theory emphasizes both the importance of supportive relationship partners, beginning in infancy, for developing a sense of security, and the adaptive benefits of this sense. In this article, we consider bolstering the sense of attachment security as a means of reducing and overcoming prejudice, discrimination, and racism. We review basic concepts of attachment theory, focusing on what we call the broaden-and-build cycle of attachment security. We review studies showing that the sense of attachment security is associated with reduced prejudice and less discriminatory attitudes and behavior toward people outside one's own social or racial group. Finally, we propose theoretical ideas and research suggesting that attachment security can protect against the adverse psychological effects of others' acts of prejudice and discrimination toward oneself. We conclude that, despite large gaps in the research literature, attachment theory is a useful conceptual framework for understanding and combatting prejudice, discrimination, and racism.

RevDate: 2021-09-09

Eguchi Y, Yoshinaka H, Hayashi N, et al (2021)

Accessory breast cancer in the inframammary region: a case report and review of the literature.

Surgical case reports, 7(1):203.

BACKGROUND: Although a few cases of accessory breast cancer (ABC) have been reported, most were in the axillary region. We encountered an extremely rare case of ABC in the inframammary region (IMR).

CASE PRESENTATION: The patient was a 68-year-old postmenopausal woman who had noticed a congenital accessory nipple in her left IMR with slight, occasional discharge 20 years ago. Recently, she noticed a mass under the accessory nipple and visited a nearby clinic; fine-needle aspiration cytology of the mass revealed that it was malignant. She presented to our department 2 weeks after she had noticed the mass. Physical and imaging examinations showed an irregular tumor mass 1.7 × 1.4 × 1.0 cm in size connected to the accessory nipple beneath the left normal breast. Neither distant metastasis nor lymph node swelling was observed. Ultrasound-guided core needle biopsy revealed the mass to be invasive ductal carcinoma. We diagnosed her tumor as ABC in the left IMR; cT1cN0M0: stage IA. Curative wide resection with sentinel node biopsy was performed. Intraoperative evaluation of the frozen section revealed a hot and green ipsilateral axillary lymph node that was free from carcinoma; therefore, nodal dissection was avoided. Histopathological examination including immunochemical staining revealed that the tumor was invasive ductal carcinoma arising from the accessory breast tissue, scirrhous type, 1.7 × 1.4 × 1.0 cm in size, with a solid intraductal component. There was no lymphovascular infiltration, and the surgical margin was 1.5 cm or more. The tumor was estrogen and progesterone receptor-positive, Her2/neu-negative, and had a Ki-67 labeling index of 20%. There was no involvement of the three hot and/or green nodes. The final classification was pT1cN0(sn)M0: stage IA. Letrozole 2.5 mg/day will be administered for 5 years as adjuvant hormonal therapy.

CONCLUSIONS: A cutaneous and/or subcutaneous lesion except for proper breast tissue on the milk line, or mammary ridge from axilla to groin may be an accessory breast tissue. Its serial abnormalities must be worried malignant potential to ductal carcinoma which needs some imaging and pathological examinations for definitive diagnosis and appropriate treatment according to the usual orthotopic breast cancer without delay.

RevDate: 2021-09-11

Sazawal S, Ryckman KK, Das S, et al (2021)

Machine learning guided postnatal gestational age assessment using new-born screening metabolomic data in South Asia and sub-Saharan Africa.

BMC pregnancy and childbirth, 21(1):609.

BACKGROUND: Babies born early and/or small for gestational age in Low and Middle-income countries (LMICs) contribute substantially to global neonatal and infant mortality. Tracking this metric is critical at a population level for informed policy, advocacy, resources allocation and program evaluation and at an individual level for targeted care. Early prenatal ultrasound examination is not available in these settings, gestational age (GA) is estimated using new-born assessment, last menstrual period (LMP) recalls and birth weight, which are unreliable. Algorithms in developed settings, using metabolic screen data, provided GA estimates within 1-2 weeks of ultrasonography-based GA. We sought to leverage machine learning algorithms to improve accuracy and applicability of this approach to LMICs settings.

METHODS: This study uses data from AMANHI-ACT, a prospective pregnancy cohorts in Asia and Africa where early pregnancy ultrasonography estimated GA and birth weight are available and metabolite screening data in a subset of 1318 new-borns were also available. We utilized this opportunity to develop machine learning (ML) algorithms. Random Forest Regressor was used where data was randomly split into model-building and model-testing dataset. Mean absolute error (MAE) and root mean square error (RMSE) were used to evaluate performance. Bootstrap procedures were used to estimate confidence intervals (CI) for RMSE and MAE. For pre-term birth identification ROC analysis with bootstrap and exact estimation of CI for area under curve (AUC) were performed.

RESULTS: Overall model estimated GA had MAE of 5.2 days (95% CI 4.6-6.8), which was similar to performance in SGA, MAE 5.3 days (95% CI 4.6-6.2). GA was correctly estimated to within 1 week for 85.21% (95% CI 72.31-94.65). For preterm birth classification, AUC in ROC analysis was 98.1% (95% CI 96.0-99.0; p < 0.001). This model performed better than Iowa regression, AUC Difference 14.4% (95% CI 5-23.7; p = 0.002).

CONCLUSIONS: Machine learning algorithms and models applied to metabolomic gestational age dating offer a ladder of opportunity for providing accurate population-level gestational age estimates in LMICs settings. These findings also point to an opportunity for investigation of region-specific models, more focused feasible analyte models, and broad untargeted metabolome investigation.

RevDate: 2021-09-08

Kar H, Altindağ SD, Etit D, et al (2021)

Clinicopathological features of mammary Paget's Disease: A single center experience in Turkey.

Turkish journal of medical sciences [Epub ahead of print].

BACKGROUND/AIM: Paget?s disease (PD) of the breast is a very rare presentation of breast malignancy, accounting for 1?3% of all primary breast tumors. We aimed to evaluate and compare the clinicopathological featuresand clinical outcome of PD accompanied by in situ carcinoma and invasive cancer.

MATERIALS AND METHODS: We used the archive of our pathology laboratory retrospectively for age, gender, history of surgery, histopathological findings, treatment modalities and follow-up information. We used the Kaplan-Meier method for survival analysis.

RESULTS: There were 46 female patients diagnosed with PD. In 39 (84.7%) patients invasive carcinoma accompanied PD, while 7 (15.3%) patients had ductal carcinoma in situ (DCIS). The median age at diagnosis was 53.5 years. The median follow-up period was 47 months. Of the 39 invasive carcinoma 10 (25.6%) died during the follow-up period. Invasive ductal carcinoma group had a mean overall survival of rate of 57.8 ± 6.6 months. According to univariate analysis only the tumor type was found to impact overall survival (p < 0.001) Conclusions: The current study displayed the tumor type as the only parameter affecting overall survival in the invasive carcinoma group. Although it was not statistically significant, breast cancers accompanied by PD were found to be predominantly advanced stage tumors, high grade, hormon receptor negative and HER2 positive. Key words: Paget?s disease, breast carcinoma, pathology, molecular subtype, immunohistochemistry.

RevDate: 2021-09-07

Scheiber D, Zweck E, Albermann S, et al (2021)

Human myocardial mitochondrial oxidative capacity is impaired in mild acute heart transplant rejection.

ESC heart failure [Epub ahead of print].

AIMS: Acute cellular rejection (ACR) following heart transplantation (HTX) is associated with long-term graft loss and increased mortality. Disturbed mitochondrial bioenergetics have been identified as pathophysiological drivers in heart failure, but their role in ACR remains unclear. We aimed to prove functional disturbances of myocardial bioenergetics in human heart transplant recipients with mild ACR by assessing myocardial mitochondrial respiration using high-resolution respirometry, digital image analysis of myocardial inflammatory cell infiltration, and clinical assessment of HTX patients. We hypothesized that (i) mild ACR is associated with impaired myocardial mitochondrial respiration and (ii) myocardial inflammation, systemic oxidative stress, and myocardial oedema relate to impaired mitochondrial respiration and myocardial dysfunction.

METHODS AND RESULTS: We classified 35 HTX recipients undergoing endomyocardial biopsy according International Society for Heart and Lung Transplantation criteria to have no (0R) or mild (1R) ACR. Additionally, we quantified immune cell infiltration by immunohistochemistry and digital image analysis. We analysed mitochondrial substrate utilization in myocardial fibres by high-resolution respirometry and performed cardiovascular magnetic resonance (CMR). ACR (1R) was diagnosed in 12 patients (34%), while the remaining 23 patients revealed no signs of ACR (0R). Underlying cardiomyopathies (dilated cardiomyopathy 50% vs. 65%; P = 0.77), comorbidities (type 2 diabetes mellitus: 50% vs. 35%, P = 0.57; chronic kidney disease stage 5: 8% vs. 9%, P > 0.99; arterial hypertension: 59% vs. 30%, P = 0.35), medications (tacrolimus: 100% vs. 91%, P = 0.54; mycophenolate mofetil: 92% vs. 91%, P > 0.99; prednisolone: 92% vs. 96%, P > 0.99) and time post-transplantation (21.5 ± 26.0 months vs. 29.4 ± 26.4 months, P = 0.40) were similar between groups. Mitochondrial respiration was reduced by 40% in ACR (1R) compared with ACR (0R) (77.8 ± 23.0 vs. 128.0 ± 33.0; P < 0.0001). Quantitative assessment of myocardial CD3+ -lymphocyte infiltration identified ACR (1R) with a cut-off of >14 CD3+ -lymphocytes/mm2 (100% sensitivity, 82% specificity; P < 0.0001). Myocardial CD3+ infiltration (r = -0.41, P < 0.05), systemic oxidative stress (thiobarbituric acid reactive substances; r = -0.42, P < 0.01) and myocardial oedema depicted by global CMR derived T2 time (r = -0.62, P < 0.01) correlated with lower oxidative capacity and overt cardiac dysfunction (global longitudinal strain; r = -0.63, P < 0.01).

CONCLUSIONS: Mild ACR with inflammatory cell infiltration associates with impaired mitochondrial bioenergetics in cardiomyocytes. Our findings may help to identify novel checkpoints in cardiac immune metabolism as potential therapeutic targets in post-transplant care.

RevDate: 2021-09-04

Peila R, Xue X, Cauley JA, et al (2021)

A Randomized Trial of Calcium Plus Vitamin D Supplementation and Risk of Ductal Carcinoma In Situ of the Breast.

JNCI cancer spectrum, 5(4):pkab072.

Background: The effect of calcium plus vitamin D (CaD) supplementation on risk of ductal carcinoma in situ (DCIS) of the breast, a nonobligate precursor of invasive ductal carcinoma, is not well understood. In this secondary analysis, we examined this association in the Women's Health Initiative CaD trial over approximately 20 years of follow-up.

Methods: A total of 36 282 cancer-free postmenopausal women (50-79 years) were randomly assigned to daily (d) calcium (1000 mg) plus vitamin D (400 IU) supplementation or to a placebo. Personal supplementation with vitamin D (≤600 IU/d, subsequently raised to 1000 IU/d) and calcium (≤1000 mg/d) was allowed. The intervention phase (median = 7.1 years), was followed by a postintervention phase (additional 13.8 years), which included 86.0% of the surviving women. A total of 595 incident DCIS cases were ascertained. Hazard ratios (HRs) plus 95% confidence intervals (CIs) were calculated.

Results: The intervention group had a lower risk of DCIS throughout follow-up (HR = 0.82, 95% CI = 0.70 to 0.96) and during the postintervention phase (HR = 0.76, 95% CI = 0.61 to 0.94). The group that used CaD personal supplements in combination with the trial intervention had a lower risk of DCIS compared with the trial placebo group that did not use personal supplementation (HR = 0.72, 95% CI = 0.56 to 0.91).

Conclusions: CaD supplementation in postmenopausal women was associated with reduced risk of DCIS, raising the possibility that consistent use of these supplements might provide long-term benefits for the prevention of DCIS.

RevDate: 2021-09-10
CmpDate: 2021-09-10

Watanabe J, Nakamoto S, T Sugino (2021)

The Real-world Outcomes of Patients With Advanced Invasive Lobular Carcinoma of the Breast Compared With Invasive Ductal Carcinoma: A Review at a Single Institution.

Anticancer research, 41(9):4619-4627.

BACKGROUND: The real-world outcomes of patients with advanced invasive lobular carcinoma (ILC) of the breast are unclear because of its rarity.

PATIENTS AND METHODS: We identified 435 patients with estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced breast cancer treated at our Institute between 2002 and 2019, and analyzed their outcomes retrospectively.

RESULTS: We identified 29 patients with advanced ILC. At presentation, they had a lower rate of lung metastasis (p=0.0053) but a higher rate of stomach metastasis (p=0.0379) compared with other patients with advanced breast cancer. Median overall survival did not differ; however, multivariate analyses showed that ILC histopathology was a risk factor for poorer overall survival (hazard ratio=3.43, p=0.0038) in patients with de novo stage IV ER+ HER2- breast cancer. Patients with ILC showed a markedly different patten of subsequent metastasis, such as less in the lung and more in the stomach, leptomeninges, and bone marrow.

CONCLUSION: According to our retrospective study, in patients with de novo stage IV ER+ HER2- breast cancer, ILC histopathology was associated with increased risk of death.

RevDate: 2021-09-02

Guo F, Yi Z, Wang W, et al (2021)

Profile, treatment patterns, and influencing factors of anthracycline use in breast cancer patients in China: A nation-wide multicenter study.

Cancer medicine [Epub ahead of print].

BACKGROUND: Anthracycline-based chemotherapy (ABC) is one of the standard therapies against breast cancer. However, few guidelines are currently available to optimize the use of ABC. Therefore, the present analysis aimed at determining the profile and treatment patterns of ABC and the association of clinicopathological characteristics with ABC selection.

METHODS: We retrospectively analyzed the data of a nation-wide multicenter epidemiological study, which collected the medical records of breast cancer patients receiving chemotherapy in different settings from seven geographic regions in China (NCT03047889).

RESULTS: In total, 3393 patients were included, with 2917 treated with ABC. Among them, 553 (89.8%), 2165 (81.7%), and 814 (25.7%) were subjected to ABC as neoadjuvant, adjuvant, and advanced chemotherapy, respectively. The most frequently used regimens were anthracycline-taxane-based combinations for neo- and adjuvant chemotherapy, along with taxanes and oral fluorouracils for the palliative stages. In the overall cohort, patients aged < 40 or 40-65 (p < 0.001), in premenopause (p < 0.001), without comorbidities (p = 0.016), with invasive ductal carcinoma (p= 0.001), high lymph node involvement (p < 0.001), in the pTNM stage II, III, or IV versus stage I (p < 0.001), subjected to mastectomy (p < 0.001) or subjected to sentinel lymph node biopsy combined with axillary lymph node dissection (p = 0.044), or with a decreased disease-free survival (p < 0.001) were more likely to be recommended to ABC.

CONCLUSION: Taken together, ABC remained the mainstay of breast cancer treatment, especially in neo and adjuvant therapy. ABC was mainly used as a combination therapy, and the correlation between influencing factors and ABC choice varied during different settings, indicating the preference and different perspectives of medication considered by medical oncologists regarding the use ABC in China.

RevDate: 2021-09-09
CmpDate: 2021-09-09

Zingue S, Atenguena EO, Zingue LL, et al (2021)

Epidemiological and clinical profile, and survival of patients followed for breast cancer between 2010 and 2015 at the Yaounde General Hospital, Cameroon.

The Pan African medical journal, 39:182.

Introduction: approximately 6000 Cameroonian women died of cancer in 2018, and the breast is the most affected with 2625 new cases. The aim of this study was to establish a pattern of malignant breast tumours in Yaoundé (Cameroon).

Methods: this study was a descriptive and analytical retrospective study of breast cancer between January 2010 and December 2015 in Yaoundé General Hospital (YGH) after the Institutional ethics committee approval. The variables studied were the socio-demographic characteristics, risk factors for breast cancer, types of tumours and type of treatments. The 5-year survival was analyzed by the Kaplan-Meier method. The adjusted hazard ratios and their 95% confidence intervals were calculated to assess the association between studied variables and patient survival through the cox regression using SPSS 23 software. The difference was considered significant at p < 0.05.

Results: among the 344 files collected in this study, breast cancer patients were predominantly female (96.64%, n = 288) aged 45.39 ± 13.35 years, with invasive ductal carcinoma (68.03%, n = 270), located in the left breast (52%, n= 147). The average tumour size was ~6.5 ± 0.3 cm and diagnosed in grade II of Scarf Bloom Richardson (SBR) in 60% (n= 150) of cases. The 5-year survival was 43.3%. Factors associated with this poor survival were the religion (aHR 5.05, 95% CI: 1.57 - 16.25; p = 0.007 for animist and aHR 4.2, 95% CI: 1.53 - 11.46; p = 0.005 for protestant), location of the tumour (aHR 6.24, 95% CI: 1.58 - 24.60; p = 0.012), tumor height (aHR 0.21, 95% CI: 0.04 - 1.11; p = 0.011) and the time spent before medical treatment (aHR 5.12, 95% CI: 0.39 - 8.38; p = 0.011).

Conclusion: the young age, large tumour size and high histological grade in our studied population suggest a weak awareness of women about breast cancer. Action should be taken in early screening to improve the management of breast cancer in Cameroon.

RevDate: 2021-09-02
CmpDate: 2021-09-02

Jesenková A, Mergancová J, Mergancová J, et al (2021)

Phyllodes tumor and its malignization into invasive ductal carcinoma a case report.

Rozhledy v chirurgii : mesicnik Ceskoslovenske chirurgicke spolecnosti, 100(6):295-301.

INTRODUCTION: Phyllodes tumors of the breast are rare and very distinct types of mammary neoplasms. They are characterized by their biphasicity, i.e. the presence of stromal and epithelial components at the same time. Malignancy is determined by the degree of stromal differentiation. The coexistence of the malignant epithelial component is a very rare phenomenon. Dozens of cases of simultaneous phyllodes tumor and epithelial malignancy have been reported so far. Nevertheless, the biological nature of this process is still an unexplained and a controversial topic.

CASE REPORT: In this paper, we present a case of a patient with a suddenly enlarging lesion in the breast. According to the first surgical resection, a diagnosis of high-grade malignant phyllodes tumor was made with fibrosarcoma differentiation, stromal overgrowth and suppression of the epithelial component. Examination of scar resistence in early postoperative period revealed a triple-negative invasive low-differentiated breast carcinoma with very high proliferative activity, thus malignization of the epithelial component of the tumor occurred. Shortly, a diagnosis of second recurrence was made, treatment included axillary lymph node dissection (ALND) with a negative histological findings. The patient underwent complex adjuvant chemotherapy and radiotherapy and remained disease free 3 years after the surgery.

CONCLUSION: Coexistence of phyllodes tumor and the breast carcinoma is very rare. The article describes the first published case, which documents the subsequent development of invasive low-differentiated ductal carcinoma immediately after resection of high-grade phyllodes tumor. Treatment and prognosis are generally determined by the characteristics of the carcinomatous component.

RevDate: 2021-09-14

Meng J, Yang Q, Wan W, et al (2021)

Physicochemical properties and adaptability of amine-producing Enterobacteriaceae isolated from traditional Chinese fermented fish (Suan yu).

Food chemistry, 369:130885 pii:S0308-8146(21)01891-4 [Epub ahead of print].

The formation of biogenic amines (BAs) is an important potential danger in traditional fermented fish (Suan yu), and Enterobacteriaceae play an important role in the formation of BAs. The amine production abilities of 97 strains of Enterobacteriaceae screened from traditional fermented Suan yu were analyzed by reversed-phased high-performance liquid chromatography (HPLC). The genotypic diversity of amino acid decarboxylase on 23 strains of high-yield BAs was verified by PCR. Enterobacteriaceae with the highest production of amines was determined by analysis of the effects of physicochemical factors (pH, NaCl, temperature, and aerobic/anaerobic) on BA production and principal component analysis (PCA). The adaptability of the strains was examined using surimi simulation fermentation system, and the correlations among the indicators were analyzed using Cytoscape. Results showed that 97 strains of Enterobacteriaceae had strong amine-producing ability. Furthermore, 23 strains producing high yields of putrescine, cadaverine, and histamine were identified. All of the strains carried Idc, odc, speA, speB, and adiA, and five strains carried hdc. pH mainly affected the BA production of amine-producing bacteria. Three strains (Enterobacter asburiae 26C3, Klebsiella pneumoniae 47C2, and Morganella morganii 45C3) had the best amine-producing ability and used as the inoculated group. In this group, the values of BA (228.70-290.05 mg/kg) and the total volatile base nitrogen (TVB-N, 173.87-221.87 mg/100 g) exceeded the limit. Moreover, myofibrillar protein degradation was significant as indicated by the sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis and decreased FAA content. Cytoscape software and principal component analysis (PCA) indicated that Enterobacteriaceae and pH were related to BA formation in Suan yu. These results provide a theoretical basis for controlling the BA of fermented fish products.

RevDate: 2021-09-04

Ghalkhani E, Akbari MT, Izadi P, et al (2021)

Assessment of DAPK1 and CAVIN3 Gene Promoter Methylation in Breast Invasive Ductal Carcinoma and Metastasis.

Cell journal, 23(4):397-405.

Objective: Metastasis might be latent or occur several years after primary tumor removal. Currently used methods for detection of distant metastasis have still some limitations. Blood tests may improve sensitivity and specificity of currently used screening procedures. The present study was designed to investigate promoter methylation status of DAPK1 and CAVIN3 genes in plasma circulating free DNA (cfDNA) samples in Iranian invasive ductal carcinoma (IDC) patients. We also investigated association of two gene promoter methylations with breast cancer (BC) and metastatic BC was also assessed.

Materials and Methods: In this case-control study, MethySYBR assay was performed to determine DAPK1 and CAVIN3 promoter methylation status in breast IDC from 90 patients and 30 controls. Based on clinicopathological information, patient samples subdivided into stage I, II/III and IV groups (each group contained 30 individuals).

Results: According to the results an increased promoter methylation level of the DAPK1 gene in BC patients was observed. It was found that as disease progressed, the percentage of methylation was changed while it was not significant. Methylation changes in metastatic and non-metastatic BC revealed that methylation levels were significantly increased in metastatic than non-metastatic group. Analysis revealed that promoter methylation of CAVIN3 gene in BC patients was significantly increased. The observed methylation changes from less to more invasive stages were not significant in the CAVIN3 gene. Moreover, promoter methylation was changed in metastatic rather than non-metastatic condition, although it was not significant.

Conclusion: Promoter hypermethylation of c and CAVIN3 genes in plasma are associated with the risk of BC and they can be potential diagnostic biomarkers along with current methods. Additionally, association of aberrant DAPK1 promoter methylation with metastasis suggests its potential usage as a non-invasive strategy for metastatic BC diagnosis.

RevDate: 2021-08-30

Ameli F, Ghafourina Nassab F, Masir N, et al (2021)

Tumor-Derived Matrix Metalloproteinase-13 (MMP-13) Expression in Benign and Malignant Breast Lesions.

Asian Pacific journal of cancer prevention : APJCP, 22(8):2603-2609.

INTRODUCTION: Breast carcinoma is the most common malignancy and the leading cause of cancer death in women. Matrix metalloproteinase-13 (MMP-13) is a hypothetical prognostic marker in invasive breast cancer. This study aimed to determine MMP-13 expression in benign and malignant breast lesions and to evaluate the correlation between MMP-13 expression and tumor characteristics in invasive ductal carcinoma (IDC).

MATERIALS AND METHOD: We evaluated cytoplasmic expression of MMP-13 based on staining index using immunohistochemistry (IHC) in epithelial cells, stromal fibroblasts of IDC (n=90) and benign epithelial breast (n=90) lesions. Correlation between IHC and tumor size, lymph node status, distance metastasis, estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu was assessed.

RESULTS: MMP-13 expression was 45% and 38.8% in malignant epithelial cells and peritumoral fibroblasts, respectively. Only low level of MMP-13 expression was seen in benign breast lesions (8.8% in epithelial component and 2.2% in stromal fibroblasts), while high level of MMP-13 expression was noted in malignant tumors, mainly grade II or III. Cytoplasmic MMP-13 expressions in epithelial tumor cells was correlated significantly with peritumoral fibroblasts. MMP-13 expression was directly correlated with distant metastasis and tumor stage in epithelial tumoral cells and was inversely correlated with progesterone expression in both tumoral and stromal cells.

CONCLUSION: This study showed that MMP-13 was a moderator for tumor invasion and metastasis and could be an independent predictor of poor prognosis in breast cancer. The role of MMP-13 in predicting the risk of malignant transformation in benign lesions should be further investigated.

RevDate: 2021-09-22

Zhang J, Chang CL, Lu CY, et al (2021)

Paravertebral block in regional anesthesia with propofol sedation reduces locoregional recurrence in patients with breast cancer receiving breast conservative surgery compared with volatile inhalational without propofol in general anesthesia.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 142:111991.

PURPOSE: We examined locoregional recurrence (LRR) in patients with breast invasive ductal carcinoma (IDC) receiving breast conservative surgery (BCS) under propofol-based paravertebral block-regional anesthesia (PB-RA) versus sevoflurane-based inhalational general anesthesia (INHA-GA) without propofol. All-cause death and distant metastasis were secondary endpoints.

PATIENTS AND METHODS: Patients with breast IDC receiving BCS were recruited through propensity score matching and categorized into INHA-GA with sevoflurane and PB-RA with propofol groups. Cox regression analysis was performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS: In the multivariate Cox regression analysis, the adjusted HR (aHR; 95% CI) of LRR for the PB-RA with propofol group was 0.67 (0.46-0.99) compared with the INHA-GA with sevoflurane group. The aHRs of LRR for differentiation grade II, grade III, the American Joint Committee on Cancer clinical stage II, stage III, pathological tumor (pT) stage 2, pT stage 3-4, pathological nodal (pN) stage 2-3, and Her-2 positivity were 1.87 (1.03-3.42), 2.31 (1.20-4.44), 1.67 (1.09-2.56), 2.43 (1.18-4.97), 1.17 (1.03-1.19), 1.28 (1.13-2.24), 1.20 (1.05-2.22), and 1.59 (1.01-2.51), respectively, compared with those for differentiation grade I, clinical stage I, pT1, pN0, and HER-2 negativity. The aHR of LRR for adjuvant radiotherapy was 0.60 (0.38-0.97) compared with that for no adjuvant radiotherapy.

CONCLUSION: PB-RA with propofol might be beneficial for reducing LRR in women with breast IDC receiving BCS compared with INHA-GA without propofol.

RevDate: 2021-09-15

Jimbo H, Horimoto Y, Okazaki M, et al (2021)

Drug-induced aortitis of the subclavian artery caused by pegfilgrastim: a case report.

Surgical case reports, 7(1):197.

BACKGROUND: Pegfilgrastim is a modified version of granulocyte-colony stimulating factor (G-CSF), with a polyethylene glycol (PEG) that prolongs its half-life in peripheral blood. It is prophylactically administered during chemotherapy to prevent severe febrile neutropenia. G-CSF-related aortitis is a rare side effect but reports of this disease have been increasing in recent years, probably due to PEGylation. Herein, we report a case who developed pegfilgrastim-induced aortitis, localized to the right subclavian artery, during adjuvant chemotherapy. Her condition recovered without the use of steroids.

CASE PRESENTATION: A 58-year-old woman was diagnosed with invasive ductal carcinoma of the left breast. She had a medical history of contralateral breast cancer and pyelonephritis. Following curative surgery for her left breast cancer, she received adjuvant chemotherapy. Two days after the first course of dose-dense paclitaxel, pegfilgrastim was used as planned. Eight days after the administration of pegfilgrastim, she developed a high fever of 38 °C and visited the emergency outpatient clinic 3 days after. Blood tests revealed an increased inflammatory response, and contrast-enhanced computed tomography (CT) revealed a wall thickening of the subclavian artery, suggesting aortitis caused by pegfilgrastim. She was hospitalized on day 15 when CRP increased to 21.5 mg/dL and the high fever continued. Blood and urine culture tests were negative throughout. Pegfilgrastim-induced aortitis was suspected and she was observed without the use of steroids. Seven days later, her fever abated. A contrast-enhanced CT scan on day 26 showed the subclavian artery wall thickening had disappeared. The patient continues to be afebrile and is currently on weekly paclitaxel without use of G-CSF.

CONCLUSIONS: The onset of this disease is known to usually occur within 2 weeks after the first pegfilgrastim administration. Aortitis localized to the subclavian artery is relatively rare with the most frequent site being the aortic arch. Clinicians should be aware of the timing and location of onset of this disease.

RevDate: 2021-08-31

Mandapathil M, Szczepanski MJ, Jackson EK, et al (2021)

Breast Cancer Cell-Derived Adenosine Enhances Generation and Suppressor Function of Human Adaptive Regulatory T Cells.

Journal of personalized medicine, 11(8):.

INTRODUCTION: Adaptive regulatory T cells (Tr1) are induced in the periphery by environmental stimuli. CD73 expression and adenosine (ADO) production by tumor cells may influence Tr1 generation and their immunosuppressive activity.

MATERIAL AND METHODS: Tr1 were generated in co-cultures of CD4+CD25neg T cells, autologous immature dendritic cells (iDC), and irradiated ADO-producing CD73+ or non-producing CD73neg breast cancer (BrCa) cell lines (TU). The expression of ectonucleotidases and other surface markers on Tr1 was determined by flow cytometry. Tr1-mediated suppression of proliferation was evaluated in CFSE-based assays. Luciferase-based ATP detection assays and mass spectrometry were used to measure ATP hydrolysis and ADO levels. Cytokine levels were measured by ELISA or Luminex. CD73 expression on tumor cells or T cells in TU tissues was assessed by immunofluorescence.

RESULTS: CD73+ TU induced higher numbers of Tr1 cells (p < 0.01) than CD73neg TU. Tr1TU73+ hydrolyzed more exogenous ATP, produced more ADO, and mediated higher suppression than Tr1TU73neg (p < 0.05 for all). ARL67156, an ectonucleotidase inhibitor, and ZM241385, A2A receptor antagonist, reduced suppression of proliferation mediated by Tr1TU73+ cells (p < 0.01). Basal-like primary BrCa cells expressed higher levels of ectonucleotidases and induced more Tr1 than less aggressive primary luminal-like BrCa.

CONCLUSION: BrCa producing ADO (CD73+ TU) favor the induction of Tr1, which expresses CD39 and CD73, hydrolyzes ATP to ADO, and effectively suppresses anti-tumor immunity.

RevDate: 2021-08-30

Kwong A, Shin VY, Ho CYS, et al (2021)

Germline PALB2 Mutation in High-Risk Chinese Breast and/or Ovarian Cancer Patients.

Cancers, 13(16):.

The prevalence of the PALB2 mutation in breast cancer varies across different ethnic groups; hence, it is of intense interest to evaluate the cancer risk and clinical association of the PALB2 mutation in Chinese breast and/or ovarian cancer patients. We performed sequencing with a 6-gene test panel (BRCA1, BRCA2, TP53, PTEN, PALB2, and CDH1) to identify the prevalence of the PALB2 germline mutation among 2631 patients with breast and/or ovarian cancer. In this cohort, 39 mutations were identified with 24 types of mutation variants, where the majority of the mutations were frame-shift mutations and resulted in early termination. We also identified seven novel PALB2 mutations. Most of the PALB2 mutation carriers had breast cancer (36, 92.3%) and were more likely to have family history of breast cancer (19, 48.7%). The majority of the breast tumors were invasive ductal carcinoma (NOS type) (34, 81.0%) and hormonal positive (ER: 32, 84.2%; PR: 23, 60.5%). Pathogenic mutations of PALB2 were found in 39 probands with a mutation frequency of 1.6% and 1% in breast cancer and ovarian cancer patients, respectively. PALB2 mutation carriers were more likely have hormonal positive tumors and were likely to have familial aggregation of breast cancer.

RevDate: 2021-08-29

Shulman D, Shnitzer-Akuka M, M Reifen-Tagar (2021)

The cost of attributing moral blame: Defensiveness and resistance to change when raising awareness to animal suffering in factory farming.

PloS one, 16(8):e0254375.

Social change campaigns often entail raising awareness of harm caused by people's behavior. For example, campaigns to reduce meat eating frequently highlight the suffering endured by animals. Such messages may simultaneously attribute moral blame to individuals for causing the harm described. Given people's motivation to protect their moral self-image, we expected that information about the suffering of animals in the meat industry presented with a blaming (versus absolving) frame would generate greater defensiveness and correspondingly resistance to change in support of veg*nism (veganism/vegetarianism). We ran three studies to test this expectation. In two studies, we found that raising awareness of animal suffering using a blaming frame increased defensiveness, leading to lower veg*n-supporting attitudes and behavioral intentions. In one study, our hypothesis was not supported, however, a mini-meta analysis across the three studies suggests the overall pattern is robust. This work expands our understanding of the role of moral self-image preservation in defensiveness and resistance to change, and has applied relevance for the development of effective communication strategies in social and moral campaigns.

RevDate: 2021-08-26

Elboga U, Sahin E, Kus T, et al (2021)

Superiority of 68Ga-FAPI PET/CT scan in detecting additional lesions compared to 18FDG PET/CT scan in breast cancer.

Annals of nuclear medicine [Epub ahead of print].

PURPOSE: We compared the ability of 68Ga-FAPI PET//CT with 18FDG PET/CT imaging techniques to detect additional lesions in breast cancer patients that may affect further chemotherapy options.

METHODS: A total of 48 patients with breast cancer underwent concurrent 68Ga-FAPI-04 and 18FDG PET/CT regardless of whether they had received chemotherapy or not in the last month before imaging. Both modalities were compared according to various parameters: clinical/pathological features, number of lesions detected, activity uptake (SUVmax), and the effect on the evaluation of response to treatment in the post-chemotherapy group.

RESULTS: This retrospective study included 48 patients with breast cancer (mean age 53.3 ± 11.7 years; IDC 89.6%; ILC 10.4%). In the comparison of both modalities, no statistical significance was obtained in terms of the pathological characteristics of the patients. More lesions were demonstrated in all categorized regions in 68Ga-FAPI PET/CT imaging with higher uptake values compared to 18FDG PET/CT in this study. In the treatment response evaluation of the post-chemotherapy group, 12 cases (12/24) who were evaluated as PMR, CMR, or SD according to 18FDG PET/CT results were later accepted as PD due to newly detected lesions in complementary 68Ga-FAPI PET/CT imaging and treatment of patients was managed accordingly by clinicians.

CONCLUSION: It was determined that 68Ga-FAPI PET/CT was superior to 18FDG PET/CT in terms of accuracy and it was thought that 68Ga-FAPI PET/CT could be utilized as an additional complementary imaging to 18FDG PET/CT. Moreover, 68Ga-FAPI PET/CT, with its significant theranostic potential, could become a key element in predicting the pathological response of breast cancer patients in further researches.

RevDate: 2021-09-23

Wang Z, Zhu S, Zhao J, et al (2021)

The heterogeneity of intraductal carcinoma of the prostate is associated with different efficacy of standard first-line therapy for patients with metastatic castration-resistant prostate cancer.

The Prostate, 81(15):1191-1201.

BACKGROUND: To explore whether metastatic castration-resistant prostate cancer (mCRPC) patients with distinct intraductal carcinoma of the prostate (IDC-P) subtypes respond differently to abiraterone and docetaxel treatment.

METHODS: We retrospectively analyzed data of 170 mCRPC patients receiving abiraterone or docetaxel as first-line therapy. PSA response, PSA progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed based on the presence of IDC-P and its subpatterns.

RESULTS: IDC-P was confirmed in 91/170 (53.5%) patients. Among them 36/91 (39.6%) and 55/91 (60.4%) harbored IDC-P patterns 1 and 2, respectively. Patients with IDC-P pattern 1 shared similar clinical outcomes to those without IDC-P in both abiraterone and docetaxel treatment. However, against cases without IDC-P or with IDC-P pattern 1, patients with IDC-P pattern 2 had markedly poorer prognosis in either abiraterone (mPSA-PFS: 11.9 vs. 11.1 vs. 6.1 months, p < 0.001; mrPFS: 18.9 vs. 19.4 vs. 9.6 months, p < 0.001) or docetaxel (mPSA-PFS: 6.2 vs. 6.6 vs. 3.0 months, p < 0.001; mrPFS: 15.1 vs. 12.6 vs. 5.5 months, p < 0.001) treatment. For patients without IDC-P, docetaxel had comparable therapeutic efficacy with abiraterone. However, the efficacy of docetaxel was significantly inferior to abiraterone in patients with either IDC-P pattern 1 (mPSA-PFS: 6.6 vs. 11.1 months, p = 0.021; mrPFS: 12.6 vs. 19.4 months, p = 0.027) or pattern 2 (mPSA-PFS: 3.0 vs. 6.1 months, p = 0.003; mrPFS: 5.5 vs. 9.6 months, p = 0.007).

CONCLUSION: Compared to docetaxel, abiraterone exhibited better efficacy in patients with IDC-P of either pattern. However, IDC-P pattern 2 responded unsatisfactorily to either abiraterone or docetaxel therapy. Novel therapeutic strategies for IDC-P pattern 2 need further investigations.

RevDate: 2021-09-23
CmpDate: 2021-08-26

Pauliuk S, Heeren N, Berrill P, et al (2021)

Global scenarios of resource and emission savings from material efficiency in residential buildings and cars.

Nature communications, 12(1):5097.

Material production accounts for a quarter of global greenhouse gas (GHG) emissions. Resource-efficiency and circular-economy strategies, both industry and demand-focused, promise emission reductions through reducing material use, but detailed assessments of their GHG reduction potential are lacking. We present a global-scale analysis of material efficiency for passenger vehicles and residential buildings. We estimate future changes in material flows and energy use due to increased yields, light design, material substitution, extended service life, and increased service efficiency, reuse, and recycling. Together, these strategies can reduce cumulative global GHG emissions until 2050 by 20-52 Gt CO2-eq (residential buildings) and 13-26 Gt CO2e-eq (passenger vehicles), depending on policy assumptions. Next to energy efficiency and low-carbon energy supply, material efficiency is the third pillar of deep decarbonization for these sectors. For residential buildings, wood construction and reduced floorspace show the highest potential. For passenger vehicles, it is ride sharing and car sharing.

RevDate: 2021-08-25

Morigny P, Kaltenecker D, Zuber J, et al (2021)

Association of circulating PLA2G7 levels with cancer cachexia and assessment of darapladib as a therapy.

Journal of cachexia, sarcopenia and muscle [Epub ahead of print].

BACKGROUND: Cancer cachexia (CCx) is a multifactorial wasting disorder characterized by involuntary loss of body weight that affects many cancer patients and implies a poor prognosis, reducing both tolerance to and efficiency of anticancer therapies. Actual challenges in management of CCx remain in the identification of tumour-derived and host-derived mediators involved in systemic inflammation and tissue wasting and in the discovery of biomarkers that would allow for an earlier and personalized care of cancer patients. The aim of this study was to identify new markers of CCx across different species and tumour entities.

METHODS: Quantitative secretome analysis was performed to identify specific factors characteristic of cachexia-inducing cancer cell lines. To establish the subsequently identified phospholipase PLA2G7 as a marker of CCx, plasma PLA2G7 activity and/or protein levels were measured in well-established mouse models of CCx and in different cohorts of weight-stable and weight-losing cancer patients with different tumour entities. Genetic PLA2G7 knock-down in tumours and pharmacological treatment using the well-studied PLA2G7 inhibitor darapladib were performed to assess its implication in the pathogenesis of CCx in C26 tumour-bearing mice.

RESULTS: High expression and secretion of PLA2G7 were hallmarks of cachexia-inducing cancer cell lines. Circulating PLA2G7 activity was increased in different mouse models of CCx with various tumour entities and was associated with the severity of body wasting. Circulating PLA2G7 levels gradually rose during cachexia development. Genetic PLA2G7 knock-down in C26 tumours only partially reduced plasma PLA2G7 levels, suggesting that the host is also an important contributor. Chronic treatment with darapladib was not sufficient to counteract inflammation and tissue wasting despite a strong inhibition of the circulating PLA2G7 activity. Importantly, PLA2G7 levels were also increased in colorectal and pancreatic cancer patients with CCx.

CONCLUSIONS: Overall, our data show that despite no immediate pathogenic role, at least when targeted as a single entity, PLA2G7 is a consistent marker of CCx in both mice and humans. The early increase in circulating PLA2G7 levels in pre-cachectic mice supports future prospective studies to assess its potential as biomarker for cancer patients.

RevDate: 2021-09-15

Aftab F, Ahmed S, Ali SM, et al (2021)

Cohort Profile: The Alliance for Maternal and Newborn Health Improvement (AMANHI) biobanking study.

International journal of epidemiology pii:6356791 [Epub ahead of print].

RevDate: 2021-09-13

Yun NK, Slostad JA, Naqib A, et al (2021)

Histologic Discordance Between Primary Tumor and Nodal Metastasis in Breast Cancer: Solving a Clinical Conundrum in the Era of Genomics.

The oncologist [Epub ahead of print].

Next-generation sequencing (NGS) technologies have become increasingly used for managing breast cancer. In addition to the conventional use of NGS for predicting recurrence risk and identifying potential actionable mutations, NGS can also serve as a powerful tool to understand clonal origin and evolution of tumor pairs and play a unique role in clarifying complex clinical presentations. We report an unusual case of early-stage breast cancer in which the primary tumor and draining axillary node were histologically discordant. The primary tumor was invasive lobular carcinoma, whereas the nodal metastasis was invasive ductal carcinoma. This discordance led us to question whether the tumors had the same origin. NGS performed on both specimens identified no overlapping variants, leading us to conclude that the patient had two separate primary breast cancers, with the nodal tumor representing metastasis from an occult breast cancer. DNA sequencing of the primary tumor and the nodal metastasis allowed us to predict the patient's recurrence risk, and we initiated adjuvant chemotherapy and hormonal therapy based on these results. This case illustrates the utility of NGS for successfully managing a rare and challenging case. KEY POINTS: A degree of molecular concordance is expected for tumors originating from a common stem or progenitor cell. The histological discordance and absence of any genomic overlap should raise suspicion for two separate primary tumors. Paired DNA sequencing of the primary tumor and nodal metastasis can inform clinical decisions when primary breast tumor and axillary metastasis are histologically discordant. Molecular/Precision Oncology Tumor Board is the best setting to facilitate such decisions in these challenging cases. Paired DNA sequencing under these rare circumstances may suggest an occult breast tumor.

RevDate: 2021-09-23
CmpDate: 2021-08-31

Gonzalez-Rellan MJ, Fondevila MF, Fernandez U, et al (2021)

O-GlcNAcylated p53 in the liver modulates hepatic glucose production.

Nature communications, 12(1):5068.

p53 regulates several signaling pathways to maintain the metabolic homeostasis of cells and modulates the cellular response to stress. Deficiency or excess of nutrients causes cellular metabolic stress, and we hypothesized that p53 could be linked to glucose maintenance. We show here that upon starvation hepatic p53 is stabilized by O-GlcNAcylation and plays an essential role in the physiological regulation of glucose homeostasis. More specifically, p53 binds to PCK1 promoter and regulates its transcriptional activation, thereby controlling hepatic glucose production. Mice lacking p53 in the liver show a reduced gluconeogenic response during calorie restriction. Glucagon, adrenaline and glucocorticoids augment protein levels of p53, and administration of these hormones to p53 deficient human hepatocytes and to liver-specific p53 deficient mice fails to increase glucose levels. Moreover, insulin decreases p53 levels, and over-expression of p53 impairs insulin sensitivity. Finally, protein levels of p53, as well as genes responsible of O-GlcNAcylation are elevated in the liver of type 2 diabetic patients and positively correlate with glucose and HOMA-IR. Overall these results indicate that the O-GlcNAcylation of p53 plays an unsuspected key role regulating in vivo glucose homeostasis.

RevDate: 2021-08-21

Moghimi M, K Khodadadi (2021)

Dermatomyositis following Biosimilar Trastuzumab in a Breast Cancer Patient: A Case Report.

Case reports in oncology, 14(2):1134-1138.

Trastuzumab, as a recombinant IgG1 kappa, is a humanized monoclonal antibody against human epidermal growth factor receptor 2. Accordingly, it is widely used in breast cancers at early and advanced stages. Dermatomyositis is a rare adverse event of trastuzumab therapy, which is not well documented yet. In this study, a patient was treated for invasive ductal carcinoma with some symptoms of rash and generalized fatigue. These symptoms started after the fifth cycle of trastuzumab, which were gradually deteriorating. This patient's medical and family histories were unremarkable. The progression of the disease was ruled out as a possible cause of dermatomyositis, and the laboratory evaluation revealed a moderate increase in serum muscle protein (CPK). So, trastuzumab treatment was discontinued, and by passing 1 month from the start of prednisolone and hydroxychloroquine, the patient had no symptoms.

RevDate: 2021-08-21

Kim SJ, Lee JH, Park WJ, et al (2021)

Bioinformatic Exploration for Prognostic Significance of Sphingolipid Metabolism-Related Genes in Invasive Ductal Carcinoma Using the Cancer Genome Atlas Cohort.

International journal of general medicine, 14:4423-4434.

Introduction: Sphingolipid metabolism is a highly controlled process that is involved in regulating bioactive lipid signaling pathways and serves important roles in several cellular processes in breast cancer. Invasive ductal carcinoma (IDC), which is characterized by the malignant proliferation of the ductal epithelium and stromal invasion, is the most common type of breast cancer. Recent advances in genetic research have accelerated the discovery of novel prognostic factors and therapeutic targets for the disease. The aim of the present study was to investigate the expression and prognostic significance of sphingolipid metabolism-related genes in female IDC.

Methods: The present study used gene expression RNAseq data obtained from The Cancer Genome Atlas breast invasive carcinoma (TCGA BRCA) datasets.

Results: Sphingolipid metabolism-related genes exhibited dysregulated mRNA expression levels in IDC. The Student's t-test revealed that SMPDL3B, B4GALNT1, LPAR2, and LASS2 were significantly upregulated, while LASS3, LPAR1, B4GALT6, GAL3ST1, HPGD, ST8SIA1, UGT8, and S1PR1 were significantly downregulated in female IDC tissues compared with normal solid tissues. Kaplan-Meier survival analyses revealed that high SMPDL3B mRNA expression levels were associated with good prognosis in female IDC, suggesting that SMPDL3B plays a tumor suppressor role. To the best of our knowledge, the present study was the first to report that dysregulated expressions of SMPDL3B are significantly associated with age, estrogen receptor status, progesterone receptor status, and histological subtype.

Conclusion: Taken together, our study indicated that SMPDL3B may have a pathophysiological role and serve as a novel prognostic biomarker in IDC.

RevDate: 2021-09-03

Omi Y, Kamio H, Yoshida Y, et al (2021)

Breast metastasis from medullary thyroid carcinoma: a report of a case.

Surgical case reports, 7(1):188.

BACKGROUND: Metastasis to the breast is rare. We herein report a patient with metastatic medullary thyroid carcinoma to the breast for whom measuring the calcitonin level was an important clue to the correct diagnosis.

CASE PRESENTATION: A 54-year-old woman visited our hospital for the treatment of recurrent metastatic medullary thyroid carcinoma due to multiple endocrine neoplasia 2A and breast cancer. Positron emission tomography performed before the operation for metastatic medullary thyroid carcinoma recurrence in the neck showed the accumulation of 18F-fluorodeoxyglucose in the bilateral breast at sites other than the disease in the neck. Ultrasonography revealed multiple tumors in both breasts. A core needle biopsy of three breast tumors was performed. Microscopically, the tumor cells showed solid growth and did not show a tubular structure. She was diagnosed with triple-negative invasive ductal carcinoma. Post-operative positron emission tomography was performed as the serum calcitonin level increased after the operation. The accumulation of 18F-fluorodeoxyglucose in the bilateral breast tumors and lymph nodes in the neck was noted. The possibility of the breast tumors being metastasis of metastatic medullary thyroid carcinoma was considered. Needle aspiration was performed for three breast tumors. The calcitonin level of the washout fluid was measured and found to be ≥ 17,500 pg/mL. Immunohistochemistry showed that the tumor cells were calcitonin-positive and gross cystic disease fluid protein-15-negative. Vandetanib was started as recurrent metastatic medullary thyroid carcinoma with breast metastasis was finally diagnosed. The serum calcitonin level decreased after 1 month.

CONCLUSION: Although breast metastasis of medullary thyroid carcinoma is rare, a correct diagnosis is indispensable for appropriate treatment. When a breast tumor shows atypical morphological features for breast cancer according to the histopathology in a patient with a history of cancer, metastasis to the breast should be considered. Calcitonin measurement of the needle washout fluid was useful for confirming metastatic medullary thyroid carcinoma.

RevDate: 2021-08-20
CmpDate: 2021-08-20

Shabanov GA, Rybchenko AA, Lugovaya EA, et al (2021)

[Biological age estimation based on the spectral analysis of the human brain bioelectric activity.].

Advances in gerontology = Uspekhi gerontologii, 34(3):466-471.

For the first time, the research work offers a method of estimating human biological age based on the spectral analysis of the brain bioelectric activity. IDC decentralization index, which could consider summary degree of reduction of the background neurotrophic influences of the brain activating system on the peripheral tissues and organs, was developed. The close to linear dependence of the IDC index on the age of healthy people aged 10-90 as well as on the oncological patients' cancer G1-G4 cells differentiation was obtained. The cell disorders and mutations in relation with the age from 10 to 90 could be seen in growth of the IDC index from 100 to 900 units. The greater amount of the cell mutations in the oncological patients with the G1-G4 differentiation resulted in the IDC index growth up to the 3 000 units and more. All the obtained data allowed estimating the real biological age after a 10-minute registration of the human brain bioelectric activity. The accuracy increased with the averaging several surveys taken from one particular person. The technology will be highly efficient for scientific researches in the field of gerontology, monitoring of healthy people, revealing of risk groups, and for controlling of the cancer patients' medical treatment.

RevDate: 2021-08-20

Rafiq MT, A Hamid MS, E Hafiz (2021)

Effect of Progressive Resistance Strength Training on Body Mass Index, Quality of Life and Functional Capacity in Knee Osteoarthritis: A Randomized Controlled Trial.

Journal of multidisciplinary healthcare, 14:2161-2168.

Purpose: This study aimed to investigate the effectiveness of progressive resistance strength training of the lower limb rehabilitation protocol (LLRP) on body mass index (BMI), quality of life, and functional capacity in patients with knee osteoarthritis (OA) who were overweight and obese.

Patients and Methods: Fifty-six patients were allocated into either the Rehabilitation Protocol Group (RPG) or the Control Group (CG) by a computer-generated random number. The patients in the RPG performed the strengthening exercises of the LLRP and followed the instruction of daily care (IDC). The patients in the CG only followed the IDC as a usual care. Gait Speed Test, quality of life, and BMI were taken at pre-test and post-test measurements. Paired samples t-test and two way mixed analysis of variance were used to analyze the change of BMI within and compare the difference of BMI between the groups, respectively. Wilcoxon signed ranked test and Mann-Whitney U-test were used to analyze the changes of quality of life and functional capacity within and compare the differences of quality of life and functional capacity between the groups, respectively.

Results: The patients in the RPG reported a significant reduction in BMI (p = 0.025), improvement in quality of life (p ≤ 0.001), and functional capacity (p ≤ 0.001) within group. The patients in the CG also reported a significant improvements in quality of life (p < 0.05). The improvement in quality of life score was greater in the patients with RPG than the CG (p = 0.053).

Conclusion: The progressive resistance strength training of LLRP is effective in terms of reducing BMI, improving quality of life and functional capacity.

Trial Registration: Name: Iranian Registry of Clinical Trials. Number: IRCT20191221045846N3. Enrollment of first participant: 27-07-2020.

RevDate: 2021-08-20

Kohli P, Penumadu P, Srivastava N, et al (2021)

Primary Extra-Uterine Endometrial Stromal Sarcoma and Synchronous Breast Cancer: A Double Whammy: A Case report.

Journal of obstetrics and gynaecology of India, 71(3):326-329.

Endometrial stromal sarcoma is an uncommon gynecological tumor. Extra-uterine endometrial stromal sarcoma (EESS), the extra-uterine variant of its relatively more common counterpart, is even rarer with only few documented case reports. We report a case of a 40-year woman with bilateral adnexal tumors and synchronous invasive ductal breast carcinoma (IDC) posing a diagnostic challenge. The histopathology of specimen confirmed the diagnosis of EESS in the absence of florid endometriosis and synchronous hormone-positive infiltrating duct cancer in the breast. Patient was started on adjuvant endocrine therapy and is disease free at the end of 2 years. To the best of our knowledge, this is the first documentation of synchronous presentation of IDC and EESS, highlighting the possible role of hyper-estrogenemia as an etiological factor.

RevDate: 2021-08-18

Madhavan BK, Han Z, Sickmann A, et al (2021)

A laser-mediated photo-manipulative toolbox for generation and real-time monitoring of DNA lesions.

STAR protocols, 2(3):100700.

With the advancement of laser-based microscopy tools, it is now possible to explore mechano-kinetic processes occurring inside the cell. Here, we describe the advanced protocol for studying the DNA repair kinetics in real time using the laser to induce the DNA damage. This protocol can be used for inducing, testing, and studying the repair mechanisms associated with DNA double-strand breaks, interstrand cross-link repair, and single-strand break repair. For complete details on the use and execution of this protocol, please refer to Kumar et al. (2017, 2020).

RevDate: 2021-09-15

Salih AM, Hammood ZD, Pshtiwan LRA, et al (2021)

Intermammary breast cancer; the first reported case.

International journal of surgery case reports, 86:106223.

INTRODUCTION: Cancer of the breast is the most common cancer among females. The current study aims to report and discuss a rare case of breast cancer in the intermammary region.

CASE REPORT: A 61-year-old lady presented with intermammary swelling for three months. Ultrasound examination showed a hypoechoic micro lobulated mass with internal vascularity seated on the chest wall. There was pathological lymphnodes in the right axilla. Core needle biopsy suspected invasive ductal carcinoma of no specific type. The patient was referred to an oncology center receiving 21 cycles of radiotherapy and hormonal therapy.

DISCUSSION: The most common site of the occurrence of breast cancer is the upper outer quadrant (found in one-third of patients), followed by the upper inner quadrant (9.4%)-both lower outer and inner quadrants (5.2%) and rarely in the central portion. Intermammary breast cancer is an infrequent finding.

CONCLUSION: Although it is extremely rare, breast cancer could occur in the intermammary region. It has the same management strategy as breast cancer.

RevDate: 2021-08-16

Cerimele F, Tagliati C, Salvatori F, et al (2021)

Invasive ductal carcinoma mammographic findings: Correlation with age, breast composition and tumor size.

Breast disease pii:BD201072 [Epub ahead of print].

BACKGROUND/OBJECTIVE: The aim of this study was to identify the mammographic findings associated with malignancy in different age groups, taking into account breast composition (BC) and lesion size.

METHODS: Preoperative mammograms of 1023 invasive ductal carcinomas were retrospectively evaluated. According to the American College of Radiology Breast Imaging Reporting and Data System, cancer mammographic findings were classified as mass, calcifications, architectural distortion and asymmetry, and breasts were assessed as non-dense (A or B BC) and dense (C or D BC). Patient cohort was subdivided into three age groups (group 1: <50 years of age; group 2: between 50 and 69; group 3: ≥70 years of age).

RESULTS: Significant results of multinomial logistic regression were the association between mass and non-dense breast (p < 0.0001) and the association between mass and tumor size larger than 15 mm (p = 0.0049).

CONCLUSIONS: Mass finding of invasive ductal breast carcinoma is associated with breast composition and tumor size.

RevDate: 2021-08-16

Dieng O, Laurence V, Logerot C, et al (2021)

Eribulin combined with radiation therapy in a young patient re-irradiated for a new lesion of breast cancer.

Eribulin is widely used in the treatment of metastatic breast cancer, with a manageable toxicity profile. This aggressive disease often requires systemic and local treatments, comprising surgery or radiotherapy. However, eribulin is usually discontinued during radiation therapy due to the lack of data concerning the safety of this combination, especially in the setting of repeat locoregional radiation therapy. Our patient was diagnosed with ER positive invasive ductal carcinoma of the left breast initially treated by surgery, radiation therapy, chemotherapy, and hormone therapy. She then received various lines of chemotherapy for multiple triple-negative relapses in the left axillary region. Since October 2020, she has been treated by eribulin. In order to improve local control, it was decided to add local radiation therapy to the region of recurrence in addition to systemic therapy. She underwent radiation therapy concomitantly with eribulin from February to March 2021. Treatment was very well tolerated, and no acute toxicity was reported. This is the first published case of repeat locoregional radiation therapy in combination with eribulin.

RevDate: 2021-08-31

Kobayashi H, Nakai T, Nakanishi Y, et al (2021)

Phylogenetic analysis of combined lobular and ductal carcinoma of the breast.

Molecular medicine reports, 24(4):.

Breast cancer manifests in diverse forms, with particular reference to various cell types harboring different mutations and gene expression profiles. To elucidate the clonal relationship between cancer cells in tumors composed of both ductal and lobular phenotypes, two combined lobular and ductal carcinoma (CLDC) cases were analyzed, including one mixed ductal‑lobular carcinoma (MDL) lesion, by direct sequencing of the mitochondrial DNA D‑loop, digital PCR targeting of chromosomes 1q and 16q, as well as next‑generation sequencing. DNA was extracted from formalin‑fixed paraffin‑embedded tissue sections of different histological types, including invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, lobular carcinoma in situ, flat epithelial atypia, non‑neoplastic mammary gland and extramammary organs, using laser‑assisted microdissection. Mutations detected by the comprehensive cancer panel were validated by SYBR green allele‑specific quantitative PCR (RRM1, AKT1, PIK3CA, RALGDS, EGFR, TP53, IL21R, DPYD, SGK1, CDH1, TIMP3 and KMT2C). CLDC, which shared the basic genetic alterations of 1q gain or 16q loss, progresses to invasive lobular or ductual carcinoma with the accumulation of further mutations. Cancer cells contained in an MDL lesion shared closely related genetic alterations, suggesting that these cells have the same origin, despite different histological features, namely 'lobular' or 'ductal'. By contrast, multiple lesions located away from the main tumor, diagnosed as CLDC (excluding an MDL lesion) were not always identical with different genetic alterations, despite being diagnosed as ductal carcinoma in situ. Thus, MDL should be defined as a distinct category separate from CLDC, whose components of 'lobular' and 'ductal' may have the same cellular origin.

RevDate: 2021-08-17

Goldstein Ferber S, Shoval G, Zalsman G, et al (2021)

Between Action and Emotional Survival During the COVID-19 era: Sensorimotor Pathways as Control Systems of Transdiagnostic Anxiety-Related Intolerance to Uncertainty.

Frontiers in psychiatry, 12:680403.

Objectives: The COVID-19 pandemic and aligned social and physical distancing regulations increase the sense of uncertainty, intensifying the risk for psychopathology globally. Anxiety disorders are associated with intolerance to uncertainty. In this review we describe brain circuits and sensorimotor pathways involved in human reactions to uncertainty. We present the healthy mode of coping with uncertainty and discuss deviations from this mode. Methods: Literature search of PubMed and Google Scholar. Results: As manifestation of anxiety disorders includes peripheral reactions and negative cognitions, we suggest an integrative model of threat cognitions modulated by sensorimotor regions: "The Sensorimotor-Cognitive-Integration-Circuit." The model emphasizes autonomic nervous system coupling with the cortex, addressing peripheral anxious reactions to uncertainty, pathways connecting cortical regions and cost-reward evaluation circuits to sensorimotor regions, filtered by the amygdala and basal ganglia. Of special interest are the ascending and descending tracts for sensory-motor crosstalk in healthy and pathological conditions. We include arguments regarding uncertainty in anxiety reactions to the pandemic and derive from our model treatment suggestions which are supported by scientific evidence. Our model is based on systematic control theories and emphasizes the role of goal conflict regulation in health and pathology. We also address anxiety reactions as a spectrum ranging from healthy to pathological coping with uncertainty, and present this spectrum as a transdiagnostic entity in accordance with recent claims and models. Conclusions: The human need for controllability and predictability suggests that anxiety disorders reactive to the pandemic's uncertainties reflect pathological disorganization of top-down bottom-up signaling and neural noise resulting from non-pathological human needs for coherence in life.

RevDate: 2021-09-24

Roberts WC, M Jeong (2021)

Frequency of Peripartum Cardiomyopathy Among Women With Idiopathic Dilated Cardiomyopathy.

The American journal of cardiology, 157:101-106.

Among women with idiopathic dilated cardiomyopathy (IDC), the percent who develop heart failure (HF) in the peripartum period (during pregnancy or within 6 months of parturition) compared with those women who develop HF outside the peripartum period is unclear. We studied 72 women with IDC who underwent orthotopic heart transplantation for severe HF, the onset of which was in the peripartum period in 8 (11%) and outside the period in 64 (89%). Comparison of many clinical and morphologic variables between these 2 groups showed significant differences only in the ages of onset of HF, age when orthotopic heart transplantation was performed, and the frequency of the presence of diabetes mellitus. Examination of the hearts in the 2 groups disclosed no significant differences. Thus, separation of the peripartum IDC cases from the nonperipartum IDC cases by either clinical or cardiac morphologic variables is difficult.

RevDate: 2021-09-20
CmpDate: 2021-09-07

Fine RE, Gilmore RC, Dietz JR, et al (2021)

Cryoablation Without Excision for Low-Risk Early-Stage Breast Cancer: 3-Year Interim Analysis of Ipsilateral Breast Tumor Recurrence in the ICE3 Trial.

Annals of surgical oncology, 28(10):5525-5534.

BACKGROUND: The ICE3 trial is designed to evaluate the safety and efficacy of breast cryoablation, enabling women older than 60 years with low-risk early-stage breast cancers to benefit from a nonsurgical treatment and to avoid the associated surgical risks.

METHODS: The ICE3 trial is a prospective, multi-center, single-arm, non-randomized trial including women age 60 years or older with unifocal, ultrasound-visible invasive ductal carcinoma size 1.5 cm or smaller and classified as low to intermediate grade, hormone receptor (HR)-positive, and human epidermal growth factor receptor 2 (HER2)-negative. Ipsilateral breast tumor recurrence (IBTR) at 5 years was the primary outcome. A 3-year interim analysis of IBTR was performed, and the IBTR probability was estimated using the Kaplan-Meier method.

RESULTS: Full eligibility for the study was met by 194 patients, who received successful cryoablation per protocol. The mean age was 75 years (range, 55-94 years). The mean tumor length was 8.1 mm (range, 8-14.9 mm), and the mean tumor width was 7.4 mm (range, 2.8-14 mm). During a mean follow-up period of 34.83 months, the IBTR rate was 2.06% (4/194 patients). Device-related adverse events were reported as mild in 18.4% and moderate in 2.4% of the patients. No severe device-related adverse events were reported. More than 95% of the patients and 98% of the physicians reported satisfaction with the cosmetic results at the clinical follow-up evaluation.

CONCLUSIONS: Breast cryoablation presents a promising alternative to surgery while offering the benefits of a minimally invasive procedure with minimal risks. Further study within a clinical trial or registry is needed to confirm cryoablation as a viable alternative to surgical excision for appropriately selected low-risk patients.

RevDate: 2021-09-15

Chamalidou C, Fohlin H, Albertsson P, et al (2021)

Survival patterns of invasive lobular and invasive ductal breast cancer in a large population-based cohort with two decades of follow up.

Breast (Edinburgh, Scotland), 59:294-300.

BACKGROUND: Invasive lobular carcinoma (ILC) comprises 8-15 % of all invasive breast cancers and large population-based studies with >10 years of follow-up are rare. Whether ILC has a long-time prognosis different from that of invasive ductal carcinoma, (IDC) remains controversial.

PURPOSE: To investigate the excess mortality rate ratio (EMRR) of patients with ILC and IDC and to correlate survival with clinical parameters in a large population-based cohort.

MATERIAL AND METHODS: From 1989 through 2006, we identified 17,481 patients diagnosed with IDC (n = 14,583) or ILC (n = 2898), younger than 76 years from two Swedish Regional Cancer Registries. Relative survival (RS) during 20 years of follow up was analysed.

RESULTS: ILC was significantly associated with older age, larger tumours, ER positivity and well differentiated tumours. We noticed an improved survival for patients with ILC during the first five years, excess mortality rate ratio (EMRR) 0.64 (CI 95 % 0.53-0.77). This was shifted to a significant decreased survival 10-15 years after diagnosis (EMRR 1.49, CI 95 % 1.16-1.93). After 20 years the relative survival rates were similar, 0.72 for ILC and 0.73 for IDC.

CONCLUSIONS: During the first five years after surgery, the EMRR was lower for patients with ILC as compared to patients with IDC, but during the years 10-15 after surgery, we observed an increased EMRR for patients with ILC as compared to IDC. These EMRR between ILC and IDC were statistically significant but the absolute difference in excess mortality between the two groups was small.

RevDate: 2021-08-14

He X, Anthony DC, Catoni Z, et al (2021)

Pulmonary tumor embolism: A retrospective study over a 30-year period.

PloS one, 16(8):e0255917.

BACKGROUND: Pulmonary tumor embolism (PTE) is difficult to detect before death, and it is unclear whether the discrepancy between antemortem clinical and postmortem diagnosis improves with the advance of the diagnostic technologies. In this study we determined the incidence of PTE and analyzed the discrepancy between antemortem clinical and postmortem diagnosis.

METHODS: We performed a retrospective autopsy study on patients with the history of malignant solid tumors from 1990 to 2020 and reviewed all the slides of the patients with PTE. We also analyzed the discrepancies between antemortem clinical and postmortem diagnosis in 1999, 2009 and 2019 by using the Goldman criteria. Goldman category major 1 refers to cases in which an autopsy diagnosis was the direct cause of death and was not recognized clinically, but if it had been recognized, it may have changed treatment or prolonged survival.

RESULTS: We found 20 (3%) cases with PTE out of the 658 autopsy cases with solid malignancies. Out of these 20 cases, urothelial carcinoma (30%, 6/20) and invasive ductal carcinoma of the breast (4/20, 20%) were the most common primary malignancies. Seven patients with shortness of breath died within 3-17 days (average 8.4±2.2 days) after onset of the symptoms. Pulmonary embolism was clinically suspected in seven out of twenty (35%, 7/20) patients before death, but only two patients (10, 2/20) were diagnosed by imaging studies before death. The rate of Goldman category major 1 was 13.2% (10/76) in 1999, 7.3% (4/55) in 2009 and 6.9% (8/116) in 2019. Although the rate of Goldman category major 1 appeared decreasing, the difference was not statistically significant. The autopsy rate was significantly higher in 2019 (8.4%, 116/1386) than in 2009 (4.4%, 55/1240).

CONCLUSIONS: The incidence of PTE is uncommon. Despite the advances of the radiological techniques, radiological imaging studies did not detect the majority of PTEs. The discrepancy between the antemortem clinical and the postmortem diagnosis has not improved significantly over the past 30 years, emphasizing the value of autopsy.

RevDate: 2021-08-12

Gan J, Z Zhang (2021)

Relationship between ultrasound values and pathology and metastasis in patients with breast cancer.

American journal of translational research, 13(7):8207-8213.

PURPOSE: This study was designed to investigate the relationship between ultrasound values of breast cancer and its pathology and metastasis.

METHODS: A retrospective study was conducted on 80 patients diagnosed with breast cancer by pathologic examination in our hospital. The tumor size, tumor type, tumor grade, and the presence of distant metastasis were recorded. Vascular invasion, molecular subtype, pathobiologic indicators, and other measures were analyzed to explore the correlation between ultrasound measurements and pathology and metastasis in breast cancer patients.

RESULT: The proportion of ultrasound scores did not differ significantly among the groups (P > 0.05). The enrolled subjects were grouped according to tumor types (intraductal carcinoma, invasive ductal carcinoma, invasive lobular carcinoma, and special types), tumor grade (grade 1-3), metastasis, vascular invasion, and pathobiologic indicators (positive or negative ER/PR and HER-2 expression). These factors affected the ultrasound scores of breast cancer patients, resulting in significant differences in the proportions of scores between the groups (P < 0.05).

CONCLUSION: The ultrasound scores of breast cancer are closely related to its pathologic changes, and this has implications for the types of pathological tissues, biologic indicators, and presence of metastasis. Therefore, ultrasound values may be useful as a primary pathologic screening method for breast cancer patients.

RevDate: 2021-08-12

Eren Karanis Mİ, Küçükosmanoğlu İ, Ünlü Y, et al (2021)

Increased expression of ASRGL1 in invasive ductal carcinoma and its association with estrogen-progesterone receptor status of tumors.

American journal of translational research, 13(7):7928-7934.

AIMS: Human asparaginase-like protein 1 (ASRGL1) is closely related to tumor growth. ASRGL1 can significantly promote cell proliferation and suppress apoptosis. To date, high levels of expression of ASRGL1 have been reported in various tumors, but the function of ASRGL1 in carcinogenesis is still not well understood. In this study, we aimed to immunohistochemically investigate the expression of ASRGL1 in non-neoplastic breast tissue and invasive ductal carcinoma.

METHODS AND RESULTS: ASRGL1 was evaluated immunohistochemically in 148 invasive ductal carcinomas and 105 nonneoplastic breast tissue samples to assess the impact on breast cancer development and its association with clinicopathologic features. ASRGL1 was observed positive in 63 (42.6%) and negative in 85 (57.4%) invasive ductal carcinoma. In nonneoplastic breast tissue, 24 (22.9%) cases were ASRGL1 positive and 81 (77.1%) were negative. A significant difference was observed between invasive ductal carcinoma and nonneoplastic breast tissue in terms of ASRGL1 expression, and ASRGL1 expression was increased in invasive ductal carcinoma (P = .001). Most estrogen receptor-negative tumors and progesterone receptor-negative tumors were also negative with ASRGL1 and the difference was significant (P = .006 and P = .001, respectively). The correlation between the ASRGL1 expression of the tumors and event-free survival or overall survival was not significant (P>.05).

CONCLUSIONS: ASRGL1 may play a role in increasing cell proliferation and breast cancer development. ASRGL-1 expression in breast cancer closely correlates with the hormone receptor status of the tumor. In breast cancer, ASRGL-1 expression does not contribute to predicting tumor behavior.

RevDate: 2021-08-21
CmpDate: 2021-08-10

Mani L, Tzachor A, P Cole (2021)

Global catastrophic risk from lower magnitude volcanic eruptions.

Nature communications, 12(1):4756.

RevDate: 2021-09-08
CmpDate: 2021-09-08

Tokarz J, Möller G, Artati A, et al (2021)

Common Muscle Metabolic Signatures Highlight Arginine and Lysine Metabolism as Potential Therapeutic Targets to Combat Unhealthy Aging.

International journal of molecular sciences, 22(15):.

Biological aging research is expected to reveal modifiable molecular mechanisms that can be harnessed to slow or possibly reverse unhealthy trajectories. However, there is first an urgent need to define consensus molecular markers of healthy and unhealthy aging. Established aging hallmarks are all linked to metabolism, and a 'rewired' metabolic circuitry has been shown to accelerate or delay biological aging. To identify metabolic signatures distinguishing healthy from unhealthy aging trajectories, we performed nontargeted metabolomics on skeletal muscles from 2-month-old and 21-month-old mice, and after dietary and lifestyle interventions known to impact biological aging. We hypothesized that common metabolic signatures would highlight specific pathways and processes promoting healthy aging, while revealing the molecular underpinnings of unhealthy aging. Here, we report 50 metabolites that commonly distinguished aging trajectories in all cohorts, including 18 commonly reduced under unhealthy aging and 32 increased. We stratified these metabolites according to known relationships with various aging hallmarks and found the greatest associations with oxidative stress and nutrient sensing. Collectively, our data suggest interventions aimed at maintaining skeletal muscle arginine and lysine may be useful therapeutic strategies to minimize biological aging and maintain skeletal muscle health, function, and regenerative capacity in old age.

RevDate: 2021-08-09

Zhang JQ, Cheng TM, Lin WC, et al (2021)

Impact of Smoking-Related Chronic Obstruction Pulmonary Disease on Mortality of Invasive Ductal Carcinoma Patients Receiving Standard Treatments: Propensity Score-Matched, Nationwide, Population-Based Cohort Study.

Cancers, 13(15):.

PURPOSE: the survival effect of smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) is unclear for patients with invasive ductal carcinoma (IDC) receiving standard treatments.

METHODS: we recruited women with clinical stage I-III IDC from the Taiwan Cancer Registry Database who had received standard treatments between 1 January 2009 and 31 December 2018. The time-dependent Cox proportional hazards model was used to analyze all-cause mortality. To reduce the effects of potential confounders when all-cause mortality between Groups 1 and 2 were compared, 1:2 propensity score matching (PSM) was performed. We categorized the patients into two groups based on COPD status to compare overall survival outcomes: Group 1 (current smokers with COPD) and Group 2 (nonsmokers without COPD group).

RESULTS: PSM yielded 2319 patients with stage I-III IDC (773 and 1546 in Groups 1 and 2, respectively) eligible for further analysis. In the multivariate time-dependent Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) of all-cause mortality for Group 1 compared with Group 2 was 1.04 (0.83-1.22). The aHRs (95% CIs) of all-cause mortality for ≥1 hospitalization for COPDAE within one year before breast surgery was 1.51 (1.18-2.36) compared with no COPDAE.

CONCLUSION: smoking-related COPD was not a significant independent risk factor for all-cause mortality in women with stage I-III IDC receiving standard treatments. Being hospitalized at least once for COPDAE within one year before breast surgery is highly associated with high mortality for women with IDC receiving standard treatments. The severity of smoking-related COPD before treatments for breast cancer might be an important prognostic factor of survival. Thus, the information of the severity of COPD before treatment for breast cancer might be valuable for increasing the survival rate in treatment of breast cancer, especially in the prevention of progress from COPD to COPDAE.

RevDate: 2021-08-07

Hashmi AA, Riaz R, Zia S, et al (2021)

Impact of Histological Type and Grade on the Diagnostic Accuracy of Intraoperative Frozen Section for Detecting Breast Cancer Metastasis to Axillary Sentinel Lymph Nodes.

Cureus, 13(7):e16146.

Introduction Intraoperative sentinel lymph node (SLN) evaluation is the standard of care in patients with clinically node-negative breast cancer. The most common histological subtype of breast carcinoma is invasive ductal carcinoma (IDC), followed by invasive lobular carcinoma (ILC). Alternatively, histological grades vary from grades G1 to G3. Therefore, in this study, we evaluated the diagnostic accuracy of frozen section (FS) for detecting breast cancer metastasis to SLNs with respect to histological subtypes and grades. Methods A retrospective observational study was conducted in the Department of Histopathology at Liaquat National Hospital and Medical College, Pakistan, from January 2013 till December 2020, over a duration of eight years. A total of 540 cases of primary breast cancer, undergoing upfront breast surgery were included in the study. Intraoperatively, SLNs were identified and sent for FS. After FS reporting, the remaining tissue was submitted for final (paraffin) section examination after formalin fixation, and results of FS and final (paraffin) sections were compared. Results The mean age of the patients included in the study was 52.05±12.42 years, and the median number of SLNs was three (ranging from one to 14). The overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of intraoperative FS were 88.2%, 100%, 100%, 92.5%, and 95.2%, respectively. The sensitivity of FS for IDC was 88.3%, whereas it was 85.7% for ILC. Alternatively, the sensitivity of FS for grade G1, G2, and G3 tumors was 78.3%, 91.5%, and 90.2%, respectively. The false-negative rate for grade G1 tumors was 21.7%, which was higher than G2 and G3 tumors (8.5% and 9.8%, respectively). Similarly, the false-negative rate for cases where the number of SLNs was more than three was only 5.4%, which was lower than cases with a single and two to three SLNs sent on FS (23.1 and 14.7%, respectively). Conclusion The sensitivity of intraoperative FS for detecting ILC metastasis to axillary SLNs was not substantially different from IDC; however, histological grade affects the sensitivity of FS diagnosis, with lower-grade tumors having low sensitivity. Moreover, increasing the number of SLNs sent intraoperatively on FS improves the sensitivity of FS for detecting breast cancer metastasis to axillary SLNs.

RevDate: 2021-09-20
CmpDate: 2021-09-20

Shelly S, Liraz Zaltsman S, Ben-Gal O, et al (2021)

Potential neurotoxicity of titanium implants: Prospective, in-vivo and in-vitro study.

Biomaterials, 276:121039.

Titanium dioxide (TiO2) is a frequently used biomaterial, particularly in orthopedic and dental implants, and it is considered an inert and benign compound. This has resulted in toxicological scrutiny for TiO2 in the past decade, with numerus studies showing potential pathologic downstream effects. Herein we describe case report of a 77-year-old male with subacute CNS dysfunction, secondary to breakdown of a titanium-based carotid stent and leading to blood levels 1000 times higher (3 ppm) than the reported normal. We prospectively collected tissues adjacent to orthopedic implants and found a positive correlation between titanium concentration and time of implant in the body (r = 0.67, p < 0.02). Rats bearing titanium implants or intravascularly treated with TiO2 nanoparticles (TiNP) exhibited memory impairments. A human blood-brain barrier (BBB) in-vitro model exposed to TiNP showed paracellular leakiness, which was corroborated in-vivo with the decrease of key BBB transcripts in isolated blood vessels from hippocampi harvested from TiNP-treated mice. Titanium particles rapidly internalized into brain-like endothelial cells via caveolae-mediated endocytosis and macropinocytosis and induced pro-inflammatory reaction with increased expression of pro-inflammatory genes and proteins. Immune reaction was mediated partially by IL-1R and IL-6. In summary, we show that high levels of titanium accumulate in humans adjacent to orthopedic implants, and our in-vivo and in-vitro studies suggest it may be neurotoxic.

RevDate: 2021-09-23

Luz FAC, Araújo RA, MJB Silva (2021)

Decreased Survival of Invasive Ductal Breast Cancer Patients With Two Macrometastatic Lymph Nodes Among Few Resected Ones: Should Current Sentinel-Lymph-Node Guidelines Be Revised?.

Frontiers in oncology, 11:669890.

Purpose: Sentinel-lymph-node (SLN) biopsy (SLB) is an efficient and safe axillary surgical approach with decreased morbidity than total axillary lymph node dissection (ALND) in initial patients (T1-T2). Current guidelines strongly suggest avoiding completion of ALND in patients with one or two positive SLNs that will be submitted to whole-breast radiation therapy, but must be done when three SLNs are affected.

Methods: We performed a SEER-based study with breast invasive ductal carcinoma patients treated between 2010 and 2015. Optimal cutoffs of positive LNs predictive of survival were obtained with ROC curves and survival as a continuous variable. Bias was reduced through propensity score matching. Cox regression was employed to estimate prognosis. Nomograms were constructed to analyze the predictive value of clinicopathological factors for axillary burden.

Results: Of 43,239 initial patients that had one to three analyzed LNs, only 425 had two positive LNs and matched analysis demonstrated no survival difference versus pN2 patients [HR: 0.960 (0.635-1.452), p = 0.846]. The positive-to-analyzed LN proportion demonstrated a strong prognostic factor for a low rate (1 positive to ≤1.5 analyzed) [HR = 1.567 (1.156-2.126), p = 0.004], and analysis derived from the results demonstrated that a "negative LN margin" improves survival. Nomograms shows that tumor size is the main factor of axillary burden.

Conclusion: Macrometastasis of two LNs is a poor prognostic factor, similar to pN2, in SLNB (-like) patients; more extensive studies including preconized therapies must be done in order to corroborate or refute the resistance of this prognostic difference in patients with two macrometastatic lymph nodes within few resected.

RevDate: 2021-08-30

Tractenberg RE, Frost JK, Yumoto F, et al (2021)

Validity of the Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB) who void or use indwelling catheters.

Spinal cord, 59(9):948-958.

STUDY DESIGN: Descriptive Psychometrics Study OBJECTIVES: Neurogenic lower urinary tract dysfunction (NLUTD), or "neurogenic bladder" is a common and disruptive condition for individuals with spinal cord injury (SCI) and disease (including multiple sclerosis, MS). Our team has developed patient-centered instruments of urinary symptoms specific to patients with NLUTD, across bladder management methods. Validity evidence is needed to support the use of two new instruments, Urinary Symptom Questionnaires for people with Neurogenic Bladder (USQNB) for those who manage their bladder with indwelling catheters (IDC), or who void (V).

SETTING: Online surveys completed by individuals in the United States with NLUTD due to either SCI or MS who manage their bladder with indwelling catheters (SCI, n = 306; MS, n = 8), or by voiding (SCI, n = 103; MS, n = 383). A total of n = 381 USQNB-IDC respondents (five control groups), and 351 USQNB-V respondents (four control groups), contributed to our convergent and divergent validity evidence.

METHODS: Data were collected online to estimate key aspects of psychometric validity (content, reflection of the construct to be measured; face, recognizability of the contents as representing the construct to be measured; structural, the extent to which the instrument captures recognizable dimensions of the construct to be measured). Divergent and convergent validity evidence was derived from multiple control groups, while evidence of criterion validity was derived from attribution of each item to their experience "with a UTI".

RESULTS: Evidence of face, content, criterion, convergent, and divergent validity was compiled for each instrument.

CONCLUSIONS: The instruments demonstrate adequate, multi-dimensional, validity evidence to recommend their use for decision-making by patients, clinicians, and researchers.

RevDate: 2021-09-23
CmpDate: 2021-09-07

Kedrzycki MS, Leiloglou M, Chalau V, et al (2021)

The Impact of Temporal Variation in Indocyanine Green Administration on Tumor Identification During Fluorescence Guided Breast Surgery.

Annals of surgical oncology, 28(10):5617-5625.

BACKGROUND: On average, 21% of women in the USA treated with Breast Conserving Surgery (BCS) undergo a second operation because of close positive margins. Tumor identification with fluorescence imaging could improve positive margin rates through demarcating location, size, and invasiveness of tumors. We investigated the technique's diagnostic accuracy in detecting tumors during BCS using intravenous indocyanine green (ICG) and a custom-built fluorescence camera system.

METHODS: In this single-center prospective clinical study, 40 recruited BCS patients were sub-categorized into two cohorts. In the first 'enhanced permeability and retention' (EPR) cohort, 0.25 mg/kg ICG was injected ~ 25 min prior to tumor excision, and in the second 'angiography' cohort, ~ 5 min prior to tumor excision. Subsequently, an in-house imaging system was used to image the tumor in situ prior to resection, ex vivo following resection, the resection bed, and during grossing in the histopathology laboratory to compare the technique's diagnostic accuracy between the cohorts.

RESULTS: The two cohorts were matched in patient and tumor characteristics. The majority of patients had invasive ductal carcinoma with concomitant ductal carcinoma in situ. Tumor-to-background ratio (TBR) in the angiography cohort was superior to the EPR cohort (TBR = 3.18 ± 1.74 vs 2.10 ± 0.92 respectively, p = 0.023). Tumor detection reached sensitivity and specificity scores of 0.82 and 0.93 for the angiography cohort and 0.66 and 0.90 for the EPR cohort, respectively (p = 0.1051 and p = 0.9099).

DISCUSSION: ICG administration timing during the angiography phase compared with the EPR phase improved TBR and diagnostic accuracy. Future work will focus on image pattern analysis and adaptation of the camera system to targeting fluorophores specific to breast cancer.

RevDate: 2021-08-30

Tractenberg RE, Frost JK, Yumoto F, et al (2021)

Reliability of the Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB) who void or use indwelling catheters.

Spinal cord, 59(9):939-947.

STUDY DESIGN: This is a descriptive psychometrics study.

OBJECTIVES: Neurogenic lower urinary tract dysfunction (NLUTD), also called Neurogenic Bladder (NB), is a common and disruptive condition in a variety of neurologic diagnoses. Our team developed patient-centered instruments, Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB), specific to people with NLUTD who manage their bladders with intermittent catheterization (IC), indwelling catheters (IDC), or who void (V). This article reports evidence of reliability of the IDC and V instruments.

SETTING: Online surveys completed by individuals in the United States with NLUTD due to spinal cord injury (SCI), or multiple sclerosis (MS) who manage their bladder with IDC (SCI, n = 306), or by voiding (SCI, n = 103; MS, n = 383).

METHODS: Reliability estimates were based on endorsement of the items on the USQNB-IDC and USQNB-V. Reliability evidence was representativeness of these symptoms for a national sample (by determining if endorsement > 10%); internal consistency estimates (by Cronbach's alpha and item correlation coefficient, ICC); and interrelatedness of the items (by inferred Bayesian network, BN). We also tested whether a one-factor conceptualization of "urinary symptoms in NLUTD" was supportable for either instrument.

RESULTS: All items were endorsed by >20% of our samples. Urine quality symptoms tended to be the most commonly endorsed on both instruments. Cronbach's alpha and ICC estimates were high (>0.74), but not suggestive of redundancy. BNs showed interpretable associations among the items, and did not discover uninterpretable or unexpected associations. Neither instrument fit a one-factor model, as expected.

CONCLUSIONS: The USQNB-IDC and USQNB-V instruments show sufficient, multidimensional reliability for implementation and further study.

RevDate: 2021-09-11

Pickford AK, Michel-Todó L, Dupuy F, et al (2021)

Expression Patterns of Plasmodium falciparum Clonally Variant Genes at the Onset of a Blood Infection in Malaria-Naive Humans.

mBio, 12(4):e0163621.

Clonally variant genes (CVGs) play fundamental roles in the adaptation of Plasmodium falciparum to fluctuating conditions of the human host. However, their expression patterns under the natural conditions of the blood circulation have been characterized in detail for only a few specific gene families. Here, we provide a detailed characterization of the complete P. falciparum transcriptome across the full intraerythrocytic development cycle (IDC) at the onset of a blood infection in malaria-naive human volunteers. We found that the vast majority of transcriptional differences between parasites obtained from the volunteers and the parental parasite line maintained in culture occurred in CVGs. In particular, we observed a major increase in the transcript levels of most genes of the pfmc-2tm and gbp families and of specific genes of other families, such as phist, hyp10, rif, or stevor, in addition to previously reported changes in var and clag3 gene expression. Increased transcript levels of individual pfmc-2tm, rif, and stevor genes involved activation in small subsets of parasites. Large transcriptional differences correlated with changes in the distribution of heterochromatin, confirming their epigenetic nature. Furthermore, the similar expression of several CVGs between parasites collected at different time points along the blood infection suggests that the epigenetic memory for multiple CVG families is lost during transmission stages, resulting in a reset of their transcriptional state. Finally, the CVG expression patterns observed in a volunteer likely infected by a single sporozoite suggest that new epigenetic patterns are established during liver stages. IMPORTANCE The ability of malaria parasites to adapt to changes in the human blood environment, where they produce long-term infection associated with clinical symptoms, is fundamental for their survival. CVGs, regulated at the epigenetic level, play a major role in this adaptive process, as changes in the expression of these genes result in alterations in the antigenic and functional properties of the parasites. However, how these genes are expressed under the natural conditions of the human circulation and how their expression is affected by passage through transmission stages are not well understood. Here, we provide a comprehensive characterization of the expression patterns of these genes at the onset of human blood infections, which reveals major differences with in vitro-cultured parasites. We also show that, during transmission stages, the previous expression patterns for many CVG families are lost, and new patterns are established.

RevDate: 2021-08-03

McCray E, Naron R, White S, et al (2021)

Metastatic Breast Cancer Masked as Constipation.

Cureus, 13(6):e16031.

Even though screening mammography has been attributed to decreased mortality in recent decades, breast cancer is one of the leading causes of death among women in the United States. Disruption of screening protocols and variation in the presentation may alter the course of detection and management. We report a case of hormone receptor-positive breast cancer that presented as vague gastrointestinal symptoms in a patient with a delayed workup for a self-discovered breast lump during the coronavirus disease global pandemic. A 48-year-old woman with a history of gastroesophageal reflux and hypertension presented to the emergency department with primary complaints of constipation and abdominal distention with associated flatus and nausea. Vitals were within normal limits, and physical examination was notable for abdominal distention and diffuse tenderness to palpation. Labs demonstrated hypercalcemia and an unremarkable complete blood count. A chest X-ray showed a right hilar mass, and a CT chest revealed multiple lytic bone lesions diffusely scattered throughout the entire skeleton; no hilar mass was noted on the CT chest. A CT scan of the abdomen and pelvis incidentally revealed a right breast mass. A bone marrow biopsy identified invasive ductal carcinoma. Mammography and biopsy of the breast mass identified estrogen receptor/progesterone receptor-positive invasive ductal carcinoma, consistent with the bone marrow biopsy, confirming the diagnosis of metastatic breast cancer. Unpredicted disruptions in screening processes may result in delayed cancer diagnoses. This case illustrates the importance of routine self-breast examinations, screening mammography, and maintaining a broad differential diagnosis.

RevDate: 2021-08-03

Kapoor MM, TW Moseley (2021)

Fluid-filled breast: A unique clinical presentation of invasive micropapillary carcinoma.

Radiology case reports, 16(9):2731-2735.

Invasive micropapillary carcinoma is a rare variant of invasive ductal carcinoma of the breast. This variant has been described as clinically aggressive due to its high frequency of lymphovascular invasion, axillary nodal metastases, and a greater degree of loco-regional recurrence. Invasive micropapillary carcinoma can have a variety of imaging presentations, typically presenting as an irregular mass. This case report describes a unique presentation of invasive micropapillary carcinoma and illustrates the propensity of invasive micropapillary carcinoma to secrete fluid and have a lack of regional lymphadenopathy. The challenges of the accompanying diagnostic imaging-work up are discussed.

RevDate: 2021-07-31

Chu SY, Foong JH, Lee J, et al (2021)

Oral diadochokinetic rates across languages: Multilingual speakers comparison.

International journal of language & communication disorders [Epub ahead of print].

BACKGROUND: It is unclear whether oral diadochokinetic rate (oral-DDK) performance is affected by different languages within a multilingual country.

AIMS: This study investigated the effects of age, sex, and stimulus type (real word in L1, L2 vs. non-word) on oral-DDK rates among healthy Malaysian-Malay speakers in order to establish language- and age-sensitive norms. The second aim was to compared the nonword 'pataka' oral-DDK rates produced by Malaysian-Malay speakers on currently available normative data for Hebrew speakers and Malaysian-Mandarin speakers.

METHODS & PROCEDURES: Oral-DDK performance of 90 participants (aged 20-77 years) using nonword ('pataka'), Malay real word ('patahkan'), and English real word ('buttercake') was audio recorded. The number of syllables produced in 8 seconds was calculated. Mixed analysis of variance (ANOVA) was conducted to examine the effects of stimulus type (nonword, Malay, and English real word), sex (male, female), age (younger, 20-40 years; middle, 41-60 years; older, ≥61 years), and their interactions on the oral-DDK rate. Data obtained were also compared with the raw data of Malaysian-Mandarin and Hebrew speakers from the previous studies.

OUTCOMES & RESULTS: A normative oral-DDK rate has been established for healthy Malaysian-Malay speakers. The oral-DDK rate was significantly affected by stimuli (p < 0.001). Malay real word showed the slowest rate, whereas there was no significant difference between English real word and nonword. The oral-DDK rate for Malay speakers was significantly higher than Mandarin and Hebrew speakers across stimuli (all p < 0.01). Interestingly, oral-DDK rates were not affected by age group for Malay speakers.

Stimuli type and language affect the oral-DDK rate, indicating that speech-language therapists should consider using language-specific norms when assessing multilingual speakers.

WHAT THIS PAPER ADDS: What is already known on the subject Age, sex, and language are factors that need to be considered when developing oral-DDK normative protocol. It is unclear whether oral-DDK performance is affected by different languages within a multilingual country. What this paper adds to existing knowledge No ageing effect across real word versus nonword on oral-DDK performance was observed among Malaysian-Malay speakers, contrasting with current available literature that speech movements slow down as we age. Additionally, Malaysian-Malay speakers have faster oral-DDK rates than Malaysian-Mandarin and Hebrew speakers across all stimuli. What are the potential or actual clinical implications of this work? Establishing normative data of different languages will enable speech-language therapists to select the appropriate reference dataset based on the language mastery of these multilingual speakers.

RevDate: 2021-08-17
CmpDate: 2021-08-17

Thomson-Luque R, Votborg-Novél L, Ndovie W, et al (2021)

Plasmodium falciparum transcription in different clinical presentations of malaria associates with circulation time of infected erythrocytes.

Nature communications, 12(1):4711.

Following Plasmodium falciparum infection, individuals can remain asymptomatic, present with mild fever in uncomplicated malaria cases, or show one or more severe malaria symptoms. Several studies have investigated associations between parasite transcription and clinical severity, but no broad conclusions have yet been drawn. Here, we apply a series of bioinformatic approaches based on P. falciparum's tightly regulated transcriptional pattern during its ~48-hour intraerythrocytic developmental cycle (IDC) to publicly available transcriptomes of parasites obtained from malaria cases of differing clinical severity across multiple studies. Our analysis shows that within each IDC, the circulation time of infected erythrocytes without sequestering to endothelial cells decreases with increasing parasitaemia or disease severity. Accordingly, we find that the size of circulating infected erythrocytes is inversely related to parasite density and disease severity. We propose that enhanced adhesiveness of infected erythrocytes leads to a rapid increase in parasite burden, promoting higher parasitaemia and increased disease severity.

RevDate: 2021-08-11
CmpDate: 2021-08-04

Sazawal S, Ryckman KK, Mittal H, et al (2021)

Using AMANHI-ACT cohorts for external validation of Iowa new-born metabolic profiles based models for postnatal gestational age estimation.

Journal of global health, 11:04044.

Background: Globally, 15 million infants are born preterm and another 23.2 million infants are born small for gestational age (SGA). Determining burden of preterm and SGA births, is essential for effective planning, modification of health policies and targeting interventions for reducing these outcomes for which accurate estimation of gestational age (GA) is crucial. Early pregnancy ultrasound measurements, last menstrual period and post-natal neonatal examinations have proven to be not feasible or inaccurate. Proposed algorithms for GA estimation in western populations, based on routine new-born screening, though promising, lack validation in developing country settings. We evaluated the hypothesis that models developed in USA, also predicted GA in cohorts of South Asia (575) and Sub-Saharan Africa (736) with same precision.

Methods: Dried heel prick blood spots collected 24-72 hours after birth from 1311 new-borns, were analysed for standard metabolic screen. Regression algorithm based, GA estimates were computed from metabolic data and compared to first trimester ultrasound validated, GA estimates (gold standard).

Results: Overall Algorithm (metabolites + birthweight) estimated GA to within an average deviation of 1.5 weeks. The estimated GA was within the gold standard estimate by 1 and 2 weeks for 70.5% and 90.1% new-borns respectively. Inclusion of birthweight in the metabolites model improved discriminatory ability of this method, and showed promise in identifying preterm births. Receiver operating characteristic (ROC) curve analysis estimated an area under curve of 0.86 (conservative bootstrap 95% confidence interval (CI) = 0.83 to 0.89); P < 0.001) and Youden Index of 0.58 (95% CI = 0.51 to 0.64) with a corresponding sensitivity of 80.7% and specificity of 77.6%.

Conclusion: Metabolic gestational age dating offers a novel means for accurate population-level gestational age estimates in LMIC settings and help preterm birth surveillance initiatives. Further research should focus on use of machine learning and newer analytic methods broader than conventional metabolic screen analytes, enabling incorporation of region-specific analytes and cord blood metabolic profiles models predicting gestational age accurately.

RevDate: 2021-07-30
CmpDate: 2021-07-30

Deng Y, Li FL, Qin HY, et al (2021)

[Application Test of the AI-Automatic Diagnostic System for Ki-67 in Breast Cancer].

Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition, 52(4):693-697.

Objective: To study the different methods of artificial intelligence (AI)-assisted Ki-67 scoring of clinical invasive ductal carcinoma (IDC) of the breast and to compare the results.

Methods: A total of 100 diagnosed IDC cases were collected, including slides of HE staining and immunohistochemical Ki-67 staining and diagnosis results. The slides were scanned and turned into whole slide image (WSI), which were then scored with AI. There were two AI scoring methods. One was fully automatic counting by AI, which used the scoring system of Ki-67 automatic diagnosis to do counting with the whole image of WSI. The second method was semi-automatic AI counting, which required manual selection of areas for counting, and then relied on an intelligent microscope to conduct automatic counting. The diagnostic results of pathologists were taken as the results of pure manual counting. Then the Ki-67 scores obtained by manual counting, semi-automatic AI counting and automatic AI counting were pairwise compared. The Ki-67 scores obtained from the manual counting (pathological diagnosis results), semi-automatic AI and automatic AI counts were pair-wise compared and classified according to three levels of difference: difference ≤10%, difference of >10%-<30% and difference ≥30%. Intra-class correlation coefficient (ICC) was used to evaluate the correlation.

Results: The automatic AI counting of Ki-67 takes 5-8 minutes per case, the semi-automatic AI counting takes 2-3 minutes per case, and the manual counting takes 1-3 minutes per case. When results of the two AI counting methods were compared, the difference in Ki-67 scores was all within 10% (100% of the total), and the ICC index being 0.992. The difference between manual counting and semi-automatic AI was less than 10% in 60 cases (60% of the total), between 10% and 30% in 37 cases (37% of the total), and more than 30% in only 3 cases (3% of the total), ICC index being 0.724. When comparing automatic AI with manual counting, 78 cases (78% of the total) had a difference of ≤10%, 17 cases (17% of the total) had a difference of between 10% and 30%, and 5 cases (5%) had a difference of ≥30%, the ICC index being 0.720. The ICC values showed that there was little difference between the results of the two AI counting methods, indicating good repeatability, but the repeatability between AI counting and manual counting was not particularly ideal.

Conclusion: AI automatic counting has the advantage of requiring less manpower, for the pathologist is involved only for the verification of the diagnosis results at the end. However, the semi-automatic method is better suited to the diagnostic habits of pathologists and has a shorter turn-over time compared with that of the fully automatic AI counting method. Furthermore, in spite of its higher repeatability, AI counting, cannot serve as a full substitute for pathologists, but should instead be viewed as a powerful auxiliary tool.

RevDate: 2021-09-11

Meyer D, Kames J, Bar H, et al (2021)

Distinct signatures of codon and codon pair usage in 32 primary tumor types in the novel database CancerCoCoPUTs for cancer-specific codon usage.

Genome medicine, 13(1):122.

BACKGROUND: Gene expression is highly variable across tissues of multi-cellular organisms, influencing the codon usage of the tissue-specific transcriptome. Cancer disrupts the gene expression pattern of healthy tissue resulting in altered codon usage preferences. The topic of codon usage changes as they relate to codon demand, and tRNA supply in cancer is of growing interest.

METHODS: We analyzed transcriptome-weighted codon and codon pair usage based on The Cancer Genome Atlas (TCGA) RNA-seq data from 6427 solid tumor samples and 632 normal tissue samples. This dataset represents 32 cancer types affecting 11 distinct tissues. Our analysis focused on tissues that give rise to multiple solid tumor types and cancer types that are present in multiple tissues.

RESULTS: We identified distinct patterns of synonymous codon usage changes for different cancer types affecting the same tissue. For example, a substantial increase in GGT-glycine was observed in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed invasive ductal and lobular carcinoma (IDLC) of the breast. Change in synonymous codon preference favoring GGT correlated with change in synonymous codon preference against GGC in IDC and IDLC, but not in ILC. Furthermore, we examined the codon usage changes between paired healthy/tumor tissue from the same patient. Using clinical data from TCGA, we conducted a survival analysis of patients based on the degree of change between healthy and tumor-specific codon usage, revealing an association between larger changes and increased mortality. We have also created a database that contains cancer-specific codon and codon pair usage data for cancer types derived from TCGA, which represents a comprehensive tool for codon-usage-oriented cancer research.

CONCLUSIONS: Based on data from TCGA, we have highlighted tumor type-specific signatures of codon and codon pair usage. Paired data revealed variable changes to codon usage patterns, which must be considered when designing personalized cancer treatments. The associated database, CancerCoCoPUTs, represents a comprehensive resource for codon and codon pair usage in cancer and is available at https://dnahive.fda.gov/review/cancercocoputs/ . These findings are important to understand the relationship between tRNA supply and codon demand in cancer states and could help guide the development of new cancer therapeutics.

RevDate: 2021-07-30
CmpDate: 2021-07-30

Fan T, Wang CQ, Li XT, et al (2021)

MiR-22-3p Suppresses Cell Migration and Invasion by Targeting PLAGL2 in Breast Cancer.

Journal of the College of Physicians and Surgeons--Pakistan : JCPSP, 31(8):937-940.

OBJECTIVE: To investigate the expression of miR-22-3p in breast cancer and the mechanism of targeting PLAGL2 to inhibit the invasion and migration in human breast cancer.

STUDY DESIGN: An experimental study.

PLACE AND DURATION OF STUDY: Department of Oncology and Department of General Surgery, The People's Hospital of China Three Gorges University, China, from March 2019 to December 2020.

METHODOLOGY: The miR-22-3p expression level in 41 paired human primary breast invasive ductal carcinoma tissues and para-cancer tissues was obtained by real-time fluorescence quantitative reverse transcriptase PCR (qRT-PCR). The effect of miR-22-3p on the proliferation of breast cancer cells was detected by growth curve method. Online software TargetScan was used to predict the target genes of miR-22-3p. The prediction results were verified by luciferase reporter gene assay and qRT⁃PCR.

RESULTS: MiR-22-3p expression was significantly decreased in the breast cancer tissues than in para⁃carcinoma normal breast tissues (p<0.05). Over-expression of miR-22-3p can inhibit the proliferation of MCF-7 cells significantly. Pleomorphic adenoma gene-like protein 2(PLAGL2) is the predicted target gene of miR-22-3p. MiR-22-3p binds to its predicted target gene PLAGL2-3'UTR. The expression of miR-22-3p was negatively correlated with PLAGL2 in MCF-7 cells.

CONCLUSION: MiR-22-3p could suppress the proliferation of breast cancer by targeting PLAGL2. This suggests that miR-22-3p may be a strategy of choice for targeted therapy of breast cancer. Key Words: Breast cancer, MiR-22-3p, PLAGL2, Cell proliferation.

RevDate: 2021-07-28

Chung HL, Tso HH, Middleton LP, et al (2021)

Axillary Nodal Metastases in Invasive Lobular Carcinoma Versus Invasive Ductal Carcinoma: Comparison of Node Detection and Morphology by Ultrasound.

AJR. American journal of roentgenology [Epub ahead of print].

Background: Invasive lobular carcinoma is more subtle on imaging compared with invasive ductal carcinoma; nodal metastases may also differ on imaging between these. Objective: To determine whether invasive lobular carcinoma and invasive ductal carcinoma differ in the detection rate by ultrasound (US) of metastatic axillary nodes and in metastatic nodes' US characteristics. Methods: This retrospective study included 695 women (median age 53 years) with breast cancer in a total of 723 breasts (76 lobular, 586 ductal, 61 mixed), with biopsy-proven axillary nodal metastases and who underwent pretreatment US. A single breast radiologist reviewed US images in patients with suspicious nodes on US and classified node number, size, and morphology. Morphologic assessment used a previously described classification based on the relationship between node cortex and hilum. Nodal findings were compared between lobular and ductal carcinoma. A second radiologist independently classified node morphology in 241 cancers to assess interreader agreement. Results: A total of 99 metastatic axillary nodes (15 lobular, 66 ductal, 18 mixed) were not visualized on US and were diagnosed by surgical biopsy. The remaining 624 metastatic nodes (61 lobular, 520 ductal, 43 mixed) were visualized on US and diagnosed by US-guided FNA. Thus, US detected the metastatic nodes in 80.3% for lobular carcinoma versus 88.7% for ductal carcinoma (p=.04). Among metastatic nodes detected by US, retrospective review identified ≥3 abnormal nodes in 50.8% of lobular carcinoma versus 69.2% of ductal carcinoma (p=.003); node size was ≤2.0 cm in 65.6% for lobular carcinoma versus 47.3% for ductal carcinoma (p=.03); morphology was type III/IV (diffuse cortical thickening without hilar mass effect) rather than type V/VI (marked cortical thickening with hilar mass effect) in 68.9% for lobular carcinoma versus 28.8% for ductal carcinoma (p<.001). Interreader agreement assessment for morphology exhibited kappa coefficient of 0.63 (95% CI, 0.54-0.73). Conclusion: US detects a lower percentage of nodal metastases in lobular than ductal carcinoma. Nodal metastases in lobular carcinoma more commonly show diffuse cortical thickening and with less hilar mass effect. Clinical Impact: A lower threshold may be warranted to recommend biopsy of suspicious axillary nodes detected on US in patients with lobular carcinoma.

RevDate: 2021-09-22

Demir S, Nawroth PP, Herzig S, et al (2021)

Emerging Targets in Type 2 Diabetes and Diabetic Complications.

Advanced science (Weinheim, Baden-Wurttemberg, Germany), 8(18):e2100275.

Type 2 diabetes is a metabolic, chronic disorder characterized by insulin resistance and elevated blood glucose levels. Although a large drug portfolio exists to keep the blood glucose levels under control, these medications are not without side effects. More importantly, once diagnosed diabetes is rarely reversible. Dysfunctions in the kidney, retina, cardiovascular system, neurons, and liver represent the common complications of diabetes, which again lack effective therapies that can reverse organ injury. Overall, the molecular mechanisms of how type 2 diabetes develops and leads to irreparable organ damage remain elusive. This review particularly focuses on novel targets that may play role in pathogenesis of type 2 diabetes. Further research on these targets may eventually pave the way to novel therapies for the treatment-or even the prevention-of type 2 diabetes along with its complications.

RevDate: 2021-08-30

Lopez Salazar V, Karikari RA, Li L, et al (2021)

WITHDRAWN: Adipocyte Deletion of ADAM17 Leads to Insulin Resistance in Association with Age and HFD in Mice.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 35 Suppl 1:.

Withdrawal: Valeria Lopez Salazar, Rhoda Anane Karikari, Lun Li, Rabih El-Merahbi, Maria Troullinaki, Moya Wu, Tobias Wiedemann, Alina Walth, Manuel Gil Lozano, Maria Rohm, Stephan Herzig, Anastasia Georgiadi. Adipocyte Deletion of ADAM17 Leads to Insulin Resistance in Association with Age and HFD in Mice (2021). The FASEB Journal. 35:s1. doi: 10.1096/fasebj.2021.35.S1.00447. The above abstract, published online on May 14, 2021 in Wiley Online Library (wileyonlinelibrary.com), has been withdrawn by agreement between the authors, FASEB, and Wiley Periodicals Inc. The withdrawal is due to a request made by the authors prior to publication. The Publisher apologizes that this abstract was published in error.

RevDate: 2021-07-29

Ramani SK, Rastogi A, Nair N, et al (2021)

Hyperechoic Lesions on Breast Ultrasound: All Things Bright and Beautiful?.

The Indian journal of radiology & imaging, 31(1):18-23.

Ultrasound (US) lexicon of the Breast Imaging Reporting and Data System (BI-RADS) defines an echogenic breast mass as a lesion that is hyperechoic in comparison with subcutaneous adipose tissue. However, at sonography, only 0.6 to 5.6% of breast masses are echogenic and the majority of these lesions are benign. approximately, 0.5% of malignant breast lesions appear hyperechoic. The various benign pathologic entities that appear echogenic on US are lipoma, hematoma, seroma, fat necrosis, abscess, pseudoangiomatous stromal hyperplasia, galactocele, etc. The malignant diagnoses that may present as hyperechoic lesions on breast US are invasive ductal carcinoma, invasive lobular carcinoma, metastasis, lymphoma, and angiosarcoma. Echogenic breast masses need to be correlated with mammographic findings and clinical history. Lesions with worrisome features such as a spiculated margin, interval enlargement, interval vascularity, or association with suspicious microcalcifications on mammography require biopsy. In this article, we would like to present a pictorial review of patients who presented to our department with echogenic breast masses and were subsequently found to have various malignant as well as benign etiologies on histopathology.

RevDate: 2021-07-28

Rafiq MT, Hamid MSA, Hafiz E, et al (2021)

Feasibility and acceptability of instructions of daily care in overweight and obese knee osteoarthritis participants.

INTRODUCTION: Knee osteoarthritis (OA) is a weight-bearing joint disease and more common in the overweight and obese persons. The objective of the study was to assess the feasibility and acceptability of instructions of daily care (IDC) on pain, mobility and body mass index (BMI) among knee OA participants who are overweight or obese.

MATERIAL AND METHOD: The study was an open-label randomized controlled trial of six-weeks. Forty overweight and obese participants with knee OA were randomly divided into two groups by a computer-generated number. The participants in the Instruction Group (IG) were provided with leaflets explaining IDC for the duration of six-weeks. Both groups were instructed to take low doses of the non-steroid anti-inflammatory drug (NSAIDs) on alternate days. The outcome measures were pain, mobility and BMI. The feasibility and acceptability of knee pain and mobility were assessed using a questionnaire designed by experts in rehabilitation.

RESULTS: Participants in the IG reported more statistically significant pain relief as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index score (p=0.001) and improvement in mobility (p=0.000) assessed by the Timed Up and Go test score after six weeks compared to the Control Group (CG). Both groups did not demonstrate any significant change in BMI (p-value > 0.05), The results of descriptive statistics showed a significantly higher satisfaction score to participants who received a combination of IDC and NSAIDs, indicating an acceptable intervention.

CONCLUSION: The IDC are effective and acceptable in terms of improving pain and mobility and should be recommended as the usual care of treatment.

RevDate: 2021-09-26

Offermann A, Joerg V, Hupe MC, et al (2021)

CDK19 as a diagnostic marker for high-grade prostatic intraepithelial neoplasia.

Human pathology, 117:60-67 pii:S0046-8177(21)00128-3 [Epub ahead of print].

High-grade prostatic intraepithelial neoplasia (HGPIN) is a facultative precursor lesion of prostate cancer (PCa). Multifocal HGPIN in needle biopsies in the absence of PCa indicates a higher risk of cancer detection in subsequent biopsies. Therefore, a reliable diagnosis of HGPIN is of high clinical relevance guiding the management of patients with cancer-negative biopsies. Detection of HGPIN is merely based on morphological features while biomarkers aiding in the diagnosis of HGPIN and its differentiation from benign glands and other glandular lesions are lacking yet. Here, we investigated the expression of cyclin-dependent kinase 19 (CDK19) by immunohistochemistry on prostate needle biopsies of 140 patients who were all diagnosed with PCa using whole-tissue sections and compared CDK19 levels between HGPIN, PCa, and adjacent benign glands. In addition, CDK19 was compared with AMACR expression in a subset of intraductal carcinomas (IDCs) on radical prostatectomy (RP) specimens. HGPIN was present in 65.7% of biopsies and in 88% associated to adjacent PCa. CDK19 overexpression defined as moderate to high CDK19 expression visible at low magnification was found in 82.6% of HGPIN. In contrast, 89.3% of benign glands were CDK19-negative or demonstrated only low CDK19 expression highlighting a high sensitivity and specificity to accurately detect HGPIN based on CDK19 expression levels. CDK19 was overexpressed in 59% of PCa but did not correlate significantly with the expression of intermingled HGPIN. On RP, CDK19 and AMACR showed no significant difference in the detection rate of IDC. In summary, assessment of CDK19 facilitates accurate and simplified diagnosis of HGPIN with high sensitivity and specificity and aides the differentiation to non-neoplastic glandular alterations. Considering the high clinical significance of diagnosis HGPIN that still has a limited reproducibility among pathologists, we suggest CDK19 as diagnostic biomarker for HGPIN.


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

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Curriculum Vitae for R J Robbins

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